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COMITET DE REDACIE

Redactor ef:
Dan PRELIPCEANU
Redactor-efi
adjunci:
Drago MARINESCU
Aurel NIRETEAN
COLECTIV REDACIONAL
Doina COZMAN
Liana DEHELEAN
Marieta GABO GRECU
Maria LADEA
Cristinel TEFNESCU
Ctlina TUDOSE
Secretari de redacie: Elena CLINESCU
Valentin MATEI
CONSILIU TIINIFIC
Vasile CHIRI (membru de onoare
al Academiei de tiine Medicale,
Iai)
Michael DAVIDSON (Professor, Sackler
School of Medicine Tel Aviv Univ.,
Mount Sinai School of Medicine,
New York)
Virgil ENTESCU (membru al Academiei de
tiine Medicale, Satu Mare)
Ioana MICLUIA (UMF Cluj-Napoca)
erban IONESCU (Universitatea
Paris VIII, Universitatea TroisRivieres, Quebec)
Mircea LZRESCU (membru de onoare al
Academiei de tiine Medicale,
Timisoara)
Juan E. MEZZICH (Professor of Psychiatry
and Director, Division of Psychiatric
Epidemiology and International
Center for Mental Health, Mount
Sinai School of Medicine, New York
University)
Teodor T. POSTOLACHE, MD (Director,
Mood and Anxiety Program,
Department of Psychiatry,
University of Maryland School of
Medicine, Baltimore)
Sorin RIGA (cercettor principal gr.I)
Dan RUJESCU (Head of Psychiatric
Genomics and Neurobiology
and of Division of Molecular and
Clinical Neurobiology, Department
of Psychiatry, Ludwig- MaximiliansUniversity, Munchen)
Eliot SOREL (George Washington
University, Washington DC)
Maria GRIGOROIU-ERBNESCU
(cercettor principal gr.I)
Tudor UDRITOIU (UMF Craiova)

ARPP

REVISTA
ROMN
de
PSIHIATRIE

ROMANIAN JOURNAL OF PSYCHIATRY

ASOCIAIA ROMN
DE PSIHIATRIE I PSIHOTERAPIE

Vol XVII

www.romjpsychiat.ro

CNCSIS B+

Nr. 3

September 2015

QUARTERLY

p-ISSN: 1454-7848

e-ISSN: 2068-7176

CUPRINS
ARTICOLE SPECIALE
& Actualiti diagnostice n tulburrile de personalitate

41

Aurel Niretean, Lukacs Emese, Tudor Niretean, Istvan Zsolt Szasz, Adrian Horvath, Adina Mari

& Evaluarea riscului suicidar n practica clinic - o experien suedez

44

Ileana S. Constantin

ARTICOLE DE SINTEZ
& Simptomele negative n schizofrenie: de la Kraepelin la DSM 5

48

Octavia O Cpn, Ioana V Micluia

& Personalitatea de tip D la pacienii cu boli cardiovasculare

51

Eva K Lakatos, Elena Minciu, Lrnd J Lakatos, Anna Keszegpal, Aurel Niretean, Adina Mari

& Aspecte clinico-evolutive n tulburarea afectiv bipolar, episodul maniacal (1)

56

Mdlina Vrabie, Victor Marinescu, Anca Talaman, Ioana Micluia

ARTICOLE ORIGINALE
& Tulburri de somatizare la copii i adolesceni - o perspectiv local din judeul Galai

63

Marcela Cmpean, Carmen Truescu, Cristina Petrescu-Ghenea, Alecsandra Irimie-Ana,


Cristina G. Anghel, Liana Kobylinska, Iuliana Dobrescu

& Studiu non-intervenional de observare a utilizrii antipsihoticelor atipice n activitatea clinic


uzual n managementul pacienilor acui spitalizai cu schizofrenie din Europa Central i de Est 68
Radu Teodorescu, Elmars Rancans, Gabor Feller, Dan Prelipceanu

& Corelaii cognitive i emoionale ale simptomelor de stres posttraumatic la mecanicii


de locomotiv expusi la traume la locul de munc.

77

Elisabeta Raco-Szabo, Andrea Glicz-Nagy, Alina Luca

CAZ CLINIC
& Provocri diagnostice la o pacient cu tulburare psihotic dup transplant hepatic

84

Anca Talaman, Alexandra Dolfi, Mihaela Nae, Iulia Roca

INSTRUCIUNI PENTRU AUTORI

Revista Romn de Psihiatrie este indexat de Consiliul Naional al Cercetrii tiinifice din
nvmntul Superior la categoria B+. Apare trimestrial.
Colegiul Medicilor din Romnia acord abonailor la aceast publicaie 5 credite EMC/an.
Articolele tiinifice publicate n revist sunt creditate cu 80 credite EMC/articol.
Revista Romn de Psihiatrie este editat de Asociaia Romn de Psihiatrie i Psihoterapie
i Asociaia Medical Romn

88

SPECIAL ARTICLES

PERSONALITY DISORDERS DIAGNOSTIC


ACTUALITIES
Aurel Niretean1, Lukacs Emese2, Tudor Niretean3, Istvan Zsolt Szasz4,
Adrian Horvath5, Adina Mari6
Abstract:
Personality disorders always reassert themselves as
a field of controversies. Nowadays, the psychiatric
and social complications of the patients' behavior
with personality disorders are of a particular
diversity and severity. They may be favored, masked
or shaped by the social and cultural environment.
Therefore, the earliness and accuracy of the
diagnosis become especially important. This must be
a n e l a b o r a t e d p ro c e s s , c l i n i c a l l y a n d
psychometrically well-founded, but culturally and
morally conditioned.
Key words: personality disorders, diagnostic, sociocultural factors

Rezumat:
Tulburarile personalitatii se reconfirma mereu ca un
domeniu al controverselor. Astazi,complicatiile
psihatrice si sociale ale comportamentului
pacientilor cu tulburari de personalitate sunt de o
diversitate si gravitate particulara. Ele pot fi
favorizate,mascate sau modelate de mediul sociocultural. De aceea precocitatea si acuratetea
diagnosticului devin deosebit de importante. Acesta
trebuie sa fie un proces elaborat, fundamentat clinic
si psihometric dar conditionat cultural si moral.
Cuvinte cheie: tulburarile de personalitate,
diagnostic, factori socio-culturali

The human person has a structural complexity that


explains the perspectives diversity from which it can be
approached. The hypercomplex structure, biologically,
psychologically, socially and spiritually conditioned,
integrates a hierarchy of needs and existential values, as
well as of inclinations and abilities to satisfy them and
follow them. Personal traits are inherited, respectively
acquired by education, socialization and by cultural and
spiritual acquisitions during the different stages of
personogenesis (1).
The personality structure is reflected in the
individual behaviour that is appropriate to the diversity of
life's roles and in interpersonal relations. In this respect,
the traits which confer persistence and stability to the
behaviour of the person and make him/her thus
predictable, are the dominantly inherited ones a classic
example would be shyness regarded as a predictive
element of social phobias. These types of traits they
accompany and feed on childhood experiences, and are the
ones that mostly correspond to social rules and
expectations allowing since the end of the first decade of
life inter-individual differentiations. The latter ones are
subsequently emphasized also by the contribution of the
acquired traits, so that at the personological maturity age
from the end of the third decade of life the individual
behaviour becomes stable and reflects both the dominantly
inherited intimate Self and biologically conditioned, and
the social Self socially and culturally and spiritually
conditioned (2).
At maturity the human person is aware of

who he is and what he is and has common


motivations and existential values with those around him.
This means a way of thinking, of feeling, of acting and of
being, consequently, of seeking the meaning of his own
life and a happiness formula as durable as possible. Selfimage and self-esteem are mutually inter-conditioning
and ensuring adaptation and efficiency in the roles of life
and in the relationships with the people around.
When harmony between the structural
components of a person is missing or is only partial due
to a deviant personogenesis we found ourselves on the
territory of pathological personalities or personality
disorders. Overall, they are characterized by a quasipermanent adaptation deficit in the existential roles which
represent a source of individual and collective suffering
unaware or partially aware of.
Pathological personalities incorporate a
diversity of maladaptive traits, which may be
conjuncturally shaded away or masked by significant
intellectual or creative abilities, by tolerance or
indifference to entourage and by the particularities of the
professional role. As the harmoniously structured
personalities, they are ego-syntonic, but they transfer the
entire responsibility of the personal intentions and actions
on those around them and create themselves gradually a
system of norms and rules of conduct, but also of
egocentric values. From this perspective disharmonic
behaviour emphasizes in its turn the inter-individual
differences (2).

MD, PhD, Professor, Chief of Psychiatry Department, UMF Trgu Mure


MD, PhD, Psychiatry Clinic II, UMF Trgu Mure
MD Psychiatry resident, PhD Candidate, Assistant Professor, UMF Trgu Mure
4
MD Psychiatry resident, PhD Candidate, Psychiatry Clinic II, UMF Trgu Mure
5
MD, Psychiatrist, PhD Candidate, Psychiatry Clinic II, UMF Trgu Mure
6
Senior psychologist,Pediatric Clinic No,1 ,UMF.Tg.Mures
2

41

Aurel Niretean, Lukacs Emese, Tudor Niretean, Istvan Zsolt Szasz, Adrian Horvath, Adina Mari: Personality
Disorders Diagnostic Actualities
Self-image and self-esteem become
thereby fragile and inauthentic, contradictory or they are
in a paradox relationship. All pathological personalities
seek through the mentioned methods access to a
version of selfish happiness, solitary and lacking depth
and authenticity.
For the reasons thus outlined the diagnosis
of the personality disorders becomes a complex process of
which accuracy depends of a multitude of variables.
Among these, the ego-syntonic character of psychobehavioral manifestations and the congruence between
maladaptive traits and biographical experiences which
condition and favour each other, have a prevailing role. In
the same context, the diagnostic approach is influenced by
demographic factors, the mentality and preconceptions of
the entourage, by the frequent association with episodes
and disease of Axis I, as well as by the relativity of rules,
conduct patterns and contemporary community values.
Any diagnostic approach in the given
context means simultaneously also a moral approach
appropriate to its stigmatizing character favoured by the
ignorance of the medical sphere and profane world, by
negative semantic conditioning, by self-perception and
poor self-control of the maladaptive traits, by the negative
impact of biographical narrative descriptions and of
course by the always unpleasant consequences of the
disharmonic behaviour on the entourage.
Currently, in diagnosing personality
disorders, important are the maladaptive manifestations
and their effects on the entourage, next to the development
of the intentionality of personal attitudes and acts. These
are to the disadvantage of the current condition and the
biographic moment lived. Starting from the premise that
patients' narrations have an egocentric, unstable and
manipulative character, the diagnosis has a particular
complexity integrating clinical interviews and structured
ones, a great variety of scales and questionnaires that aim
towards among other various references both
biographic memory and subjective well-being.
Heteroanamnesis and autobiographical narration contents
have a particular role.
Personality Disorders represent a distinct
nosologic category that imprint in a specific manner on
everyday behaviour, being at the same time quantitative
versions of certain essential and general dimensions of the
normal personality. This is why the categorical
personologic diagnosis must always be followed by a
complementary dimensional approach. This double
perspective confers to it a dynamic and staged character in
which there are integrated demographic, social and
economic, cultural, spiritual and moral references. The
diagnosis approach thus structured pleads for the fact that
the personality dimensions may modify in time and in
relation to factors of environment and confer also by this
means complexity and accuracy to the therapeutic and
rehabilitative interventions.
Nowadays, from the categorical
perspective are kept the three clusters - A, B and C,
corresponding to bizarre, eccentric and dissocial
personalities, respectively to the anxious ones to which
are added the personopathies due to a medical condition
and that is temporary epilepsy, in which the intercritical
behaviour is dominated by affective lability, by
impulsivity, by aggressiveness, by paranoidism and
42

apathy. A second large category is represented by mixed


personality disorders and unspecified ones with the
criterion of partial diagnoses present.
Altogether, from the categorical
perspective, the level of accuracy of the diagnosis
diminishes with age in Cluster B personality disorder, and
increase with age in Cluster C personality disorder, and it
is not dependant of this demographic reference in Cluster
A personality disorder, the accuracy of the diagnosis being
for all three clusters higher in the rural environment.
Cluster A personality disorders and antisocial PD are
encountered predominantly in male gender, and
borderline PD, histrionic PD and dependence PD in
female gender.
In pathological personalitites diagnosis
according to DSM V we start from the premise that in the
same patient are encountered criteria belonging to other
personopathic types. Therefore if a patient does not
reunite the complete criteria for one or more personality
disorders there is outlined a version of diagnostic framing
simultaneously categorical and dimensional, that includes
also personopathic entities defined only by traits.
Diagnostic criteria common to all personality disorders
are the functioning level in roles and the presence of
pathological traits. Within this frame are described six
personality disorders which integrate various
combinations of maladaptive traits schizotypal PD,
borderline PD, antisocial PD, narcissistic PD, avoidant
PD and obsessive-compulsive PD, and four personality
disorders defined only by traits schizoid PD, paranoid
PD, histrionic PD and dependence PD which may be
integrated to a significant extent into the first six (3).
The assessment of pathological traits which
should allow diagnosis framing, resorts to a dimensional
model suggested by the five-factors model Big Five. Thus,
there are described binoms negative affectivity /
affective stability, detachment / extroversion,
antagonism/agreeableness, disinhibition /consciousness
and psychoticism / lucidity (4)(5). Each dimension
matches five facets a total of 25 representing the
clinical dominant components. Starting from this model it
has been elaborated the personality inventory PID- 5
which is used for the staged assessment of personality
dimensions and facets as well as for structuring
therapeutic strategy and assessing its efficiency.
The personality functioning in life's roles is
targeting two components, and that is, the Self and the
interpersonal sector. The Self integrates identity,
consciousness and self-esteem, self-evaluation skills and
regulation of emotions and self-direction. To the
interpersonal sector corresponds the empathy even
under circumstances of disaccord with those around but
also the ability to understand the consequences of one's
own behaviour and the behaviour of others. They are
associated with intimacy, that is the ability to maintain
harmonious and stable interpersonal relations. It has been
elaborated within this frame the Level of Personality
Functioning Scale that allows the evaluation of the
affectation level of different components of the Self and of
the interpersonal sector on a scale from 1 to 4.
Thus there are set out the specific
diagnostic criteria for pathological personality and that is
the presence of one or more pathological facets of
personality, significant deficiencies in the functioning of

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


the Self and of the interpersonal, predictable behaviour in
different life situations next to the presence of a stable
adaptive deficit, but independent of the educational level,
other medical conditions and abusive consumption of
psychotropic substances.
It should be stressed the fact that the dimensional
perspective allows nuanced diagnostic formulations
linkable to the temporal identity, and also facilitates the
understanding of the personological continuum
normality-abnormality mental illness (6). Thus,
neuroticism and extroversion decrease with age,
consciousness and agreeableness intensify in time, and
openness to experience from the model of the BIG FIVE
factors increases with age in individualistic type of
societies. Additionally a significant level of agreeableness
influences positively the self-esteem, life satisfactions,
the curiosity and next to an increased consciousness,
favours interpersonal communication, openness to
experience as well as cultivation of virtues. This way the
psychoticism decreases and life quality and longevity are
increasing. The increased levels of openness to experience
determine in individualist societies early development
of dominant psychological traits of the two genders,
cultivate selfishness and egocentrism but also they mask
them to the same extent and the adherence to social rules.
Nevertheless the dimension of openness is low in all
pathological personalities.
In individualist type of sociocultures, the
particularities of education favour high levels of
neuroticism, extroversion and openness to experience.
Whereas in cooperative traditional type of sociocultures
are favoured agreeableness, consciousness and those
facets of extroversion that cultivate empathic closeness.
According to professional options regarded as
first order reference of the psychological maturity these
are congruent with temperamental traits, dominantly
inherited in cooperative type of societies and with
character traits, socially and culturally conditioned in
individualist type of societies.
In the same context, the stable traits of
personality have an adaptive role in traditional societies of
cooperative type, and character traits, socially and
culturally conditioned fulfill a similar role in individualist
type of societies. Antisocial type traits are rare in
cooperative type of societies in both genders and there are
more frequent in individualist type of societies having a
preponderant extension currently in female gender.
In the diagnostic formulation of the personality
disorder must be also taken into account the fact that in
both genders maladaptive traits of adults vitiate the
personogenesis in childhood age, the behaviour models
and adulterate existential values favoring the formation of
certain unstable-impulsive and anxious type of traits.
Also, adult maladaptive traits disrupt the functioning in
roles of those around, affect quasi-constantly
interpersonal relationships and favour the development in
a close human environment of certain selfish adaptive
strategies. There are frequently enough assortative
associations - including marriages - between persons with
similar maladaptive traits who have separately, but also
together, similar biographical experiences.
The spiritual dimensions - including those
assignable to various religions of personality may mask,
shape or shade away maladaptive conducts. Thus,

although the need of sacred is appropriate to each human


being, the abilities of self-transcendence derived from it
are diminished in all pathological personalities (7).
Religious practices may favour except the
fundamentalist ones - extroversion, agreeableness,
consciousness and openness to intellectual and spiritual
experiences. They promote virtues dominantly the
Christian ones, but also the ones ensuring communication
and closeness primarily humanist between people and
communities. Psychoticism decreases and latent personal
aptitudes and resources are mobilized. Overall, longevity
and life quality are favoured (8).
It should be stressed also the importance in the
base diagnostic approach of the temporal dimension of
the identity. Therefore, in the age interval 16-21 years old,
the personality disorder diagnosis is formulated only if the
adaptive deficit lasts over 12 months in persons of male
gender from environments with low social an economical
level. On the other hand in young people the unstable,
dependent type of traits, the originality and
nonconformism may be attributed to age. Introversion and
consciousness have the same significance in third age.
The personality disorder diagnosis at an adult age
is relativized by the multiple comorbidities with the Axis I
diseases, by overestimation of the economic and social
environment influences, as well as the hospitalization or
detention conditions in which often are performed the
personological evaluations. Often behaviour disorders are
masked by the roles of life or ignored by the community
mentality. In third age, the intervention of cognitive
factors, the more fragile somatic condition, the rarefaction
of the social support network and of the existential roles,
influence negatively the accuracy of pathological
personalities diagnosis.
The psychiatrist's responsibility in formulating
the personality disorder diagnosis is a most particular one
because of the diversity of prejudices and expectations of
the profane world, but also of the medical one, the
particularities of contemporary social and cultural
dynamics and of gravity stigmatization ethically similar
with the one in the psychoses field.
And maybe in the last resort it is often difficult
to know if an ugly image or an adored one is inside us or
outside.
REFERENCES
1.Nirestean A sub.red. Personalitate si deschidere spirituala. Tg.Mures:
University Press, 2009
2.Lazarescu M, Nirestean A. Tulburarile de personalitate. Iasi:
Ed.Polirom, 2007
3.Diagnostic and Statistical Manual of Mental Disorders, 5th ed.,
American Psychiatric Association, 2013
4.Mattei JF. The development of markers for the BIG-V Factors
structures. Psychological Assesment 1992, 4, 26-42
5.Costa PT, Mc Crae RR. Revised NEO Personality Inventory and the
NEO-Five-Factor Inventory professional manual. Psychological
Assesment Resources, Odessa FL, 1992
6.Widiger TA, Simonsen E. Alternative Dimensional Models of
Personality Disorders: Finding a Common Groand. Journals of
Personality Disorders 2005, 2, 110-130
7.Trimble MR. The soul in the brain. Baltimore: John Hopkins
University Press, 2007
8.Joseph R. The transmitter to God. University Press of California,
Berkeley, 2001

***
43

SPECIAL ARTICLES

SUICIDE RISK ASSESSMENT IN CLINICAL


PRACTICE A SWEDISH EXPERIENCE
Ileana S. Constantin 1
Abstract:
According to WHO's estimates, every 40 seconds one
person dies by committing suicide somewhere in the
world. The consequences on family, close friends
and community are devastating and, in certain
cases, persist for the rest of their lives. Given the
extent and impact of such phenomenon, the suicide is
nowadays seen as a major public health issue and
preventing it has become a priority for all healthcare
systems around the world. In Sweden, as well as in
various other countries across the globe,
professional associations and government bodies
make constant efforts to improve existing clinical
guidelines and protocols
for management of
suicidal patients. Protocols for a structured suicide
risk assessment account for a significant share
among the regional healthcare programs. This paper
aims at reviewing such a protocol and debating upon
the major issues by relying on both the literature and
the author's recent clinical experience as a
psychiatrist within the Swedish mental health system.
Key words: suicide risk, structured assessment

The World Health Organization (WHO) defines


suicide as one's deliberate act of self-destruction. Often
described as an impulsive act, it is predominantly the
outcome of a genuine suicidal process involving a gradual
progression from the loss of all hope to the actual planning
of the suicidal act. As this process may span long periods of
time, sometimes years (1), numerous authors consider that
many cases of suicide (actually a vast majority) can be
prevented (2,3). Properly assessing at which exact stage in
the suicidal process the patient is creates optimal
conditions for an adequate intervention (4). Suicide risk
assessment, as it is currently done in Sweden, is a
structured approach performed according to
recommendations and clinical guidelines outlined in
regional healthcare programs.
STRUCTURED ASSESSMENT OF SUICIDE RISK
WORKING PROTOCOL (1)
1.ASSESSING RISK FACTORS
There is a long list of factors known to increase
the risk of suicide. We consider demographic factors (such
as age, sex, marital status), unemployment, the lack of a
functional social support network, underlying mental
pathology, somatic problems (especially those pathologies

Rezumat :

Conform statisticilor OMS, la fiecare 40 de secunde


undeva in lume o persoana decedeaza ca urmare a
unui act suicidar. Consecintele asupra familiei,
cercului de apropiati si comunitatii sunt devastatoare
si persista in unele cazuri pentru tot restul vietii.
Avand in vedere dimensiunile si impactul acestui
fenomen, in prezent suicidul este considerat o
problema majora de sanatate publica iar preventia
lui un obiectiv prioritar pentru sistemele sanitare din
intreaga lume. In Suedia, ca si in numeroase alte tari
ale lumii exista o preocupare constanta a asociatiilor
profesionale si institutiilor guvernamentale pentru
imbunatatirea ghidurilor clinice si a protocoalelor
de lucru referitoare la ingrijirea pacientului cu risc
suicidar. O pondere semnificativa in cadrul
programelor regionale de ingrijire o detin
protocoalele de lucru pentru evaluarea structurata a
riscului de suicid. Articolul propune o trecere in
revista a unui astfel de protocol cu discutii asupra
aspectelor importante bazandu-se atat pe informatii
din literatura de specialitate cat si pe experienta
clinica recenta a autorului ca medic specialist in
sistemul psihiatric suedez.
Cuvinte cheie: risc suicidar, evaluare structurata

involving or expected to involve physical pain in their


course), substance abuse or addiction, separation, suicide
among family members or close friends and a personal
history of attempted suicide. This last factor is deemed to
be the most important of known risk factors (5); the more
violent the methods previously used, the higher the risk
for a new attempt (6).
To have a clear, fast and structured image on
existing risk factors, we will use SAD the Sad Persons
Scale (7); the resulting score is documented in the
patient's record. (Table 1)
2.SUICIDAL PROCESS MAPPING USING THE
SUICIDE LADDER
The Suicide Ladder (8) is a tool used to
measure how far along the patient has gotten in the
suicidal process, from depressive mood and feeling of
hopelessness to making active plans and preparations
towards committing suicide. Questions are organized in
such a way so as to look progressively into this process.
The investigator will stop at that specific stage of the
process when the patient's answer is a plausible denial.
(Fig.1)

1
M.D.Psychiatry. Personal address: Bd. Constructorilor 24, Bl.19, Sc A, Ap 28, Sector 6, Bucuresti.
Contact: ileana_cons@yahoo.com, phone no. 0723574524

44

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015

Figure 1. Suicide Ladder (8) sample questions


corresponding to each level

Factor
S=Sex (male)
A=Age (<19 or >45 years)
D=Depression
P=Previous suicide attempts
E=Ethanol abuse
R=Rational thinking loss
S=Social support lacking
O=Organized plan
N=No spouse
S=Sickness (chronic, debilitating disease)

Points
1
1
1
1
1
1
1
1
1
1

Table 1. SAD PERSONS scale. Source: Patterson et al. (7)


Results of this assessment must be documented in the
patient's record. An example of standard statement is:
Suicide Ladder shows that the patient seems to
acknowledge his/her wish to die, but plausibly denies
suicidal thoughts or plans.
3.REVIEW OF RISK SITUATIONS / TRIGGERS AND
PROTECTIVE FACTORS
It is a well-known fact that risk stems out of a
patient's experience about a particular circumstance rather
than the circumstance itself. Special attention should be
paid to the feelings of loneliness, despair and
hopelessness, poor impulse control, sleep deprivation,
chronic physical pain, anxiety attacks, loss or threatened
loss of a key person. Experienced social humiliation (the
loss of one's job, for instance) and professional
reinsertion, which may entail painful clashes, carry a
higher risk. The use of alcohol or incipient abstinence may
be difficult moments when the patient's ability to manage
their suicidal ideation is impaired. Violence (by or against
the patient) may be trigger for the suicidal act (9).
A thorough investigation of a patient's history
also reveals protective factors, including the existence of a
functional social support network and the patient's feeling
of belonging; personal, cultural or religious values
according to which the suicidal act is taboo; dependent
children; fear of physical pain or mutilation following a
self-aggressive act.

The review of risk situations and protective


factors must always be rooted in patient's reality as their
significance is individual. The patient's feedback is
crucial. It is not uncommon for the patient to identify
themselves the circumstances increasing the risk of
suicide or decreasing suicidal ideation. Results of this
review and discussions with the patient on the topic must
be documented in the patient's record.
4.USE OF CLINICAL ASSESSMENT SCALES AND
EVALUATION TOOLS
Such structured assessment tools represent an
important help for the practitioner; their use is
recommended in assessment guidelines and protocols,
always with the proviso that they can only aid in and never
replace clinical judgment (10).
To assess a patient who has not yet attempted
suicide, we have often used the SSI-Scale for Suicide
Ideation (11). This scale ensures a multifaceted scoring of
the suicidal process: the patient's attitude towards life or
death, the nature of suicidal thoughts (duration, frequency,
the sense of being in control of the act in case of suicidal
impulses, arguments for and against the suicidal gesture),
the nature of the imagined attempt (planning, timing,
method, method accessibility, the feeling of being able to
actually do it), preparations (goodbye letter, finals actions
such as writing one's will, making donations, signing life
insurances, etc).
After an attempted suicide, patients should be
assessed using SIS - Suicidal Intent Scale (12), which
enables a thorough review of the objective and subjective
circumstances around the actual attempt. Issues such as
the presence or absence of someone else near the patient,
measures taken by the patient to prevent anyone else from
getting near them for help, the timing of the attempt, trying
to ask for help during or after the attempted suicide, and
the type of attempt (planned or impulsive) are considered.
Of equal importance is the patient's own perceptual
expectancy of the outcome, for instance if the
administered dose of tablets was thought to be fatal or not.
Finally, this scale provides an image of the severity of the
actual suicide attempt and inherently plays a major part in
assessing any subsequent suicide risk.
We always include and document in the patient's
medical record their own rating of the risk of committing
suicide. The patient rates this risk with a grade from 1 to
10, where 1 is I will never take my own life and 10 I
have made up my mind, I do not want to live anymore.
5.INTERVIEWING FAMILY MEMBERS
Family members may only be interviewed with
the patient's prior consent. Possible types of direct verbal
(clear-cut messages such as I kill myself if you leave) or
indirect verbal (I cannot continue to live like this) and
direct non-verbal (collects pills, procures a gun, etc) or
indirect non-verbal (making one's will, signing an
insurance policy, etc) suicidal communications may come
up. This discussion helps complete the image on the
patient's overall situation with information about life
circumstances, risk factors, triggers for suicidal thoughts
and resources that might and must be used for the
treatment plan.
6.GLOBAL ASSESSMENT OF THE ACTUAL
SUICIDE RISK
This approach should begin by streamlining the
45

Ileana S. Constantin: Suicide Risk Assessment In Clinical Practice A Swedish Experience

information obtained during the previous stages of the


process. Depending on severity, the risk will be rated as
low, medium or high. It is not uncommon to see the
suicide risk is difficult to assess as the most appropriate
rating, which means that the assessor cannot exclude a
major risk. The lack of proper contact with the patient
during the interview, the patient's attitude of rejecting the
dialogue, a patient under substance influence, conflicting
information may be as many reasons underlying such
difficulty in rating the risk.
A practical way to embed insights collected so far
and to help assess the severity of the suicide risk is
described in the table below (13). (Table 2)
7.COMPREHENSIVE DOCUMENTATION OF THE
SUICIDE RISK ASSESSMENT IN THE PATIENT'S
RECORD

All important aspects must be written down in


the patient's medical record. This is how the health
practitioner justifies their clinical judgment, the reasons
for the risk rating and consequently their choice of the best
therapeutic approach. This assessment is also important
for other members of the medical team, who have
therefore access to vital information in order to ensure a
proper attitude in their relationship with the patient.
Improved know-how of the therapeutic team translates
into high-quality care in the medical practice. As a matter
of fact, in the Swedish healthcare system, the suicide risk
assessment is not exclusively the duty of the attending
physician; the psychologist or the nurse in charge
regularly assesses and documents the suicide risk in the
patient's record and turns to the physician for help
whenever necessary.

GUIDELINES FOR STRUCTURED SUICIDE RISK ASSESSMENT


Low or absent risk

Medium risk/risk difficult to


assess

Level 1-3
None

Level 4-6
Few

Thoughts of death may


occur, denies suicide wish

Vague suicidal plans, evasive


answers

Suicidal
communication

Occasionally absent /
present in tense situations or
under the influence of
alcohol

Communication present with


intricate feelings of shame,
menace or manipulation

Clear, repetitive messages


related to persistent and severe
suicidal ideation

Previous suicide
attempts

None

Previous, less planned


attempt, passive method

Previous, well-planned
attempts

Overall picture
of suicidal
process

No previous suicide history

Self-aggressive behavior,
previous attempts to commit
suicide by intoxication

Severe, recurrent episodes of


suicidal ideation, suicidal
plans and previous, wellplanned suicide attempts

Problems,
resources and
relationships

There are problems, but also


resources for solving them;
good relationship with the
family and therapeutic
alliance with the medical
team

Recurrent relationship issues,


mixed messages from the
family. The relationship with
the staff may range from
flattery to hostility.

Somatic disorder

None

Mild pathology

Psychiatric
disorder

None

Depression, obsessive
compulsive disorder,
impulsiveness

None

Regular abuse of alcohol


associated with depression,
guilt and aggressiveness
during/after consumption

Suicide Ladder
Risk factors
Conscious
predisposition to
suicide

Abuse/addiction

Table 2. Suicide risk assessment criteria -risk categories. Source: (13)

46

High risk
Level 7-9
Many
Structured suicidal plans,
active suicide method in the
near future

Major losses. Sporadic


contacts with the family,
marked by conflicts. Previous
hospitalizations the meaning
of which the patient did not
understand, the patient feels
mentally abused.
Incurable, painful, invalidating
diseases
Severe depressive disorder,
bipolar disorder,
schizophrenia, severe
personality disorders
Severe alcohol or drug abuse /
addiction, subsequent social
exclusion

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


Example of documenting the suicide risk assessment in
the patient's electronic file (fictitious patient):
Patient with multiple risk factors: male, 50, prior
diagnostic of recurrent depressive disorder, under
treatment for 10 years; multiple therapeutic attempts
involving various antidepressants,
no significant
improvements (as the patient describes it). Patient feels
like he has a poor quality of life due to multiple relapses
and is reluctant to new therapeutic trials for fear of side
effects. Currently unemployed, he was laid off 4 months
ago for not properly fulfilling his job responsibilities. Lots
of guilt and shame because of this. Financial distress. He
lives alone; wife died 3 years ago, no children. No
relatives living within call, has a sister who lives in
another town and whom he sees twice a year. Poor social
support network, there is only one neighbour that the
patient sees about twice a week. Patient has avoided
meeting him lately because he sees no point in doing it
anymore. Describes feelings of hopelessness; the future
seems dark. His mother committed suicide when he was
10; the patient recalls that she used to be sad all the
timejust like me. He experiences chronic back pain for
which the family doctor prescribed a treatment. Over the
past few months, the patient requested twice that the
current dose of medication be increased as it was no longer
effective, but his request was denied. He felt humiliated
and treated like a drug addict. He denies alcohol use.
Medical history shows no previous suicide attempts.
According to the Suicide Ladder, the patient
displays suicidal ideation in the form of thoughts recurring
several times a day, especially when he is in pain and in the
evening when preparing to go to sleep. He has succeeded
in resisting these thoughts so far, but feels this is more and
more difficult and he is tired. Despite denying suicidal
plans, he admits that he started to collect pills one month
ago, though he later changed his mind and gave them back
to the drug store in order to no longer keep them in the
house.
Medical history does not show any protective
factor. The patient himself says that I have no reason that
might stop me from dying today.
Rating scales: Patient's self-rating of the risk of
taking his own life today is 6 on a scale of 1 to 10. He
says:it may go up to 9 when I am in pain. SSI: 22 points
The patient has no family to see him off for admission to
the hospital. He does not want us to contact his sister
because we see each other very rarely and our
relationship is not so close anyway.
The suicide risk is rated as high both now and in

the long term due to the presence of major depressive


disorder, multiple risk factors (SAD: 6 points) and the lack
of protective factors, to a difficult psychological and social
situation that the patient sees as stigmatizing and to the
lack of proper social support network, in conjunction with
the outcome of clinical scale scoring. A particular issue is
the chronic pain identified by the patient as a major trigger
of suicidal ideation, which significantly increases the
patient's likelihood of committing suicide.
The structured suicide risk assessment must be
repeated and documented at specific key time points
(changes in patient's clinical condition, before modifying
the supervision level, before granting of home leaves,
before discharge), but also whenever necessary (5). Last
but not least, we should remember that a properly
conducted assessment interview may and must be a crisis
intervention enabling an empathic contact with the patient
and providing them with a secure environment where they
can talk about their thoughts.
References:
1.Lindstrm K, Elofsson B, Ferm M et al. Vrdprogram om
suicidprevention fr vuxna.Jnkping: Landstinget i Jnkping ln,
2005, 1-28.
2. Wasserman D (red). Suicide: An Unnecessary Death. London: CRC
Press, 2001, XXI-29.
3. World Health Organization. Preventing Suicide: a global imperative.
Geneva: WHO Press, 2014, 1-92.
4.Runeson B, Samuelsson M, sberg M. Vrd av sjlvmordsnra
patienter-en kunskapsversikt. Socialstyrelsen, 2003,1-83.
5.Renberg E, Sunnqvist C, Westrin , Waern M, Jokinen J, Runeson B.
Suicidnra patienter-kliniska riktlinjer fr utredning och vrd.
Stockholm: Svenska Psykiatriska Freningen, 2013, 1-92
6. Runeson B, Tidemalm D, Dahlin M, Lichtenstein P, Lngstrm N.
Method of attempted suicide as predictor of subsequent successful
suicide: national long term cohort study. BMJ 2010;341:c3222.
7. Patterson WM, Dohn HH, Bird J, Patterson GA Evaluation of suicidal
patients: the SAD PERSONS scale. Psychosomatics 1983; 24(4):343-5,
348-9.
8. Beskow J. (red). Sjlvmord och sjlvsmordsprevention. Om
livsavgrande gonblick.Lund: Studentlitteratur, 2000
9. Capusan A, Andersson B. Vrdprogram fr suicidprevention hos
vuxna. stergtland: Landstinget i stergtland, 2010, 1-26.
10. Runeson B. Regionalt Vrdprogram-Suicidnra patienter.
Stockholm: Stockholms lns landsting, 2010, 1-78.
11. Beck A.T, Kovacs M, Weissman, A.. Assessment of suicidal
intention: the scale for suicide ideation.J. Consult. Clin. Psychol. 1979;
47:343352.
12. Beck AT, Schuyler D, Herman I. Development of Suicidal Intent
Scale. In: Beck AT, Resnick HLP, Lettieri J (eds). The prediction of
suicide. Bowie, MD: Charles Press,1974, 45-56.
13.Nordlund S, Hellstrm J, Sparring S. Vrdprogram fr suicidnra
patienter. Srmland: Landstinget Srmland, 2014, 79.

***

47

REVIEW ARTICLES

NEGATIVE SYMPTOMS OF SCHIZOPFRENIA:


FROM KRAEPELIN TO DSM V
Octavia O Cpn1, Ioana V Micluia2
Abstract:
The diagnosis of schizophrenia comprises mainly
negative and positive, cognitive, disorganized and
affective symptoms. The negative symptoms reflect the
absence or the lack of emotional and behavioral
functioning and the positive symptoms stand for add-ons to
normal experiences. This paper depicts a journey through
the concept of negative symptoms, from its early
description up to the perspective embraced by DSM V. The
notion of negative symptoms has regained its' importance
due to the poor functional outcome associated with these
symptoms and because the current available
antipsychotics can control the positive symptoms, in most
of the patients, while they are poorly effective against
negative ones.
Keywords: historical perspective, diminished expressivity,
avolition/apathy.

Rezumat:
Diagnosticul de schizofrenie cuprinde simptome pozitive,
negative, cognitive, afective si deorganizare. Simptomele
negative reflect absena sau deficitul funcionrii
emoionale i profesionale, iar simptomele pozitive
reprezint o exagerare a experienelor normale. Lucrarea
de fa descrie conceptul de simptome negative de la
originile sale pn la perspectiva adoptat n DSM V.
Noiunea de simptome negative i-a rectigat importana
datorit asocierii acestor simptome cu o capacitate
sczut de funcionare global i datorit faptului c
tratamentele actuale controleaz simptomele pozitive, la
cei mai muli pacieni, dar au o eficacitate diminuat
asupra simptomelor negative.
Cuvinte cheie: perspectiv istoric, diminuarea
expresivitii, avoliie/apatie.

INTRODUCTION
Schizophrenia is a chronic, debilitating disorder
of the young adult, with a multifactorial etiology,
characterized by significant dysfunctions in cognition,
thought process, perception, affect and social functioning.
The diagnosis of schizophrenia is based on
positive, negative, cognitive, disorganized and affective
symptoms. The dichotomy between negative and positive
symptoms reflects for the negative symptoms the absence
or the lack of emotional and behavioral functioning and for
the positive symptoms add-ons to normal experiences.(1)
These terms were first used by the neurologist Sir John
Reynolds to describe the loss or the excess of vital
properties which he observed in patients with epilepsy.
(2)
The negative symptoms of schizophrenia
encompass blunted affect, alogia, apathy, abulia, social
withdrawal, anhedonia. The positive symptoms, which
were known in the classical literature as productive
symptoms, comprise hallucinations and delusions. (3)
EARLY DESCRIPTIONS OF NEGATIVE SYMPTOMS
The description of negative symptoms goes back
over a century to Kraepelin's dementia praecox concept.
Kraepelin considered the affect deficit as a core symptom
of the disease and to be underpinning the motivational
deficits: the lack of interest, the indifference, the lack of
pleasure. He sustained this model based on the assumption
that all mental processes include an affective component.
Kraepelin named the disease dementia praecox because he
ascribed the emotional deficit to a degenerative process.
(1, 4)
Kurt Schneider in 1959 used a different system of

classification for the symptoms of schizophrenia, he


introduced the terms of first rank and second rank
symptoms. The first rank symptoms are all positive
symptoms while the blunted affect is considered to be a
second rank symptom (1).
CONCEPTUALIZATIONS
There are different studies that led to the
dichotomy between positive and negative symptoms,
from which the most important conceptualizations belong
to Crow, Andreasen and Carpenter.
Crow's model (1980) distinguishes two types of
schizophrenia: type I dominated by positive symptoms
and in which case the brain imaging does not reveal
structural abnormalities and type II characterized, from a
clinical point of view, by a deficit syndrome (negative
symptoms) and brain imaging emphesising underlying
structural changes.(5)
In 1982, Andreasen considered that positive and negative
symptoms of schizophrenia were the extremes of one
dimension (the bipolar theory) and attributed the
appearance of negative symptoms to a dopaminergic
deficit. She defined five constitutive factors of the
negative symptoms: alogia, flat affect, avolition/apathy,
anhedonia/asociality and attentional impairment. (6) It is
noteworthy that these factors are the same as used today,
with the exception of attentional impairment.
Carpenter in 1988 introduced a new perspective
towards negative symptoms, distinguishing the primary
negative symptoms from the secondary ones, which can
be caused by depression, extrapyramidal syndrome
induced by antipsychotics, positive symptoms (the
paranoid social withdrawal), hospitalism or lack of

1
Assistant Professor, PhD student in Psychiatry, Department of Neuroscience, Iuliu Haieganu University of Medicine and Pharmacy, No. 8 Victor Babe
Street, 400012, Cluj-Napoca, Romania. Email: octavia.capatina@umfcluj.ro
2
Professor of Psychiatry, Head of Psychiatry Department, MD, PhD, Department of Neuroscience, Iuliu Haieganu University of Medicine and
Pharmacy, No. 8 Victor Babe Street, 400012, Cluj-Napoca, Romania. Email: ioanamiclu@yahoo.com

48

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


stimulation. Diagnosing a primary negative symptom
implies excluding the potential causes for secondary
negative symptoms.(7) Both primary and secondary
negative symptoms can be temporary or enduring, and
both are associated with poor functional outcomes and
poor response to current treatments.(8) Carpenter also
defines the deficit subtype of schizophrenia in patients
with primary enduring negative symptoms that cannot be
explained as sequelae of depression or other
psychopathology.(3) The deficit syndrome can be found in
drug-nave patients and perhaps in a third of chronic
patients.(7)
A current approach to negative symptoms is
based on identifying the persistence of these symptoms
during periods of clinical stability regardless of them
being primary or secondary as long as they don't respond
to treatment.(8) In clinical trials on persistent negative
symptoms it is recommended a minimal severity level,
PANSS scores >3 for at least one of the following
symptoms: blunted affect, poor rapport, passive
withdrawal, emotional withdrawal, lack of spontaneity
and a restricted severity of the potential confounders:
depression, parkinsonism, positive symptoms and social
deprivation. The duration of persistent negative
symptoms can be less than 12 months, but preferably more
than 6 months. (9, 10, 11)
The International Classification of Diseases
Tenth Edition (ICD-10)-Chapter F and the Diagnostic and
Statistical Manual of Mental Disorders Fourth Edition
Text Revision (DSM-IV-TR) are authoritative documents
for defining mental disorders. ICD-10 adopted as criteria
for schizophrenia Schneider's first rank symptoms and
also included negative symptoms such as marked apathy,
paucity of speech, and blunting or incongruity of
emotional responses (it must be clear that these are not due
to depression or neuroleptic medication). (12) DSM-IVTR recognizes the negative symptoms (blunted affect,
alogia and avolition) as being one the five core features of
schizophrenia. (13)
MOVING TO DSM-V
There have been controversial opinions in the
last decade over the constituent factors of the negative
symptoms, so in 2006 the National Institute of Mental
Health (NIMH) - the Measurement and Treatment
Research to Improve Cognition in Schizophrenia
(MATRICS) project- gathered experts in this matter to
establish which factors should be included. As a result of
this consensus the following factors were included:
blunted affect, alogia, social withdrawal, avolition and
anhedonia. (14) The validity of these factors was reviewed
in subsequent studies. (15, 16). It was also suggested, in
the NIMH-MATRICS consensus that these five factors
can be classified in two domains: diminished expressivity
and avolition/apathy.
Diminished expressivity
encompasses blunted affect and alogia while
avolition/apathy includes social withdrawal, amotivation
and anhedonia. Subsequently this hypothesis was
validated by several studies. (14, 17, 18)
Recent studies, from 2013 and 2014, confirmed
the existence of the two domains, but more importantly,
they emphasized the fact that the domains should be
analyzed separately, due to the different clinical
presentation, but mostly because of the different outcomes
of the patients, in terms of functioning and quality of life.
(19, 20)

This is the point of view is also embraced in the DSM V. In


the DSM-V the negative symptoms are considered one of
the five defining domains among hallucinations,
delusions, abnormal psychomotor function and
disorganized speech. A new approach of DSM-V is the
fact that these symptoms are quantifiable on a scale from 0
to 4, which might be useful in terms of evaluation and
comparison. According to DSM-V, the negative
symptoms comprise: 1. avolition, including decreased
motivation, social withdrawal (asociality) and
anticipatory anhedonia and 2. diminished emotional
expression covering blunted affect and poverty of speech
(alogia). Avolition stands for the lack of goal and
initiative, while the diminished expressivity implies the
reduced emotional expression represented in verbal or
non-verbal modes (decreased spontaneity, fluency and
quantity of speech, reduced facial expressions, gestures,
body movements). (21)
CONCLUSIONS
Negative symptoms are considered, nowadays,
to be a core feature of the phenomenology of
schizophrenia, being a distinct domain and representing a
separate therapeutic target. (14)
The prevalence of primary negative symptoms
according to recent studies is around 52%-57% in
outpatients with schizophrenia. (22, 23) It has been
suggested that the negative symptoms have a greater
impact on everyday functioning than other categories of
symptoms. They may affect the patients' capacity to work
or study, to maintain relationships, to participate in
everyday activities, and to live independently (24). These
outcomes were confirmed after the statistical control of
the possible sources of secondary negative symptoms
(depression, extrapyramidal symptoms, positive
symptoms, hospitalism, lack of environmental
stimulation) (25). Schizophrenia has strong economic
impact, given the costs of medical care for inpatients or
outpatients, the community services, treatments, social
services. The socioeconomic burden of this disease
implies direct costs like hospitalization and medication
and indirect costs: social support and the loss of
employment. A worldwide study conducted between 2011
and 2013 showed that only 15% of the patients with
schizophrenia are employed, which infers that the greatest
costs of schizophrenia are related to unemployment (26).
Present treatments, like first-generation
neuroleptics and second-generation antipsychotics,
mostly address the positive symptoms, while the negative
ones are poorly influenced (27). The persistence of these
symptoms holds back the reinstatement of the patients,
making them incapable to fulfill their social, professional
or family roles.
References:
1. Marneros A, Andreasen NC, Tsuang MT et al. Negative versus positive
schizophrenia. Berlin, Heidelberg: Springer-Verlag, 1991, 1-109.
2. Pearce JM. Positive and negative cerebral symptoms: the roles of
Russell Reynolds and Hughlings Jackson. J. Neurol. Neurosurg.
Psychiatry 2004; 75: 1148-76.
3. Gaebel W. Schizophrenia: current science and clinical perspective.
Dusseldorf: Wiley-Blackwell, 2011, 1-20.
4. Minkowski E. Schizofrenia. Bucureti: IRI, 1999, 31-96.
5. Crow TJ. The two-syndrome concept: origins and current status.
Schizophr. Bull. 1985; 11(3):471-86.
6. Andresen NC. Negative symptoms in schizophrenia. Definition and
reability. Arch Gen Psychiatry 1982; 39(7):784-8.

49

Octavia O Cpn, Ioana V Micluia: Diagnosing Personality Disorders:A Modern View

7. Carpenter WT Jr, Heinrichs DW, Wagman AM. Deficit and nondeficit


forms of schizophrenia: the concept. Am J Psychiatry 1988; 145(5):57883.
8. Galderisi S, Mucci A, Bitter I et al. Eufest Study Group. Persistent
negative symptoms in first episode patients with schizophrenia: results
from the European First Episode Schizophrenia Trial. Eur
Neuropsychopharmacol 2013; 23(3):196-204.
9. Marder SR, Kirkpatrick B. Defining and measuring negative
symptoms of schizophrenia in clinical trials. Eur
Neuropsychopharmacol 2014; 24(5):737-43.
10. Marder SR, Alphs L, Anghelescu IG et al. Issues and perspectives in
designing clinical trials for negative symptoms in schizophrenia.
Schizophr Res. 2013; 150(2-3):328-33.
11. Buchanan RW. Persistent negative symptoms in schizophrenia: an
overview. Schizoph. Res. 2007; 33:1013-1022.
12. World Health Organization. The ICD-10 Classification of Mental and
Behavioural Disorders. In: International Classification of Diseases and
Related Health Problems Tenth Edition. Bucureti: All Educational,
1998, 103-116.
13. American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders Fourth Edition Text Revision. Bucureti:
APLR, 2003, 298-319.
14. Kirkpatrick B, Fenton WS, Carpenter WT Jr et al. The NIMHMATRICS consensus statement on negative symptoms. Schizophr Bull.
2006; 32(2):214-9.
15. Messinger JW, Trmeau J, Antonius D, et al. Avolition and
expressive deficits capture negative symptom phenomenology:
Implications for DSM-5 and schizophrenia research. Clin Psychol Rev.
2011; 31(1):161168.
16. Oorschot M, Lataster T, Thewissen V et al. Emotional Experience in
Negative Symptoms of SchizophreniaNo Evidence for a Generalized
Hedonic Deficit. Schizophr Bull. 2013; 39(1):217225.
17. Strauss GP, Keller WR, Buchanan RW, et al. Next-generation
negative symptom assessment for clinical trials: validation of the brief
negative symptom scale. Schizophr. Res. 2012; 142:88-92.

50

18. Nayaka M, Ohmori K. A two factor structure for the deficit syndrome
in schizophrenia. Psyciatry Res. 2008; 158: 256-259.
19. Strauss GP, Horan WP, Kirkpatrick B et al. Deconstructing negative
symptoms of schizophrenia: avolition-apathy and diminished expression
clusters predict clinical presentation and functional outcome. J Psychiatr
Res. 2013; 47(6):783-90.
20. Rocca P, Montemagni C, Zappia S et al. Negative symptoms and
everyday functioning in schizophrenia: A cross-sectional study in real
world-setting. Psychiatry Res. 2014; 218:284-289.
21. American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders Fifth Edition. Arlington, VA: American
Psychiatric Publishing, 2013, 87-123.
22. Sicras-Mainar A, Maurino J, Ruiz-Beato E et al. Impact of negative
symptoms on healthcare resource utilization and associated costs in adult
outpatients with schizophrenia: a population-based study. BMC
Psychiatry 2014; 6:214:225.
23. Bobes J, Arango C, Garcia-Garcia M et al. CLAMORS Study
Collaborative Group: prevalence of negative symptoms in outpatients
with schizophrenia spectrum disorders treated with antipsychotics in
routine clinical practice: findings from the CLAMORS study. J Clin
Psychiatry 2010; 71:280-286.
24. Rabinowitz J, Levine SZ, Garibaldi G et al. Negative symptoms have
greater impact on functioning than positive symptoms in schizophrenia:
analysis of CATIE data. Schizophr Res. 2012; 137(1-3):147-50.
25. Fervaha G, Foussias G, Agid O et al. Impact of primary negative
symptoms on functional outcomes in schizophrenia. Eur Psychiatry
2014; 29(7):449-55.
26. Zaprutko T, Kus K, Bilobryvka R, et al. Schizophrenia and
Employment: Evaluation From Professionals Point of View. Psychiatr
Q. 2015. [Epub ahead of print]
27. Harvey PD. Assessment of everyday functioning in schizophrenia:
implications for treatments aimed at negative symptoms. Schizophr Res.
2013; 150(2-3):353-5.
***

REVIEW ARTICLES

TYPE D PERSONALITY IN PATIENTS WITH


CARDIOVASCULAR DISEASES
Eva K Lakatos1,2, Elena Minciu2, Lrnd J Lakatos3, Anna Keszegpal4,
Aurel Niretean5, Adina Mari6
Abstract:
The etiologies and pathogenesis of cardiovascular
diseases (CVD) include not only biological factors but
psychosocial and behavioral ones as well. When one
considers the rhythm and the socio-economic
particularities of our contemporary society of hyperconsumption, evaluating the contributions of personality
factors, in the determinism and dynamics of CVD,
becomes a paramount medical and social goal. In the last
20-25 years, researches have begun to regain the interest
in the role of personality in the outcome of patient with
CVD. A new personality type, the type D or "distressed"
personality was introduced as a vulnerability factor of
patients with heart disease. It is a common structure, its
prevalence in the general population being between 13 to
25 percent and it's even higher in patients with CVD. It
refers to a personality type designating individuals who
are inclined to experience emotional and interpersonal
difficulties, which is likely to affect physical health and
combines the traits negative affectivity (NA) and social
inhibition (SI). The combination of these two personality
traits has shown to reliably predict adverse outcome in
several groups of patients suffering from CVD,
independently from the conventional biological risk
factors. The researchers and clinicians should take into
account in clinical practice the predisposition of the
patients to psychological distress, which is easy
assessable with DS14, in order to improve their physical
and mental health and to positively influence the
progression of CVD in this group of patients with
increased risk.
Key words: negative affectivity, social inhibition, type D
personality, cardiovascular diseases, coronary artery
disease

Rezumat:
Etiologia i patogeneza bolilor cardiovasculare (BCV)
include att factori somatici ct i factori psihosociali i
comportamentali. n condiiile ritmurilor i
particularitilor social-economice din societatea
contemporan de hiperconsum, evaluarea contribuiei
factorilor personologici n determinismul i dinamica
BCV devine un deziderat de prim importan medical i
social. n ultimii 20-25 ani cercetrile au nceput s-i
recanalizeze interesul pe rolul personalitii n
prognosticul pacienilor cu BCV. Un nou tip de
personalitate, personalitatea de tip D sau distresseda
fost introdus, ca un factor de vulnerabilitate caracteristic
pacienilor cu boal cardiac. Aceasta se ntlnete
frecvent, prevalena n populaia general fiind ntre 1325% iar n rndul pacienilor cu BCV fiind chiar mai
ridicat. Se refer la un tip de personalitate, care
desemneaz indivizi nclinai spre a experimenta
dificulti emoionale i n relaiile interpersonale, care
pot afecta starea de sntate i combin ca trsturi
afectivitatea negativ (AN) i inhibiia social (IS).
Fuziunea acestor dou trsturi n personalitatea de tip D
prezice n mod credibil prognosticul negativ la mai multe
grupuri de pacieni cu BCV, independent de factorii de
risc biomedicali convenionali. Cercettorii i clinicienii
ar trebui s ia n considerare n practica clinic
predispoziia pacientului la distress-ul psihologic, care
poate fi uor de evaluat cu DS14, n vederea de a
mbunti starea de sntate mintal i fizic i de a
influena pozitiv progresia BCV la acest grup de pacieni
cu risc crescut.
Cuvinte cheie: afectivitate negativ, inhibiie social,
personalitate de tip D, boal cardiovascular, boal
coronarian ischemic

P E R S O N A L I T Y A N D C A R D I O VA S C U L A R
DISEASES (CVD)
The etiologies and pathogenesis of CVD as
hypertension, coronary artery disease (CAD) and heart
failure are complex. These include both biological factors
such as increased blood pressure, increased inflammation
and increased cardiac sympathetic tone (1, 2), and a wide
variety of psychosocial and behavioral factors as
depression (3, 4), chronic stress (5), anxiety (5, 6),

decreased social support (7), and personality (8, 9, 10).


These psychological factors often aggregate in cardiac
patients thus further increasing the risk of CV events (5,
11, 12, 13).
Personality is a dynamic and a highly complex
structure, biologically, psychosocially and culturally
conditioned. It constitutes the fundamental component of
the terrain upon which psychopathological disorders
appear and develop. Its structure integrates a complex of

PhD student, University of Medicine and Pharmacy Targu-Mures, Str. Gh. Marinescu, Nr. 38, Jud. Mures, 540139, Romania.
MD, resident physician Cardiology, I. Cardiology Clinic for Adults, Emergency Institute of Cardiovascular Diseases and Transplantation Targu-Mures,
Str. Gh. Marinescu, nr. 50, Jud. Mures, 540136, Romania.
3
MD, Urology Specialist, Urology Department, Top-Med Medical Center, Str. Dorobantilor, Nr. 1-3, Targu Mures, Jud. Mures, 540103, Romania.
4
MD, resident physician Dermatovenerology, Department of Dermatovenerology, Emergency County Hospital Oradea, Str. Republicii, Nr. 37, Jud. Bihor,
410167, Romania.
5
MD, PhD, Professor, Chief of Psychiatry Department, University of Medicine and Pharmacy Targu-Mures, Romania, Str. Gh. Marinescu, Nr. 38, Jud.
Mure, 540139, Romania.
6
Senior psychologist,Pediatric Clinic No,1 ,UMF.Tg.Mures
2

51

Eva K Lakatos, Elena Minciu, Lrnd J Lakatos, Anna Keszegpal, Aurel Niretean, Adina Mari: Type D Personality In
Patients With Cardiovascular Diseases
cognitive, emotional, volitional-instinctual, motivational
and relational features, called dimensions. These
dimensions are general human features present, in varying
degrees, in all individuals with normal personality, in the
disharmonic structures of personality and are markers of
vulnerability for both psychiatric and somatic diseases.
All the population, normal and pathological people as
well, have the same dimensional universe, the same
substrate structure. Abnormal, maladaptive features of
personality, even those considered as diagnostic criteria
for some specific personality disorders can be met in
normal individuals (14). Recognizing these maladaptive
personality features is important from the perspective of
somatic diseases, especially CVD, because they
determine lifestyle, behavior such as low adherence to
treatment, neglect of physical activity, unhealthy diet and
smoking.
Non-psychopathological behavioral
characteristics were associated for the first time with
somatic diseases in the 1950s when M. Friedman and
Rosenman discovered (1959) a cluster of symptoms and
behavioral signs that predispose to risk of heart disease,
defined as type A behavior pattern. This pattern is one of
the competitive types with a tendency to interact with
others in an aggressive or hostile manner (12). It includes
ambitiousness, aggressiveness, competitiveness,
impatience, muscle tenseness, alertness, rapid and
empathic vocal style, irritation, cynicism, hostility and
increased potential for anger.Hostility was considered one
of the core features (15, 16, 17).
Psychological reverse of type A is the type B behavior
pattern that describes tolerant, tempered individuals,
which are not at increased risk for heart disease.
During the 1970s and 1980s several clinical trials
have evaluated the role of type A as a predictor of adverse
CV events related to CAD, establishing a small
relationship between angiographically determined CAD
and type A behavior pattern among younger patients (18).
Subsequently, due to these relatively unsatisfactory
results related to the type A behavior pattern, personality
factors have been mostly neglected in CV research since
(19, 20). Depression and to a lesser extent anxiety entered
into the spotlight. Although depression and depressive
symptoms are strong predictors of onset and progression
of heart disease (21, 22), the attempts to successfully
reduce biomedical risk factors (RF) by treating depression
have yielded mixed findings (23, 24).
In the last 20-25 years, researches have begun to
regain the interest on the role of personality in health and
disease (25, 26). This renewed attention is justified by the
fact that personality features may have greater
explanatory power than depression (5, 27, 28). There is
growing evidence that underline that dimensions such as
neuroticism are the base of psychiatric diagnoses such as
major depression (29, 30). Personality can have a
significant predictive value regarding the prognosis of
patients with CVD. Because of the known clustering of
unfavorable psychosocial characteristics (5), it is
important that a personality approach is taken in
identifying those patients who are at increased risk for
emotional stress-related cardiac events.
In 1995 a new personality type was introduced as a
vulnerability characteristic of patients with heart disease:
52

the type D or "distressed" personality (27, 31, 32). This


combines the traits negative affectivity (NA) and social
inhibition (SI) (8, 31). Both are viewed as global traits,
considered relevant in many situations. As in other models
of personality, these traits reflect emotional and
behavioral consistency. The combination of these two
personality traits has shown to reliably predict adverse
outcome in several groups of patients suffering from CVD
(33, 34, 35). Although the relationship between type D
personality and CV events is increasingly recognized, the
mechanisms underlying this relationship are largely
unclear.
FEATURES OF TYPE D PERSONALITY
The description of the type D personality or
distressed was started from the existing personality
theory, according to which the interaction of specific traits
may have harmful effects on the health condition (5). The
term distressed refers to a discrete personality
configuration designating individuals who are inclined to
experience emotional and interpersonal difficulties,
which is likely to affect physical health (35). This differs
from other psychological measures which are currently
being evaluated as predictors in the prognosis of CVD
such as social support or major depressive disorder.
Although major depression reflects a psychopathological
condition, type D personality is a common structure, its
prevalence being in the general population between 13 to
25 percent and it's even higher in the patients with CVD,
26%-53% (34, 36, 37, 38).
Type D individuals have fewer interpersonal
relationships and tend to feel uncomfortable in the
presence of strangers (31). The tendency seen in type D
individuals to experience negative emotions and to inhibit
self-expression in a social context is a synthesis of the
traits NA and SI (13). The amalgamation of the two
constructs, NA and SI into the type D personality has been
demonstrated empirically in patients with CAD (39, 40).
Individuals with type D personality score highly on the
mentioned personality dimensions.
NEGATIVE AFFECTIVITY
It is a complex personality trait defined as the
tendency to experience negative emotions, including
depressed mood, anxiety, anger and hostile feelings (41).
This tendency was observed in a significant proportion of
cardiac patients (13). Individuals scoring high on NA do
not only experience states of dysphoria and tension but
also have a negative view of self, report more somatic
symptoms and have an attention bias towards adverse
stimuli (42). Individuals characterized by high NA find
themselves more often exposed to stressful events and
tend to react more intensely to them (43). NA is closely
related to neuroticism, because it correlates highly (r =
0.68) with the Neuroticism scale from the NEOFive
Factor Inventory in healthy participants and with the
Neuroticism scale (r = 0.64) from the Eysenck Personality
Questionnaire in patients with ischemic heart disease (13,
44, 45, 46, 47).
SOCIAL INHIBITION
Represents the stable tendency of inhibiting the
expression of emotions, thoughts and behavior in social
interactions. It is defined as the tendency to avoid the
potential dangers of social interaction and anticipate
negative reactions or disapproval of others. Individuals

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


scoring high on SI frequently feel inhibited, tense,
uncomfortable and insecure in the company of others and
therefore prefer to keep distance in social relations. In
concert with these behavioral predispositions, highly
socially inhibited individuals are less likely to seek social
support (48, 49). A negative correlation has been shown
between SI and extraversion in healthy participants (r = 0.59) and cardiac patients (r = - 0.65) (37). Avoidance
temperament, a concept closely linked to SI, has also been
associated with neuroticism (r = 0.86), behavioral
inhibition (r = 0.65) and negative emotionality (r = 0.93)
(50). In conclusion, SI is a global trait associated with high
negative emotionality and personal distress and refers to
individual differences in reticence, withdrawal and nonexpression (13).
SI is a moderator, it attenuates the effects of NA on
clinical outcome (8, 27). Only those individuals that score
high on both subcomponents are at increased CV risk. The
prevalence of major adverse CV events (death,
myocardial infarction (MI), coronary artery bypass graft
or percutaneous coronary intervention (PCI)) for patients
with CAD with high score on NA but low score on SI is
lower than for that individuals scoring highly on both
subcomponents (51).
TYPE D PERSONALITY ASSESSMENT
Over the past years several methods of assessment
have been used to determine the type D personality. In the
beginning, a combination of scales methods was used in
order to obtain the appropriate item combination. The type
D structure was originally developed on Belgian cardiac
patients in an attempt to investigate the role of personality
traits in the prognosis of CAD. In this early study of type
D, the survivors of a MI were asked to complete the Heart
Patients Psychological Questionnaire (52), which
assessed the SI component of type D and the Trait Scale of
the Spielberger State-Trait Anxiety Inventory (53), which
assessed the second dimension (NA) of the distressed
personality. From the 105 patients 26.7% were classified
as having distressed personality (high score on both
dimensions). After a median follow-up period of 3.8
years, 15 patients had died. A significant number (n = 10)
of these patients had distressed personality (type D) (p
<0.01) (36).
In 1998 a questionnaire was introduced, consisting
of 16 items, to assess the type D personality. In the DS16
all items are answered on a 5-point Likert scale ranging
from 0 (false) to 4 (true). It yields four personality types,
but only those who score high on both subcomponents
were classified as having a type D personality. The
psychometric qualities and the prognostic power of the
scale have proven satisfactory for Belgian cardiac patients
with Cronbach's of 0.89 and 0.82 and test-retest
reliability of 0.78 and 0.87 for NA and SI, respectively
(46).
Nowadays, the type D personality is assessed using
the DS14 scale. The DS16 was revised to include the most
prominent low-order traits from the NA and SI domains. It
includes 7 items that assess NA and 7 items that assess SI.
Similar to DS16, all items are answered on a 5-point Likert
scale ranging from 0 (false) to 4 (true). It yields four
personality types, but only those who score above a
predetermined, standardized, cut-off score of 10 on both
subcomponents are classified as having a type D
personality. The psychometric properties of the DS14 are

good with Cronbach's of 0.88 for NA and 0.86 for SI.


Temporal stability over a 3-month period was high (r =
0.82 and 0.72 for NA and SI, respectively)(37). It has been
validated in several languages (54, 55), making it widely
applicable. Because of its brevity, DS14 proved to be a
practical screening instrument for the influence of
psychosocial factors in clinical practice (11).
TYPE D PERSONALITY AND CV EVENTS
Type D personality is defined by a high score on
both NA and SI. The merger of the two constructs into the
type D personality was empirically demonstrated in
patients with CAD (39, 40). Cardiac patients with this type
D profile have not only an increased risk of emotional
distress but also an increased risk of adverse CV events (8,
36). In a study of patients with CAD, deaths from cardiac
causes were four times more common in those with type D
personality compared with non-type D patients, even after
controlling for conventional RF (8). The same thing was
observed in a later study performed on more than 300
CAD patients, who received optimal treatment in terms of
medication, surgery and rehabilitation over 5 years. Type
D personality in these patients had a significant predictive
value (OR = 8.9, p = 0.0001), independent of biomedical
factors, such as left ventricular ejection fraction, age and
despite appropriate treatment. Co-occurrence of these
conventional RF further increased the risk of poor
outcome even more (9). Both high levels of baseline stress
(OR = 2.01, p = 0.054) and presence of type D personality
(OR = 2.90, p = 0.003) were independent predictors of CV
events over a 5-year period. This result highlights that type
D is a stable construct that helps in risk stratification above
and beyond more temporary states, such as in this case,
current stress levels (56). Type D personality and older age
were independent predictors of the development of cancer
in patients with CAD (57).
A study investigated the effect of type D
personality on the occurrence of adverse events at 9
months in patients with CAD after PCI and implantation
of bare metal stents or sirolimus-eluting stents. Type D
patients had a cumulative increased risk of adverse events
compared with non-type D subjects (58).
Another study suggested that patients with type D
personality and implantable cardioverter defibrillator (for
primary or secondary prevention of sudden cardiac death)
were more likely to suffer from anxiety or symptoms of
depression. Type D personality (OR=7.03), use of
psychotropic medication (OR=8.16) and lack of social
support (OR=0.97) were independent determinants (p
<0.05) of symptoms of anxiety in these patients. Type D
personality remained a significant determinant of
symptoms of depression among other contributors
(OR=7,40) (59). It independently predicts the onset of
depressive symptoms in patients with CAD and PCI (60).
This result supports the idea that personality factors may
underlie the presence of depressive disorder (13,29, 30).
Type D patients have higher levels of circulating tumor
necrosis factor alpha (TNF-) and soluble TNF-
receptors that are predictors of mortality in congestive
heart failure (61, 62).
CV patients with type D personality accuse more
frequently impaired physical and mental health status
compared to their non-type D counterparts (62). This
might be the result of their inadequate symptom and
illness perception (63). Individuals with type D
53

Eva K Lakatos, Elena Minciu, Lrnd J Lakatos, Anna Keszegpal, Aurel Niretean, Adina Mari: Type D Personality In
Patients With Cardiovascular Diseases
personality may be more likely to be more aware of
normal bodily sensations and to interpret them as painful
or pathological (42), and also, they tend to believe that
their illness will have more serious consequences and that
treatment will be less effective (64). This health condition
reported by patients has been shown to have a significant
predictive value over indicators of disease severity in
predicting mortality and rehospitalization (63).
Type D personality is associated with an unhealthy
lifestyle (e.g. smoking, alcohol consumption, physical
inactivity) (65), medication non-adherence (66) and
inadequate consultation behavior(67, 68).
CONCLUSIONS
Type D personality was associated with increased
morbidity and mortality in different CV populations
independently of conventional biomedical RF (69, 70)
and with an increased prevalence of CV RF (71).
Individuals with this type of personality have an increased
risk of developing psychiatric and medical disorders (31,
32).
When one considers the rhythm and the socioeconomic particularities of our contemporary society of
hyper-consumption, evaluating the contributions of
personality factors, in the determinism and dynamics of
CVD, becomes a paramount medical and social goal.
Studies have shown that type D personality is an important
and easily assessable negative prognostic predictor that
should be considered in clinical practice. It can be
regarded as a psychopathological condition that can affect
health and longevity and may require psychosocial and /
or pharmacologicalinterventions (72).
Further studies are needed to determine how to deal, from
a therapeutic point of view, with individuals that have type
D personality, in order to improve their physical and
mental health and to positively influence the progression
of CVD in this group of patients with increased risk.
Without conflicts of interest. No funding was necessary for this
research.
Abbreviations: CAD- coronary artery disease, CVcardiovascular, CVD- cardiovascular diseases, NA- negative affectivity,
OR- Odds Ratio, PCI- percutaneous coronary intervention, RF- risk
factor, SI- social inhibition, TNF-- tumor necrosis factor alpha.

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***

55

ORIGINAL ARTICLES

Clinical and evolutional aspects in bipolar disorder, manic


episode (1)
Mdlina Vrabie1, Victor Marinescu2, Anca Talaman3,Ioana Micluia4
Abstract:
To understand the maniac-depressive illness, to diagnose
it precisely and to treat it in an efficient way, it is necessary
to get familiarized to what Kraepelin called common
fundamental features of the disease.
The models of maniacal and depressive symptoms clearly
have a cyclic character, but the aspects of overlapping,
transition as well as the fluctuating ones are extremely
important in the description and understanding of the
entire disease. The natural course and results of manicdepressive illness contribute to its defining and
differentiation from schizophrenia. If the clinician
understands the natural course, it may help them answer
the questions of a patient regarding the most important
estimation of all, namely prognosis: will it come and
when?
Key words: bipolar, manic, depressive.

Rezumat:
Pentru a nelege boala maniaco-depresiva, pentru a o
diagnostica cu precizie i pentru a o trata n mod eficient, e
necesara familiarizarea cu ceea ce Kraepelin numea
"caracteristicile comune fundamentale" ale bolii.
Modelele de simptome maniacale si depresive au n mod
clar caracter ciclic, dar aspectele de suprapunere, de
tranziie, precum si cele fluctuante sunt extrem de
importante n descrierea i nelegerea de ansamblu a
bolii. Cursul natural i rezultatele bolii maniacodepresive contribuie la definirea i diferenierea ei de
schizofrenie. Pentru clinician, nelegerea cursului
natural poate sa-l ajute sa rspunda la ntrebrile unui
pacient despre cea mai important estimare a tuturor,
prognosticul: Va reveni, i cnd?

Acknowledgement:
"This paper is published under the frame of European
Social Fund, Human Resources Development Operational
Programme 2007-2013, project no.
POSDRU/159/1.5/S/138776"/ "Acest articol este publicat
prin Fondul Social European, Programul Operational
Dezvoltarea Resurselor Umane 2007-2013, contract nr.
POSDRU/159/1.5/S/138776"

physical and mental activity levels, greater energy (with a


corresponding decreased need for sleep), irritability,
perceptual acuity, paranoia, heightened sexuality and
impulsivity. The degree, type and chronicity of these
cognitive, perceptual and behavioral changes determine
the major sub-classification of mania, namely hypomania
or mania. In hypomania, the above changes are generally
moderate and may or may not result in serious problems
for the individual experiencing them. In more intense
episodes, however, they deeply disrupt the lives of
patients, their families and society.
Mood in acute mania is not well described by the classic
writers, perhaps because extreme changes in cognition and
behaviour are more clearly observable than subjective
mood states. However, two thousand years ago, Aretaeus
of Cappadocia noted that those who are manic are gay,
active and expensive. They are naturally joyous, they
laugh and they joke: they show off in public with crowned
heads as if they were returning victorious from the games;
sometimes they laugh and dance all day and all night (2).
Kraepelin (1), writing centuries later agreed, but stressed
the instability of the manic mood: Mood is unrestrained,
merry, exultant, occasionally visionary or pompous, but
always subject to frequent variation, easily changing to
irritability and irascibility or even to lamentation and
weeping.

To understand the maniac-depressive illness, to diagnose it


precisely and to treat it in an efficient way, it is necessary to
get familiarized to what Kraepelin called common
fundamental features of the disease.
The models of maniacal and depressive symptoms clearly
have a cyclic character, but the aspects of overlapping,
transition as well as the fluctuating ones are extremely
important in the description and understanding of the
entire disease. Thus, Kraepelin (1) wrote: The
delimitation of the individual clinical forms of the malady
is in many respects wholly artificial and arbitrary.
Observation not only reveals the occurrence of gradual
transitions between all the various states, but it also shows
that within the shortest space of time the same morbid case
may pass through most manifold transformations.
Manic states are usually characterized by heightened
mood, more and faster speech, quicker thought, brisker

1
Psychiatry MD, PhD Student in Psychiatry, University of Medicine & Pharmacy Iuliu Hatieganu Cluj-Napoca, Romania, 7Ward,Clinical Hospital of
Psychiatry Al. Obregia Bucharest, Romania (madalina.vrabie@yahoo.com)
2
Senior Psychiatry, PhD, Lecturer at Department of Psychiatry, University of Medicine & Pharmacy Carol Davila, Bucharest, Romania,
7Ward,Clinical Hospital of Psychiatry Al. Obregia Bucharest, Romania
3
Senior Psychiatry, PhD, Assistant Professor, Department of Psychiatry, University of Medicine & Pharmacy Carol Davila, Bucharest, Romania,
9Ward,Clinical Hospital of Psychiatry Al. Obregia Bucharest, RomaniaDepartment of Psychiatry, University of Medicine & Pharmacy Carol
Davila, Bucharest, Romania
4
Professor Doctor, Head of Psychiatry Department, University of Medicine & Pharmacy Iuliu Hatieganu Cluj-Napoca,Romania, Second Psychiatric
Clinic, Emergency County Hospital Cluj-Napoca, Romania,

56

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


Bleuler (3) commented that thought remains relatively
intact in the less severe forms of mania: The thinking of
the manic is flighty. He jumps by by-paths from one
subject to another, and cannot adhere to anything. With
this the ideas run along very easily and involuntarily, even
so freely that it may be felt as unpleasant by the patient. . . .
Because of the more rapid flow of ideas, and especially
because of the falling off of inhibitions, artistic activities
are facilitated even though something worth while is
produced only in very mild cases and when the patient is
otherwise talented in this direction.
Thinking becomes fragmented and often psychotic in
acute mania. Coherence gives way to incoherence; rapid
thinking proceeds to racing and disjointed thinking;
distractibility becomes all-pervasive. Paranoid and
grandiose delusions are common, as are illusions and
hallucinations. In Kraepelin's description (1), patients
show themselves sensible and approximately oriented but
extraordinarily distractible in perception. Sometimes it is
quite impossible to get into communication with them;
they usually understand emphatic speech and even give
isolated suitable replies, but they are influenced by every
new impression; they digress and go into endless details.
Activity and behavior are greatly increased and
diversified in mania. Patients appear to be indefatigable;
they are rash, virulently opinionated and interpersonally
aggressive. For many patients, excessive energy translates
directly into pressured writing in an inordinate production
of written declarations, poetry and artwork.
The progression from hypomania to acute mania is usually
accompanied not only by instability of mood and a sense
of impending doom or premonitions of madness, but also
by increasingly erratic behaviour. Rush (4) made this
clear in his monograph Medical Inquiries and
Observations upon the Diseases of the Mind: Its
premonitory signs are watchfulness, high or low spirits,
great rapidity of thought, and eccentricity in conversation
and conduct; sometimes pathetic expressions of horror,
excited by the apprehension of approaching madness;
terrifying or distressing dreams; great irritability of
temper, jealousy, instability in all pursuits; unusual acts of
extravagance manifested by the purchases of houses, and
certain expensive and unnecessary articles of furniture
and hostility to relations and friends. Sexual or erotic
excitement is common in mania. Aretaeus of Cappadocia
(150 AD) (5), for example, wrote that "a period lewdness
and shamelessness" exists in mania. Likewise, Kraepelin
(1) noted that sexual excitability is increased and leads to
hasty engagements, marriages by the newspaper,
improper love adventures, conspicuous behaviour,
jealousy and matrimonial discord.
Particularly dramatic and extreme among the clinical
features of acute mania are the frenetic seemingly aimless
and occasionally violent activities of manic patients.
Bizarre, driven, paranoid, impulsive and grossly
inappropriate behaviour patterns are typical.
Delirious mania, or Bell's mania, is a relatively rare grave
form of mania characterized by severe clouding of
consciousness. When Bell (6) described the syndrome at
the middle of the 19th century, he noted its sudden onset
and the symptoms of severe insomnia, loss of appetite,
disorientation, paranoia and extremely bizarre
hallucinations and delusions. Kraepelin (1) also remarked
the syndrome's acute onset and noted that patients were

stupefied, confused, bewildered, in addition to being


completely disoriented in terms of time and place. At the
basis of the illness he found a dreamy and profound
clouding of consciousness, and extraordinary and
confused hallucinations and delusions. Griesinger (7)
also emphasized the acute onset of the syndrome and
observed that the primary emotion experienced by
patients is anxiety. Bond (8) noted that acute delirious
mania can be distinguished by its sudden onset, with or
without premonitory signs of irritability, insomnia or
emotional withdrawal; the presence of the hypomanic or
manic syndrome at some point during the illness;
development of the signs and symptoms of delirium, a
personal and/or family history of mania or depression, and
responsiveness to standard treatments for mania.
Mood during delirious mania may shift quickly between
extreme melancholia and mania suggesting a clinical link
to mixed states. In Kraepelin's (1) words, mood is "very
changing, sometimes anxiously despairing (thoughts of
death), timid and lachrymose, distracted, sometimes
unrestrainedly merry, erotic and ecstatic, sometimes
irritable or unsympathetic and indifferent". The extreme
cognitive and perceptual changes during delirious mania
are primarily manifested through clouding of
consciousnesses, hallucinations and delusions. The
profoundly disturbed and psychotic behaviour of delirious
mania underlines the origin of the phrase raving maniac.
Chronic mania was observed and described by many early
clinicians, including Pinel (9), Esquirol (10), Griesinger
(7), Schott (11), Kraepelin (1), and Wertham (12).
According to Schott (11), only the lack of recovery
distinguished the chronic from the acute form of the
illness. A first manic episode after the age of 40 was
thought to put the patient at much higher risk for
chronicity than one occurring earlier (13), an observation
consistent with the result of subsequent research. Wertham
(12) presents the central features of chronic mania:
reduced intellectual productivity and general activity
levels, increased behavioral stereotypy, and a general
intellectual weakening. Hare (14), in an excellent
historical review of the concept of mania, discussed the
declining interest in the subject of chronic mania after the
19th century. He partially attributed it to the decreasing
morbidity of manic illness and sustained that
improvements in general health and hygiene has resulted
in significant changes in the manifestation, severity and
consequences of mania. (15)
The seven B criteria for the diagnostic of
mania/hypomania may be reminded by DIGFAST
mnemonic formula. Mania / hypomania are present when
three (if mood is euphoric) or four DIGFAST criteria (if
mood is irritable) are present.
In mania, unlike
hypomania, there is a significant dysfunction in the social
and/or professional field. Thus, a patient having a
corresponding number of DIGFAST criteria and who is
not deteriorated or a psychopath or who does not need
hospitalization may be considered in a hypomanic
episode. (16)
DIGFAST mnemonic formula for Mania / Hypomania:
Distractibility: the incapacity to stay focused on a task for
a long time
Sleep deficit: reduced need for sleep coupled with the
increase of energy in manic/hypomanic patients (it must
be differentiated from insomnia from the major depressive
57

Mdlina Vrabie, Victor Marinescu, Anca Talaman,Ioana Micluia: Clinical And Evolutional Aspects In Bipolar Disorder,
Manic Episode (1)
episode)
Grandiosity: high, non-realistic self-trust or
hallucinations
Flight of ideas: speedy thoughts
Activity increase: excessive increase of activity for a goal
in the social or sexual field, school or work
Talkativeness: significantly more talkative than in the
euthymia periods
Indiscretion: dysfunctional activities focused on one's
self such as excessive expenses, unprotected sex with
foreigners and other impulsive behaviours. (16)
Mania is a complex volatile and fluctuating
mixture of symptoms. "The form and ways which mania
manifests are manifold" said Aretaeus (5) nearly 2000
years ago. "Some are cheerful and like to play others
passionate and of destructive type who seek to kill others
as well as themselves". Although classically described as a
state of extraordinary energy and activity, mania can also
present clinically as manic stupor or "catatonia".
Manic mood, frequently characterized as elated and
grandiose, as often as not is riddled with depression, panic
and extreme irritability; mania without significant mixed
features is what is known as classic mania. For years,
mania was differentiated mistakenly from schizophrenia
because it reputedly lacked a thought disorder. Now it is
recognized as an often floridly psychotic condition.
Manic episodes differ from person to person and in the
same individual from time to time, although Falret (17, 18)
and Kraepelin (1) noted a tendency for constancy in
symptom patterns across episodes in the same individual.
Wellner and Marstal (19) reporting on a study of 279
manic episodes in 221 patients, concluded that atypical
attacks are followed by atypical, and typical by typical
significantly more often than not (P = 0.002), indicating
the patients' inclination to reproduce the type of their
psychoses". Beigel and Murphy (20) found that patients
with multiple manic attacks tended to show similar
behavior and mood patterns during subsequent episodes.
Two more recent studies (21, 22) demonstrated that manic
and mixed episodes show diagnostic stability over time;
the interepisode stability of depressive mixed states, while
significant, is much less pronounced than is the case for
manic states (23).
Goodwin and Jameson (15) wrote that the symptomatic
profile of catatonia is extremely consistent over episodes,
whereas Casidy and colleagues (24), who evaluated 77
bipolar patients during two distinct manic episodes for 2
years, concluded that manic symptomatology generally
remains consistent from one episode to the other. More
precisely, they found out that the severity of mania,
dysphoria, hedonic activation, psychosis and irritable
aggression tend to correlate to each other over episodes,
but not psychomotor symptoms. Regardless of the degree
of constancy of the clinical picture across attacks, it is
clear that symptoms vary widely during any given manic
episode as it progresses through different stages. These
stages, characterized by Carlson and Goodwin (25), begin
with elation or irritability, evolve into a more severe form
of arousal and hyperactivity escalate, and culminate in
floridly psychotic disorganization.
Research (15) on mood symptoms in mania, shows that
most patients, on average, are depressed (46 percent) or
labile (49 percent) nearly as often as they are euphoric (63
percent) or expansive (60 percent); they are irritable (71
58

percent) even more often. The depression, irritability and


mood lability are generally seen less often in early stages
of an episode, although few studies have specified the
stage, level or severity of mania at the time of observation.
Winokur and colleagues (26) observed depressed mood in
68 percent of their manic patients. They found that short
depressive contaminations in the manic episode were
significantly more common in women (79 percent) than in
men (49 percent). Like many investigators, they were
especially impressed by the volatility of mood during
manic episodes.
Nonpsychotic cognitive symptoms are common during
mania. Grandiosity and flight of ideas subjectively
experienced as racing thoughts were observed in
approximately three quarters of the manic patients. Less
clearly and more variably defined were distractibility,
poor concentration and confusion. Definitions were very
wide-ranging for confusion from somewhat confused
an unable to follow the gist of conversation to the more
severe clinical use of the term to denote disorientation and
serious memory disturbance. (15)
Here we use as a definition of thought disorder the one
provided by Solovay and colleagues (27): thought
disorder "is not intended to denote a unitary dimension or
process; rather, it refers to any disruption, deficit or
slippage in various aspects of thinking, such as
concentration, attention, reasoning or abstraction".
Certain psychotic features of mania and bipolar
depression delusions and hallucinations - are relevant
but not central to the concept of thought disorder.
Andreasen (28) noticed that most manic patients, unlike
schizophrenic patient, have a reversible thought disorder.
Apart from a continuous pressure to speak, they showed
an almost complete recovery over time. Hallucinations
occur less frequently than delusions in both the manic and
depressed phases of bipolar illness. Hallucinatory
phenomena seem to represent the extreme end of the
symptomatic picture, being nonexistent in milder forms of
depression and mania and most pronounced in the gravest
(most delirious) states. Hallucinations during mania are
often ecstatic and religious in nature, brief and fleeting in
duration and inconstant in their modality of expression.
They appear qualitatively, at least in the few studies in
which they have been approached, to be more similar to
organic than to schizophrenic psychoses. Gender
differences in the experience of hallucinatory phenomena
are unclear, though there is some evidence that women are
more likely to report having had hallucinations.
Like Bauer and colleagues (29), Akiskal and colleagues
(30) concluded that rather than euphoria/irritability, the
central defining focus of mania should be psychomotor
activation. This conclusion is consistent with the emphasis
of Heinroth (31) and Koukopoulos (32), which says that
excitement is the fundamental state of the bipolar
subgroup of manic-depressive illness. By incorporating
new features of mania derived from EPIMAN study (30)
(for example, pathological gregariousness and
overfamiliarity) and using clinical expertise, different
groups of investigators have developed a factorial
structure of mania that incorporates psychomotor
activation as the major criterion, along with mood
disturbance, other signs and symptoms, and a lack of
insight and judgment. Practically, all investigations of
mania structure noticed the basic dimensions: a mood

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


component characterized as preponderantly euphoric or
dysphoric, psychomotor activation, psychotic features
and irritability and/or aggression.
As noted earlier, Carlson and Goodwin (25) described
progressive stages of mania, from mild hypomania to
delirious psychotic mania. The stages were inferred from a
study of 20 unmedicated bipolar patients who had
experienced a manic episode at some time during their
hospitalization. Patients' longitudinal course was divided
into three stages, with predominant mood as the primary
criterion from the euphoria of stage I to the anger and
irritability of stage II, to the severe panic of stage III. In
some of the patients, the onset of mania (the switch) was
gradual, clearly unfolding in a sequence until the full
syndrome had developed. In others, the onset was sudden
and dramatic; even in these cases, the earlier stages were
present and transient. According to Carlson's and
Goodwin's affirmations (25), the initial phase of mania
(stage I) typically is characterized by increased activity;
by a labile mood that can be euphoric, irritable or both; and
by expansive, grandiose and overconfident thoughts.
Thinking remains coherent but is often tangential. Patients
describe this change as "going high" and frequently report
racing thoughts. In some cases, "high" does not go beyond
stage I which corresponds to hypomania. But many
episodes progress to the next stage. Psychomotor activity
increases evident in the more rapid speech and the
mood state becomes more labile, characterized by a
mixture of euphoria and dysphoria. Irritability turns into
open hostility and anger and the accompanying behavior
often is explosive and assaultive. As racing thoughts
progress to a definite flight of ideas, cognition becomes
increasingly disorganized. Preoccupations intensify with
grandiose and paranoid trends that are apparent as
delusions. This level, which corresponds to acute mania, is
referred to as stage II.
In some patients, the manic episode progresses further to
an undifferentiated psychotic state (stage III) experienced
by the patient as clearly dysphoric, usually terrifying and
accompanied by frenzied movement. Thought processes
that earlier had been difficult to follow become incoherent
and definite loosening of associations is often seen.
Delusions are commonly bizarre and idiosyncratic, and
some patients experience ideas of reference,
disorientation and delirium-like state. This phase of the
syndrome is difficult to distinguish from other acute
psychoses, at least superficially. In general, as the manic
episode unfolds, stage I is dominated by elation (or
irritability) and grandiosity, stage II by increasing
hyperactivity and arousal, and stage III by florid psychotic
disorganization. In the Carlson and Goodwin study (25),
many of the rated items showed continuous distributions,
whereas others showed definite thresholds involving
apparently qualitative shifts. The level of psychomotor
activity escalated continuously through all three stages
and ratings for manic mood increased in a similar way
through stages I and II. Ratings of psychosis, by contrast,
were not clearly distributed along a continuum. As can be
seen, stage III mania was characterized by the relatively
abrupt and initial appearance of hallucinations, formal
thought disorder in Schneiderian sense and organic
delirium. Bipolar affective disorder is a lifelong illness
having a variety of forms, phases and subdivisions. (33)
Bipolar disorder is frequently unrecognized, erroneously

diagnosed and inadequately treated. A survey on the


members of US bipolar association "Chapters" showed
that more than 33% asked for professional help within one
year since the appearance of symptoms. Out of these, 69%
were erroneously diagnosed (especially suffering from
unipolar depression), and there was an average of four
physicians seen before obtaining a precise diagnostic and
more than 33% waited for more than 10 years before
getting a diagnostic (33), a finding astonishingly similar to
the previous survey. (33)
As in many research domains, the studies of evolution of
the manic-depressive illness involve methodological
complexities that should be taken into account when we
interpret the results of a study. Two aspects are extremely
important.
The first refers to the patient selection. Index
hospitalization required in many older studies may cause
the overestimation or underestimation of relapses.
Underestimation may appear when the patient, during a
single hospitalization, experiences several episodes of
rapid cycling that are considered as a single episode. On
the other hand, overestimation may result from the
information gathered from hospitalizations as these
exclude patients who experienced a single episode, those
who recovered without hospitalization as well as those
who have never had a relapse. While some recent studies
avoided these issues by recruiting patients from the
general community, other samples were elaborated by
clinical centers where sicker patients and the patients
resilient to treatment are overrepresented. Indeed, the lots
from clinical centers are not, by definition, representative
since a substantial proportion of bipolar population does
not receive treatment at a given moment. The second
problem refers to diagnostic. Many of the classical studies
regarding the natural evolution of the disease do not make
the difference between recurrent bipolar and unipolar
subgroups.
Apart from these problems, a traditional methodological
issue is the lack of a generally accepted convention for the
collection of data regarding the evolution of manicdepressive illness or the definition of recovery and
relapse. Standardized methods to track the course of the
disease proposed both for retrospective studies (34; 35)
and prospective ones (36; 37) have improved this
situation, but they are far from being enforced universally.
These methods are useful both in the clinical enter and in
research. Moreover, associations not recognized
beforehand between the debut of the periods and the life
events or other stress factors may be helpful in
understanding psychotherapy and behavioral
management.
The age when manic-depressive disorder most often starts
is important for the genetically vulnerable persons and
their physicians and they may give clues about the future
evolution. (Goodwin and Jamison, 2007) collected data
from 15 studies published after 1990 which reported the
average age of 22.2 years upon the diseases onset. As for
the gender, the difference between men and women was
not significant (38; 39; 40).
It is interesting that after 1990, the average is 6 years less
than the weighted average obtained from the 22 pre-1990
studies examined in the first edition (41) while using the
same inclusion criteria. Since data are not normally
distributed, these figures may be misleading. Averages
59

Mdlina Vrabie, Victor Marinescu, Anca Talaman,Ioana Micluia: Clinical And Evolutional Aspects In Bipolar Disorder,
Manic Episode (1)
may be increased by a relatively small number of patients
having, for example, a tardy onset. When reporting
average age to onset, it usually belongs to the early
twenties.
Some of the variations of individual studies are related to
different criteria for onset. In general, the age when the
first symptoms occur is younger than the age when
patients meet the diagnostic criteria, and the age of the first
clinical contact is usually higher (the first hospitalization
is a measure that says very little about the onset age).
Some studies used the age upon the first clinical contact
based on the assumption that the information about initial
symptoms might be too imprecise.
Indeed the literature is consistent in finding a significant
time gap between onset of the illness and the first
treatment. Meeks (42) found that mean age at first
symptoms in a bipolar and unipolar population was almost
6 years younger than age at first treatment. A demographic
study of the first 261 patients in the Stanley Bipolar
Foundation (which may represent patients on the more
severe end of the spectrum) revealed an 8-year difference
between age at first diagnostic and age at first medical
treatment (22.9 and 30.4 years, respectively), whereas age
at first symptoms was only 2 years before age at diagnostic
onset (40). In a Stanley Foundation recruitment survey
administered by Kupfer and colleagues (43), more than 50
percent of a large bipolar sample indicated that they had
received no treatment for their first affective episode.
Thus it is to be expected that age at first treatment is a weak
indicator of onset.
The lower age at onset is reported in more recent studies.
Researchers have advanced several hypotheses to explain
this reduction in age at onset. Changes in nosology and
illness definition could be a partial explanation.
The increasing use of antidepressants and stimulants in
teenagers and children may help induce the onset of
bipolar disorder at an earlier age in those already
susceptible (44, 45, 46). This phenomenon might be
consistent with what we know about the effect of
antidepressants on mania induction and cycle
acceleration, but more research is necessary to draw a
solid conclusion.
The switch into mania or hypomania may be the
consequence of active treatment for bipolar depression,
some drugs, such as tricyclic antidepressants and
venlafaxine have bigger chances to cause the switch than
others. Bu this increase of the switch rate might not be
visible until after 10 weeks of treatment. To notice this
switch, studies should include scales to define the event
phenomenology (e.g. hypomania or mania) and its
severity. These may be best used immediately after the
clinical finding of switch occurrence. Long-term
treatment is usually necessary in the bipolar disorder. (47)
Similar to the association of antidepressants is the
hypothesis that the increased use of recreational drugs and
alcohol among the youth contributes to the decrease of age
at onset. Here, again, consistent evidence is missing and it
is difficult to establish a unidirectional association
between the onset of affective symptoms and the onset of
drug consumption. (48)
Very late onset of the bipolar affective disorder (e.g. after
60) has been generally considered rare (49, 50). Patients
with very late onset are less likely to have a family history
60

of the disorder and more likely to be organically impaired.


Tohen and colleagues (51) compared two groups of
elderly patients, one with late onset mania (first episode
after age 65) and one with multiple manic episodes before
age 65. The first group was significantly more likely to
experience neurological abnormalities (15). These
observations highlight the importance of differential
diagnosis of primary mood disorders and mood disorders
that occur secondary to specific neuropathology.
It is not clear yet to what extent grouping patients by age at
onset really identifies distinct subgroups with differential
phenomenology, pathophysiology, family history,
outcomes and/or treatment response. Studies examining
family history in early versus late onset groups have
generally shown more genetic loading for recurrent mood
disorder associated with early onset.11 But age at onset
did not differ significantly in several studies comparing
patients with mixed and pure mania (52, 53, 54), and it
does not appear to be a distinguishing feature of bipolar I
versus bipolar II disorder (55). On the other hand, early
onset has shown rather consistent correlations with certain
clinical features, including rapid cycling, presence of
comorbid anxiety disorder, suicidal behavior, psychotic
features, and treatment resistance. Carlson and colleagues
(56) reported that patients with an early onset (before the
age of 19) had significantly worse outcomes on a variety
of measures than those with later onset (after the age of
19). (15)
An examination of a large group of Stanley Bipolar
Foundation patients showed significant correlations
between early onset (up to the age of 17) and greater
incidence of learning disabilities, rapid cycling and family
history of bipolar disorder (40), while Ernst and Goldberg
(57) found that onset below the age of 19 was associated
with more rapid cycling and comorbid substance abuse.
Engstrom and colleagues (58) reported lower levels of
treatment response and significantly greater number of
suicide attempts in early versus late onset patients in a
Swedish population.
Although the evidence for a connection between early
onset and the complicating illness features is compelling,
one must be cautious when using cross-sectional studies to
distinguish damaging effects of the illness from the socalled clinical subtype features. Thus, bad outcomes in
early onset patients could be a factor of longer duration of
illness rather than a phenotypic characteristic.
Another author described the clinical features, evolution
and results during a 1-year period after the first manic
episode in the patients with bipolar disorder (BD). The
analysis of recurrence of mood episodes showed that
46.7% of patients survived without a mood episode during
1 follow-up year, and the average time until the occurrence
of another mood episode was 7.9 months. Early onset was
the only variable that predicted significantly the
recurrence of mood episodes. When examined separately,
survival rates were 76% for a manic episode and 58.7% for
a depressive episode.
These results suggest that recurrences are common after
the first manic episode, more than half patients
experiencing a mood episode within 12 months.
Aggressive treatment strategies for the prevention of
depressive episodes are necessary in the management of
bipolar affective disorder with an early onset. (48)

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


The association between psychotic features and early
onset among bipolar patients has considerable support in
the literature. Angst (59) cited 10 studies reporting this
relationship, a conclusion supported by Blumenthal and
colleagues (60), in their study of the Amish and confirmed
by subsequent research (61, 62, 63). Despite all these,
adolescent-onset mania is not always associated with
psychotic features, as shown by cross-sectional
comparison studies (64, 65). A more recent cross-sectional
study comparing early with non-early onset groups failed
to find a significantly higher presence of psychotic
features (66). However, cross-sectional studies cannot
determine subsequent development of psychosis and may
easily miss prior psychotic features, especially if
investigators rely on patient recall. Taken as a whole, the
evidence for a connection between psychotic features and
younger age at onset is strong.
In another study, twenty-four patients at their first manic
episode were followed-up for 4 years after their recovery
from the manic episode. Patients did not have prior manic
or depressive episodes documented. The presence of
psychotic features during the index episode and the
alcoholism history were significantly statistic predictors
for a shorter period of remission. Occupational status
decreased to baseline predicted the poor overall social
adaptation after the 4 years (67). Coupled with the
association between the deterioration of pre-morbid
functioning and the psychosis level discussed above, this
evidence supports the hypothesis that the pervasive
psychotic features indicate a more severe form of illness
which sometimes involves early syndrome manifestations
and it is more frequently characterized by pre-morbid
deterioration.
Considered together, findings of longitudinal studies of
manic-depressive patients not taking prophylactic
medication indicate that most patients especially those
studied in the past 35 years had more than one episode.
Most patients with major affective disorder (e.g. manicdepressive illness described by Krepelin) have a recurrent
course. Many textbooks, apparently relying on older data,
fail to emphasize this point sufficiently. The near-total
probability of recurrence is supported by recent research.
In a 4-yar naturalistic follow-up study of 75 bipolar
patients, only 28 percent remained in remission (68). In
the National Institute of Mental Health's (NIMH)
Collaborative Program on the Psychobiology of
Depression-Clinical Studies (CDS), relapse into a new
episode within 5 years was observed in 81 to 91 percent of
patients, the variability in percentage being related to the
polarity of the index episode (69).
Some differences among studies relate to varying
definitions of what counts as an episode. Some studies
underestimate recurrence because they rely only on
hospitalization as a marker of episodes. 20 Other studies
may be prone to overestimate recurrence because of
treatment factors, such as the use of antidepressants and
the selection of lithium clinic patients for study.
As for the question on the contribution of antidepressant
drugs, it is important to note that the highest relapse rates
are generally the most recent. Koukopoulos and
colleagues (70) and Wehr and Goodwin (71) suggested
that the increased use of antidepressants may have
influenced the results. Indeed, in his analysis of the
incidence of manic switches in one hospital (studied over

six decades), Angst (72) noted a four times increase when


the pretreatment decades were compared with the
decades after ECT and when antidepressant drugs became
widely used.
It is clear that wellbeing and functioning are inversely
proportional to the number of bipolar episodes and thus
the strategies for the reduction of relapses must be
observed rigorously, mainly the reduction of bipolar
depression difficult to treat (33).Unfortunately, the
inadequate use of antidepressants in the undiagnosed
bipolar disorder may result in more severe cycling(33).
Good compliance is important, but we must be aware of
the fact that the deterioration of memory and verbal
learning in bipolar disorder might passively limit the
adherence to treatment (33).
Optimal results in the bipolar disorder are obtained by an
adequate consistent treatment, in concordance with mood
stabilizers, personal training to cope with stress and risk
factors, and the family support.
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ORIGINAL ARTICLES

Somatization Disorders in Children and Adolescents - a


local perspective from the Galai County
Marcela Campean1, Carmen Trutescu2, Cristina Petrescu-Ghenea3, Alecsandra
Irimie-Ana3, Cristina G. Anghel4, Liana Kobylinska3, Iuliana Dobrescu5
Abstract
Introduction: In Child and Adolescent Psychiatry somatic
disorders are as frequent as they are difficult to diagnose.
Children and their familes oftenly go from specialist to
specialist in search of diagnosis and releaf.
The objective was to analyze the prevalence of
psychosomatic disorders in neuropsychiatric patients, to
idenfity predictive factors for a positive outcome and to
check the impact of psychiatric intervention on clinical
outcome.
Method: This retrospective observational study was
conducted in the Neuropsychiatry Department of St
Ioan Emergency Hospital for Children, Galati. All
patients aged between 6 and 18 years that were admitted
with somatic complaints that were not otherwise justified
by a medical condition were included in this research.
Using charts abstraction, the following variables were
recorded: socio-demographic data (age, gender), type of
consult (interdisciplinary or requested by family), clinical
data (signs and symptoms at presentation, duration from
debut of symptoms to presentation) and type of treatment
and clinical evolution. For qualitative data analysis
contingency tables calculated by Chi-Square or Fisher 's
exact test and for quantitative data, t test was used. We
used a significance level of less than 0.05.
Results: A total of 548 patients diagnosed during 19972003 ( 69.53 % female). The average age was 12.93 +/2.74. An important part of the sample, 87.04 % of patients
were referred by a pediatrician and in 12.96 % of cases the
family was the one who requested the consultation . The
most common symptom at presentation was headache in
children .
Conclusion: The multidisciplinary approach and
compliance to treatment were found to be factors
predicting a positive outcome.
Key words: Somatoform disorders, children, adolescents,
evaluation, treatment, clinical outcome

Rezumat
Introducere: n Psihiatria Copilului i Adolescentului
tulburarile somatice sunt pe ct de frecvente pe att de
dificil de diagnosticat. Copiii i familiile lor ajung frecvent
de la un specialist la altul n cutarea unui diagnostic i a
unei rezolvri.
Obiectivul studiului a fost de a analiza ponderea tulburrii
psihosomatice la pacienii neuropsihiatrici, pentru
idenficarea factorilor de predicie pentru un prognostic
bun i pentru a verifica impactul tratamentului psihiatric
asupra rezultatului clinic.
Materiale i metode: Am realizat un studiu retrospectiv
observaional de tip serii de cazuri n cadrul
Departamentului de Neuropsihiatrie a Spitalului Clinic de
Urgen pentru Copii "Sf Ioan" din Galati. Au fost inclui
548 pacieni ntre 6 i 18 ani. S-a realizat o baza de date in
care am inclus urmtorii parametri: datele sociodemografice, tipul consultului (interdisciplinar sau
solicitat de familie), date clinice (semne i simptome de la
prezentare, durata de la debutul simptomelor la
prezentare) i tipul de tratament i evoluia clinic. Pentru
analiza datelor calitative s-au alcatuit tabele de
contingenta calculate cu testul Chi 2 sau Testul exact al lui
Fisher iar pentru datele cantitative s-a folosit Testul t test.
S-a folosit un nivel de semnificatie mai mic de 0,05.
Rezultate: Un total de 548 pacieni diagnosticati in
perioada 1997-2003 au fost inclui. Vrsta medie a fost de
12.93+/-2.74 ani iar 69,53% au fost de sex feminin. O
parte important din eantion, 87,04% dintre pacieni a
fost trimisi de un medic pediatru, iar n 12,96% din cazuri
familia a fost cea care a solicitat consultul. Cel mai
frecvent simptom la prezentare la copii a fost cefaleea.
Concluzie: Abordarea multidisciplinar i complianta la
tratament s-au dovedit a fi factori care prezic un rezultat
pozitiv.
Cuvinte cheie: Tulburare somatoforma, evaluare,
tratament, prognostic

1
Child and Adolescent Neuropsychiatry Specialist, MD, PhDs, Neuropsychiatry Department, St Ioan Emergency Hospital for Children, Galati,
Romania
2
Child and Adolescent Psychiatry Specialist, MD, PhDs, Clinical Psychology Department, Carol Davila University of Medicine and Pharmacy,
Bucharest, Romania
3
Child and Adolescent Psychiatry Resident, MD, PhDs, Child and Adolescent Psychiatry Department, Prof. Dr. Al. Obregia Clinical Hospital of
Psychiatry
4
Child and Adolescent Psychiatry Specialist, Univ. Assistant, MD, PhD, Child and Adolescent Psychiatry Department, Carol Davila University of
Medicine and Pharmacy
4.Senior Child and Adolescent Psychiatrist, MD, PhD, Head of Child and Adolescent Psychiatry Department, Carol Davila University of Medicine and
Pharmacy, Bucharest, Romania
Corresponding author:
Cristina Petrescu-Ghenea
Prof. Dr. Al. Obregia Clinical Hospital of Psychiatry, Berceni Road, No. 4, Bucharest, Romania, 021/3344266; e-mail:
cristina.petrescughenea@gmail.com
Spitalul Clinic de Urgen pentru Copii "Sf. Ioan", Centrul de Sanatate Mintala,
Str. Gheorghe Asachi nr.2, Galai.

63

Marcela Campean, Carmen Trutescu, Cristina Petrescu-ghenea, Alecsandra Irimie-ana, Cristina G. Anghel, Liana
Kobylinska, Iuliana Dobrescu: Somatization Disorders In Children And Adolescents - A Local Perspective From The
Galati County
INTRODUCTION
Although quite common in children and
adolescents, somatoform disorders have been given little
attention by researchers in this population. Somatoform
disorders are characterised by physical symptoms or
complaints about pain that cannot be explained by a
medical problem or effect of a substance. (1) Their
symptoms are not intentionally produced or faked by the
child and are believed to be associated with psychological
factors like strong emotions or situations that threaten the
individual's physical or psychological integrity.
Behavioral or emotional problems are more likely to be
observed in children that exhibit
psychosomatic
symptoms (2).
ICD-10 subdivides these disorders into
somatization disorder, undifferentiated somatoform
disorder, hypochondriacally disorder, somatoform
autonomic dysfunction, persistent somatoform pain
disorder, and other somatoform disorders. (3) Of all these
somatoform disorders, the most commonly seen in
children and adolescents is persistent somatoform pain
disorder. In DSM-5, somatoform disorders are called
somatic symptom and related disorders. Somatization
disorder and undifferentiated somatoform disorder from
the DSM-IV-TR were combined to become somatic
symptom disorder, a diagnosis which no longer requires a
specific number of somatic symptoms. (4)
The prevalence of somatoform complaints in 2-17
years old population is 8-24% depending also on study
design. (5-9) In a general population study, somatic
complaints were found in 11% of girls, and 4% of boys.
(10)
Psychosomatic symptoms in adolescents
represent a transient response to stress and conflict and
usually are the beginning of psychopathological conditions
that can frequently lead to depression and anxiety in
adulthood. Lieb and Zimmermann in 2002 concluded that
somatizations are primary forms of coping strategies. (11)
Also several researchers, as Maloney in 1980 and
later on, Lieb in 2007, have noted that children with
somatoform symptoms are directly influenced by familial
climate and they often shape their symptoms after family
members or close friends. (12,13)
In children or adolescents, psychosomatic
symptoms are difficult to evaluate - children are taken by
their families to a specialist, in search of diagnosis and
relief and are usually characterized by a lack of adherence
to psychiatric medication and psychotherapy. Stigma can
play a big part in this process, especially because the
diagnosis of such disorders is complex as they may appear
as medical conditions. Patients with these disorders
typically present to general medical settings or in pediatrics
departments rather than directly to mental health settings.
Another factor in the delay of evaluation and
intervention for somatic disorders in pediatric population
can be the lack of coherence in the multidisciplinary team
that should cooperate to better solve these cases.
Specialists that form these teams often do not fully
understand and respect the role of the other members of the
team. For example, once a child is referred to the mental
health department he can still remain under symptomatic
treatment in the pediatrics department, even if there is no
evidence of organic disease. This attitude can make
64

adherence to psychiatric treatment much more difficult to


obtain.
The aim of this study is to get a better
understanding of somatoform disorders in children and
adolescents in order to be able to elaborate future guides
and protocols for the assessment and treatment of this
category of disorders.
MATERIAL AND METHODS
A retrospective observational case series study
was conducted in the Neuropsychiatry Department of St
Ioan Emergency Hospital for Children, Galati. There
were included all patients between 6 and 18 years of age
that were admitted with somatic complaints not otherwise
justified by a medical condition during 1997-2003. Patient
records were examinated. Out of a total of 54906 patients
consulted in the department in the mentioned period, a
random sample of 548 have met ICD 10 criteria for
D i s s o c i a t i v e d i s o r d e r, Te n s i o n h e a d a c h e ,
Undifferentiated somatoform disorder, Somatization
disorder and were included in the study. Patients with
Psychosis and/or Pervasive developmental disorders were
excluded from this study. All the other subjects referred
with a comorbid psychiatric diagnosis were included.
In this article, the term somatoform symptoms
is used for somatic symptoms without underlying organic
cause. The term somatoform disorders (SD) refers to the
category of disorders according to the ICD.
Using charts abstraction the following variables
were recorded: socio-demographic data (age, gender,
family structure), type of consult (interdisciplinary or
requested by family), clinical data (signs and symptoms at
presentation, triggering or stressor factors, duration from
onset of symptoms to presentation), type of treatment
(specific medication, psychiatric counselling for patient
and family targeting the modification of stressor
conditions, symptomatic medication prescribed in
Paediatrics Department) and clinical evolution. We
mention that children were assessed about the presence or
absence of symptoms and parents were questioned with
regard to the impact of symptoms, healthcare services
utilisation and past diagnoses and family history of
psychiatric or neurologic disease.
Results are presented as absolute numbers and
percentages. The statistical software package PASS and
NCSS 2003 has been used to conduct data analysis.
Contingency tables were elaborated for qualitative data
and calculated using Chi-Square test or Fisher's Exact
Test. Quantitative data were analyzed using descriptive
statistics and t test. The level of significance was
established at 0.05 (one-tailed).
RESULTS
The mean age (+/- SD) of the admitted patients
was 12.93+/-2.74 with a majority of 83,20% adolescents,
aged 11 to 18 years old. Out of the total number of
subjects, 381 (69.53%) were females and 167 (30.47%)
were males, with 79.55% living in an urban area. More
girls than boys (Female: Male=3.48:1) presented
somatoform complaints in adolescence but in younger
children proportions were found to be similar (Female:
Male=1.36:1) and the correlation between patient's age
and sex was statistically significant (chi-square = 44.86,

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


p< 0.01). The sample was divided in age intervals of two
years. The number of female patients was higher than that
of male patients in almost all age intervals with one
exception, namely the interval between 6 and 8 years,
where male patients exceeded female patients.
An important part of the sample was referred by a
pediatrician 87.04%, whereas in 12.96% of the cases, the
family was the one who asked for the consultation in the
Neuropsychiatry Department.
The number of cases diagnosed with
Somatization Disorder was relatively constant between
1997 and 2003 with minimal variation tendencies and two
lows in 1998 and 2002.

Figure 1. The frequency with which SD was diagnosed in the


clinic

Female patients presented, on average, with


more somatic complaints than males (n1=381, n2=167, Ttest statistic= 4.96, p<0.01). A statistically relevant
correlation was found between the age and the presence of
pain other than headache (chi-square=15.64, p<0.01).
These complaints had a peak of occurrence between 14
and 16 years of age and then abruptly dropped between 16
and 18 years. An association between gender and pain
other than headache was also found, with females having
these complaints more frequently (chi-square statistic
=10.87, p<0.01).

Figure 2. The correlation between pain other than headache and


the age of subjects

In our sample 31.02% of the patients presented


headache and this symptom was more frequent in females
than in males. The correlation was statistically significant
(chi-square statistic is 4.18, p=0.04). Also, cardiovascular
symptomatology was more frequent in female patients
(Fisher statistic=17.88, p<0.01). A similar correlation as
the one found between pain other than headache and age
was found for cardiovascular symptoms (chi-square
statistic is 15.39, p<0.01), muscle tone modifications (chisquare statistic is 21.62, p<0.01), hypoesthesia (chisquare statistic is 17.91, p<0.01) and vertigo (chi-square
statistic is 21.03, p<0.01), on one hand, and age on the
other hand. These were also more frequent between 12 and
16 years and dropped in prevalence after this age.
The core symptoms (ordered by the frequency of
occurance) were headache (21%), changes in muscle tone
(16%), cardiovascular accuses (14%), respratory accuses
(12%), pain other than headache (12%), gastrointestinal
complaints (8%), and hipoesthesia (6%). Taking age into

account, the second most frequent complaint after


headache was gastrointestinal in young children and
muscle tone modifications in adolescents (The chi-square
statistic is 8.54, p<0.01). 63% of the patients were
polisymptomatic, presenting with more than one of the
simptoms mentioned above.
Patient history data revealed that 55.41% of the
patients had parents affected by chronic illnesses. Also,
ones from single parent households and those who
declared tense family climate, had in average, more
somatic complaints than subjects who came from
harmonious family environments (single parent: T-value
is 2.65, p<0.01; tense family: T-value is 2.65, p<0.01).
The most common stress factor in our lot was
school pressure 50.09%, followed by living within tense
families 29,62% and being exposed to a new environment
20,29%.
A statistically significant correlation was found
between family condition and the persistence of
somatoform complaints. Children living within tense
families had, on average, a higher number of somatic
complaints than those for whom the trigger was
represented by school pressure (T-value is 2.36, p<0.01) or
exposure to a new environment (T-value is 2.70, p<0.01).
No significant correlation was found between children
coming from tense families and those exposed to a new
environment as far as the somatic complaints were
concerned.
Considering family options, the patients
followed 5 types of intervention: 32.66% received
medication focused on symptoms prescribed in pediatric
services, 33.58% received counseling and psychiatric
treatment and 32.12% opted for both symptomatic and
psychiatric treatment. A small percentage opted only for
counseling 0.18% or for only psychiatric medication
1.46%. From patients treated only in the Neuropsychiatry
department, 47.99% attended more than 10 sessions of
psychotherapy, 38.83% required less than 10 sessions and
13.19% did not attend any psychotherapy or counseling.
Taking into account the duration of symptoms
after diagnosis had been made, the sample was divided
into four categories: less than 3 months (12.04%), 36months (35.04%), 6-24 months (49.64%) and more than
24 months (3.28%). For children older than 10 symptoms
persisted between 6 and 24 months. On the other hand, in
younger children symptoms resolved from 3 to 6 months
(The chi-square statistic is 21.41, p=0.04).
The clinical approach could be correlated with
the persistence of symptoms. In our sample, the shortest
period during which symptoms were present was reported
for children with psychiatric intervention (counseling and
medication). The longest period of accuses was met in
patients treated entirely in pediatric clinic. Patients treated
with psychotherapy and psychopharmacologic treatment
had a length of symptoms after diagnosis had been made
of less than 6 months. Those for whom the elected
treatment was either symptomatic in a pediatrics
department or combined were found to have had a longer
than 6 months duration of symptoms (The chi-square
statistic is 286.38, p<0.01). Studying the outcome of these
patients by taking into consideration the number of
symptoms (mono versus polysymptmatic), the presence or
absence of chronic disease in their parents and type of
family, as defined above, correlations could be established
between these domains.
65

Marcela Campean, Carmen Trutescu, Cristina Petrescu-ghenea, Alecsandra Irimie-ana, Cristina G. Anghel, Liana
Kobylinska, Iuliana Dobrescu: Somatization Disorders In Children And Adolescents - A Local Perspective From The
Galati County
A longer than 6 months duration of symptoms had been
found in patients exhibiting polysymptomatic accuses, as
well as in those whose parents had a chronic illness (chisquare statistic is 28.05, p< 0.01). Patients coming from a
harmonious family environment generally had a total
duration of symptoms after diagnosis less than 6 months.
As far as the rest of the patients were concerned, namely
those coming from single parent families and families
where tensions were reported, symptoms were found to
last for more than 6 months (The chi-square statistic is
33.09, p< 0.01).

Figure 3. The correlation between the type of treatment and


duration of symptoms shows better outcomes for those patients
who received psychiatric care

Figure 4. Correlation between family type and the duration of


symptoms after the diagnosis had been made

DISCUSSIONS
The mean age and sex distribution, with the
majority of patients referred for somatic symptoms being
females in their teens and almost equal proportions for
younger boys and girls is concordant to the findings in
Campo's study from 1999 by which he tried to classify
somatic disorders in the pediatric population analyzing
data from 21065 children. (14) Somatic symptoms
generally occur more commonly in females than males
with a ratio of 5:1, epidemiology that is similar to the
gender proportion of subjects in our study. (15) It might be
that a smaller sample had a little influence on the
proportion found in our study (Female: Male=3.48:1), this
also being the proportion found in adolescents and not all
the sample. A sensibly higher number of male patients
during the interval between 6 and 8 years of age, could be
attributed to bigger difficulties in boys during the
beginning of school that coincides with the specified age
period. A 2011 report of the United States National Center
for Education Statistics informs that boys are 30 percent
more likely to flunk or drop out of school. (16)
The high rate of patients referred by a
pediatrician (87.04%) is in total agreement with general
data about somatization disorders. Presenting as organic
disease, parents bring their children into mental health
departments only after all objective causes for those
symptoms could be ruled out.
66

With Romania being in a transition period from


the Communist regime to a Democratic one during 19972003, 1997 representing its adherence to NATO and 2004
the year when Romania became a member of de European
Union, also the Mental Health System was dramatically
transformed. Psychiatrists begun to use the International
Classification of Disease and the growing possibility to
attend international professional meetings lead to a big
change in the way diagnosis was made and by this, in
epidemiology. At this point we whiteness the same
alarming growth in Autism Spectrum Disorders and
Attention Deficit Hyperactivity Disorder as our
colleagues around the world. Nevertheless, Somatoform
Disorders show minimal variation tendencies.
Existing literature reports headache,
gastrointestinal symptoms, musculoskeletal pain,
dizziness, nausea and fatigue as most frequent accuses
similarly to our findings. (8, 17) In our lot, tension
headache was the most frequent symptom, although the
majority of children were polisymptomatic. Our findings
are consistent with data in Mohapatra's review from 2014,
which states that the prevalence of symptoms associated
with somatization in the pediatric population is high,
placing recurrent abdominal pain accounts for 5% of
pediatric office visits on the second place after headaches
that have been reported to affect 20% to 55% of all
children and 10% of teenagers reporting frequent
headaches, chest pain, nausea, and fatigue. (18) With
31.02% of our patients presenting with headache our data
falls into the limits found by Mohapatra in general
literature. We can also speculate that our finding that pain,
muscle tone modifications, hypoesthesia and vertigo have
a peak in occurrence around the age of 12 and 16 years old
is due to the fact that between these ages children are
exposed to high degrees of school and educational
pressure that overlap the tense period of adolescence. This
finding is also in accordance with the fact that school
pressure was reported to be most common stress factor in
our sample (50.09%). Pehlivanturk found 55% of the
subjects in his study to have poor school performance.
(19)
There had been identified the following familial
risk factors as being associated with SD: somatization or
organic disease of parents, psychopathology in close
family members, dysfunctional family climate, traumatic
experiences, and insecure attachment (20). Campo found
that 40% of somatizers had psychosocial problems as
coming from families with lower parental educational
and/or minority background (14). In our sample children
living within tense families had, on average, a higher
number of somatic complaints than those for whom the
trigger was represented by school pressure. Familial risk
factors as single parent households, families where
frequent tensions were reported, as well as parents having
chronic illnesses of their own could be correlated with a
longer than 6 months duration of symptoms after the
diagnosis had been made. Working with children and
families through counseling and psychoeducation, we are
able to modify the climate, while developing abilities to
express feelings and wishes.
Also, accuses persist for a longer period of time
in patients showing a wider range of symptoms, which
shows our findings to be similar with literature data:
polysymptomatic patients have a poorer prognostic and

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


need longer and more intensive interventions.
The study has some limitations first concerning
the fact that the sample represents local experience and for
sure it must be extended to presentdate. Sample
representativeness has to be regarded with caution.
Research on hospital samples may indicate mainly
characteristics of sample selection.
Another shortcoming, found in most of similar
studies is that the authors did not conduct medical
examinations or if examinations were conducted, the
information provided was often insufficient to judge
whether it was thorough, accurate, and recent.
The retrospective nature of the study also
represents one of its limits. Recall bias could have
influenced the accurate recollection of actual health-care
utilization, the doctor's diagnosis, usage of medication,
and determination of onset.
More research is needed to highlight the factors
related to the outcome of psychosomatic complaints in
children and adolescents. We consider this study a starting
point for future epidemiological research in aim to get a
clearer view of somatic disorders during childhood and
adolescence.
CONCLUSIONS
The key in improving the outcome of children
and adolescents presenting with somatoform accuses is
the multidisciplinary team and a good relationship
between all the team members. This collaboration
between pediatric specialists and mental health services
for children leads to early detection of triggers and a faster
access to early specific interventions.
Although somatoform accuses are usually
transitory in children, we still need some additional ways
to decrease the length of symptoms in aim to:
Reduce stigmatization and feeling of being ill
Increase good academic and social functioning
Reduce the cost for medical services.
In this local research we found that there are
significant correlations between the duration of symptoms
and family climate, clinical approach and the complexity
of clinical onset manifestations.
For these children, both types of intervention,
environmental - on family climate and self development,
could impact the entire functioning of the future adult.
That is why, early referral to mental health professionals
can help avoiding unnecessary investigations and delay in
diagnosis and treatment of somatoform disorders in
children.
ACKNOWLEDGEMENT:
This paper is supported by the Sectorial Operational
Programme Human Resources Development (SOP HRD),
financed from the European Social Fund and by the
Romanian Government under the contract number
POSDRU/159/1.5/S/137390

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The natural course of DSM-IV somatoform disorders and syndromes
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Somatization in pediatric primary care: association with
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15.Aro H, Taipale V. The impact of timing of puberty on psychosomatic
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***

67

ORIGINAL ARTICLES

A non-interventional study to observe real-life usage of


atypical antipsychotics in the acute inpatient
management of schizophrenia in Central and Eastern
Europe
Radu Teodorescu1, Elmars Rancans2, Gabor Feller3, Dan Prelipceanu1
Abstract
Background: Despite the majority of guidelines
recommending that atypical antipsychotics (AAP) should
be used as monotherapy during acute psychotic episodes
in subjects with schizophrenia, in the United States and
Western Europe first-generation antipsychotics (AP),
polypharmacy, and lower than the minimally effective
recommended doses of AAP are frequently administered.
Few data exist to show whether the same is true in Central
and Eastern Europe.
Objective: To examine the discrepancies between current
clinical practice and guideline recommendations for the
management of acute psychotic episodes in patients with
schizophrenia.
Methods: This was a non-interventional, multinational,
multicentre study (RECONNECT-S GAMMA) to describe
the management of subjects with schizophrenia
hospitalised due to an acute psychotic episode. Study
subjects (aged 18 years) conducted one visit on the day of
discharge from hospital. Demographic data, together with
data on antipsychotic treatment and concomitant
medication were collected for the hospitalisation period
and the recommendation at discharge.
Results: Of the 496 subjects, 49 (9.9%) and 418 (84.3%)
received AAP as monotherapy and in combination therapy,
respectively. Overall, the most frequently used
medications were oral quetiapine (n=129; 27.4%), oral
risperidone (n=95; 20.2%), oral olanzapine (n=104;
22.1%), and clozapine (n=73; 15.5%), with variations in
the administered doses between countries. Upon
discharge, a significant number of subjects (n=373;
75.2%) were prescribed AAP as maintenance therapy, with
335 (69.9%) prescribed the same medications at discharge
that they had been treated with during hospitalisation.
Conclusion: Current clinical practice in Central and
Eastern Europe differs from guideline recommendations,
with few schizophrenic patients receiving AAP as
monotherapy for the management of their acute psychotic
episodes.
Key words
Schizophrenia; Central and Eastern Europe; atypical
antipsychotic (AAP); acute psychotic episode; treatment
guidelines
1

Rezumat
Background:Desi majoritatea ghidurilor terapeutice
recomand utilizarea antipsihoticelor atipice (AA) ca
monoterapie n managementul episodului psihotic acut al
pacienilor cu schizofrenie, att n SUA precum si n
Europa Occidental, deseori acesti pacieni sunt tratai cu
antipsihotice de prim generaie, combinaie de
antipsihotice (polifarmacie) ori doze subterapeutice de
AA. Comparativ, exist mai puine date referitoare la
managementul acestor pacieni n Europa Central si de
Est.
Obiective: Evaluarea discrepanelor ntre practica clinic
si ghidurile terapeutice n managementul episodului
psihotic acut la pacienii cu schizofrenie.
Metod: Studiu non-intervenional, multinaional,
multicentric (RECONNECT-S GAMMA) n scopul
descrierii managementului episodului psihotic acut la
pacienii cu schizofrenie spitalizai pentru un astfel de
episod. Pacienii studiai (vrsta 18 ani) au avut o vizit
de studiu n ziua externrii. Au fost colectate date
demografice si date referitoare la tratamentul antipsihotic
si medicaia concomitent administrate n perioada
spitalizrii precum si recomandrile la externare.
Rezultate: Din 496 pacieni, 49 (9,9%) au fost tratai cu
AA n monoterapie si 418 (84,3%) au fost tratai cu terapie
de combinaie. Pe ansamblu cele mai folosite
medicamente au fost quetiapina oral (n=129; 27,4%),
risperidona oral (n=95; 20,2%), olanzapina oral
(n=104; 22,1%) si clozapina oral (n=73; 15.5%), cu
variaii de administrare ntre ri. La externare unui
numr semnificativ (n=373; 75.2%) de pacieni (n=373;
75,2%) i-a fost prescrise AA ca medicaie de ntreinere, un
numr de 335 (69.9%) primind aceeasi medicaie cu care
au fost tratai pe perioada spitalizrii.
Concluzii: Practica clinic obisnuit n Eudopa Central
si de Est difer fa de ghidurile terapeutice, un numr mai
mic de pacieni cu schizofrenie primind AA ca
monoterapie pentru episodul psihotic acut.
Cuvinte cheie
Schizofrenie; Europa Centrala si de Est; antipsihotic
atipic; episod psihotic acut; ghiduri de tratament

Prof. Dr. Alexandru Obregia Clinical Psychiatry Hospital, Bucharest, Sos. Berceni nr. 10, Sector 4, Bucharest, Romania
Department of Psychiatry and Narcology, Riga Stradina University, 2 Tvaika Street, Riga, LV-1005, Latvia
Department Psychiatry, Mental Hygiene and Addictology, Petz Aladr County Teaching Hospital, 9023 Gyr, Vasvry Pl u. 2-4, Hungary
Corresponding author
Professor Dan Preliceanu
Address: Prof. Dr. Alexandru Obregia Clinical Psychiatry Hospital, Bucharest, Sos. Berceni nr. 10, Sector 4, Bucharest, Romania
Tel./Fax: +40-21-334.84.06
Email: prelipceanudan@yahoo.com
2

68

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


Introduction
Schizophrenia is a severe form of mental illness, which
has been estimated by the World Health Organization to
affect approximately 24 million people worldwide (1).
Although there are relatively few new cases of
schizophrenia diagnosed each year, the prevalence is high.
A review of studies reporting prevalence of schizophrenia,
that included data from 46 countries, revealed median
values, per 1,000 persons for the distribution of
prevalence estimates, of 4.6, 3.3 and 4.0 for point (21
studies), period (34 studies) and lifetime (24 studies)
prevalence of schizophrenia (2). Prevalence data in
Romania has not been recorded since 1987, when the
lifetime prevalence of schizophrenia in an urban
environment was reported as 10.1 per 1,000 (3).
Furthermore, the schizophrenia prevalence rate in 2011
was documented as 9.4 per 1,000 in Latvia (4).The disease
burden tends to be much lower in most of Europe, the
USA, Australia and Japan compared to countries in
Eastern Asia, Oceania and the Middle East (5). In 2004,
the age-standardised disability-adjusted life years
(DALY), per 100,000 population, attributable to
schizophrenia range from 322 in Indonesia to 164 in
Australia, whilst Hungary, Latvia and Romania have
estimates of 207, 204 and 237, respectively (6).
Patients diagnosed with schizophrenia present with a
range of symptoms including long duration, bizarre
delusions, negative symptoms, and non-affective
psychosis (7). Over 50% of patients fail to receive
appropriate care, and therefore often have symptoms
which persist for long periods of time (1). Long-term
administration of antipsychotic medication has been
shown to be the most effective strategy to improve the
prognosis of schizophrenia (8). However, a systematic
review of 39 studies reported a 41% mean rate of
antipsychotic non-adherence in schizophrenia (9); this
leads to exacerbations and relapses in patients that often
require hospitalisation. A significant challenge for
clinicians in the management of patients with
schizophrenia is the occurrence of acute psychotic
episodes (10); however, there is limited information
relating to the use of antipsychotics on the agitation
component during these episodes in Central and Eastern
Europe.
In Hungary, physicians follow the Ministry of Health's
guidelines (edited and compiled by the Hungarian
Psychiatric Professional College) for the treatment of
schizophrenia. Although treatment recommendations
have been published by the Latvian Psychiatric
Association (11), they are solely recommendations and
therefore not imposed on psychiatrists. In both Latvia and
Romania, the treatment approach to schizophrenia is very
much in line with internationally recognised guidelines,
including those of the American Psychiatric Association
(APA) and National Institute for Health and Care
Excellence (NICE). Guidelines published by the APA
recommend that selection of an antipsychotic agent be
guided by the patient's past medication history, current
symptoms, and comorbidities, other concurrent
treatments, and preferences (1213). The guidelines state
that, for schizophrenic patients in the acute phase, secondgeneration antipsychotic monotherapy should be
considered as the first-line option; this recommendation is
based on the decreased risk of extrapyramidal side effects
and tardive dyskinesia associated with second-generation

compared with first-generation agents (1213).


Despite the guidelines usually recommending a
preference for atypical antipsychotic (AAP) monotherapy
during acute psychotic episodes in schizophrenic patients,
evidence shows that first-generation antipsychotics,
polypharmacy, intramuscular route of administration, and
AAP at lower than recommended doses are being
frequently used to treat acute episodes (8). For example, in
Hungary a study conducted at the Semmelweis University
in Budapest and the Galfi Bela HC Institution in Pomaz,
revealed that although AAP use increased from 1998 to
2002, typical antipsychotics were still used in clinical
practice (14). A more recent study investigating the
prescribing pattern of psychotropic drugs to 1,304 patients
in eight psychiatric hospitals in Albania, Croatia,
Macedonia, Serbia and Romania reported that only 6.8%
of patients received AAP as monotherapy, whilst 26.5%,
42.1% and 22.1% received them in combination with two,
three or four other antipsychotic medications, respectively
(15). Overall, only 40% of patients were prescribed AAP,
while 63% received typical antipsychotics (15). This
suggests that in addition to guidelines, physicians use their
discretion and experience when determining the most
appropriate treatments for their patients. Also since typical
antipsychotics are cheaper than AAP (16), cost and
availability could be additional factors they consider.
There is a need, therefore, for further research to examine
the discrepancies between current clinical practice and
guideline recommendations. The aim of the
RECONNECT-S GAMMA study was to describe the reallife usage of AAP in the acute inpatient management of
schizophrenia, in order to gain an understanding of current
treatment practices and identify any disparities that may
exist between these and guideline recommendations in
Central and Eastern Europe.
Methods
Study Design
This was a non-interventional, multicentre study,
registered as NCT01491412, to describe the management
of subjects with schizophrenia who were hospitalised due
to an acute psychotic episode. Thirty-three investigators
participated in the study: 15 in Romania, 10 in Latvia and
eight in Hungary. For the purpose of serving the study
objectives, selection of participating sites aimed to ensure
that the schizophrenic patient population of the three
countries was accurately represented. Sites throughout the
three countries were included that provide specialised care
to a wide range of schizophrenic patients, including
patients who have recently been diagnosed, patients with
chronic disease history, patients with difficult-to-treat
schizophrenia, and patients who require tranquillisation. A
total of 496 study subjects were recruited; 211 from
Romania, 183 from Hungary and 102 from Latvia.
Subjects attended one visit on the day of their discharge
after hospitalisation due to an acute psychotic episode;
during this visit data on demographics, diagnosis, and
medical history were recorded. In addition, data on
antipsychotic treatment and concomitant medication were
collected for the hospitalisation period, together with the
recommendation at discharge.
Study Subjects
Subjects were eligible for enrolment in the study if they
were 18 years or older, met the diagnostic criteria for
schizophrenia stated in The Diagnostic and Statistical
Manual of Mental Disorders, 4th edition (DSM-IV), and

69

Radu Teodorescu, Elmars Rancans, Gabor Feller, Dan Prelipceanu: A Non-interventional Study To Observe Real-life
Usage Of Atypical Antipsychotics In The Acute Inpatient Management Of Schizophrenia In Central And Eastern Europe
were hospitalised due to an acute psychotic episode. The
study required that the subject had the ability to
understand and comply with the requirements of the study,
as judged by the investigator. Written informed consent
was obtained from the subject and/or his/her legal
representative (as per local regulatory requirements).
Ethical approval was obtained for each study site in
Hungary and Latvia. Only health authority approval was
required in Romania; this was obtained from the National
Medicine and Medical Devices Agency.
Exclusion criteria consisted of current participation in a
clinical trial or previous enrolment in the current study (in
the case of re-hospitalisation).
Study Objectives
The primary objective of the study was to describe the use
of AAP in subjects with schizophrenia during
hospitalisation due to an acute psychotic episode, by
evaluation of drug, dose, mode and length of
administration of the medication.
Secondary objectives included: evaluation of the use of
AAP as monotherapy and the use of combinations of
antipsychotics during the hospitalisation period;
investigation of the main criteria used for selection of an
antipsychotic to treat acute episodes of schizophrenia;
description of the use of psychometric scales to evaluate
the disease symptoms during the hospitalisation period;
investigation of the use of concomitant psychiatric
medications (other than atypical antipsychotics) during
hospitalisation; the correlation between antipsychotic
medication used during hospitalisation and maintenance
therapy recommended upon discharge.
Safety
This non-interventional study was designed without a
specific safety objective, therefore no safety data were
pro-actively collected. Spontaneously-mentioned safety
events were reported as required by post-marketing
pharmacovigilance regulations.
Statistical Analyses
A descriptive analysis approach (including frequency
tables) was used owing to the non-interventional design of
the study. As appropriate, a two-sided 95% confidence
interval was obtained for the population estimation of the
variables. All calculations and summaries were produced
using SAS Version 9.2 (SAS 2009), with medications
coded using the WHO drug dictionary, version 12.1.
Results
Patient demographics and baseline characteristics
The study was conducted between December 2011 and
May 2012. Patient demographics are shown in Table 1. Of
the 496 subjects enrolled in the study, all met the inclusion
criteria and none of the exclusion criteria applied to these
subjects; 243 participants (49.0%) were male. Participants
had a mean age standard deviation (SD) of 43.5 11.58
years, and a mean number of years of education SD of
11.6 2.64. All subjects were Caucasian (race data
missing for one subject) and the majority were in receipt
of sickness pension (61.7%), unemployed (13.1%), or
retired (10.7%). Over 40% of study subjects reported
psychosocial problems and approximately 8% had made
one or more suicide attempt(s).
Overall, 34.1% of patients had concurrent psychiatric
conditions in addition to their primary schizophrenia
diagnosis (Table 2). In Hungary, 76.5% of patients were
reported to have a concomitant psychiatric condition,
compared with just 6.9% and 10.4% of patients from
Latvia and Romania, respectively. One hundred and fifty
70

seven subjects (31.7%) had other general medical


conditions: 46 (9.3%) had hypertensive diseases, 34
(6.9%) had diseases of the digestive system, 28 (5.6%) had
obesity and other hyperalimentation comorbidities, while
23 (4.6%) had diabetes mellitus. Prior to enrolment,
332/496 subjects (66.9%) were being treated with at least
one antipsychotic medication. The most frequently
reported antipsychotic agents were: risperidone (16.5%);
quetiapine (15.5%); and olanzapine (12.5%).
Primary objectives
Length of hospital stay varied between countries with the
shortest mean hospital stays being observed in Romania
followed by Hungary and Latvia (22.6, 31.3 and 37.0
days, respectively) (Table 3). The majority of subjects
(479/496, 96.6%) were treated with at least one AAP
(Table 4), the most frequently prescribed were quetiapine
(27.4%), oral risperidone (20.2%) and oral olanzapine
(22.1%). A smaller percentage of subjects received oral
aripiprazole (7.7%), intramuscular risperidone (6.0%) or
intramuscular olanzapine (1.9%). In addition, 14/496
study subjects (2.8%) did not receive treatment with an
AAP, and 3/496 study subjects (0.6%) received something
other than an antipsychotic medication. Variation was
observed between daily doses of AAP most commonly
administered in different countries. The highest average
daily dose for oral risperidone was observed in Latvia and
the lowest in Hungary. While the highest and lowest
observed average daily doses of oral olanzapine were in
Hungary and Romania, respectively, the reverse was
observed for oral quetiapine, with daily doses being
lowest in Hungary and highest in Romania.
Secondary objectives
Use of monotherapy or combination therapy and
concomitant psychiatric medication
Although the majority of subjects (479, 96.6%) received at
least one AAP during hospitalisation, only 49/479 subjects
(9.9%) received AAP as monotherapy, while 12/479
subjects received more than one AAP (Table 5). Overall,
418 subjects (84.3%) were treated with AAP in
combination with other psychiatric medications: 20
(4.0%) with a combination of atypical and typical
antipsychotics, 307 (61.9%) with an AAP and another
psychiatric medication, and 91 (18.3%) with an AAP, a
typical antipsychotic and another psychiatric medication
(Table 6). Of the 418 (84.3%) subjects who received at
least one concomitant psychiatric medication: 267
(53.8%) were treated with antiepileptics; 180 (36.3%)
with anxiolytics; 125 (25.2%) with antipsychotics; and
101 (20.4%) with antidepressants.
Criteria used for selection of an antipsychotic
The most frequently stated rationales for the selection of
the AAP medication chosen were medication history
(41.9%) and current symptoms (43.8%).
Use of psychometric scales to evaluate patients'
symptoms
The majority of study subjects (93.3%) were evaluated in
accordance with the clinical experience of the consulting
physician; psychometric scales were not used to evaluate
disease symptoms during hospitalisation for any of the
subjects enrolled in this study.
Maintenance therapy upon discharge
Upon discharge, most study subjects (n=373; 75.2%) were
prescribed AAP as maintenance therapy (Table 6).
However, the prescription pattern was different for
Hungary, with only 52.5% prescribed AAP, compared
with 99.0% and 83.4% in Latvia and Romania,

Romanian Journal of Psychiatry, vol. XVII, No.1, 2015


respectively. Overall, of the 479 subjects treated with an
AAP during hospitalisation, 335 (69.9%) were prescribed
the same medication(s) at discharge that they had received
during hospitalisation.
Discussion
This study provides evidence for the type, dose, mode and
length of administration of AAP used in the management
of acute psychotic episodes in subjects with schizophrenia
in Central and Eastern Europe. There was a significant
d i ff e r e n c e o b s e r v e d b e t w e e n t h e t r e a t m e n t
recommendations for AAP monotherapy contained within
the guidelines (1213) and current real-life clinical
practice, where the use of polypharmacy is common. A
large observational study of the outcomes of antipsychotic
treatment for schizophrenia in Europe reported by Haro
and colleagues demonstrated that combination therapy is
commonly used in schizophrenia (8). The findings of
RECONNECT-S GAMMA support this observation, with
just 49/496 individuals receiving AAP as monotherapy for
an acute episode of schizophrenia, while the vast majority
(418/496, 84.3%) of study subjects received combination
therapy with AAP and one or more additional psychotic
medication(s). Various factors exist which may affect the
choice of medication prescribed to schizophrenic patients.
For example, in Romania, since the patient is usually
treated in hospital, the medication administered by the
physician is greatly influenced by the availability of drugs
in the hospital pharmacy. Lack of availability could
prevent psychiatrists from being able to select a
medication which they feel is most appropriate for their
patient based on their clinical knowledge.
Although the majority of subjects received AAP as
combination therapy in Hungary and Romania the
majority of additional medications administered were
other psychiatric medications and included antiepileptics,
anxiolytics and antidepressants, not only typical
antipsychotics. We suggest that according to historic
tradition, mood stabilisers and anxiolytics were used to
manage patients' symptoms in order to improve their
clinical outcomes and social functioning (17). The
reduced use of typical antipsychotics, however, is
promising since they are associated with an increased risk
of extrapyramidal side-effects and tardive dyskinesia
(13). In Latvia, the use of typical antipsychotics was far
higher, with 18.6% receiving atypical antipsychotics in
combination with typical antipsychotics, and 52.0%
receiving both atypical and typical antipsychotics in
combination with other additional psychiatric
medications. This could potentially be because the
existing reimbursement system and allocated finances
only permit 60% of schizophrenic outpatients to receive
AAP. This is taken into consideration when patients are
treated during their stay in hospital, and rather than
switching from an atypical to a typical antipsychotic at
discharge, physicians decide at treatment initiation which
patients should be treated with a typical or atypical
antipsychotic.
The outpatient treatment of individuals with
schizophrenia is challenging owing to the high frequency
of missed appointments, resistance to treatment and low
adherence to medication, that are frequently observed in
this patient population (1819). Monotherapy with AAP is
the recommended first-line strategy (12,13,20); however,
no single agent is suitable for the universal treatment of all
patients. Therefore, an individualised treatment strategy is
frequently applied, whereby the agent prescribed is

selected according to factors such as physicians' previous


experience and patient response to medication (8). This
approach may ultimately result in the application of
polypharmacy as a treatment approach which can be
difficult to study in randomised controlled clinical trials
(21).
There were some differences in the study populations
between the three countries included within the study.
While a similar percentage of the study population was
male in Hungary and Romania (41.0% and 44.5%,
respectively), the percentage of male participants was
much greater in Latvia (72.5%). Although there are no
major gender differences in morbidity with schizophrenia
in Latvia, psychiatric departments are segregated between
male and female patients, and the imbalance is attributed
to a greater proportion of physicians in the male
departments taking part in the study. The mean age of
participants in Hungary (46.4 years) was greater than the
mean ages of participants in Romania and Latvia (42.1 and
40.9 years, respectively). Similarly, the percentage of
study participants who were retired was greater in
Hungary (39%, presumed due to early retirement perhaps
due to disability) compared to Latvia (1%) and Romania
(13%). In Hungary the percentage of people in receipt of
sickness benefit (48.6%) was lower than in Latvia and
Romania (71.6% and 68.2%, respectively), and
potentially occurred because there was a greater number
of people in employment (29% of participants in Hungary
were employed compared with 4% in Latvia and 7% in
Romania).
A number of inter-country differences in comorbidities
were also observed between the three countries. For
example, 76.5% of study subjects from Hungary reported
having a concurrent psychiatric condition (other than
schizophrenia) compared with 6.9% from Latvia and
10.4% from Romania. These differences may be
accounted for by systematic screening for these
comorbidities in Hungary compared with Latvia or
Romania. The average daily dose for oral risperidone was
highest for Latvia and lowest for Hungary, with the highest
average daily dose of oral olanzapine administered in
Hungary and lowest in Romania. We suggest that the
average dose variation reflected the severity of individual
patients' cases of schizophrenia, psychiatrists' personal
experience with administration of the medication, and
evaluation of the benefit-risk ratio to their patient. The
average length of hospital stay also varied between
countries; it was shortest in Romania and longest in
Latvia. In Romania hospitals are under a great deal of
administrative pressure to shorten the length of stay of
patients in psychiatric hospitals; arguments for this are
derived from US literature which describes movement
towards hospitalisation durations of 910 days for acute
psychotic episodes (22). This could therefore in part
account for mean hospitalisation stays being considerably
shorter in Romania than the other two countries.
Mean AAP dose recommendations were followed by
physicians in all three countries in this study. A similar
proportion of patients from each country received at least
one AAP prior to hospitalisation: 123 (67.2%) subjects in
Hungary; 56 (54.9%) in Latvia; and 153 (72.5%) in
Romania. Additionally, 53.8% of patients received
antiepileptic therapy and 20.4% were treated with
antidepressants. The relatively high rate of use of these
agents may be because of symptomatic motives such as
mood, aggressive behaviour or impulsivity in patients.
71

Radu Teodorescu, Elmars Rancans, Gabor Feller, Dan Prelipceanu: A Non-interventional Study To Observe Real-life
Usage Of Atypical Antipsychotics In The Acute Inpatient Management Of Schizophrenia In Central And Eastern Europe
Post-discharge prescription patterns in Romania and
Latvia were highly similar to the hospitalisation
prescription pattern but were markedly different in
Hungary; in Latvia and Romania 99.0% and 83.4% of
patients respectively, were prescribed the same
medication at discharge as during hospitalisation, while in
Hungary only 52.5% were. In Romania it is customary to
continue in-hospital medication patterns upon discharge
unless there is good reason to add or remove a medication.
As a result, prescription patterns would generally not be
expected to differ. However in Hungary, on discharge
patients commonly return to their own doctor, who may
then use his or her own personal experience to determine
the appropriate treatment once the acute episode has been
controlled.. This can lead to a change in patients'
medication in terms of antipsychotic and/or dose, or
switching to monotherapy. These findings illustrate
further how individualised treatment strategies and
common clinical practice can influence the treatment of
acute episodes of schizophrenia, leading to the observed
differences between different countries. Given the nonrandomised nature of the current study, the above findings
should be interpreted conservatively, and additional
studies may be required to further elucidate the
prescribing practices within these countries.
In conclusion, this study indicated that although the
majority of subjects with schizophrenia were treated with
AAP for acute psychotic episodes during hospitalisation,
they were commonly used in combination with other
psychiatric medications, rather than as monotherapy.
These treatment practices are contrary to current guideline
recommendations and further studies to investigate the
resulting outcomes for patients, and whether such
disparities exist in other countries, are warranted.
Table 1. Patient demographics
Variable

Gender
Age (years)
Total number of
education years
(years)

Current
employment
status

Suicide attempts
during last two
years
Psychosocial
problems

SD=Standard deviation
72

Male
Female
n
Mean
SD
N
Mean
SD
Employed
Self-employed
Unemployed
Sickness
pension
Retired
Student
Other
Unknown
Missing
0
1-2
3 or more
Unknown
No
Yes
Unknown

Role of funding source


This study was sponsored by AstraZeneca.
Contributors
Radu Teodorescu served as International Coordinating
Investigator in Romania; Gabor Feller served as National
Coordinating Investigator, Hungary; Elmars Rancans
served as National Coordinating Investigator, Latvia; Dan
Prelipceanu served as Principal Investigator in Romania.
Author disclosures
Gbor Feller has served as adviser or speaker for Eli Lilly,
Janssen-Cilag, Egis, and AstraZeneca.
Dan Prelipceanu has no conflict of interests to declare.
Elmar Rancans has served as advisor or speaker for
AstraZeneca, Gedeon Richter, Janssen Pharmaceuticals,
Lundbeck, Sanofi-Aventis and Servier.
Radu Teodorescu has served as advisor or speaker for
AstraZeneca, Bristol-Myers Squibb and Eli Lilly.
Acknowledgements
This manuscript was prepared in line with guidelines
established by the International Committee of Medical
Journal Editors (ICMJE) and published in its Uniform
Requirements of Manuscripts Submitted to Biomedical
Journals. The authors would like to thank Toby Galbraith,
PhD, and Charlotte Simpson, PhD, of IMC Healthcare
Communication who provided medical writing support,
supported by AstraZeneca.
Abbreviations
APA=American Psychiatric Association
AAP=acute atypical antipsychotic
DALY=disability-adjusted life year
NICE=National Institute for Health and Care Excellence

Hungary
(N=183)
n (%)
75 (41.0)
108 (59.0)
181
46.4
11.63
171
11.1
2.84
29 (15.8)
1 (0.5)
22 (12.0)
89 (48.6)

Latvia
(N=102)
n (%)
74 (72.5)
28 (27.5)
92
40.9
11.96
86
11.9
2.06
4 (3.9)
4 (3.9)
15 (14.7)
73 (71.6)

Romania
(N=211)
n (%)
94 (44.5)
117 (55.5)
209
42.1
10.87
181
12.0
2.63
7 (3.3)
0 (0.0)
28 (13.3)
144 (68.2)

Overall
(N=496)
n (%)
243 (49.0)
253 (51.0)
482
43.5
11.58
438
11.6
2.64
40 (8.1)
5 (1.0)
65 (13.1)
306 (61.7)

39 (21.3)
0 (0.0)
3 (1.6)
0 (0.0)
0 (0.0)
152 (83.1)
20 (10.9)
5 (2.7)
6 (3.3)
89 (48.6)
89 (48.6)
5 (2.7)

1
0
4
0
1
93
7
2
0
63
38
1

13 (6.2)
0 (0.0)
14 (6.6)
0 (0.0)
5 (2.4)
186 (88.2)
5 (2.4)
1 (0.5)
19 (9.0)
115 (54.5)
92 (43.6)
4 (1.9)

53 (10.7)
0 (0.0)
21 (4.2)
0 (0.0)
6 (1.2)
431 (86.9)
32 (6.5)
8 (1.6)
25 (5.0)
267 (53.8)
219 (44.2)
10 (2.0)

(1.0)
(0.0)
(3.9)
(0.0)
(1.0)
(91.2)
(6.9)
(2.0)
(0.0)
(61.8)
(37.3)
(1.0)

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


Table 2: Medical history of patients

Concurrent secondary
psychiatric conditions
[a],
n (%)
General medical
conditions, n (%)

No

Hungary
(N=183)
43 (23.5)

Latvia
(N=102)
95 (93.1)

Romania
(N=211)
189 (89.6)

Overall
(N=496)
327 (65.9)

Yes

140 (76.5)

7 (6.9)

22 (10.4)

169 (34.1)

No
Yes
Missing

96 (52.5)
86 (47.0)
1 (0.5)

85 (83.3)
16 (15.7)
1 (1.0)

150 (71.1)
55 (26.1)
6 (2.8)

331 (66.7)
157 (31.7)
8 (1.6)

123 (67.2)

56 (54.9)

153 (72.5)

332 (66.9)

Treatment with at least one


antipsychotic medication, n (%)

[a] These subjects had comorbid psychiatric conditions (with primary diagnosis of schizophrenia).
Table 3: Length of hospital stay (days)

Mean
SD
Min
Max
95% CI*

Hungary
(N=183)
31.3
48.82
2.0
500.0
[24.2, 38.5]

Latvia
(N=102)
37.0
14.05
7.0
84.0
[34.3, 39.8]

Romania (N=211)
22.6
31.41
3.0
383.0
[18.3, 26.8]

Overall
N=496
28.8
36.99
2.0
500.0
[25.5, 32.0]

*Normal approximation for the mean.


Min=minimum; max=maximum; SD=standard deviation; CI=confidence interval.
Table 4. Summary of dosage of atypical antipsychotic treatment, by route of administration, during
hospitalisation

Atypical antipsychotic medication


95% CI[a]

Hungary
(N=183)
n (%)
178 (97.3)
[93.7, 99.1]

Latvia
(N=102)
n (%)
101 (99.0)
[94.7,100.0]

Romania
(N=211)
n (%)
200 (94.8)
[90.9, 97.4]

Overall
(N=496)
n (%)
479 (96.6)
[94.6, 98.0]

Quetiapine
Oral Route
Mean (mg)
SD
Median
Min, Max
Risperidone
Oral Route
Mean (mg)
SD
Median
Min, Max
IM Route
Mean
SD
Median
Min, Max
Olanzapine
Oral Route

42 (24.4)
42 (24.4)
583.9
222.36
600.0
75.0, 800.0
31 (18.0)
20 (11.6)
3.9
1.48
4.0
1.0, 6.0
11 (6.4)
37.1
19.10
50.0
4.0, 50.0
49 (28.5)
42 (24.4)

36 (35.6)
36 (35.6)
608.3
237.10
600.0
100.0, 1100.0
28 (27.7)
28 (27.7)
5.1
1.66
4.5
2.0, 8.0
0 (0.0)
----12 (11.9)
11 (10.9)

51 (25.9)
51 (25.9)
611.8
207.51
600.0
200.0, 1200.0
64 (32.5)
47 (23.9)
4.7
2.17
4.0
2.0, 12.0
17 (8.6)
11.0
15.76
2.6
1.7, 50.0
53 (26.9)
51 (25.9)

129 (27.4)
129 (27.4)
601.7
219.51
600.0
75.0, 1200.0
123 (26.2)
95 (20.2)
4.7
1.93
4.0
1.0, 12.0
28 (6.0)
21.2
21.23
5.3
1.7, 50.0[a]
114 (24.3)
104 (22.1)

73

Radu Teodorescu, Elmars Rancans, Gabor Feller, Dan Prelipceanu: A Non-interventional Study To Observe Real-life
Usage Of Atypical Antipsychotics In The Acute Inpatient Management Of Schizophrenia In Central And Eastern Europe

Mean (mg)
SD
Median
Min, Max
IM Route
Mean
SD
Median
Min, Max
Clozapine
Oral Route
Mean (mg)
SD
Median
Min, Max
Amisulpride
Oral Route
Mean (mg)
SD
Median
Min, Max
Aripiprazole
Oral Route
Mean (mg)
SD
Median
Min, Max
Ziprasidone
Oral Route
Mean (mg)
SD
Median
Min, Max
Paliperidone
Oral Route
Mean (mg)
SD
Median
Min, Max
Sertindole
Oral Route
Mean (mg)
SD
Median
Min, Max

17.4
5.42
20.0
5.0, 30.0
7 (4.1)
165.9
142.84
210.0
15.0, 300.0[a]

17.3
4.67
20.0
10.0, 20.0
0 (0.0)a
-----

14.9
6.44
15.0
5.0, 30.0
2 (1.0)
210.0
275.77
210.0
15.0, 405.0[b]

29 (16.9)
29 (16.9)
228.4
154.65
200.0
25.0, 550.0
10 (5.8)
10 (5.8)
390.0
159.51
350.0
200.0, 600.0
26 (15.1)
26 (15.1)
24.2
7.44
30.0
15.0, 30.0
3 (1.7)
3 (1.7)
106.7
41.63
120.0
60.0, 140.0
14 (8.1)
14 (8.1)
10.7
1.94
12.0
6.0, 12.0
0 (0.0)
0 (0.0)
-----

32 (31.7)
32 (31.7)
184.3
176.59
162.5
10.0, 900.0
11 (10.9)
11 (10.9)
818.2
244.21
800.0
400.0, 1200.0
6 (5.9)
2 (2.0)
22.5
10.61
22.5
15.0, 30.0
7 (6.9)
6 (5.9)
103.3
29.44
100.0
80.0, 160.0
0 (0.0)
0 (0.0)
----7 (6.9)
7 (6.9)
18.7
2.21
20.0
15.0, 20.0

12 (6.1)
12 (6.1)
379.2
119.58
400.0
200.0, 500.0
22 (11.2)
22 (11.2)
581.8
230.19
600.0
200.0, 1000.0
8 (4.1)
8 (4.1)
14.1
3.76
15.0
7.5, 20.0
4 (2.0)
4 (2.0)
105.0
50.0
110.0
40.0, 160.0
0 (0.0)
0 (0.0)
----1 (0.5)
1 (0.5)
12.0
-12.0
12.0, 12.0

16.2
5.96
20.0
5.0, 30.0
9 (1.9)
175.7
158.71
210.0
15.0,
(300/405.0)[c]
73 (15.5)
73 (15.5)
233.9
171.86
200.0
10.0, 900.0
43 (9.1)
43 (9.1)
597.7
263.21
1200.0
200.0, 1200.0
40 (8.5)
36 (7.7)
21.9
7.98
17.5
7.5, 30.0
14 (3.0)
13 (2.8)
104.6
35.73
100.0
40.0, 160.0
14 (3.0)
14 (3.0)
10.7
1.94
12.0
6.0, 12.0
8 (1.7)
8 (1.7)
17.9
3.14
20.0
12.0, 20.0

Note: Average daily dose for subjects with dose frequency recorded as PRN (as needed) were calculated using once per
day. If dose frequency was missing, once daily was assumed unless otherwise stated. If route of administration was
missing, oral route was assumed.
Min=minimum; max=maximum; SD=standard deviation.
[a] Recommended maximum dose administered every 2 weeks
[b] Recommended maximum dose administered every 4 weeks
[c] Administration of 300 mg and 405 mg of olanzapine represents two different dosing schedules. Administration of
300 mg depot injection every 2 weeks (in Hungary) is equivalent to a 20 mg daily dose, whereas administration of 405
mg depot injection every 4 weeks (in Romania) is equivalent to a 10 mg daily dose.

74

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


Table 5. Summary of atypical antipsychotic treatment as monotherapy/combination during hospitalisation

Hungary
(N=183)
n (%)
178 (97.3)

Latvia
(N=102)
n (%)
101 (99.0)

Romania
(N=211)
n (%)
200 (94.8)

Overall
(N=496)
n (%)
479 (96.6)

21 (11.5)
6 (3.3)

2 (2.0)
3 (2.9)

26 (12.3)
3 (1.4)

49 (9.9)
12 (2.4)

151 (82.5)

96 (94.1)

171 (81.0)

418 (84.3)

0 (0.0)
138 (75.4)
13 (7.1)

19 (18.6)
24 (23.5)
53 (52.0)

1 (0.5)
145 (68.7)
25 (11.8)

20 (4.0)
307 (61.9)
91 (18.3)

Subjects with no AAP medications


1 AP (mono)
>1 AP only
AP + other

4 (2.2)
0 (0.0)
0 (0.0)
4 (2.2)

1 (1.0)
0 (0.0)
0 (0.0)
1 (1.0)

9 (4.3)
1 (0.5)
0 (0.0)
8 (3.8)

14 (2.8)
1 (0.2)
0 (0.0)
13 (2.6)

Subjects with other than an


antipsychotic medication

1 (0.5)

0 (0.0)

2 (0.9)

3 (0.6)

Subjects with at least one (? 1) AAP


medication
1 AAP (mono)
>1 AAP only
AAP in combination with
other psychotic medications
AAP + AP
AAP + other
AAP + AP + other

AAP = Atypical antipsychotic medication.


AP = Antipsychotic medication (not including atypical antipsychotic).
Other = Other psychotic medication (mood stabilisers, antidepressants, anxiolytics, anticholinergic agents and
anti-dementia drugs).
Table 6. Summary of atypical antipsychotic treatment as maintenance

Atypical antipsychotic (AAP)


medication prescribed as maintenance
therapy
95% CI[a]
Same AAP medications used during
hospitalisation and at discharge[b]
Yes
No

Hungary
(N=183)
n (%)

Latvia
(N=102)
n (%)

Romania
(N=211)
n (%)

Overall
(N=496)
n (%)

96 (52.5)

101 (99.0)

176 (83.4)

373 (75.2)

[45.0, 59.9]

[94.7,100.0]

[77.7, 88.2]

[71.2, 78.9]

88 (49.4)
90 (50.6)

83 (82.2)
18 (17.8)

164 (82.0)
36 (18.0)

335 (69.9)
144 (30.1)

[a] Normal approximation for the proportion of the population with atypical antipsychotic medication as
maintenance therapy.
[b] Denominator is the number of subjects treated with atypical antipsychotic medication during hospitalisation.
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***

ORIGINAL ARTICLES

Cognitive and emotional correlates of posttraumatic


stress symptoms in train drivers exposed to work
trauma
Corina Doroga1, Adriana Bban2
Abstract :
Introduction.International research highlights the
occupational risk of train drivers of being exposed to
potentially traumatic incidents and consequently
developing posttraumatic symptoms and other comorbid
dysfunctions. Although frequency of ,,person under train
incidents is high, only a few of the exposed train drivers
report subsequent posttraumatic stress symptoms.
Objectives. The purpose of the current study is to find
factors that differentiate train drivers who report PTSD
symptoms as a result of PUT incident exposure and to
explore these individual differences as risk factors for
subsequent PTSD symptom development.
Methods. 129 train drivers exposed to PUT incidents
completed a demographic questionnaire, the Impact of
Event Scale-Revised, the General Health Questionnaire,
the Posttraumatic Cognitions Inventory and the
Peritraumatic Distress Inventory.
Results. Statistical analysis of data revealed important
differences in posttraumatic cognitions and peritraumatic
emotional impact of the PUT incidents between train
drivers that reported significant PTSD symptoms and
those without symptoms. Also, we found that self-blame
partially mediates the relationship between peritraumatic
distress and PTSD symptoms.
Conclusions. Findings highlight the need to include
cognitive and emotional risk factors in prevention and
intervention programs tailored for train drivers exposed to
PUT incidents.
Keywords: trauma, PTSD, risk factors, train drivers,
person-under-train incidents

Rezumat :
Introducere.O serie de cercetri internaionale au
evideniat riscul ocupaional al mecanicilor de locomotiv
de a fi expui la incidente feroviare cu potenial traumatic
i de a dezvolta simptome de stres posttraumatic i alte
tulburri comorbide.Dei frecvena incidentelor
,,persoan sub tren este crescut, puini dintre mecanicii
de locomotiv expui la acestea, raporteaz ulterior
simptome de stres posttraumatic.
Obiective. Scopul studiului actual este de a identifica ce
anume i difereniaz pe mecanicii cu simptome de stres
posttraumatic cauzate de implicarea n incidentele
traumatice i de a explora diferenele individuale ca
factori de risc pentru dezvoltarea ulterioar a
simptomelor postraumatice.
Metode. 129 de mecanici de locomotiv expui la
incidente PST au completat un chestionar demografic,
Scala Revizuit a Impactului Evenimentelor, Indexul Strii
generale de sntate, Inventarul cogniiilor
posttraumatice i Inventarul distresului peritraumatic.
Rezultate.Analiza statistic a datelor a evideniat
diferene importante privind cogniiile posttraumatice i
impactul emoional peritraumatic al incidentelor PST
ntre mecanicii de locomotiv cu simptome de stres
posttraumatic i cei ce nu raporteaz ulterior simptome. n
particular, am identificat c relaia dintre distresul
peritraumatic i simptomele de stres traumatic este
mediat parial de auto-blamare.
Concluzii. Rezultatele obinute evideniaz necesitatea de
a include factorii de risc cognitivi i emoionali n
programele de prevenie i intervenie specifice pentru
mecanicii de locomotiv implicai n incidentele PST.
Cuvinte cheie: trauma, tulburarea de stres posttraumatic,
factori de risc, mecanici de locomotiv, incidente
,,persoan-sub-tren

INTRODUCTION
Post traumatic stress disorder (PTSD) represents
the most investigated form of a posttraumatic reaction.
According to the DSM IV TR (2000), the current standard
for diagnosing mental disorders, PTSD is characterized by
three distinct types of symptoms including reexperiencing of the event, avoidance patterns and
persistent hyperarousal(1). Although epidemiological
studies highlight that most people are confronted at least
once in their lifetime with events of traumatic intensity,
prevalence of posttraumatic stress disorder in the general
population is relatively low (2).
Thus, traumatic exposure is neccesary, but not

enough for developing PTSD. In consequence, researchers


have directed their efforts to identifing the most influential
risk factors that predict specific symptom development
(3,4). Meta-analytic studies emphasized the relevance of
distinct risk factors classified as pretraumatic,
peritraumatic and posttraumatic. Conclusions (3,4)
highlight the importance of traumatic event particularities,
as well as individual characteristics that may put the
person at risk of being traumatised. In light of recent
findings, instead of dealing with isolated risk factors, there
is a need to see how these factors interact influencing the
person's reaction to trauma and the experience of
subsequent symptoms.Thus, trauma researchers' current

1
PhD student, psychologist, Trafic Safety Psychological Laboratory at CF Clinical Hospital, Campeni street, no 3 A, Cluj-Napoca, Romania,
correspondence e-mail: cdoroga@yahoo.com
2
PhD, University Professor, Faculty of Psychology and Educational Sciences, Babes-Bolyai University, Cluj-Napoca, Romania

77

Corina Doroga, Adriana Bban: Cognitive And Emotional Correlates Of Posttraumatic Stress Symptoms In Train Drivers
Exposed To Work Trauma
recomandations strongly suggest the need to identify risk
pathways or mechanisms, underlying their relationship to
outcome variables (5). Diversity of identified risk factors
and different trajectories of vulnerability are proof of the
fact that one cannot evaluate trauma reaction outside of
the specific context of confrontation.
Person-under-train (PUT) accidents are serious
rail incidents, resulting in violent death or injury of
persons, because of accidentally or intentionally falling in
front of the moving train (6). They consist of railway
suicides, accidents or collisions of vehicles with the
locomotive at level crossings. Being frequently exposed
to these work incidents, train drivers are susceptible of
developing posttraumatic reactions, and researchers have
tried to identify risk factors that raise train drivers'
vulnerability to trauma.
Most studies investigate circumstantial factors
that may influence train drivers's response to trauma, like
frequent exposure to job related incidents or severity of
their consequences (7,8). Studies support the need to
investigate the role of individual differences in the
development and maintenance of PTSD symptoms in train
drivers involved in PUT incidents(9,10).
Current perspective on the development and
persistence of PTSD symptoms emphasizes the role of
cognitive appraisal of the traumatic experience as a
fundamental mediator in the posttraumatic adaptation
process (11). Cognitive models of PTSD (12-14) assert
that dealing with trauma produces alterations in the
generic cognitive schemas about the world, self and
others. Exposed persons' perspective and belief system is
being affected by the traumatic event, so that the world is
perceived to be unsafe and threatening, and the self is seen
as lacking the resources and skills needed to cope with the
adversive environment (14,15).
Presence of these negative beliefs about oneself
and the world, as a result of a traumatic encounter,
represents the essential vulnerability factor for specific
PTSD symptoms. Catastrophic interpretation that these
central negative beliefs generate, involves retrospective
exaggeration of traumatic events, and/or the permanent
appraisal of being at risk to be exposed to a new
trauma(14).
Cognitive distortions about the world and the self
proved to be strong predictors of PTSD diagnosis, as they
can discriminate between all trauma exposed individuals,
those that developed clinically significant symptoms
(16,17). Studies in samples with various types of trauma
provide strong empirical support for the relationship
between the altered beliefs about the self and the world
and
the frequency and severity of posttraumatic
symptoms (16-19). Also, challenging and modifing these
beliefs in cognitive-behavioral therapy for traumatised
people has been effective in reducing specific symptoms
PTSD (20).
In terms of work related trauma confrontation
one study found that posttraumatic stress was predicted by
pretrauma catastrophic thinking in a sample of firefighters
exposed to on the job traumatic incidents (21). This risk
factor may be essential for train drivers as well, because,
although most of them are confronted with at least one
PUT incident during their years of duty, studies show that
just a few develop persistent PTSD symptoms (9).
According to a french study(7), the traumatic potential of
78

these incidents is mainly determined by the fact that the


train driver may feel responsible for the death of the
victims.
Another relevant risk factor for the development and
persistence of PTSD symptoms, is peritraumatic
emotional reactivity. A meta-analysis of risk factors for
PTSD (4), highlighted that compared with pretraumatic
factors (like previous traumatic history, family
psychopathology, etc.), peritraumatic response was a
stronger predictor (intensity of emotional reactivity
during trauma, life threat perception during adversive
event, peritraumatic dissociation).
Context of traumatic encounter does not imply
life threat for the train driver and also dissociation is less
likely to occur in these specific confrontations. In stead,
differences in peritraumatic emotional intensity may be of
relevance for the susbsequent development of PTSD
symptoms in these proffesionals, as a particularity of
trauma related to accidents. Studies provide empirical
support for the relationship between increased intensity of
emotional reaction during traumatic confrontation with
motor vehicle accidents, disasters and subsequent PTSD
symptoms (22-26).
An interesting and complex risk path or
mechanism combines these two factors: the appraisal of
the traumatic event and the peri-traumatic emotional
reaction to it. Interpretation of the event may influence the
subsequent development of the peri-traumatic reaction,
which further on, will lead to the reinterpretation of the
event and of the peritraumatic reaction to it (5). This
chained reaction to PUT incidents may influence train
drivers' subsequent distress levels, and we consider
further investigating it.
2.OBJECTIVES:
The present study aims to investigate differences
in appraisal and emotional reactivity to PUT incidents
between train drivers that report PTSD symptoms and
those who do not report being affected by these incidents .
Also, we want to investigate the way that cognitive
interpretation and emotional reaction to PUT incidents
combine in predicting subsequent distress in exposed train
drivers.
Specific objective 1: To investigate differences between
train drivers who report severe symptoms of PTSD and
those without symptoms, in terms of the investigated risk
factors. H 1a: We expect to identify a significantly higher
level of negative posttraumatic cognitions for train drivers
that report symptoms of PTSD as opposed to train drivers
(without PTSD symptoms). H 1b: Also, we expect that the
intensity of peritraumatic distress will be significantly
more frequently reported as higher by train drivers that
report PTSD symptoms as opossed to the symptom free
train drivers.
Specific Objective 2: To investigate the relationship
between risk factors (posttraumatic cognitions, intensity
of peritraumatic distress) and reported level of PTSD
symptoms. H 2a: We expect to find a positive significant
relationship between risk factors (posttraumatic
cognitions, peritraumatic distress intensity) and high
levels of PTSD symptoms. H 2b: Also, we hypothesize
that posttraumatic cognitions mediate the relationship
between intensity of peritraumatic emotional reaction to
PUT incidents and subsequent PTSD symptoms.

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


3. MATERIALS AND METHODS:
3.1.Procedure
As a first step we obtained the approval for
research objectives and procedure from the Head of the
Railway Regional Department of Cluj, that allowed us
access to train drivers involved in Traffic Safety. Selection
of participants was done on a voluntary basis. Of the 176
initially approached train drivers, 12 refused to
participate, and 35 declared they never had an PUT
incident. Questionnaires and an informed consent were
completed individually, during three proffesional training
meetings.
3.2.Participants
129 drivers (mean age = 37.8, SD= 8.19)
belonging to locomotive depots in Cluj, Dej, Bistrita and
Brasov were included in the final sample. The average
frequency of PUT incidents throughout train driver's
career was 3.43 (SD= 2.86).
3.3.Instruments
3.3.1. Impact of Events Scale-Revised -IES-R
(27) has been used extensively to identify the specific
symptoms of PTSD in relation to a specific traumatic
event. The questionnaire contains 22 items, has adequate
psychometric qualities and it is used to assess the three
categories of posttraumatic symptoms: reexperiencing the
traumatic event, avoidance and hypervigilance, according
to diagnostic criteria for PTSD in DSM IV. Also, the
questionnaire has adequate power to discriminate
between people with severe symptoms of PTSD and less
affected persons (28). In our sample, internal consistency
was appropriate(=0.89).
3.3.2. Index of general health GHQ-28 (29).
GHQ-28 is commonly used as a screening tool,
highlighting the increased risk for certain mental
disorders: severe depression, symptoms of anxiety and
sleep disorders, somatic disorders, social difficulties
(isolation from others).Internal consistency for the present
sample was adecquate(=0.71).
3.3.3. Posttraumatic cognitions inventory
(PTCI) was developed by Foa, et al.(1999) to assess
cognitive distortions that dealing with trauma may
produce. With excellent psychometric qualities, the
instrument is a measure commonly used in research of
posttraumatic pathology. Subscales of negative cognitions
about the self and the world prove relevant predictors of
the onset and maintenance of PTSD symptoms (17-19,
21). Also, the questionnaire adequately discriminates
individuals who meet diagnostic criteria for PTSD (16).
For the present sample, internal consistency was
appropriate ( 0.82).
3.3.4. Peritraumatic distress inventory-PDI (30)
is a useful tool in investigating emotional reactivity to
trauma. The instrument has adequate psychometric
qualities and is an effective method for assessing the
diagnostic criterion A2 for PTSD. According to factorial
analysis conducted by the authors, the instrument
measures two independent factors: intensity of emotional
reactivity and perception of life being threatened during
the traumatic event. Internal consistency for the study is
appropriate ( 0.77).
3.3.5. Demographic questionnaire regarding personal
information (age, tenure, marital status, etc.), number of
PUT incidents, details of the most significant incident.
4. RESULTS :

4.1. Evaluation of differences between train


drivers that reported PTSD symptoms and those without
symptoms
Testing the first hypothesis required dividing the
sample into three categories.The first category consisted
of those who reported no psychological distress as a
consequence of PUT experiences. 13 participants were
included in this category, reporting complete absence of
PTSD symptoms, although they were exposed to PUT
incidents. Also the number of general psychological
symptoms, assessed using the GHQ-28 questionnaire is
significantly reduced in this category when compared to
the other train drivers (t = 3.48, p = 0.02).
We followed current reccomendations (28) and
used the cut-off value of 33 (of max. 88, on the global IESR scale) to differentiate train drivers who report clinically
significant PTSD symptoms. 16 of the participants had
scores above 33, corresponding to a of clinical level of
PTSD symptoms' intensity.
The third group (N = 100) consisted of the
majority of train drivers involved in the study, who
reported some specific PTSD symptoms, because of the
PUT incidents, but their scores were low when compared
to the cut-off value used in screeening for PTSD.
To assess differences between the three groups in
terms of the risk factors investigated, we performed a
series of analyses of variance ANOVA one-way for each of
the evaluated factors. Table 1 summarizes the descriptive
data for the three categories of participants and the
significance of differences between them.
According to performed ANOVA analysis, the
three categories of train drivers-without PTSD symptoms,
with few PTSD symptoms and with clinically relevant
PTSD symptoms, reported statistically significant
differences in beliefs about self, the world, the level of
self-blame and the intensity of peritraumatic distress. As
hypothesized, train drivers without symptoms of PTSD
had significantly lower average levels of negative
cognitions when compared to the category of train drivers
with more severe and frequent PTSD symptoms. Results
comparing means of the two groups are depicted in Table
2, for each type of cognition separately, for the global
cognition scale, as for the peritraumatic distress intensity.
Differences between groups confirm that, unlike
train drivers that did not report symptoms of PTSD, more
affected train drivers make negative interpretations of self
and world and also make internal attributions of
responsibility for the incidents.
In terms of reported peritraumatic emotional reaction, the
average reactivity reported by train drivers in the group
without PTSD symptoms (m = 11.61, S.D. = 1.12) was
significantly lower than that of the group with symptoms
of PTSD (m = 15.06, S.D. = 3.21). Greater peritraumatic
intensity of distress was reported by train drivers that also
report more frequent PTSD symptoms (t = - 3.67, df = 27,
p = 0.00).
4.2. Assessment of the relationship between risk factors
a n d r e p o r t e d P T S D s y m p t o m s
In assessing risk factors for the development of
PTSD symptoms for train drivers involved in PUT
incidents, we identified significant associations between
variables that discriminated between train drivers that
report symptoms of PTSD and those who are not affected
by such events. These factors are summarized in Table 3.
79

Corina Doroga, Adriana Bban: Cognitive And Emotional Correlates Of Posttraumatic Stress Symptoms In Train Drivers
Exposed To Work Trauma
In line with findings from other studies, current findings
support the positive association of posttraumatic
cognitions about the self (r = 0.45, p = 0.01) and the world
(r = 0.27, p = 0.01) and reported PTSD symptoms. The
more negative the individual views the self and the world,
the higher the level of posttraumatic symptoms he reports.
When considering effect size of significant correlations,
the relationship between negative cognitions about the
self and the frequency of PTSD symptoms has the
strongest pragmatical impact (r = 0,20) among the three
types of posttraumatic cognitions. Perception of self as
incompetent, or lacking ability to cope with trauma may
be a relevant predictor of persistence of PTSD symptoms
for train drivers involved in PUT incidents.
Also self-blaming cognitions were significantly
positively associated with PTSD symptoms (r = 0.38, p =
0.01). The determination coefficient for this relationship
also demonstrates a strong effect size (r= 0,14). If the
train driver considers himself blameworthy for causing
the incident, the level of PTSD symptoms he reports will
be greater. Relationship with this risk factor is particularly
relevant because the context of PUT incidents leaves room
for negative interpretation on the adequacy of their
behavioral reaction in the situation and may cause the train
driver to hold himself responsible for the accident.
Peritraumatic distress intensity was also
significantly positively correlated with the presence of
posttraumatic stress symptoms (r = 0.41, p = 0.01), with a
strong effect size (r = 0, 16). If the intensity of
peritraumatic emotional distress was reported to be high,
subsequent reported levels of PTSD symptoms were also
higher.
Results confirm our expectations regarding relevant
cognitive and emotional correlates of PTSD symptoms for
train drivers involved in PUT incidents.
4.3. Mediation analysis
According to current criteria for mediation
analysis (31), we checked if posttraumatic cognitions
satisfy necessary conditions as mediator of the
relationship between emotional peritraumatic reaction
and PTSD symptoms. The predictor needs to be associated
with both the mediator and the outcome variable and, after
controlling for the effects of the mediator, the relation
between predictor and outcome should reduce partially or
completely, accounting for partial mediation or total
mediation. Results showed that preconditions were
satisfied only for self-blame as the mediator variable,
because this was the only posttraumatic cognition that
significantly correlated to both outcome (PTSD
symptoms) and predictor (peritraumatic emotional
intensity). The diagram below shows results of the
mediational analysis we performed.
The recommended methodology (31) uses hierarchical
regression analysis to assess if the relationship between
peritraumatic emotional reaction(predictor) and PTSD
symptoms(outcome variable) modifies when controlling
for self-blame(mediator). All regression beta coefficients
were significant. Adding self-blame to the equation
significantly decreased the amount of variance in PTSD
symptoms explained by peritraumatic emotional intensity.
The Sobel test(32) used to test the indirect effect for this
mediation was found to be significant, 1,80 (p <0.03).
According to results, self-blame acts as a significant
partial mediator on the relationship between peritraumatic
80

emotional intensity and PTSD symptoms.


5. DISCUSSION AND CONCLUSIONS:
Results revealed important issues on each of the
investigated risk factors and their interaction in predicting
PTSD symptoms.
5.1. Negative cognitions about the self, world, and selfblame
Results of the present study confirm the
hypothesis derived from cognitive models of PTSD, for
train drivers exposed to trauma. It is interesting that in the
current study, negative cognitions about self, world, and
self-blame are factors that significantly differentiate train
drivers with clinical symptoms of posttraumatic stress
from those that did not exhibit such symptoms. These
results are consistent with contemporary models of PTSD
development (13, 14). According to Ehlers & Clark's
cognitive model of PTSD persistence, posttraumatic
symptoms are prevalent when appraising trauma
experiences causes a sense of serious current threat and
the perception that the individual does not have the ability
to surpass the consequences of extreme stressors.
In particular, negative cognitions about the self
and self-blame were found to be important correlates of
PTSD symptoms and differentiating factors between train
drivers that manage to adapt efficiently after PUT
experiences and those who report significant
posttraumatic distress. It is possible that exposure to PUT
incidents may determine train drivers to perceive they lack
necessary resources to cope with these reccurent traumatic
events, which, according to theoretical and empirically
supported perspectives, predicts persistent symptoms of
PTSD. Results are congruent with other studies that
involved on the job risk for trauma. For example, negative
beliefs about oneself was found to be a relevant
prospective predictor for the development and
maintenance of posttraumatic symptoms in firefighters
(21).
Particularly for train drivers exposed to PUT
incidents, internal atribution of responsibility or feeling
guilty after the traumatic encounter, seems to be
associated with later posttraumatic distress. Because they
are the agents that drive the locomotive, train drivers have
a higher probability to consider themselves blameworthy
for the accidents and responsible for fatalities. It is
important to note that most of the time the train cannot be
stopped because of high speed, and other technical limits,
so collision is often unavoidable. Interpreting their
reaction to the PUT incident as inadequate or insufficient
may elicit changes in the way train drivers perceive
themselves and the world, which in turn, leads to an
impaired posttraumatic adaptation process and the
appearance of PTSD symptoms. This particularity is
congruent with anterior research on train drivers,
highlighting the need to offer information about trauma
and posttraumatic symptoms and construct behavioral
protocols for these specific contexts (7).
Present findings on negative cognitions developed by
train drivers, also have a pragmatic impact. Negative
trauma-related cognitions can be processed in daily life
and in therapy by offering new, incompatible information
(33). Working through negative cognitions about the self
and especially self-blame, may be an efficient way to
minimize the traumatic impact of recurrent PUT incidents
in train drivers and subsequent PTSD symptoms.

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


5.2. Intensity of peritraumatic distress
Another relevant correlate for the persistence of
PTSD symptoms we found, was the magnitude of distress
retrospectively reported by the train driver during the PUT
incident. Investigation of this risk factor involves both an
emotional intensity generated by being involved in a
traumatic event (PUT incident) and psychophysiological
reactivity indices. We found that peritraumatic distress
intensity is significantly lower for train drivers that didn't
report symptoms of PTSD, and a significant correlate of
PTSD symptom levels. However, this result must be
interpreted keeping in mind that present data are
retrospective self-reports and that we couldn't control the
effects of inaccurate memory over time.
Still, results regarding the relevance of this
particular risk factor are congruent to other anterior
studies, on survivors of motor vehicle accidents (26) or
survivors of different types of disasters (34).
A surprising result was the significant
association of peritraumatic distress with self-blame. The
more train drivers reported feeling responsible for the
incidents, the stronger was the intensity of their
peritraumatic reaction. Using mediation analysis, we
tested for a chained reaction between peritraumatic
intensity of distress, negative posttraumatic cognitions
and PTSD symptoms.We found self-blame to partially
mediate the relationship of peritraumatic distress and
PTSD symptoms. This result is congruent with current
research in PTSD risk factors in stressing that synergistic
response to trauma is determined as a cumulative action of
variables.
5.3. Concluding remarks
In interpreting the results we should consider
some limitations of the current research. First, crosssectional design that we used makes it impossible to draw
any conclusions about causality. This is a first study that
highlights significant relationships between cognitive and
emotional correlates of trauma and PTSD symptoms in
train drivers involved in PUT incidents. It would be
therefore beneficial to evaluate the relationship between
predictor variables and PTSD symptoms in a longitudinal
design.
Second, we exclusively used retrospective self-report
data, a common feature in trauma research. This data
collection method does not allow precise determination of
the specific timing of symptom development and the way
they correlate with exposure to traumatic PUT incidents.
In addition, given that the assessment was done at unequal
intervals of time since the traumatic event, it is possible
that the results are influenced by the responders' memory
accuracy. We tried to control the effect of other factors in
determining traumatic symptoms, by asking participants
to report psychological distress exclusively caused by
PUT experiences. But we need to consider the possibility
that the results were influenced by other variables that
were not assessed: history of previous trauma, negative
current life events, influence of protective factors as well,
that should be considered in further research.
Also, conclusions about the reported differences between
categories of train drivers with and without PTSD
symptoms are dependent on the method of determining
the categories. The procedure used was recommended in
previous studies that reported adequate sensitivity and
specificity of IES-R for the cut-off value we used (28).

However, establishing a cut-off value is somewhat


arbitrary and taxometric studies have reccomended a
dimensional structure for PTSD as opposed to a categoric
one (35).
Although it is a first study regarding the relations
between studies variables, our results contribute to
understanding the development of posttraumatic stress
symptoms for train drivers exposed to trauma in their
professional environment. Findings support the need for
replication studies. Also, they highlight the need to include
individual risk factors, in particular posttraumatic
cognitions and peritraumatic distress, as relevant to
prevention and intervention programs tailored for train
drivers exposed to PUT incidents.
Abreviation list
PTSD: Postraumatic stress disorder
PUT incidents: ,,person-under-train incidents
IES-R: Impact of Event Scale-Revised
GHQ-28: General Health Questionnaire
PTCI : Posttraumatic Cognitions Inventory
PDI: Peritraumatic Distress Inventory
Table 1. Significant differences between the three categories of
train drivers, depending on the investigated risk factor (N = 129)

Risk
Factor

No PTSD
Group
(N= 13)
M
S.D.

Incident
frequency
Self
cognitions
World
cognitions
Self-blame

5.53
2.22
17.92
1.32
11.23
4.67
8.46
3.71
Posttraumatic 37.61
Cognitions
5.97
Intensity of
11.61
peritraumatic 1.12
distress
Life threat
13.07
perception
8.62

Below
PTSD
threshold
Group
(N=100)
M
S.D.

Above
PTSD
threshold
Group
(N=16)
M
S.D.

4.29
2.51
23.23
5.81
13.45
8.46
8.50
4.21
45.18
9.84
11.73
2.63

3.93
2.59
30.40
10.97
17.00
4.83
15.56
5.66
63.00
17.00
15.06
3.21

1.70

0.18

14.36

0.00

5.53

0.00

18.32

0.00

24.35

0.00

11.50

0.00

12.46
6.83

16.56
9.33

2.14

0.12

Risk factors for which we found significant differences between


groups are underlined
Table 2. Differences in posttraumatic cognitions and
peritraumatic distress between symptom free train drivers and
the group that reported significant PTSD symptom levels
Symptom
free group
N=13

Self posttraumatic
cognitions
World posttraumatic
cognitions
Self-blame
Global posttraumatic
cognitions
Peritraumatic
intensity of distress

T,
df, p

17.92
1.32

Significant
symptoms
group N=
16
30.40
10.97

11.23
4.67

17
4.83

- 3.24
27
p= 0.00

8.46
3.71
37.61
5.97

15.56
5.66
63
17

- 3.88
27
p= 0.00
- 5.56
19.35 p=0.00

11.61
1.12

15.26
3.21

-3.67,
27,
p=0.00

- 4.52
15.53 p= 0.00

81

Corina Doroga, Adriana Bban: Cognitive And Emotional Correlates Of Posttraumatic Stress Symptoms In Train Drivers
Exposed To Work Trauma
Table 3 Intercorrelations between risk factors and PTSD symptoms (N=129)

BravaisPearson
coef.
PTSD
symptoms
Intrusion

0.87**

Avoidance

0.93**

0.72**

0.83**

0.59**

0.68**

0.36**

0.24**

0.37**

0.35**

0.51**

0.40**

0.48**

0.48**

0.35**

0.45**

0.34**

0.43**

0.42**

0.22*

0.80**

0.27**

0.22*

0.24**

0.55**

0.31**

0.64**

0.23*

0.38**

0.30**

0.35**

0.36**

0.26**

0.71**

0.37**

0.28**

0.41**

0.42**

0.34**

0.35**

0.23*

0.25**

0.11

0.08

0.39**

Hyper
arousal
General
symptoms
Posttr.
cognitions
Self
cognitions
World
cognitions
9.Selfblame
10.Peritr.
reaction
M

10

15.61

4.82

7.20

3.80

18.51

46.62

23.58

13.66

9.37

12.13

SD

9.89

3.76

4.61

3.23

4.70

12.47

7.04

5.00

4.92

2.81

0.89

0.75

0.66

0.65

0.71

0.82

0.79

0.75

0.71

0.68

** p< 0,01
* p< 0,05

Fig. 1. Mediation diagram for peritraumatic emotional intensity as predictor of PTSD symptoms with self-blame as mediator
Self-blame
0.39**

Peritraumatic
emotional intensity

0,38**
0.41**

PTSD symptoms

0.31**

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***

83

CLINICAL CASE

DIAGNOSTIC CHALLENGES OF A PSYCHOTIC


DISORDER IN A PATIENT WITH LIVER
TRANSPLANT
ANCA TALASMAN, ALEXANDRA DOLFI, MIHAELA NAE, IULIA ROSCA
Abstract:
We present the case of a 39 year-old woman who
underwent liver transplantation in 2011 at Fundeni
Clinical Institution and who developed an acute psychotic
episode, with psychomotor agitation, persecutory
delusion, visual and auditory hallucinations, psychotic
anxiety and sleep problems 3 days after the transplant,
treated with Olanzapine. The patient was admitted to the
psychiatric emergency unit of Clinical Hospital of
Psychiatry Prof. Dr. Al. Obregia in August 2014 for a
second psychotic episode, 6 months after Olanzapine
withdrawal. Having difficulties in establishing a certitude
diagnosis, we considered many differential diagnoses
including postoperative delirium, steroid induced
psychosis and schizophrenia.
CONCLUSIONS: Similar to other populations with
chronic physical illnesses, patients with organ transplant
are at elevated risk for psychiatric symptoms and
diagnosable psychiatric disorders. Mood and anxietyrelated disorders are the most common psychiatric
illnesses observed both pre- and post transplant, although
acute cognitive impairment and delirium are often seen
shortly pre transplant and preoperatively due to metabolic
perturbations and the effects of surgery. Psychosis in
transplant populations, although rare, is a significant
concern because of its potential impact on health and wellbeing if not carefully managed. Psychiatric complications
of liver transplant can manifest in different ways and at
various time points which makes detection and
management challenging. Given the impact these have on
patient and transplant outcome, we stress the importance
of vigilance, timely, adequate intervention and of a
multidisciplinary approach of patients with liver
transplant.
Keywords: psychosis, transplant, neuropsychiatric
complications.

Rezumat
Prezentm cazul unei paciente de 39 de ani care a suferit
un transplant hepatic n 2011 la Institutul Clinic Fundeni
i care a dezvoltat agitaie psihomotorie, delir de
persecuie, halucinaii auditive i vizuale, anxietate
psihotic i insomnii la 3 zile de la transplant, fiind tratat
cu Olanzapin. Pacienta a fost admisa la unitatea de
primiri urgene a Spitalului Clinic de Psihiatrie Prof. Dr.
Alexandru Obregia n August 2014, pentru un al doilea
episod psihotic, la 6 luni dup ntreruperea tratamentului
cu olanzapin. Avnd dificulti n stabilirea unui
diagnostic de certitudine, am luat n considerare
numeroase diagnostice difereniale printre care i
deliriumul postoperator, psihoza indus de steroizi i
schizofrenia.
CONCLUZII: La fel ca i alti pacieni cu boli somatice
cronice, pacienii cu transplant de organ au un risc ridicat
de dezvoltare a simptomelor psihiatrice i a tulburrilor
psihice. Tulburrile de dispoziie i tulburrile anxioase
sunt cele mai frecvente afeciuni psihiatrice observate pre
i posttransplant, dei afectarea cognitiv i deliriumul
sunt cel mai frecvent ntlnite la scurt timp pre transplant
i n perioada preoperatorie datorit tulburrilor
metabolice i a efectelor interveniei chirurgicale. Psihoza
la pacienii cu transplant, dei rar, reprezint o
preocupare semnificativ datorit potenialului impact
asupra sntii i calitii vieii n cazurile n care nu este
bine manageriat. Complicaiile psihiatrice ale
transplantului hepatic se pot manifesta postoperator n
diverse moduri, ceea ce face diagnosticarea i tratamentul
o provocare. Avnd n vedere impactul pe care acestea l
au asupra pacientului i a prognosticului posttransplant,
subliniem importana ateniei, interveniei adecvate,
o p o r t u n e i c o l a b o r a re a m u l t i d i s c i p l i n a r .
Cuvinte cheie:
psihoz, transplant, complicaii
neuropsihiatrice.

BACKGROUND: The prevalence of neuropsychiatric


complications in liver transplant patients ranges from
8.3% to 64.5% [1,2,3,4,5]. Such complications include
delirium, brief psychotic disorder, major depression,
mania, adjustment disorder, anxiety and post-traumatic
stress disorder, seizures, cerebrovascular disorders,
insomnia, migraine, vertigo, movement disorders and
peripheral neuropathy [1,2,3]. Psychosis, including
conditions such as schizophrenia, schizoaffective
disorder, mania, and psychotic depression, is rare in
transplant recipients. Moreover, psychosis emerging

beyond the postoperative recovery period (and which can


therefore not be ascribed exclusively to acute metabolic
perturbations associated with surgery and marked
medication changes) appears to occur almost exclusively
in individuals with pre- transplant histories of such
illness. In fact, individuals with a history of psychosis are
at high risk for posttransplant recurrences. These patients
can do well posttransplant if good social supports,
adherence to medical and psychiatric directives, and good
control of psychotic symptoms are established prior to
transplant. Under these circumstances these patients do

MD, PhD, Clinical Hospital of Psychiatry Prof. Dr. Al. Obregia Bucharest, No.10 Berceni Street, email: anaanca@yahoo.com
Resident in Psychiatry, Clinical Hospital of Psychiatry Prof. Dr. Al. Obregia, Bucharest, email: dolfialexandra@gmail.com , naemhl@yahoo.com
Resident in Gastroenterology , Clinical Institute Fundeni, Bucharest, email: rosca.iulia@yahoo.com

84

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


not have rates of no adherence that differ from other
transplant recipients. The potential for good management
post transplant, plus the very negative effects if psychoses
are not well managed, make them important conditions to
consider during the pretransplant assessment. Despite
common beliefs, it is not clear that a prior psychiatric
history makes a patient more susceptible to the potential of
immunosuppressive medications, especially steroids, to
produce or exacerbate psychotic symptoms or mania (i.e.
steroid psychosis). The appropriate use of antipsychotic
medication is usually adequate to prevent or manage these
symptoms if they emerge, and care must be taken that
these medications are not discontinued in the early post
transplant phase [6,7].
We present a case of a 39 year-old woman who underwent
liver transplantation for decompensated (both vascular
and parenchyma) autoimmune hepatic cirrhosis (MELD
score=13 with liver failure) in 2011.
The patient was admitted to the psychiatric emergency
unit of Clinical Hospital of Psychiatry Prof. Dr. Al.
Obregia in August 2014 for: psychomotor agitation,
imperative and commendatory auditory hallucinations,
psychotic anxiety and sleep disorders. These symptoms
occurred during hospitalization at Fundeni Clinical
Institution in Bucharest, where she was admitted on July
30 2014 for marked fatigability, fever and jaundice. On
August 12 2014 she was transferred to our emergency unit
because she developed hallucinations, delusions and
psychomotor agitation.
HISTORY: The patient underwent the liver transplant at
Fundeni Clinical Institution where she was admitted
between 16.11.2011-01.03.2012. Post-transplant she was
administered immunosuppressive treatment with SoluMedrol, Mycophenolate Mofetil and then Tacrolimus.
The secondary diagnoses were: portal vein thrombosis,
biliary fistula, Pseudomonas Aeruginosa infection and
psychomotor agitation. During the admission for
transplant surgery at Fundeni Clinical Institution in 2011,
only 3 days after the liver transplant the patient developed
an acute psychotic episode, with psychomotor agitation,
persecutory delusion, visual and auditory hallucinations,
psychotic anxiety and sleep problems. She was consulted
by a psychiatrist who decided to start the treatment with
Olanzapine 10 mg/day. After the psychotic episode,
Tacrolimus was changed with Sirolimus which was
administered for another 4 months then replaced with
Cyclosporine because of its well known neurological
effects, the patient also developing a biliary fistula during
Sirolimus treatment. The patient was very well responsive
to the antipsychotic treatment, so she was under
Olanzapine between 2011 and 2013, when the treatment
was discontinued at the advice of her doctor because
patient's evolution was favorable and she could return to
her work as a nurse. For 6 months after discontinuation she
had a good functioning until August 2014 when she
suffered the second psychotic episode, described above.
The patient is married, has a 12 years old child and works
as a nurse. She denies the consumption of nicotine,
alcohol and caffeine. Her family history is relevant, her
mother being diagnosed with schizophrenia. The patient
had no personal psychiatric antecedents before her first
psychotic episode occurred in 2011, 3 days after liver
transplantation. Also, the personal history for other
organic diseases was negative.

PSYCHIATRIC EXAMINATION: performed on August


12 2014 revealed a conscious and co operant patient,
oriented in time and space, autopsychic and allopsychic
oriented, visual and psychic contact easily to start and
maintain, psychomotor agitation, expansive mimic and
gesture, expressive facies, bizarre behavior (she sits on the
back of the chair).
The patient presents imperative and commendatory
auditory hallucinations (I heard a song before and now,
I've heard many voices, I don't know what to think
anymore), global hypoprosexia, no memory
disturbances, accelerated flow and rhythm of thoughts,
persecutory delusions (They keep following me),
expansive mood, psychotic anxiety, disinhibition (the
voices tell me that if I don't sleep with my doctor I won't
get better), insomnia, decreased appetite and impaired
insight.
SOMATIC EXAMINATION: multiple ecchymoses on
the arms, back and belly, post-operative scar on the
abdomen, elevated blood pressure (170/110 mmHg),
tremor of the arms and elevated pulse (110 bpm) without
any other pathological signs.
PARA CLINICAL EXAMINATION: Native brain CT
was normal. The evolution of the blood tests results (only
abnormal parameters extracted) from Fundeni Institute
(admission and discharge days) and during hospitalization
in Alexandru Obregia Hospital are presented in Table 1.
COURSE AND TREATMENT: After admission on
12.08.2014 we initiated treatment with: Diazepam 10 mg,
3 tablets/day, Olanzapine 10 mg/day and Zopiclone 7.5
mg 1 tablet/day. At the recommendation of the
gastroenterologist, the psychiatric treatment was
completed with: Medrol 4 mg/day, Silivit F 1 tablet/ day,
Omeprazole 1 tablet/day, Controloc 40 mg/day and Neoral
(Cyclosporine, schedule 75 mg-0-75mg; 50-0-50; 50-050 then repeat).
The next 2 days, the evolution was stationary, the patient
being still psychomotor agitated and experiencing the
following psychiatric symptoms: psychotic anxiety,
immediate echolalia, soliloquy, accelerated flow and
rhythm of thoughts, logorrhea, visual and auditory
hallucinations (I see the devil, he took my voice and now
he takes my liver too). According to these symptoms, a
new treatment schedule was proposed on 14.08.2014,
Olanzapine being increased to 15 mg/day and Diazepam
replaced with Lorazepam 3 mg/day maximum 6 mg/day.
Zopiclone was withdrawn. During the day the patient
continued to be psychomotor agitated, auto aggressive
(continuously banged her head on the wall), having vivid
visual and auditory hallucinations (The devil is coming
for me, I have to run) which is why Olanzapine was
changed to Haloperidol 30 drops (3 mg)/day with
Midazolam i.m. added to the scheme in case of insomnia.
Because the bruising still persisted on the arms, back and
belly, Medrol was changed for Solu-Medrol perfusion
starting in dose of 1g/day (14.08-17.08) decreased to 500
mg/day (18.08), 250 mg/day (19.08), 100 mg/day (20.08),
50 mg/day (21.08) which was continued with Medrol
tablets 20 mg/day since 22.08.
During the next 4 days the psychomotor agitation
decreased but the auditory and visual hallucinations still
persisted, which is why Haloperidol was increased to 50
drops (5 mg/day) on 18.08, adding Romparkin 2
tablets/day and Lactulose syrup 3 doses/day at the
85

Anca Talasman, Alexandra Dolfi, Mihaela Nae, Iulia Rosca: Diagnostic Challenges Of A Psychotic Disorder In A Patient
With Liver Transplant
recommendation of the gastroenterologist. The rest of the
treatment scheme (Neoral, Omeprazole, Medrol, Siluvit F,
Controloc) remained unchanged. The next day (19.08) the
hallucinations were still persistent, Haloperidol being
increased to 60 drops (6 mg/day).
Since 20.08.2014, the evolution of our patient started to
improve. She became critic regarding her hallucinations
and the psychotic anxiety diminished. The hallucinations
disappeared completely on 25.08.2014 after 12 days of
treatment with haloperidol (I feel better, I don't see or
hear anything strange), and the evolution was good until
discharge, on 27.08.2014 after 15 days of hospitalization
in the psychiatric unit. She was discharged with the
following treatment scheme: Haloperidol 60 drops (6
mg)/day, Lorazepam (2 mg/day for 3 days then 1 mg/day
for 7 days then only if needed), Romparkin 2 mg 3
tablets/day. At the recommendation of her surgeon, the
scheme was completed with: Medrol 20 mg 1 tablet/day,
Neoral (same scheme as during hospitalization),
Omeprazole 20 mg 2 tablets/day, Lactulose 3 doses/day
and Silivit F 1 tablet/day.
So far, the patient has been on the same treatment as after
August 2014 discharge, her evolution was very good,
without any psychiatric symptoms and she continued to
work as a nurse. She comes for check-up every 2 months.
DISCUSSION: In the described patient postoperative
delirium was likely after the first psychotic episode
because after surgery, delirium typically evolves
immediately after emergence from general anesthesia or,
after a lucid interval, in the first 72 hours [8]. This
diagnosis was eliminated after the second psychotic
episode, as the patient didn't suffer another surgical
intervention.
Another diagnosis we considered was psychotic episode
induced by corticosteroids or immunosuppressive agents.
Corticosteroids often induce psychiatric syndromes
including depression, mania, psychosis, and delirium,
known as steroid psychosis. Calcinurin inhibitors can
cause neurologic and psychiatric side effects. Mild
symptoms to severe complications can be found when the
normal range of dose is administered. At the first episode
this diagnosis could be possible because the psychotic
symptoms evolved within a short period of time (after 3
days) from the transplant when the patient was in
treatment with Solumedrol then with Tacrolimus which
are known for their possible psychiatric adverse events. At
the second episode the patient was in treatment with
Cyclosporine which is less possible to cause psychotic
symptoms. The most frequent psychiatric symptoms
second to Cyclosporine treatment are cited to be anxiety
and depression without psychotic symptoms.
[9,10,11,12,13]
Graft rejection was considered because of initial elevated
bilirubin, but was excluded according to the results of
investigations.
In chronic liver failure manifestations of encephalopathy
are common and may reach from mild obtundation with
dementia and movement disorders to deep coma [14]. In
the early phase of acute liver failure agitation, delusional
ideas, and hyperkinesias are also common until coma
finally ensues [15]. During the August 2014 admission the
patient presented tremor of the arms which resembled
flapping tremor. Lab tests were performed and the
diagnosis was excluded because of normal laboratory
86

findings.
Hepatic artery thrombosis is a devastating complication after orthotopic
liver transplantation often requiring revascularization or retransplantation. It is associated with considerably increased morbidity
and mortality. Acute cognitive dysfunction such as delirium or acute
psychosis may occur after major surgery and may be associated with the
advent of surgical complications [6, 16]. Abdominal ultrasonography
and CT excluded this diagnosis.
Disseminated intravascular coagulation was another diagnosis taken in
consideration because of the numerous ecchymoses on the arms, legs and
belly but it was excluded because the coagulation tests were all normal.
Intra-cranial tumors were excluded as a diagnosis because the cerebral
CT didn't reveal any pathological signs.
Schizophrenia was another discussed diagnosis because of her personal
and family history, but the evolution between the two episodes and after
the second one was good, so we also thought of a psychotic status after
liver transplant.
CONCLUSIONS: Similar to other populations with chronic physical
illnesses, patients with organ transplant are at elevated risk for
psychiatric symptoms and diagnosable psychiatric disorders. Mood and
anxiety-related disorders are the most common psychiatric illnesses
observed both pre- and post transplant, although acute cognitive
impairment and delirium are often seen shortly pre- transplant and
preoperatively due to metabolic perturbations and the effects of surgery.
Psychosis in transplant populations, although rare, is a significant
concern because of its potential impact on health and well-being if not
carefully managed [17]. Psychiatric complications of liver transplant can
manifest in different ways and at various time points which makes
detection and management challenging. Given the impact these have on
patient and transplant outcome, it stresses the importance of vigilance,
timely, adequate intervention and close collaboration between
disciplines.
REFERENCES:
1. Tombazzi CR, Waters B, Shokouh-Amiri MH, Vera SR, Riely CA.
Neuropsychiatric complications after liver transplantation: role of
immunosuppression and hepatitis C.
Digestive diseases and sciences. 2006 Jun; 51(6):1079-81.
2.Campagna F, Biancardi A, Cillo U, Gatta A, Amodio P. Neurocognitive
neurological
complications of liver transplantation: a review. Metabolic brain disease.
2010 Mar; 25(1):115-24.
3. Fukunishi I, Sugawara Y, Takayama T, Makuuchi M, Kawarasaki H,
Surman OS. Psychiatric disorders before and after living-related
transplantation. Psychosomatics. 2001 Jul -Aug; 42(4):337-43.
4. Stracciari A, Guarino M. Neuropsychiatric complications of liver
transplantation. Metabolic brain disease. 2001 Jun; 16(1-2):3-11.
5. Fukunishi I, Sugawara Y, Takayama T, Makuuchi M, Kawarasaki H,
Surman OS. Association between pretransplant psychological
assessments and posttransplant psychiatric disorders in living-related
transplantation. Psychosomatics. 2002 Jan-Feb;43(1):49-54.
6. Krahn LE, DiMartini A. Psychiatric and psychosocial aspects
of liver transplantation. Liver Transplantation, 2005; 10:
11571168.
7. Fukunishi I, Sugawara Y, Takayama T, Makuuchi M, Kawarasaki H,
Surman OS, Psychiatric Disorders Before and After Living-Related
Transplantation, Psychosomatics. 2001 Jul-Aug; 42(4):337-43.
8. Carmel Bitondo Dyer, MD; Carol M. Ashton, MD, MPH; Tom A.
Teasdale, MPH, Postoperative Delirium.A Review of 80 Primary
Data Collection Studies. Arch Intern Med. 1995; 155(5):461-465.
9. Sandeep Grover, Siddharth Sarkar. Journal of Clinical and
Experimental Hepatology. December 2012, vol2(4): 382-394.
10.Wada K, Yamada N, Sato T et al. Corticosteroid induced Psychotic
and Mood Disorders. Psychosomatics 2001; 42:461- 466.
11. Patten SB, Neutel I. Corticosteroid - induced adverse psychiatric
effects. Drug Safety 2000; 22:111-22.
12. Turjanski N, Lloyd G. Psychiatric side-effects of medications:
recent developments. Advances in Psychiatric Treatment (2005), vol. 11,
5870
13. Rojas- Estape H, Iclesias Rodriguez C, Murello LG. Hospitalized
psychoses after liver transplantation. European Psychiatry 2011
vol26:395
14. Riordan SM, Williams R: Treatment of hepatic encephalopathy. N
Engl J Med 1997, 337 (7): 473479.
15. Lee WM: Acute liver failure. N Engl J Med 1993; 329 (25):
18621872.
16. Goralczyk A, Meier V, Ramadori G, Obed A, Lorf T. Acute paranoid
psychosis as sole clinical presentation of hepatic artery thrombosis after
living donor liver transplantation. BMC Surgery 2010 10.1186/14712482-10-7

Romanian Journal of Psychiatry, vol. XVII, No.3, 2015


of Psychiatry: Behavioral Sciences/Clinical Psychiatry. Philadelphia:
Lippincott Williams and Wilkins, 2003, 849-850

17. Sadock BJ, Sadock VA. Psychological Factors Affecting Medical


Condition and Psychosomatic Medicine. Kaplan and Sadock's Synopsis

***

Table 1. Evolution of the abnormal blood parameters.


Blood test

TGO (UI)
TGP (UI)
FAL
Bt (g/dl)
Bd (g/dl)
WBC(x103/ul)
NEU (%)
RBC(x106/ul)
Hb (g/dl)
HCT (%)
PLT(x103/ul)
aPTT
GGT UI
Albumin
(g/dl)
Total proteins
(g/dl)

30.07
Fundeni
Admittion

12.08
Fundeni
Discharge

41
63
124
6.2
11.0
78
4.2
10
32
208
-

70
111
343
3.3
11.7
76
4.0
10.3
32.3
207
-

13.08
Obregia 2nd
hospitalisation
day
69
169
497
2.4
1.57
8.45
81.9
4.12
10.9
33.5
210
21.3
416
-

14.08

15.08

16.08

17.08

18.08

19.08

20.08

22.08

26.08
Obregia
discharge

43
142
449
2.1
1.33
10.62
91
3.78
10
30.7
151
26
479
-

35
102
304
1.64
1.2
9.61
91
3.51
9.12
29.2
152
3.2

34
112
320
1.4
0.9
-

81
137
329
2.31
1.01
5.65
69.7
3.77
10.04
29.98
107
-

44
149
367
1.7
1.21
21.8
3.2

40
140
285
1.2
0.88
5.69
89.9
3.41
9
27.9
105
3.2

29
133
284
5.89
89
5.89
10.2
31.1
127
3.2

40
142
280
1.3
0.91
5.55
69.8
3.74
10.5
31.3
136
531.7
3.3

48
119
381
5.6
70
3.84
10.2
31.1
138
456
3.3

5.9

5.6

5.5

5.9

5.7

6.1

87

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90

Romanian Journal of Psychiatry, vol. XVII, No.1, 2015

Address to send the manuscripts is:


REVISTA ROMN DE PSIHIATRIE
ASOCIAIA ROMN DE PSIHIATRIE I PSIHOTERAPIE
Prof. Dr. Dan PRELIPCEANU
Clinical Hospital of Psychiatry Prof. Dr. Alexandru Obregia
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E-mail: aliat@artelecom.net
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www.romjpsychiat.ro - online edition

91

ROMANIAN JOURNAL
OF PSYCHIATRY
CONTENTS
EDITOR-IN-CHIEF:
CO-EDITORS:

SPECIAL ARTICLES
& Personality Disorders Diagnostic Actualities
Aurel Niretean, Lukacs Emese, Tudor Niretean, Istvan Zsolt Szasz,
Adrian Horvath, Adina Mari

41

& Suicide Risk Assessment In Clinical Practice A Swedish Experience


Ileana S. Constantin

44

Dan PRELIPCEANU
Drago MARINESCU
Aurel NIRETEAN

ASSOCIATE EDITORS:
Doina COZMAN
Liana DEHELEAN
Marieta GABO GRECU
Maria LADEA
Cristinel TEFNESCU
Ctlina TUDOSE

REVIEW ARTICLES
& Negative Symptoms Of Schizopfrenia: From Kraepelin To DSM 5
Octavia O Cpn, Ioana V Micluia

48

& Type D Personality In Patients With Cardiovascular Diseases


Eva K Lakatos, Elena Minciu, Lrnd J Lakatos, Anna Keszegpal,
Aurel Niretean, Adina Mari

51

& Clinical And Evolutional Aspects In Bipolar Disorder, Manic Episode (1) 56
Mdlina Vrabie, Victor Marinescu, Anca Talaman, Ioana Micluia
ORIGINAL ARTICLES
& Somatization Disorders In Children And Adolescents - A Local
Perspective From The Galati County
Marcela Cmpean, Carmen Truescu, Cristina Petrescu-Ghenea,
Alecsandra Irimie-Ana, Cristina G. Anghel, Liana Kobylinska, Iuliana
Dobrescu

63

& A Non-interventional Study To Observe Real-life Usage Of Atypical


Antipsychotics In The Acute Inpatient Management Of Schizophrenia In
Central And Eastern Europe
68
Radu Teodorescu, Elmars Rancans, Gabor Feller, Dan Prelipceanu
& Cognitive And Emotional Correlates Of Posttraumatic Stress Symptoms
In Train Drivers Exposed To Work Trauma
77
Elisabeta Raco-Szabo, Andrea Glicz-Nagy, Alina Luca
CLINICAL CASE
& Diagnostic Challenges Of A Psychotic Disorder In A Patient With Liver
Transplant
84
Anca Talaman, Alexandra Dolfi, Mihaela Nae, Iulia Roca
INSTRUCTIONS FOR AUTHORS

88

APR

Executive editors: Elena CLINESCU


Valentin MATEI
STEERING COMMITTEE:
Vasile CHIRI (Honorary Member
of the Romanian Academy of
Medical Sciences, Iai)
Michael DAVIDSON (Professor, Sackler
School of Medicine Tel Aviv Univ.,
Mount Sinai School of Medicine,
New York)
Virgil ENTESCU (Member of the Romanian
Academy of Medical Sciences, Satu
Mare)
Ioana MICLUIA (UMF Cluj-Napoca)
erban IONESCU (Paris VIII Universiy, TroisRivieres University, Quebec)
Mircea LZRESCU (Honorary Member of the
Romanian Academy
of Medical Sciences, Timioara)
Juan E. MEZZICH (Professor of Psychiatry
and Director, Division of Psychiatric
Epidemiology and International
Center for Mental Health, Mount
Sinai School of Medicine, New York
University)
Teodor T. POSTOLACHE, MD (Director,
Mood and Anxiety Program,
Department of Psychiatry,
University of Maryland School of
Medicine, Baltimore)
Sorin RIGA (senior researcher)
Dan RUJESCU (Head of Psychiatric Genomics
and Neurobiology
and of Division of Molecular and
Clinical Neurobiology,
Department of Psychiatry, LudwigMaximilians-University, Munchen)
Eliot SOREL (George Washington University,
Washington DC)
Maria GRIGOROIU-ERBNESCU
(senior researcher)
Tudor UDRITOIU (UMF Craiova)

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