Early Onset Psychotic Disorders

Presented by Dr Pavan Kumar Chaired by Dr V K Bhat

Definition
Early onset psychosis (EOP) Any of a number of disorders in which positive psychotic

symptoms are a prominent feature. Early onset schizophrenia (EOS) Schizophrenia with onset prior to age 18. Very early onset(VEOS)/Childhood onset(COS) schizophrenia Schizophrenia with onset prior to age 13, almost always after 5. Onset prior to age 3 should raise strong suspicion of autism spectrum disorder.

 Schizoaffective Disorder (SA) & Schizophreniform disorder

and other disorders Diagnosed using the same criteria as in adults. Early onset schizophrenia spectrum disorders (EOSS) Includes EOS, schizoaffective disorder and schizophreniform disorder with onset prior to age 18 and VEOS or COS. Multidimensionally impaired disorder (MDI) A developmental disorder beginning during childhood characterized by transient hallucinations, daily affective lability, poor social skills, and extreme emotional reactivity.

History
Schizophrenia has been reported to occur in children since

the diagnosis was introduced by Emil Kraepelin. From the early 1900s to 1980s, the term childhood schizophrenia or prepubertal schizophrenia was used to refer to a range of severe psychiatric disorders presenting in youth including autism. In DSM II & ICD 8 all childhood onset psychosis including autism grouped under a separate category of childhood schizophrenia. In the 1970s, Israel Kolvin and colleagues conducted seminal work to distinguish between primary psychotic disorders and autistic disorder. Beginning with ICD-9 and DSM-III, autism has been recognized as a distinct disorder and schizophrenia has been diagnosed using identical criteria as adults.

Epidemiology
In children, affective psychoses are considerably more

likely than schizophrenia spectrum disorders. It appears that early onset schizophrenia and affective psychoses are more common in individuals with family histories of the respective disorders. Early onset schizophrenia appears slightly more common in boys than girls.

 At age 13 years, the prevalence for all psychoses was

0.9 in 10,000, showing a steady increase during adolescence, reaching a prevalence of 17.6 in 10,000 at age 18 years. Early onset schizophrenia appears slightly more common in boys than girls

 age had a strong effect on the manifestation of positive and

negative symptoms. Positive symptoms increased linearly with age negative symptoms were most frequent on early childhood and late adolescence. Bettes and Walker (1987)

Etiology

GENETICS
individuals with early onset schizophrenia are significantly

more likely than those with adult onset schizophrenia to have chromosomal abnormalities or mutations involving genes in neurodevelopmental pathways.

Family History
Increased incidence of schizophrenia and spectrum

disorders
Increased incidence of affective disorders Youth with early onset schizophrenia are at least twice as

likely as individuals with adult onset schizophrenia to have a parent with the disorder and morbid risk of schizophrenia for parents of individuals with early onset schizophrenia ranges from 14 to 25 percent.

Early Neuropathological Manifestations

The following have been correlated with increased

incidence of schizophrenia Perinatal complications Alterations in brain structure and size Minor physical anomalies Disruption of fetal neural development (Akbarian et al., 1993; McClellan and McCurry, 1998) it seems likely these are consequences rather than causes of abnormal neurodevelopment

cannabis use
is associated with earlier age of onset of schizophrenia in

adults It is possible that subtle social and developmental impairments that precede schizophrenia are also risk factors for cannabis use Perhaps a more plausible explanation is a gene environment interaction effect whereby cannabis exposure causes schizophrenia only in those with a pre-existing susceptibility The COMT val158met polymorphism moderated the link between psychosis and adolescent-onset cannabis use, but not adult-onset cannabis use. The COMT val allele is associated with greater COMT activity (relative to the COMT met allele) and reduced dopamine transmission in the prefrontal cortex. cannabis may enhance the risk of schizophrenia in vulnerable individuals during a critical period of adolescent brain development

Early Neuropathological Manifestations

Neurointegrative defect in infants

PANDYSMATURATION Fish postulated that a special form of early abnormal neurodevelopment, "pandysmaturation", defined a priori as constituting retarded cranial development in the first year of life, combined with delay in early motor milestone attainment, was related to genetic risk for schizophrenia, and was associated with schizophrenia-spectrum disorders in young adulthood. Pandysmaturation has efficacy as an early life risk-indicator of schizophrenia-spectrum disorder in young adulthood at least in subjects at genetic risk, strengthening the evidence for a generally genetic-based neurodevelopmental model of schizophrenia-spectrum (as contrasted with affective) disorders.

neurodevelopmental disruptions
subtle differences in neuronal connectivity, especially in the

parietal, temporal, and frontal cortices and hippocampus. lead to less efficient cortical processing seem to involve disruption of normal neurodevelopmental processes, particularly those that involve maturation of the frontal cortex and its connections during the second and third decades of life These differences suggest aberrations in the normal developmental processes of synaptic refinement and pruning

 multiple disruptions or hits to these normal

neurodevelopmental processes are required for schizophrenia to develop. Such disruptions might result from genetic vulnerabilities, adversities in the intrauterine environment as a result of famine, infection, or inflammation, or various environmental exposures later in life including severe psychological stress and exposure to drugs of abuse, particularly cannabis. Early onset schizophrenia appears to have more profound neurodevelopmental disruptions than adult onset schizophrenia.

Psychological and social factors

Not causative Bio-psycho-social model applicable Mediates time of onset, course and severity No social class particularly implicated

Expressed emotion has most influence

Neurobiology
Decreased total cerebral volume decreased grey matter volume increased ventricular volume decreased midsagittal thalamic area.

(Jacobsen and Rapoport, 1998; Badura et

al., 2001) patients with EOS have a more marked differential enlargement of the lateral ventricles and change in cortical gray matter
However none of these are diagnostic

Neuroimaging
Structural imaging studies have repeatedly demonstrated

an exaggeration of the normal pattern of cortical volume loss that occurs throughout adolescence, with excessive and progressive reductions being especially prominent in the cingulate, temporal, and frontal cortices. In addition, studies of prodromal individuals, many of whom are adolescents, have shown regional gray matter volume reductions are present before overt positive symptoms and progress during the first few years of the illness particularly in cingulate, temporal, and frontal cortices.

NEUROCHEMICAL
Decreases in the brain chemistry ratio of N acetylaspartate

(NAA) to creatine (CRE)a putative marker of neuronal integrity exclusively in the pre frontal cortex and hippocampus

Neuropsychological findings
Cognitive impairments Attention executive functioning verbal recall visuospatial abilities

fine motor skills

Diagnosis and Clinical Features

All types of early onset psychosis other than MDI are

diagnosed using the same criteria as the adult forms of the disorder. the characteristics of specific symptoms often show important developmental characteristics

Hallucinations
Hallucinations are frequently multimodal, with the affected

youth seeing, hearing, or feeling the hallucinated being. Children will frequently name the hallucinated being, often using stereotypes such as an angel, the devil, or a monster or will refer to it on the basis of a physical characteristic such as the red sweater guy or the man with no skin. Youth very seldom complain about their hallucinations if not asked directly. It is also often helpful to ask family members if the child asks about being called when no one has said anything. It is important to ascertain whether the child is in control of the phenomena, which is not seen with true hallucinations, or whether he or she can only moderate his or her own response to the phenomena

DELUSIONS
Delusions are seldom highly complex or systematic prior to

age 16. Inability to utilise logical reasoning and a tendency to blur distinction between fantasy and reality makes it difficult to reliably demonstrate delusions less than 5yrs age In this age, related to fantasy figures, animals Less elaborate In older kids, related to identity disturbances, hypochondriacal, persecutory Only 50% cases have delusions

 Instead youth often report vague symptoms of everyone is

out to get me or people are laughing at me. Often reports from collateral sources are needed to determine whether such reports are delusional or reality based. Frequently, youth with early onset schizophrenia present with nonspecific symptoms such as poor attention or increased aggression.

THOUGHT DISORDER
Degree of communication dysfunction related to severity of

FTD Problems in processing verbal information Common symptoms are Formal thought disorder Loose associations Illogical thinking Impaired discourse skills Incoherence and poverty of speech

 Onset of early onset schizophrenia is often insidious,

occurring over a few years. In addition, premorbid symptoms such as being odd and socially isolated or having multiple (but generally mild) developmental delays in cognitive, motor, sensory, and social functioning are common and appear more severe than in adults with adult onset schizophrenia. it is important to ask about changes in functioning and behavior that have occurred over the past 3 to 4 years, to specifically inquire about hallucinations and delusions using language that the child understands, and to encourage the child to describe his or her experiences in detail using his or her own words.

Assessment
Detailed exhaustive interviews of the child and family ICD-10/ DSM-IV criteria can be applied Laboratory evaluations and neuro-imaging techniques

used to rule out organic psychosis Baseline rating on psychopathology scales such as the BPRS-C, Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS; Ambrosini, 2000), the Child and Adolescent Psychiatric Assessment (CAPA; Angold & Costello, 2000) and the Diagnostic Interview for Children and Adolescents (DICA; Reich, 2000). Baseline neuropsychological testing to evaluate cognitive deficits

Diagnostic Dilemmas
Misdiagnosis Bipolar disorder vs schizophrenia Causes for misdiagnosis

-Rarity of the disorder Overlap of presenting symptoms with other disorders Some children with hallucinations do not have schizophrenia (PTSD, dissociative and anxiety disorders) Developmental disorders (PDD, language disorders)

Differential Diagnosis
Misdiagnosis of early onset schizophrenia is a major

concern. Factors that may lead to misdiagnosis include children's inherent difficulties in describing psychotic symptoms that are outside their normal experience, overinterpretation of transient psychotic symptoms, and the high prevalence of positive psychotic symptoms in child psychiatric disorders other than early onset schizophrenia. However, failure to recognize early onset schizophrenia when present may slow implementation of appropriate treatments and worsen the youth's long-term prognosis.

Differential Diagnosis
Mood disorders Historically approximately half of juveniles with bipolar

disorder were misdiagnosed as schizophrenia Mania could present with florid psychosis Depression could be mistaken for negative symptoms and vice versa (McClellan and McCurry, 1999; Carlson, 1990)

 General medical conditions Delirium Seizure disorders CNS lesions (tumors, malformations, trauma) Neurodegenerative disorders (Huntingtons chorea,

lipid storage disorders) Metabolic disorders (Wilsons, endocrinopathies) Developmental disorders (velocardiofacial syndrome) Toxic encephalopathies (amphetamines, cocaine, hallucinogens, phencyclidine, alcohol, marihuana, solvents, steroids, anticholinergics and heavy metals) Infectious diseases (meningoencephalitis, HIV-AIDS)

 Non-psychotic behavioral and emotional disorders Severe emotional disorders PTSD Child maltreatment and abuse Dissociative and anxiety disorders Personality disorders

 Schizo-affective disorders Not well defined Upto a quarter of children with schizophrenia may

longitudinally develop significant affective symptoms (eggers, 1989) PDD including autism, CDD and Aspergers Obsessive compulsive disorder Developmental and language disorders

Multidimensionally impaired syndrome (MDI)

is a label applied to children who have brief transient

psychotic symptoms, emotional lability, poor interpersonal skills, normal social skills and multiple deficits in information processing. The diagnostic status of this group remains to be fully resolved. Short-term follow-up suggests that they do not develop full-blown schizophrenic psychosis. However, they have an increased risk of schizophrenia spectrum disorders among first-degree relatives and the neurobiological findings (e.g., brain morphology) are similar to those in childhood onset schizophrenia.

 At 11 year follow-up, 38% (12 of 32) of patients met criteria

for bipolar 1 disorder, 12% (4 of 32) for major depressive disorder (MDD), and 3% (1 of 32) for schizoaffective disorder. The remaining 47% of patients (15 of 32) were divided into two groups on the basis of whether they were in remission and neuroleptic-free (good outcome, n = 5) or still severely impaired and/or psychotic regardless of pharmacotherapy (poor outcome, n = 10)

Course and Prognosis

onset of overt psychotic symptoms is frequently insidious,

particularly in individuals younger than 15 years. Afterward, approximately equal proportions of youth have insidious and subacute onset, with rapid onset over the course of several days being rare. Rapid recovery from the initial episode appears rarer than in adult onset schizophrenia. In contrast, many youth with early onset schizophrenia show improvement but continue to experience significant positive symptoms despite medication adherence for 2 to 5 years. The course tends to be chronic rather than more episodic as is reported in adult onset schizophrenia.

 there appears to be significant decline in cognitive

functioning during the 4-year period surrounding onset of illness. This cognitive decline appears to reflect both biologic brain processes and interruption of normal development and learning. Suicidality was associated with more depressive symptoms and fewer negative symptoms at first episode. A recent study found that 30 percent of individuals with early onset schizophrenia attempted suicide over the first 10 years of illness with one of six of those who attempted succeeding.

 Long-term prognosis in early onset schizophrenia also

appears worse than in adult onset schizophrenia. A meta-analysis of 320 studies of outcome in adult onset schizophrenia found that about 40 percent of individuals had good outcomes, whereas about 60 percent had a chronic disabling course. In contrast, a number of studies have found that very few individuals with early onset schizophrenia (5 to 25 percent) experience good outcomes and that 75 to 80 percent have poor outcomes with about half of those having extremely poor outcome. Treatment resistance may also be more common, although this has not been adequately studied.

STAGES: Prodrome
Prodrome last from days to months Functional deterioration prior to onset of psychotic

symptoms is common Social withdrawal and isolation Idiosyncratic or bizarre preoccupations Academic failure Deteriorating self care skills Dysphoria and anxiety symptoms Aggressive behaviors

Acute Phase
Predominance of positive symptoms Significant deterioration in functioning Lasts from 1-6 months or longer Symptoms shift from positive to negative over time Duration depends on the timing of treatment and severity

of illness

Recuperative/ Recovery Phase

Lasts for several months Predominantly negative symptoms Some may develop post-schizophrenic depression In a few children, symptoms may totally resolve and the

illness may have an episodic course

Residual Phase
May last for several months or years Some negative symptoms continue to persist Overall level of functioning would be impaired

Treatment
multimodal and should include pharmacotherapy, family and

patient psychoeducation and support, and interventions in the community to support ongoing education and transition to employment when appropriate. little empiric support for specific treatments The evidence is strongest for pharmacotherapy studies have compared various atypical antipsychotics to placebo Olanzapine, Risperidone, aripiprazole various antipsychotics differ in their side-effect profiles but have few differences in efficacy treatment-resistant early onset schizophrenia respond significantly better to clozapine than to haloperidol (Haldol) or olanzapine Currently only two pilot studies of psychosocial interventions have been conducted. They show promise but clearly such interventions need to be further developed and evaluated

 Prevention and Early Detection In theory at least, the onset of schizophrenia could be

prevented if an intervention reduced the premorbid risk status or exposure to causative risk factors. The difficulty with the premorbid phenotype as currently conceived (i.e., subtle social and developmental impairments) is its extremely low specificity and positive predictive value for schizophrenia in the general population. The premorbid psychopathology in childhood-onset schizophrenia is equally non-specific with a range of diagnoses. An alternative approach is to target putative environmental risk factors such as cannabis exposure. A key argument used to support early intervention in psychosis has been the finding that a long duration of untreated psychosis is associated with poor long-term outcome in schizophrenia

 Psychosocial Interventions Psychoeducation and Family Interventions CognitiveBehavioral Therapy Cognitive Remediation

COS
poor premorbid

AOS
Similar developmental

functioning (impaired sociability) and early developmental delays more common & severe Just over 20% of cases of adolescent schizophrenia had significant early delays in either language or motor development.
Premorbid IQ mid to low

and social impairments in childhood

language and motor

developmental delays have been reported in only about 10% of individuals who develop schizophrenia in adult life
adult schizophreniform

80s, some 1015 points lower than in the adult form of the disorder

disorder assoc with childhood pandevelopmental impairments involving motor development, receptive language and IQ.

 0.9 in 10,000, showing a

1% prevalence

steady increase during adolescence, reaching a prevalence of 17.6 in 10,000 at age 18 years. Prodrome-gradual but marked decline in social and academic functioning that precedes the onset of active psychotic symptoms Child- and adolescent-onset cases are characterized by a more insidious onset, greater disorganization, negative symptoms, hallucinations in different modalities and fewer systematized or persecutory delusions

later-onset cases- higher

frequency of systematized and paranoid delusions

 Runs a chronic course, with

only a minority of cases making a full symptomatic recovery from the first psychotic episode. If full recovery does occur then it is most likely within the first 3 months of the onset of psychosis. The clinical implication is that the early course over the first 6 months is the best predictor of remission
typically chronic

short-term outcome for

schizophrenia presenting in early life appears to be worse than that of first episode adult patients

unremitting long-term course with severely impaired functioning in adult life

 schizophrenia presenting in

childhood and adolescence lies at the extreme end of a continuum of phenotypic severity. Premorbid functioning, prolonged first psychotic episode and negative symptoms at onset predict long-term outcome than categorical diagnosis The risk of premature death is increased in child- and adolescent-onset psychoses. Males overrepresented lower levels of criticism and hostility than parents of adult-onset patients

Conclusions
The last decade has seen a dramatic growth in our

understanding of the clinical course and neurobiological underpinnings of schizophrenia presenting in childhood and adolescence. It is now clear that adult-based diagnostic criteria have validity in this age group and the disorder has clinical and neurobiological continuity with schizophrenia in adults. Childhood-onset schizophrenia is a severe variant of the adult disorder associated with greater premorbid impairment, a higher familial risk, more severe clinical course and poorer outcome. The poor outcome of children and adolescents with schizophrenia has highlighted the need to target early and effective treatments and develop specialist services for this highrisk group. Unraveling neurocognitive and clinical heterogeneity should lead to improvements in our ability to deliver individually targeted treatments, as well as the ability to identify those at risk in order to prevent the onset of psychosis

THANK U