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SYCHIATRIC DISORDERS are frequently diagnosed following a traumatic brain injury (TBI),
and depression is by far the most common with reported rates ranging from 6% to 77%.118 When established diagnostic criteria are used, persons with moderate to severe TBI evidence major depression (MD) rates
ranging from 26% to 36%.57,15,17 Depression has been
associated with high rates of disability,20,21 impaired
psychosocial functioning,7,9,19,2226 and decreased life
satisfaction.27,28 When depression is chronic, psychosocial disability levels increase and life satisfaction decreases further.23,27
While the negative impact of depression after TBI
is well-recognized, diagnosing depression after TBI remains a significant challenge. The Diagnostic and Statistical Manual of Mental DisordersVersion IV (DSM-IV)29
lists a number of depressive disorders including MD,
dysthymia, depressive disorder not otherwise specified
(NOS), and depressive disorder due to a general medical
condition (GMC) that have overlapping symptoms. Rehabilitation professionals and family members often recAuthor Affiliations: Shepherd Center, Atlanta, Georgia (Drs Seel and
Macciocchi); and Virginia Commonwealth University, Richmond
(Dr Kreutzer).
Corresponding Author: Ronald T. Seel, PhD, Shepherd Center, 2020 Peachtree
Rd, NW Atlanta, GA 30309 (ron seel@shepherd.org).
100
ished interest or pleasure (A2) in persons with TBI commonly centers on difficulty enjoying activities, loss of
interest in sex, and loneliness.15,36 Poor appetite (A3)
is more frequently reported by persons with TBI than
overeating and may be a primary discriminator between
depressed and nondepressed persons with TBI.36 Rumination, self-criticism, and guilt are closely related to feelings of worthlessness (A7) and appear to highly differentiate depressed from nondepressed persons with TBI.34
Lack of confidence, discomfort around others, and social
withdrawal may be indicators of depressed mood and
feelings of worthlessness.35,36 Depressed persons with
TBI are 6 times more likely than nondepressed persons
to threaten self-harm (A9).15 Overall, persons with TBI
have a 4 times higher risk for committing suicide than
persons in the general population (please see Teasdale,37
Simpson,38 Wasserman,39 and Hawton,40 for reviews on
suicide incidence and assessment).
To meet criteria for a DSM-IV MD diagnosis, a person must also meet additional criteria including ruling
out a mixed episode of manic and depressive symptoms
(criterion B), depressive symptoms of sufficient severity to cause impairment in at least one aspect of daily
functioning (criterion C), depressive symptoms not being exclusively due to a GMC or substance use (criterion
D), and depressive symptoms not part of bereavement
(criterion E).
An underappreciated feature of MD that is not directly addressed in the DSM-IV is negative thinking,
which refers to maladaptive cognitions, beliefs, and
processes.41 Negative thinking reflects a tendency to
view ones self as defective or inadequate, a pervasive
and absolute evaluation of ones own life experience
as resulting in loss or failure, and hopelessness regarding the future.4144 Negative thinking primarily arises
from automatic thoughts or rumination,4547 in which
depressed persons focus on symptoms or other selfexperiences, using a negative self-evaluative style. Negative thinking also involves selective attention to and
magnification of negative events and feedback while
minimizing positive events and feedback.41 Becks view
of pervasive and absolute negative evaluations is most
often referred to in the depression research literature as
over general autobiographical memory.47,48
Research on negative thinking and rumination in persons with TBI has been limited, but findings have been
compelling. A large sample study found that rumination,
self-criticism, distress, and guilt were part of a symptom
cluster that most differentiated depressed from nondepressed persons with TBI.35 Another study found that
rumination in depressed persons with brain injury resulted in overgeneralized autobiographical memory and
reduced problem-solving.49 Importantly, injury severity was not related to memory and problem-solving
impairments.
101
DSM-IV criteria for major depressive episode and practical considerations for
use with TBI population
TABLE 1
DSM-IV criteria
A symptoms
(A1) Depressed mood
DSM-IV features
Associated disorders
Anxiety is a commonly reported co-occurring disorder with both early and late onset depression after TBI
with rates ranging from 41% to 77%.6,19,51 Persons with
both depression and anxiety disorders have longer symptom duration (7.5 months vs 1.5 months) than patients
with depression only.19 Co-occurring anxiety may be related to perceived stress,52 fear of job loss,22 phobias,53
and rumination.35,54 High association rates between anxiety and depression in persons with TBI are consistent
with epidemiological research in the general population that indicates anxiety disorders (57.5%, CI 53.3%
61.7%) are the most common co-occurring disorder with
depression.55 Importantly, MD was found to be a temporal antecedent of anxiety disorders in only 14.6% (CI
10.4%18.8%) of cases.55
Aggression also commonly co-occurs with depression
after TBI.5457 Aggression scores are highly associated
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102
Best current evidence of psychosocial contributory/risk factors for major depression after moderate to severe traumatic brain injury
TABLE 2
Biological/behavioral
Sleep difficulties
Falling asleep
Early awakening
Reduced sleep time
Hypothalamic-pituitary-adrenal hyperactivity
Serotonergic hypoactivity
Bilateral dorsal prefrontal cortex
Lesions
Psychological/behavioral
Anxiety, panic
Rumination
Physical symptoms
Losses, failures
Fears, harm, danger
Aggression
Substance use
Poor social skills
Problem solving
Social withdrawal
Less than high school
education
Social/environmental
Income
Poverty level
Financial problems
13 poverty level
Personal relationships
Lack of intimate partner
No close friend
Discord in close relationships
Unemployment
Unstable work history
Preinjury
Postinjury job loss
insomnia were significantly more likely to develop depression within 1 year (OR = 39.8, CI 19.880.0) than
persons with no insomnia.64
Apathetic syndrome is a common comorbidity for persons who have sustained TBI and primary apathy
related symptoms such as anhedonia, and lack of energy,
initiative, and social interaction are frequently confused
with depression.68,69 In a study with a predominately
mild TBI cohort, 11% were apathetic, 11% were depressed, 60% were both apathetic and depressed, and
18% were neither apathetic nor depressed.70
Pain is common (32%, CI 29%35%) following moderate to severe TBI71 and both early onset depression and
chronic depression may play mediating roles in higher
levels of self-reported pain.28,51,72 Postinjury onset of
headache and headache density were found to be significantly associated with depression scores.73,74
Associated neuroimaging and laboratory studies
MD in the general and TBI populations is believed
to be related to pathophysiology involving the left dorsal lateral frontal cortex and left basal ganglia and, to a
lesser extent, focal lesions in the right hemisphere and
parieto-occipital region.6,19,59,7578 Imaging studies have
also shown that hypometabolism of the lateral and dorsal frontal cortex, especially the dorsal prefrontal cortex
and cingulate gyrus, as well as increased activation in
ventral limbic and paralimbic structures including the
prelimbic cortex, the amygdale, and the medial thalamus may be associated with depressive symptoms.31,59,79
However, these patterns of anatomical dysfunction are
far from universally observed in persons with MD and
variations between studies are likely attributable to heterogeneity in MD symptoms and the existence of subtypes of depression.31,79 For more detailed reviews of this
topic, please see Drevets,80 Davidson,79 Moldover,31 and
Jorge.59
103
104
105
Unfortunately, each of the TBI studies had significant methodological issues including lack of masked
raters,15,110 gold standard not administered to all
screened participants,91,110 and using the same interview
data to score the screening scale and the gold standard.26
The meta-analytic reviews that created summative likelihood ratios generally included both high-quality studies
with low risk of bias and studies with significant methodological problems. The risk of bias in all of these studies
limits our ability to draw definitive conclusions regarding diagnostic validity.
Best current evidence suggests that the BDI-II, CESD, NFI-D, and the PHQ-9 appear to have an acceptable
ability to rule out the presence of MD as a screening
tool. Only the NFI-D and PHQ-9 demonstrated evidence of acceptably ruling out MD in persons with TBI.
The PHQ-9 appears to have a better ability to rule in
the presence of MD in TBI and primary care populations. Both The HADS and the SDS demonstrate high
rates of false-negative screens that limit our ability to
recommend their use at this time.
Differential diagnosis of MD in persons with TBI
Challenges with accurately diagnosing MD are not
unique to the TBI population. In the general population,
questions also arise regarding the most effective and efficient methods for diagnosing MD and how best to distinguish whether symptoms are related to depression versus co-occurring medical or psychiatric illnesses.34 For
example, the National Comorbidity Survey Replication
(NCS-R) studied 9000 Americans and found that 79%
of persons who had MD also had at least 1 comorbid
DSM-IV disorder, and in only 13% of cases was MD the
primary diagnosis.55
The DSM-IV provides diagnostic considerations to
differentiate MD, mood disorder due to a GMC, dementia, mixed episodes, adjustment disorder with depressed
mood, bereavement, and depressive disorder (NOS). Instructions are also provided for classifying MD as either a
single episode or recurrent, and whether severity is mild,
moderate, or severe and occurs with or without psychotic features. Our review supplements this information by presenting 4 psychiatric conditions common to
TBI and MD that require careful clinical consideration
when making a differential diagnosis of MD: apathy,
anxiety, dysregulation, and emotional lability (Table 4).
Apathy refers to primary motivational loss that
includes lack of behavioral activity, cognitive initiative, and emotional engagement in purposeful activity75
and is sometimes confused with depression, particularly in acute rehabilitation settings. A key differential
diagnostic consideration is that persons with postTBI apathy do not evidence cardinal features of depression such as sadness, irritability, hopelessness, and
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135
2204 (7)
667 (4)
SCID
SCID
SCID
SCID
SCID
SCID
BDI-II21
SCID
SCID
SCID
29
10
10
50
Reference
standard
>23
10
16
16
16
8
Cutoff score
0.98 (0.911.00)
0.88 (0.660.98)
0.81 (0.720.88)
NR
1.00 (0.461.00)
NR
1.00 (0.701.00)
1.00 (0.681.00)
NR
0.62 (0.430.77)
SENS (95%CI)
0.40 (0.300.50)
0.90 (0.830.95)
0.92 (0.830.97)
NR
0.59 (0.370.79)
NR
0.57 (0.460.68)
0.36 (0.220.53)
NR
0.92 (0.820.97)
SPEC (95%CI)
1.6 (1.41.9)
8.8 (NR)
11.3 (4.628.0)
3.3 (1.38.1)
2.4 (1.54.0)
4.2 (1.213.6)
2.3 (1.83.0)
1.6 (1.22.0)
3.3 (2.54.4)
8.2 (3.419.7)
LR-P
(95%CI)
0.03 (0.00.3)
0.14 (NR)
0.20 (0.10.3)
0.35 (0.20.8)
0.00
0.17 (0.10.3)
0.00
0.00
0.24 (0.20.3)
0.41 (0.30.6)
LR-N
(95%CI)
Abbreviations: BDI-II, Back Depression InventoryIInd Edition; CES-D, Center for Epidemiological StudiesDepression; HADS, Hospital Anxiety and Depression Scale; LR-P, likelihood ratio
of a positive test; LR-N, likelihood ratio of a negative test; NFI, Neurobehavioral Functioning Inventory; NR, not reported/could not be calculated; sample size, No. of patients tested (No.
of studies comprising summative sample size); PHQ, Patient Health Questionnaire; SCID = Structured Clinical Interview for the DSM-IV; SDS, Self-Assessment Depression Scale; SENS,
sensitivity; SPEC, specificity; TBI, traumatic brain injury.
TBI
TBI
Primary care
Primary care
3038 (10)
100
Williams (2002)
HADS WhelanGoodinson
(2009)
NFI-D Seel (2003)
PHQ-9 Fann (2005)
Gilbody (2007)
SDS Williams (2002)
Population
TBI
Primary care
Rehab-ortho
Rehab-neurol
Primary care
TBI
Sample size
27
852 (4)
101 50
Author (year)
Scale
TABLE 3
106
JOURNAL OF HEAD TRAUMA REHABILITATION/MARCHAPRIL 2010
107
Core features
Mood (intensity,
scope)
Activity level
Attitude
Awareness
Cognitions
Physiological
Coping style
Potential DSM-IV
diagnoses
Depression
Sad, irritable,
frustrated
(constant, global)
Low activity
Loss of interest,
pleasure
Overestimates
problems
Rumination on loss,
failures
Under- or
hyperaroused
Avoidance, social
withdrawal
Major depressive
episode
Mood disorder due
to GMC
Apathy
Anxiety
Dysregulation
Flat, unexcited
(constant, global)
Worried, distressed
Angry, tense
(frequent, situational)
(frequent, global)
Lack of initiative,
behavior
Lack of concern
Restless, keyed up
Overconcern
Overestimates
problems
Rumination on harm,
danger
Hyperaroused
Compliant,
dependent
Avoidance, checking
behaviors
Personality change
due to TBI
apathetic type
Cognitive disorder
NOS
Generalized anxiety
disorder
Adjustment disorder
w/depressed
mood
Dysthymic disorder
Impulsive, physically
aggressive
Argumentative
Underestimates
problems
Rumination on
tension, arousal
Underaroused or
agitated
Uncontrolled
outbursts
Personality change
due to TBI
aggressive type
Specific or social
Personality change
phobia
due to TBI
combined type
Anxiety disorder due to Impulse control
GMC
disorder nos
Adjustment disorder
w/anxiety
Anxiety disorder NOS
(mixed anxietydepressive disorder)
Abbreviations: DSM-IV, Diagnostic and Statistical Manual of Mental DisordersVersion IV; GMC, general medical condition; NOS, not
otherwise specified; TBI, traumatic brain injury.
negativistic thinking. Research in postacute rehabilitation settings indicate that persons with post-TBI apathy are underaroused, cannot fully engage in rehabilitation, and use less approach-oriented and social
supportseeking behaviors.67,113115 Conversely, patients
who are depressed actively resist or withdraw from rehabilitation and use avoidant coping strategies.68,113115
Persons with apathy may be given a DSM-IV diagnosis of personality change due to brain injury
apathetic type or in combination with significant memory and other cognitive impairments, cognitive disorder
NOS.
Anxiety and MD also share overlapping symptoms.
The core presentation of depression tends to be sadness,
irritability, and frustration or lack of interest or pleasure,
while anxiety is primarily marked by worry and distress.
Research in the general population provides strong support that anxiety is differentiated from MD by physiological hyperarousal whereas depression is differentiated by low pleasurable engagement with others.43,116118
Research also suggests that depressive rumination focuses on personal failure and loss in a more general
and global sense, while anxious rumination focuses on
harm and danger in specific situations.41,43 Persons with
TBI may meet full criteria for both depression and anxiety disorders. For persons who present with mixed features that do not meet full criteria for either disorder,
the DSM-IV offers an experimental diagnosis of mixed
anxiety-depression disorder based on the well-supported
tripartite model of depression and anxiety116118 and is
recorded as Anxiety Disorder NOS.
Persons with both dysregulation problems and MD after TBI may present with irritability, resentfulness, hostility, and aggression. Persons with dysregulation are differentiated from MD by impulsivity, physical aggression,
and uncontrolled outbursts, whereas low activity, avoidance, and social withdrawal are more typical of persons
with MD. Persons with TBI may receive dual diagnoses
of MD and a dysregulation disorder. Careful consideration of preinjury behavior is required to differentiate
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108
TABLE 5
TBI
1. While persons with TBI and in the general population experience depression similarly, clinicians should be
aware of a few distinguishing features of MD in persons with TBI:
a. Depressed mood in persons with TBI is more frequently evidenced by irritability, frustration, anger, hostility,
and aggression than by sadness and tearfulness.
b. Diminished interest or pleasure commonly centers on loss of interest in sex and loneliness in addition to
difficulty enjoying activities.
c. Loss of appetite appears to strongly differentiate depressed persons from nondepressed persons with TBI.
d. Lack of confidence, discomfort around others, and social withdrawal may be indicators of underlying
feelings of worthlessness and depression.
2. Persons with TBI are at a higher risk for suicidality than the general population. A diagnostic interview on
mood should include questions regarding suicidal thoughts, behavior, and intent.
3. Rumination, self-criticism, distress, and guilt are a symptom cluster that may best differentiate depressed
persons from nondepressed persons with TBI. Clinicians should carefully assess the presence and extent of
negativistic thinking and rumination, which can both clarify the diagnosis and inform the selection of therapy
interventions targeted for negativistic thinking.
4. Anxiety, aggression, sleep problems, alcohol use, lower-income levels, and poor social functioning appear to
be primary contributing factors to MD. Lacking well-controlled empirical etiological models as the basis for
clinical decision making, it is reasonable for clinicians to infer that persons with a greater number of these
contributory factors may be at greater risk for the development and maintenance of MD after TBI. Persons
with TBI who do not meet criteria for MD but evidence these risk factors should be educated along with their
family members on the signs of an emerging depressive disorder and be clinically followed.
5. Persons with TBI who are depressed self-report markedly greater levels of impairment and/or problems than
can be objectively quantified. Clinicians should consider high levels of self-reported physical, somatic, and
cognitive symptoms as either a prodrome or a strong indicator of the presence of MD.
6. Asking specific, concrete questions of TBI survivors appears to minimize the potential impact of anosognosia
on the validity of self-reported depression symptoms.
7. Self-report depression scales are best used to rule out the presence of depression. For persons who
screen positive for the presence of depression, a formal diagnostic interview using Diagnostic and
Statistical Manual of Mental DisordersVersion IV MD criteria is essential.
8. Psychiatric conditions common to TBI that require careful clinical consideration when making a differential
diagnosis of MD include apathy, anxiety, emotional lability, and dysregulation. It is critical for clinicians to have
working knowledge of specific symptoms that either overlap or distinguish between disorders in order to
conduct a thorough diagnostic interview.
9. For cases with complicated and highly overlapping symptom presentation, the use of the SCID is helping in
establishing a differential diagnosis.
Abbreviations: MD, major depression; TBI, traumatic brain injury; SCID, Structured Clinical Interview for DSM-IV.
109
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