The Effect of Major
Depression on Subjective
and Objective Cognitive
Deficits in Mild to
Moderate Traumatic
Brain Injury
Laury Chamelian, M.D., FRCPC
Anthony Feinstein, Ph.D., MRCPsych,
FRCPC
The effect of major depression on subjective and
objective cognitive deficits 6 months following
mild to moderate traumatic brain injury (TBI)
was assessed in 63 subjects. Patients with subjective cognitive complaints (n⳱63) were more
likely to be women, with higher Glasgow Coma
Scale (GCS) scores and have a diagnosis of major
depression. They also performed significantly
more poorly on various measures of memory, attention and executive functioning. Group differences on most but not all cognitive measures disappeared in a multivariate analysis when
controlling for depression. In mild to moderate
TBI, subjective cognitive deficits are linked in
large measure to comorbid major depression.
However, other mechanisms may also account for
these deficits.
(The Journal of Neuropsychiatry and Clinical
Neurosciences 2006; 18:33–38)
C
ognitive deficits following traumatic brain injury
(TBI) include impairments in attention, memory
and executive functioning.1–7 Patients who perform
poorly on various batteries of neurocognitive testing often complain of these difficulties.8–10 However, the association between self-reported cognitive symptoms
and performances on objective cognitive tests has not
been consistently supported by empirical data. Some investigators have concluded that subjective cognitive
complaints were not always related to neuropsychological test performance11–13 but rather to emotional difficulties.14,15 However, other studies have failed to find an
association between objective measures of cognitive
dysfunction and emotional distress.16,17 These conflicting results may be due to differing methods of evaluating self-report symptoms and objective cognitive impairment, the heterogeneity of TBI subjects in terms of
trauma severity and varying periods of assessment following head injury.
Despite the mounting evidence suggesting a strong
association between clinically diagnosed major depression and poor performance on cognitive testing
Received July 14, 2004; revised October 25, 2004; accepted November
29, 2004. From the Department of Psychiatry and Traumatic Brain Injury Clinic, Sunnybrook and Women’s College Health Sciences Centre,
University of Toronto, Toronto, Ontario, Canada. Address correspondence to Dr. Feinstein, Sunnybrook and Women’s College Health Sciences Centre, Department of Psychiatry, room FG08, 2075 Bayview
Ave., Toronto, ON, M4N 3M5; antfeinstein@aol.com (E-mail).
Copyright 䉷 2006 American Psychiatric Publishing, Inc.
J Neuropsychiatry Clin Neurosci 18:1, Winter 2006
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DEPRESSION AND COGNITIVE DEFICITS IN TBI
following mild to moderate TBI,18–23 the few studies14,16
that have investigated the relationship between selfreported cognitive difficulties, neuropsychological test
performances and emotional complaints, have relied
mainly on subjective measures of depression or on instruments that assess psychological profiles in order to
detect comorbid depressive symptoms. Additionally,
they have neglected to control for depression when investigating whether subjective cognitive complaints
accurately reflected cognitive dysfunction on objective
testing.
The focus of the current study was to investigate the
relationship between cognitive impairment assessed by
standard neuropsychological tests and subjective cognitive complaints based on a self-report questionnaire in
mild to moderate TBI 6 months following head injury.
The effect of clinically diagnosed major depression on
subjective (self-report) and objective (neuropsychological testing) indices of cognitive impairment was also explored.
METHOD
Patient Selection
The study population consisted of 63 TBI patients who
were recruited consecutively from a traumatic brain injury clinic at a tertiary care referral center. The subjects
had either sustained a mild head injury24 (Glasgow
Coma Scale [GCS]⳱13–15; loss of consciousness [LOC]
⬍20 minutes; posttraumatic amnesia [PTA] ⬍ 24 hours)
or moderate TBI (GCS⳱9–12; PTA⬎24 hours but less
than 1 week) and were between 18 to 60 years of age.
All participants had a detailed neuropsychiatry examination at 6 months posthead injury before undergoing
a battery of cognitive tests. The presence of posttraumatic “subjective cognitive” difficulties was determined
by patients’ response on three questions of the Rivermead Post Concussion Symptoms Questionnaire (RPQ):
“forgetfulness, poor memory”, “poor concentration”
and “taking more time to think”. These selected items
are the only questions from the RPQ that focus on cognition. The RPQ has been shown to be a valid measure
of symptoms commonly experienced following head injury.25
Written consent was provided from all subjects and
institutional ethics board approval was obtained for this
study.
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Data Collection
Background information.
All subjects were seen 6
months following a mild to moderate TBI. The collected
demographic and TBI-related data were: age, gender,
marital and preinjury employment status, educational
level, problem drinking (based upon the CAGE questionnaire26 and amount of alcohol consumed per week),
past psychiatric history, prior head injury and mechanism of injury. Psychotropic and/or analgesic medication use was also recorded given the CNS depressant
properties of these drugs potentially impairing cognition. For head injury severity, the following were obtained: initial GCS recorded in the emergency room,
LOC and PTA duration, and initial CT brain results.
Diagnosis of Major Depression
The study participants were interviewed with the mood
disorder section of the Structured Clinical Interview for
DSM–IV Disorders (SCID27 for DSM–IV) to establish a
diagnosis of major depression. The clinic’s neuropsychiatrist who conducted the interview was blind to the
subjects’ cognitive data.
Neuropsychological Tests
The neuropsychological battery comprised 10 tests
known to be sensitive to cognitive changes following
TBI. They included indices of attention/working memory (Weschsler Adult Intelligence Scale-III [WAISIII]28—working memory, verbal memory (California
Verbal Learning Test [CVLT-II]29—total, long delay free
recall and recognition hits), visuospatial learning and
memory (Brief Visuospatial Memory Test—Revised
[BVMT-R]30—immediate and delay total recall), information processing speed and sustained and divided attention (Paced Auditory Serial Addition Task [PASAT]31
at increasingly quicker rate of number presentation: 2.0
and 1.2 sec.), executive functioning (Wisconsin Card
Sorting Test [WCST]32—total and perseverative responses). The Vocabulary subscale of the Wechsler Abbreviated Intelligence Scale (WASI)33 was used to provide an estimate of the premorbid IQ and the Word
Memory Test (WMT)34 was administered to assess subject compliance and effort with testing.
Statistical Analysis
Univariate analyses. Patients with and without subjective cognitive complaints were compared using twotailed t tests for continuous variables, and v2 analyses
J Neuropsychiatry Clin Neurosci 18:1, Winter 2006
CHAMELIAN et al.
for categorical variables. Fisher’s exact test was reported
when appropriate. For the cognitive data, raw scores
were used for analysis.
Multivariate analyses. A multivariate analysis of covariance (MANCOVA) was performed using the variables
found statistically significant (pⱕ0.05) on univariate
analyses. Subject grouping was designated as the fixed
factor and seven of the cognitive tasks were entered as
dependent variables. Two separate MANCOVAs were
then computed across groups for each of the cognitive
measures, one adjusting for gender and injury severity
as measured by the Glasgow Coma Scale (GCS) score
and the other for depression (SCID for DSM–IV) in addition to gender and GCS score.
RESULTS
Demographic and Injury-Related Data
The mean age of the 63 patients enrolled in the study
was 33 years (SD⳱11.7) and 55.6% were male. Thirtyfour (54%) subjects reported subjective cognitive complaints on the RPQ. There were no differences in terms
of demographic and injury-related variables between
the two groups, except that those with subjective cognitive complaints had a higher GCS (t⳱ⳮ2.8, df⳱35,
p⳱0.007) and were more likely to be women (v2⳱6.2,
df⳱1, p⳱0.01) (Table 1).
Major Depression
Based on the SCID for DSM–IV, major depression occurred in 18.5% of the group with subjective cognitive
complaints but in none of those without self-reported
cognitive difficulties. The difference between the two
groups was significant (Fisher’s exact test, p⳱0.05) (Table 1).
Neurocognitive Deficits
While both groups had similar scores on their premorbid IQ and on the WMT (Table 1), patients with subjective complaints scored significantly more poorly on
measures of working memory (WAIS-III) (t⳱2.7, df⳱60,
p⳱0.01), verbal (CVLT-II recognition hits) (t⳱3.4,
df⳱42, p⳱0.001) and visuospatial memory (BVMT-R
immediate [t⳱2.9, df⳱59, p⳱0.005] and delayed total
recall [t⳱3.2, df⳱54, p⳱0.002]), attention and information processing speed (PASAT 2.0 s) (t⳱2.2, df⳱57,
J Neuropsychiatry Clin Neurosci 18:1, Winter 2006
p⳱0.03), and executive functioning (WCST total [t⳱2.4,
df⳱51, p⳱0.02] and perseverative responses [t⳱ⳮ2.9,
df⳱56, p⳱0.005]). There were no significant group differences on the CVLT-II total (t⳱1.7, df⳱61, p⳱0.09)
and long delay free recall (t⳱1.4, df⳱53, p⳱0.18) or on
the PASAT at 1, 2 presentation interval (t⳱1.8, df⳱56,
p⳱0.07).
When using MANCOVA on cognitive variables found
statistically significant during univariate analysis, with
gender and GCS score serving as covariates, the differences between the groups remained significant on almost all cognitive measures: WAIS-III working memory
(F⳱4.5, df⳱1,54, pⴔ0.04), CVLT-II recognition hits (F⳱
15.2, df⳱1,54, p⬍0.0001), BVMT-R immediate (F⳱5.9,
df⳱1,54, pⴔ0.02) and delayed total recall (F⳱8.2,
df⳱1,54, pⴔ0.006), and WCST perseverative responses
(F⳱7.2, df⳱1,54, pⴔ0.009). In a separate MANCOVA,
adjusted for depression in addition to gender and GCS
score, those with subjective cognitive complaints scored
significantly more poorly only on CVLT-II recognition
hits (F⳱7.1, df⳱1,54, pⴔ0.01), BVMT-R delayed total
recall (F⳱4.8, df⳱1,54, pⴔ0.03) and WCST perseverative responses (F⳱4.3, df⳱1,54, pⴔ0.04) (Table 2).
DISCUSSION
We demonstrated that patients with mild to moderate
TBI, who reported cognitive difficulties at 6 months following injury, performed more poorly on objective neuropsychological testing than those without subjective
cognitive complaints. This finding concurs with certain
previous mild TBI studies8–10 and has also been described in patients with HIV35,36 and in subjects with
multiple sclerosis.37,38
The potential contribution of other factors such as
prior head injury and psychotropic and/or analgesic
medication intake to subjects’ performances on cognitive testing was also assessed. Lack of statistically significant differences between the two groups on all these
variables eliminated the possibility of these factors influencing cognitive performance. Also, no differences
were noted in terms of CT scan results, a finding that is
significant given the association between neuropsychological deficits and CT scan abnormalities in patients
with these injuries.39
Our study also clarified contradictory findings from
previous investigations14,16 where the influence of psy-
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DEPRESSION AND COGNITIVE DEFICITS IN TBI
TABLE 1.
Demographic, Injury and Psychological Variables Compared Between Patients With and Without Subjective Cognitive
Complaints
No Complaint
(nⴔ29)
Demographic variables
Age
Gender (male)
Marital status (single or divorced)
Employment (employed)
Educational level
Problem drinking
Past psychiatric history
Prior head injury
31.3
21 (72.4)
20 (69.0)
21 (72.4)
13.8
15 (51.7)
3 (10.3)
5 (17.2)
Injury-related variables
Mechanism of injury (MVA-related)
Loss of consciousness
Altered level of consciousness
Yes, ⬍20 min
Yes, ⬎20 min
Post-traumatic amnesia
⬍24 hrs
⬎24 hrs but less than 1 week
GCS at the ER
Ct scan abnormalities
Psychotropic and/or analgesic use
Behavioural profile
SCID depressed
WASI Vocabulary (premorbid IQ)
Word Memory test
Unbiased response
Biased response
SD
Subjective Complaints
(nⴔ34)
10.2
2.7
34.9
14 (41.2)
17 (50.0)
25 (73.5)
13.9
11 (32.3)
7 (20.6)
7 (20.6)
16 (55.2)
26 (76.5)
15 (51.7)
12 (41.4)
2 (6.9)
18 (53.0)
13 (38.2)
3 (8.8)
22 (75.9)
7 (24.1)
13.7
14 (48.3)
11 (37.9)
27 (79.4)
7 (20.6)
14.6
14 (41.2)
21 (61.8)
0 (0)a
54.6
1.6
8.8
24 (96.0)c
1 (4.0)c
SD
t-test/X2 (df)
Sig.†
12.8
t (61)⳱ⳮ1.2
X2 (1)⳱6.2
X2 (1)⳱2.3
X2 (1)⳱0.03
t (61)⳱ⳮ0.2
X2 (1)⳱2.4
Fisher’s exact test
X2 (1)⳱0.1
0.23
0.01*
0.13
0.85
0.87
0.12
0.31
0.74
X2 (1)⳱3.2
X2 (2)⳱0.03
0.07
0.99
Fisher’s exact test
1.00
2.8
0.65
5 (18.5)b
55.0
t (35)⳱ⳮ2.8
X2 (1)⳱0.14
X2 (1)⳱3.2
0.007*
0.71
0.07
Fisher’s exact test
t (59)⳱ⳮ0.2
Fisher’s exact test
12.6
24 (85.7)d
4 (14.3)d
0.05
0.87
0.35
Values are numbers and percentages unless otherwise indicated.
*pⱕ0.05
†
Sig.⳱significance
MVA⳱Motor vehicle accident; GCS⳱Glasgow Coma Scale; SCID⳱Structured Clinical Interview for DSM-IV Disorders; WASI⳱Wechsler
Abbreviated Scale of Intelligence; SD⳱standard deviation
a
n⳱25, bn⳱27,cn⳱25, dn⳱28
TABLE 2.
Neurocognitive Test Performances Compared Between Patients With and Without Subjective Cognitive Complaints and
Resulting MANCOVAs, Adjusted For Gender, GCS Score and Major Depression
Analysis
WAIS-III working memory
CVLT-II recognition hits
BVMT-R immediate total
BVMT-R delayed total
PASAT 2.0 s
WCST total
WCST perseverative responses
No Complaint
(nⴔ29)
Subjective
Complaints (nⴔ34)
F1
df
Sig.†
F2
df
Sig.†
30.8 (6.0)
15.5 (0.8)
26.3 (6.6)
10.1 (1.8)
39.0 (8.1)
5.5 (1.1)
13.5 (12.1)
25.9 (8.1)
14.0 (2.4)
20.6 (8.6)
8.1 (2.9)
33.6 (10.3)
4.5 (1.9)
24.6 (17.1)
4.5
15.2
5.9
8.2
2.3
3.8
7.2
1, 54
1, 54
1, 54
1, 54
1, 54
1, 54
1, 54
0.04*
⬍0.0001*
0.02*
0.006*
0.14
0.06
0.009*
1.8
7.1
3.3
4.8
0.7
1.3
4.3
1, 43
1, 43
1, 43
1, 43
1, 43
1, 43
1, 43
0.18
0.01*
0.07
0.03*
0.41
0.25
0.04*
Values are mean Ⳳ SD
*pⱕ0.05
†Sig.⳱significance
F1 value based on MANCOVA with gender and GCS score serving as covariates.
F2 value based on MANCOVA adjusted for major depression in addition to gender and GCS score.
WAIS⳱Wechsler Adult Intelligence Scale; CVLT⳱California Verbal Learning Test; BVMT⳱Brief Visuospatial Memory Test; PASAT⳱Paced
Auditory Serial Addition Task; WCST⳱Wisconsin Card Sorting Test
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CHAMELIAN et al.
chological distress on cognition was evaluated based
solely on self-report instruments of depression. Once
major depression (according to DSM–IV criteria) was
controlled for, the differences between those with and
without subjective cognitive complaints disappeared on
most cognitive tests, indicating a close association between objective measure of mood (SCID-IV) and several
aspects of cognition.
However, depression did not account for all subjective
reporting of cognitive difficulties in our study since,
even after adjusting for low mood, significant differences remained between those with and without subjective cognitive complaints. Some of these individuals
with self-reported cognitive difficulties may be part of
the “miserable minority,” a term coined by Ruff et al.40
to describe mild TBI patients whose recovery is compromised by psychological factors other than depression, such as premorbid personality traits. Recent data
from functional imaging studies41–45 suggest an alternative hypothesis—namely that, in certain patients with
mild TBI, cognitive complaints may relate directly to cerebral dysfunction that can be unmasked by neuroimaging activation paradigms. Ruff et al.41 studied nine
mild head injury patients with persistent complaints
and measurable cognitive deficits, who underwent 18Fluoro-deoxyglucose (FDG) PET, a mean of 29 months
postaccident. Despite normal MRI/CT scans, the TBI
subjects, when matched against healthy comparison
subjects, demonstrated frontal and temporal hypome-
tabolism while performing a visual sustained attention
task. Alterations at the level of cerebral substrate have
been documented even in acute cases of mild TBI (i.e.,
within 1 month of injury) using the fMRI approach. In
response to increasing working memory (WM) processing load42–43 as well as to tasks that probe episodic memory,44 subjects with mild head injury have shown significant differences in brain activation patterns, relative
to healthy comparison subjects, differences that may explain mild TBI patients’ persistent cognitive complaints
and need to exert greater effort during cognitive tasks.45
CONCLUSION
In summary, mild to moderate TBI patients with persisting subjective cognitive complaints have demonstrable evidence of cognitive dysfunction. In most, but not
all patients, these objective cognitive difficulties are
linked to comorbid major depression. This clinically important observation suggests that a detailed assessment
of mood based on objective criteria should be considered in all patients who complain of cognitive problems
following such injuries.
Dr. Feinstein is supported by grants from the Canadian
Institutes of Health Research (grant #36535)
The poster presentation of this study was given at the 15th
Annual Meeting of the American Neuropsychiatric Association in Bal Harbour, Fl., February 21-24, 2004.
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