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Neuropsychological Impairment Among Manic, Depressed, and
Mixed-Episode Inpatients With Bipolar Disorder
Michael R. Basso
University of Tulsa, University of Oklahoma–
Schusterman Health Sciences Center—Tulsa, and
Hillcrest Medical Center
Natasha Lowery
University of Tulsa
Jackie Neel
Oklahoma State University College of Osteopathic
Medicine and Hillcrest Medical Center
Rod Purdie
Hillcrest Medical Center
Robert A. Bornstein
The Ohio State University
Previous research has demonstrated broad neurobehavioral abnormalities in bipolar affective
disorder (cf. G. Cassens, L. Wolfe, & M. Zola, 1990). However, there have been no
comparisons of neuropsychological function across patients with manic, depressed, or mixed
subtypes. In the present study, 37 manic, 24 mixed-episode, and 25 depressed bipolar I
inpatients and 34 control subjects were administered a brief battery of neuropsychological
tests. The multivariate and univariate effects of participant group on the neuropsychological
measures were uniformly significant ( p⬍.05). Planned contrasts revealed that the bipolar
participants performed worse than the controls, and few differences existed between the 3
patient groups. Additionally, the bipolar groups were impaired on 50% of the test battery.
These abnormalities were unlikely attributable to differences in psychiatric symptomatology,
medical illness, comorbid psychiatric diagnoses, or medication status. Findings imply
that acute mood disturbance during bipolar disorder yields significant neurobehavioral
dysfunction.
Previous research has demonstrated broad neuropsycho-
logical abnormalities in primary bipolar disorder (cf. Cas-
sens, Wolfe, & Zola, 1990). For instance, among acutely ill
patients, difficulties involving executive function, memory,
attention, speed of information processing, visual spatial
perception, and psychomotor speed have been observed
across several studies (Gourovitch et al., 1999; Hoff et al.,
1990; Martinez-Aran et al., 2000; McGrath, Scheldt, Wel-
ham, & Clair, 1997; Sax et al., 1999; Wolfe, Granholm,
Butters, Saunders, & Janowsky, 1987). These deficits may
be chronic, as similar patterns of dysfunction have been
found upon remission of acute mood episodes when patients
enter euthymic periods (Atre-Vaidya et al., 1998; Coffman,
Bornstein, Olson, Schwarzkopf, & Nasrallah, 1990; Deni-
coff et al., 1999; Ferrier, Stanton, Kelly, & Scott, 1999; van
Gorp, Altshuler, Theberge, & Mintz, 1999; van Gorp, Alt-
shuler, Theberge, Wilkins, & Dixon, 1998). Paralleling
these cognitive difficulties, research using imaging methods
has demonstrated structural and functional abnormalities
involving the frontal lobes, temporal lobes, basal ganglia,
hippocampus, amygdala, cerebellum, subcortical white mat-
ter, and cerebral ventricles among individuals with bipolar
disorder (Ali et al., 2000; Altshuler et al., 2000; Blumberg
et al., 1999; Coffman et al., 1990; Dupont et al., 1990; Figiel
et al., 1991; Hauser et al., 2000; McDonald et al., 1999;
Pearlson et al., 1997; Sax et al., 1999; Soares & Mann,
1997; Strakowski et al., 1999). Collectively, these findings
imply that neurobehavioral abnormalities are a stable char-
acteristic of the disorder.
This suggestion notwithstanding, some uncertainties re-
main. In particular, it is unclear whether cognitive and
cerebral dysfunction associated with bipolar disorder varies
according to mood state. Many previous investigations have
measured neuropsychological function among heteroge-
neous groups of bipolar patients but have not distinguished
between patients in a depressed, manic, or mixed episode.
Among studies of this type, bipolar patients displayed neu-
ropsychological performance that was significantly worse
Michael R. Basso, Department of Psychology, University of
Tulsa; University of Oklahoma–Schusterman Health Sciences
Center—Tulsa; and Hillcrest Medical Center, Tulsa, Oklahoma.
Natasha Lowery, Department of Psychology, University of Tulsa.
Jackie Neel, Department of Behavioral Health, Oklahoma State
University College of Osteopathic Medicine; and Hillcrest Medi-
cal Center. Rod Purdie, Hillcrest Medical Center. Robert A. Born-
stein, Departments of Psychiatry and Neurology, The Ohio State
University.
Portions of the data in this article were presented at the 28th
annual convention of the International Neuropsychological Soci-
ety, Denver, Colorado, February 2000. We gratefully acknowledge
the assistance of J. Carpenter regarding earlier versions of this article.
Correspondence concerning this article should be addressed to
Michael R. Basso, Department of Psychology, University of Tulsa,
600 South College Avenue, Tulsa, Oklahoma 74104. E-mail:
michael-basso@utulsa.edu
Neuropsychology Copyright 2002 by the American Psychological Association, Inc.
2002, Vol. 16, No. 1, 84–91 0894-4105/02/$5.00 DOI: 10.1037//0894-4105.16.1.84
84
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than controls (cf. Cassens et al., 1990; Gourovitch et al.,
1999; Martinez-Aran et al., 2000). Similarly, when hetero-
geneous groups of bipolar patients were examined with
imaging methods, abnormalities were commonly reported
(e.g., Dupont et al., 1990).
Some studies have attempted to examine neuropsycho-
logical effects of bipolar disorder in a more refined manner.
Rather than examining heterogeneous groups of bipolar
patients, such investigations have specifically assessed neu-
ropsychological function among individuals in either manic
or mixed-mood episodes. In these studies, bipolar patients
displayed significantly worse performance than control sub-
jects (cf. Cassens et al., 1990; Sax et al., 1999). Relatively
few studies have examined neuropsychological function
among depressed individuals with bipolar disorder. Wolfe
et al. (1987) compared patients with bipolar depression,
unipolar depression, or Huntington’s disease with a control
group. Individuals with bipolar depression performed sig-
nificantly worse than the unipolar depressives and control
group but equivalent to the patients with Huntington’s dis-
ease. Taken together, these findings suggest that bipolar
disorder yields significant neuropsychological dysfunction,
regardless of presenting mood symptoms. As yet, however,
there are, to our knowledge, no investigations that have
compared neuropsychological function of individuals with
bipolar disorder in manic, mixed, and depressed states.
Consequently, it is uncertain whether depression yields neu-
rocognitive dysfunction to the same degree as mania or
mixed features of mania and depression.
Accordingly, the present study examined neuropsycho-
logical function among groups of bipolar inpatients in a
manic, mixed, or depressed episode. These individuals were
further compared with a normal control group. On the basis
of prior research (e.g., Cassens et al., 1990), we expected
that bipolar individuals in a manic, depressed, or mixed
episode would display significantly worse performance than
control subjects. However, in comparing bipolar patients in
distinct mood states, expectations were less certain. Despite
findings to the contrary (e.g., Goldberg et al., 1993), some
data suggest that mania or mixed manic and depressed
features yield impairment consistent with schizophrenia (cf.
Hoff et al., 1990; McGrath et al., 1997). Thus, we an-
ticipated significant impairment among the manic and
mixed-feature patients. Additionally, there is evidence that
depressed bipolar patients demonstrate impairment com-
mensurate with severe neurologic illness, such as Hun-
tington’s disease (cf. Wolfe et al., 1987). Together, these
findings imply that bipolar disorder results in meaningful
neurobehavioral impairment, regardless of presenting symp-
toms. Consequently, we anticipated that impairment would
not differ significantly across manic, depressed, and mixed-
feature bipolar patients but that the patient groups would
show worse performance than a control group.
Method
Participants
Data were collected retrospectively from the records of 86
inpatients with primary diagnoses of bipolar I disorder. These
patients were seen as part of a routine diagnostic evaluation
completed during a hospital admission. Diagnoses were made in
accordance with Diagnostic and Statistical Manual of Mental
Disorders (4th ed.; DSM–IV; American Psychiatric Association,
1994) criteria by a board-certified attending psychiatrist at a teach-
ing hospital. In this taxonomy, criteria for bipolar disorder with a
manic episode include symptoms of abnormally elevated or irri-
table mood, diminished sleep, excessive involvement in pleasur-
able or goal directed activities, and flight of ideas. Criteria for
bipolar disorder with a depressed episode include history of prior
manic episode, depressed mood, anhedonia, diminished appetite or
sleep, feelings of worthlessness, and diminished ability to concen-
trate and think. For a mixed episode of bipolar disorder, the
individual meets criteria for both manic and depressive episodes.
In arriving at a diagnosis, the psychiatrist considered presenting
symptoms, diagnostic interviews, and chart histories. Although
such a diagnostic strategy is not optimal for prospective research,
it is typically accepted as adequate for retrospective research.
Indeed, several studies have demonstrated that similar diagnostic
procedures are reliable and highly commensurate with research
diagnostic criteria (cf. Fennig, Craig, Tanenberg-Karant, & Bro-
met, 1994; Maziade et al., 1992; Warner & Peabody, 1995). As
determined through interviews and review of prior medical
records, these patients had no prior loss of consciousness or
neurologic disease. Data were also collected from 31 control
subjects who were recruited from the community through public
notices. All of these participants denied current or previous psy-
chiatric symptoms or diagnoses. In screening interviews, they
further denied prior loss of consciousness or history of neurologic
illness.
As determined by the attending psychiatrist, 37 patients were
manic, 25 were depressed, and 24 displayed mixed features of
mania and depression. Among the manic, depressed, and mixed
bipolar patients, 21, 8, and 15 displayed psychotic features, re-
spectively. A chi-square test revealed no significant difference
between patient groups according to presence of psychotic fea-
tures,
2
(2, N⫽161) ⫽5.37, p⬎.05. We further examined this
issue by subdividing patient groups according to presence of
psychotic features. We then analyzed performance on neuropsy-
chological test scores in a 4 (patient group: control, manic, de-
pressed, and mixed) ⫻2 (psychotic features: present vs. absent)
multivariate general linear model. The main effect of patient group
was significant, Hotelling’s T
2
(54, 266) ⫽2.04, p⫽.001, but the
main effect of psychotic features, Hotelling’s T
2
(18, 90) ⫽1.74,
pⱖ.05, and the interaction of patient group and psychotic fea-
tures, Hotelling’s T
2
(36, 178) ⫽1.28, pⱖ.05, were not. Thus, the
groups failed to differ as a function of psychotic features. Simi-
larly, there was no difference among the three patient groups and
control subjects according to ethnic composition,
2
(9, N⫽
161) ⫽14.80, pⱖ.05; prior educational difficulties (history of
failed grades),
2
(3, N⫽161) ⫽3.08, pⱖ.05; or presence of
hypertension,
2
(3, N⫽161) ⫽4.41, p⬎.05; diabetes,
2
(3, N⫽
161) ⫽2.92, pⱖ.05; or heart disease,
2
(6, N⫽161) ⫽5.02, pⱖ
.05. Furthermore, a chi-square test showed that groups did not
differ in gender composition,
2
(3, N⫽161) ⫽6.67, pⱖ.05.
According to one-way analyses of variance (ANOVAs), the groups
did not differ significantly in age, F(3, 116) ⫽0.17, pⱖ.05, or
years of education, F(3, 116) ⫽2.06, pⱖ.05. Moreover, separate
one-way ANOVAs indicated that the patient groups did not differ
in number of comorbid psychiatric disorders, F(2, 80) ⫽2.26, pⱖ
.05; chronicity of illness (as defined by years since age of first
symptoms), F(2, 80) ⫽0.62, pⱖ.05; or onset age of symptoms,
F(2, 80) ⫽0.48, pⱖ.05. Further, the bipolar groups did not differ
with regard or prevalence of alcohol,
2
(4, N⫽161) ⫽4.72, pⱖ
85NEUROPSYCHOLOGICAL IMPAIRMENT IN BIPOLAR DISORDER
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.05, or drug abuse disorders,
2
(4, N⫽161) ⫽6.17, pⱖ.05.
Table 1 details gender, ethnicity, chronicity, onset age, age, and
education data for the participant groups. Table 2 denotes frequen-
cies of comorbid disorders.
At the time of examination, all but 8 of the patients were
receiving medication. Because medication may influence cognitive
function, we examined whether the proportion of medicated pa-
tients differed significantly between groups, and a chi-square test
revealed that they did not (p⬎.05). Furthermore, benztropine
(Leon, Canuso, White, & Simpson, 1994) and chlorpromazine
equivalent dosages (Jeste & Wyatt, 1982) were calculated for each
patient. Anticholinergic and dopamine blocking ratings were also
computed as were daily sedation ratings (Arana & Hyman, 1991;
Bezchlibnyk-Butler & Jeffries, 1991). The analyses revealed that
groups did not differ regarding benztropine, F(2, 24) ⫽0.09, pⱖ
.05; chlorpromazine, F(2, 27) ⫽1.78, pⱖ.05; anticholinergic
blockade, F(2, 51) ⫽0.68, pⱖ.05; dopamine blockade, F(2,
49) ⫽0.38, pⱖ.05; and sedation, F(2, 69) ⫽0.11, pⱖ.05
ratings. Thus, medication unlikely differed systematically across
patient groups.
Procedure
Patients were administered a brief battery of tests that have
demonstrated sensitivity to cerebral dysfunction. Given that prior
research has demonstrated that bipolar patients display deficits in
verbal memory, executive function, speed of information process-
ing, and motor function, we devised a brief battery of tests that
assessed these respective areas. In particular, the battery included
the California Verbal Learning Test (CVLT; Delis, Kramer,
Kaplan, & Ober, 1987), the F-A-S Verbal Fluency Test (Benton,
Hamsher, Varney, & Spreen, 1983), Trail Making Tests A and B
(Reitan & Wolfson, 1993), and the Grooved Pegboard Test (Klove,
1963).
Additionally, to assess severity of psychiatric symptomatology,
the Minnesota Multiphasic Personality Inventory—2 (MMPI–2;
Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) was
administered. All tests were administered and scored according to
standardization instructions by trained and supervised technicians
in a medical center setting. To clarify the degree of impairment
demonstrated relative to the control group, an overall impairment
index was calculated. For each test score, if an individual per-
formed lower than one standard deviation from the mean of the
control group, the performance was considered impaired. This
criteria is frequently used in clinical practice (cf. Heaton, Grant, &
Matthews, 1991). Consequently, total number of impaired perfor-
mances on F-A-S Verbal Fluency, Trail Making Tests A and B,
Grooved Pegboard Test, and the total recall score from the CVLT
were summed for each individual. Regarding the CVLT, we opted
to include only the total recall score in the impairment index
Table 1
Demographic Characteristics of Participant Groups
Subject
group
Education
(years) Age
(years)
Ethnicity
Gender Chronicity
(years) Age of onset
(years)
M SD M SD Female Male MSDMSD
Manic 14.38 2.74 35.65 10.43 27 (73%) Caucasian 26 (70%) 11 (30%) 10.25 11.57 25.00 16.07
7 (19%) African American
3 (8%) Native American
Mixed 13.79 2.23 36.00 8.65 21 (88%) Caucasian 21 (88%) 3 (12%) 8.56 8.29 27.65 10.35
3 (12%) African American
Depressed 13.52 2.36 35.16 10.99 23 (92%) Caucasian 18 (72%) 7 (28%) 11.83 9.02 23.87 12.52
2 (8%) African American
Control 14.91 1.86 34.09 13.88 32 (94%) Caucasian 31 (91%) 3 (9%)
1 (3%) African American
1 (3%) Asian
Table 2
Comorbidities of Participant Groups
Subject
group
Comorbidities
Medical Substance use Psychiatric
Manic 3 (8%) with diabetes 6 (16%) with past alcohol use 5 (14%) with panic (without agoraphobia)
3 (8%) with hypothyroidism 2 (5%) with current alcohol use 1 (3%) with OCD
2 (5%) with hypertension 3 (8%) with past drug use 3 (8%) with borderline PD
1 (3%) with cardiac problems 2 (5%) with current drug use 1 (3%) with obsessive compulsive PD
1 (3%) with PTSD
Mixed 1 (4%) with diabetes 3 (13%) with past alcohol use 1 (4%) with OCD
4 (17%) with hypothyroidism 1 (4%) with current alcohol use 1 (4%) with borderline PD
1 (4%) with hypertension 7 (29%) with past drug use 1 (4%) with PTSD
1 (4%) with cardiac problems 1 (4%) with current drug use
Depressed 1 (4%) with diabetes 6 (24%) with past alcohol use 6 (24%) with panic (without agoraphobia)
1 (4%) with hypothyroidism 4 (16%) with current alcohol use 4 (16%) with borderline PD
3 (12%) with hypertension 5 (20%) with past drug use 1 (4%) with bulimia
2 (8%) with cardiac problems 3 (12%) with current drug use 1 (4%) with social phobia
Note. The control group included no individual with any medical, substance use, or psychiatric comorbidities. OCD ⫽obsessive
compulsive disorder; PD ⫽personality disorder; PTSD ⫽posttraumatic stress disorder.
86 BASSO, LOWERY, NEEL, PURDIE, AND BORNSTEIN
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because it is generally considered the most reliable index from the
test (Delis et al., 1987) and because including multiple indices
from the test would likely bias the impairment index to reflect
memory deficits primarily.
Results
Multivariate ANOVAS
Scores on all cognitive tests were entered into one-way
multivariate analyses of variance (MANOVAs). Participant
group served as the between-groups factor. The MANOVA
included 14 indices from the CVLT and scores from the
remaining neuropsychological tests. The main effect of par-
ticipant group was significant, Hotelling’s T
2
(54, 275) ⫽
2.31, p⫽.001, and, subsequently, univariate one-way
ANOVAs were computed. In response to significant main
effects, Tukey least significant difference (LSD) compari-
sons were computed. This was done to delineate the nature
of group differences in performance while simultaneously
correcting for potential Type I error.
Univariate ANOVAs
CVLT standard scores. Raw scores on the CVLT were
transformed into standard scores on the basis of conversion
tables located in the CVLT manual (Delis et al., 1987).
These deviation scores detail how far each performance
deviated from that of the CVLT normative sample and are
corrected for potential age and gender differences.
As shown in Table 3, the effect of participant group was
significant for all CVLT indices, save the serial clustering
ratio. Tukey LSD comparisons showed that the three patient
groups generally displayed worse memory performance
than the control group on nearly all CVLT indices. Addi-
tionally, the manic group showed worse performance than
the mixed group on short-delay free recall and similarly
worse performance than the depressed group on long-delay
cued recall and the discrimination index.
In addition to using these standard scores regarding free
recall, cued recall, and recognition memory, we created a
percentage savings score to examine retention of informa-
tion across time. Specifically, we computed a ratio score by
dividing the raw long-delay free recall by Trial 5 recall,
thereby indicating how much information was retained sub-
sequent to learning. We further followed the example set
forth in the CVLT manual and corrected for potential dif-
ferences according to age and gender with adjusted means
(cf. Stevens, 1986). These adjusted means were analyzed in
a one-way ANOVA, and a significant difference between
groups was found. Tukey LSD contrasts showed that the
three patient groups retained less information than the con-
trol group, and there were no significant differences among
the three bipolar groups.
F-A-S Verbal Fluency. F-A-S scores were corrected for
the effect of gender, age, and education as suggested in the
test manual (Benton et al., 1983). As shown in Table 4, the
effect of participant group was significant. Tukey LSD
comparisons revealed that the patient groups generated
fewer words than the control group but that the patient
groups failed to differ from one another.
Trail Making Tests A and B. Time to complete two tests
was analyzed. As shown in Table 4, participant group
emerged as a significant main effect on both tests. For both
Trail Making Tests, Tukey LSD comparisons demonstrated
that the three patient groups performed worse than the
control group, but there were no differences between the
manic, mixed-episode, and depressed bipolar patients.
Grooved Pegboard Test. Time to complete the test for
each hand was analyzed in separate one-way ANOVAs.
Table 4 shows that the main effect of participant group was
significant for both hands. According to the Tukey LSD
Table 3
Mean California Verbal Learning Test (CVLT) Standard Scores
Measure F(3, 112)
Group
Contrasts
2
Manic Mixed Depressed Control
Total recall 18.95** 22.08 (15.06) 26.04 (15.36) 29.70 (15.56) 47.00 (12.65) abc ⬍d .04
Trial 1 6.45** ⫺1.74 (1.24) ⫺1.71 (1.12) ⫺1.17 (0.98) ⫺0.62 (1.28) ab ⬍d .05
Trial 5 19.90** ⫺3.05 (1.91) ⫺2.71 (1.85) ⫺2.26 (1.83) ⫺0.21 (1.01) abc ⬍d .03
Acquisition slope 5.22* ⫺0.61 (0.21) ⫺0.22 (0.32) ⫺0.70 (0.32) 0.39 (0.25) abc ⬍d .01
Semantic cluster ratio 6.96** ⫺0.69 (1.20) ⫺0.54 (1.14) ⫺0.43 (1.23) 0.32 (0.98) abc ⬍d .02
Serial cluster ratio 0.65 0.14 (0.88) ⫺0.13 (0.85) 0.08 (0.95) ⫺0.08 (0.87) .02
Recall consistency 12.08** ⫺1.34 (1.25) ⫺1.08 (1.50) ⫺0.75 (1.42) 0.35 (0.81) abc ⬍d .03
Short-delay free recall 13.88** ⫺2.63 (1.37) ⫺1.83 (1.61) ⫺1.87 (1.89) ⫺0.38 (1.10) abc ⬍d; a ⬍b .06
Long-delay free recall 13.70** ⫺2.69 (1.54) ⫺2.33 (1.78) ⫺2.09 (1.93) ⫺0.41 (1.10) abc ⬍d .02
Short-delay cued recall 11.02** ⫺2.11 (1.62) ⫺2.08 (1.76) ⫺1.39 (1.77) ⫺0.21 (0.98) abc ⬍d .03
Long-delay cued recall 21.33** ⫺3.08 (1.54) ⫺2.50 (1.69) ⫺1.96 (1.87) ⫺0.29 (0.97) abc ⬍d; a ⬍c .07
Recognition hits 6.48** ⫺2.03 (1.93) ⫺1.46 (2.19) ⫺1.78 (1.56) ⫺0.29 (1.19) abc ⬍d .02
Discrimination index 9.14** ⫺1.42 (1.50) ⫺1.17 (1.30) ⫺0.70 (1.01) ⫺0.06 (0.34) abc ⬍d; a ⬍c .05
% savings 22.31** 83.39 (6.45) 85.30 (4.63) 83.44 (6.11) 92.25 (2.01) abc ⬍d .02
Note. Standard deviations appear in parentheses. Total score across trials is listed as a Tscore. Percentage savings reflects age- and
gender-corrected ratio score. All remaining means reflect average zscores, indicating relative deviation from performance of the CVLT
normative sample. Eta-square values reflect effect size estimate for differences between patient groups, excluding the control group. Tukey
least significant difference contrasts are as follows: a ⫽mania, b ⫽depression, c ⫽mixed, and d ⫽controls.
*p⬍.01. ** p⬍.001.
87NEUROPSYCHOLOGICAL IMPAIRMENT IN BIPOLAR DISORDER
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contrasts, the three bipolar groups displayed slower perfor-
mance than the control group bilaterally, but there were no
significant distinctions within the participant groups.
Impairment index. Scores on the impairment index
were entered into a one-way ANOVA, and the effect of
participant group was significant, F(3, 112) ⫽16.70, p⬍
.001. As detailed in Table 4, the manic, depressed, and
mixed-episode bipolar groups had more impaired scores
than the control group, and Tukey LSD comparisons re-
vealed that these differences were significant (ps⬍.001).
No other contrast was significant. Notably, the three patient
groups averaged between three and four impaired scores out
of the six included in the impairment index.
Effect Size Analysis
It is notable that the patient groups generally displayed no
significant differences among themselves across the battery
of tests. It may be argued that the absence of significant
differences among the patient groups is attributable to in-
sufficient statistical power or too few research participants
(nota bene, cell sizes similar to those used in the present
study are generally adequate to detect meaningful effects in
behavioral research; Cohen, 1977). To address this issue, we
computed effect size estimates for the differences between
patient groups for each neuropsychological test, and these
appear in Tables 3 and 4. The largest eta-square value was
.07, and the mean estimate across the 18 test indices was .02
(SD ⫽.02). Such effect sizes are considered small.
Self-Report of Psychiatric Symptomatology
To evaluate whether symptom severity differed system-
atically between groups, scores on the MMPI–2 were com-
pared. To reduce the number of statistical tests, thereby
decreasing the likelihood of Type I error, scores on the eight
primary clinical scales were averaged. This overall mean
score was then entered into a one-way ANOVA, with pa-
tient group serving as the between-groups factor. Recent
research indicates that computing this mean score across the
clinical scales serves as the best summary indicator of
overall distress from the MMPI–2 (Graham, Barthlow,
Stein, Ben-Porath, & McNulty, in press). Mean Tscores on
this overall distress indicator appear in Table 5. The main
effect of participant group was not significant, F(3,
105) ⫽0.78, p⬎.05. These findings indicate that the three
groups did not differ significantly in levels of distress.
Discussion
Consistent with expectations, the three groups of bipolar
patients displayed worse performance than the control
group on measures of verbal memory, executive function,
speed of information processing, and dexterity. Moreover,
the manic, depressed, and mixed-feature groups had more
impaired test scores than the control group. Indeed, they
were impaired on at least 50% of the indices comprising the
impairment index. Such results accord well with previous
investigations that found that manic and mixed-episode
patients perform worse than control groups (e.g., Cassens et
al., 1990; Sax et al., 1999). The current data also parallel
those of Wolfe et al. (1987) who observed that depressed
bipolar patients display impaired neuropsychological func-
tion compared with a control group. Insofar as such neuro-
psychological deficits reflect underlying cerebral integrity,
they imply considerable cerebral dysfunction in bipolar
illness, regardless of presenting mood disturbance.
It seems relevant to denote that the groups were equiva-
lent with regard to history of comorbid medical illness (e.g.,
hypertension, diabetes, etc.), history of educational difficul-
ties, severity of self-reported symptomatology on the
MMPI–2, and other demographic characteristics. As such,
Table 4
Mean Verbal Fluency, Trail Making Tests A and B, and Grooved Pegboard Performance
Test F(3, 112)
Group
Contrasts
2
Manic Mixed Depressed Control
Verbal Fluency Test 4.26* 37.16 (10.72) 36.00 (10.42) 36.12 (11.47) 44.00 (9.16) abc ⬍d .003
Trail Making Test A 4.81* 34.97 (13.39) 33.89 (16.78) 31.04 (9.29) 24.30 (2.74) abc ⬎d .02
Trail Making Test B 5.84** 107.86 (66.08) 102.96 (52.60) 90.25 (48.38) 60.73 (24.61) abc ⬎d .02
Grooved Pegboard Test
Dominant hand 7.66** 80.58 (26.58) 90.17 (35.42) 83.12 (21.97) 61.36 (8.12) abc ⬎d .02
Nondominant hand 5.15* 90.28 (36.66) 94.25 (33.03) 90.54 (24.99) 68.76 (12.25) abc ⬎d .003
Impaired scores 18.17** 3.30 (1.90) 3.42 (1.71) 3.04 (1.54) 0.88 (1.12) abc ⬎d .01
Note. Verbal Fluency Test includes corrections for age, education, and gender. Times to completion are listed for Trail Making Tests
A and B and Grooved Pegboard Test. Standard deviations appear in parentheses. Eta-square values reflect effect size estimate for
differences between patient groups, excluding the control group. Tukey least significant difference contrasts are as follows: a ⫽mania,
b⫽depression, c ⫽mixed, and d ⫽controls.
*p⬍.01. ** p⬍.001.
Table 5
Mean T Scores on the Eight Minnesota Multiphasic
Personality Inventory—2 Clinical Scales
Patient group Overall MSD
Manic 53.87 16.95
Mixed 60.10 20.50
Depressed 53.87 21.60
Control 54.51 7.84
Note. Eta-square value for the main effect was .02.
88 BASSO, LOWERY, NEEL, PURDIE, AND BORNSTEIN
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the significant differences between the control group and
bipolar groups are unlikely due to confounding medical
factors or demographic biases.
Although the current data reveal significant differences
between the control group and individuals with acute bipo-
lar disorder, they provide no compelling evidence of signif-
icant differences among patients with manic, depressed, or
mixed features. The three groups of bipolar patients gener-
ally displayed no statistically significant differences in per-
formance across the neuropsychological test battery. Fur-
thermore, the three groups showed similar numbers of im-
paired test scores. As such, these data provide little evidence
that manic, mixed-feature, and depressed episodes yield
differential neuropsychological dysfunction in bipolar
disorder.
To some extent, these findings may be expected. For
instance, prior investigations demonstrated that acute mania
and bipolar depression correspond with significant neuro-
psychological deficit (Hoff et al., 1990; McGrath et al.,
1997; Wolfe et al., 1987). Until the current comparison of
manic, depressed, and mixed-feature patients, however, it
was unclear that the degree of impairment did not differ
significantly across these mood states. Moreover, to our
knowledge, no previous study has directly compared neu-
ropsychological function among discrete groups of manic,
depressed, and mixed-feature bipolar patients. Therefore,
the current findings provide novel information concerning
neurobehavioral function in acutely ill individuals with bi-
polar disorder.
This finding raises an important conceptual issue. Spe-
cifically, our failure to find significant differences among
the bipolar groups does not necessarily imply that equal
levels of neuropsychological dysfunction exist among
manic, depressed, and mixed-feature bipolar patients (i.e.,
“absence of evidence is not evidence of absence”). In par-
ticular, nonsignificant statistical differences may be due to
insufficient power. The effect size estimates for differences
among the patient groups were small. To obtain 80% power
(typically considered adequate for behavioral research; Co-
hen, 1977), data collection from a relatively large number of
participants would have been necessary. For instance, as
shown in Table 4, the effects size for differences between
bipolar patients was modest. To achieve 80% power, data
from 129 patients in each group (516 overall) would be
required. As suggested by Stevens (1986), the clinical
meaningfulness of such small effect sizes may be consid-
ered modest. Consequently, the likelihood that clinically
meaningful, but undetected, distinctions exist between the
bipolar groups is probably low.
To some extent, concluding that no significant neurobe-
havioral differences exist between bipolar mood states may
seem counterintuitive. For instance, the presenting symp-
toms of depression and mania are markedly different, and
patterns of cerebral dysfunction may vary across manic,
depressed, and mixed-feature episodes. In support of this
assertion, Koek et al. (1999) measured electroencephalo-
graphic activity twice in a group of 13 patients with bipolar
disorder over a 2-year period. Specifically, patients were
assessed once during a manic episode and again during a
depressive episode. The investigators found that depression
was associated with greater fronto-temporal activation in
the right than left hemisphere, whereas mania corresponded
with a converse pattern of arousal. Yet, studies using im-
aging methods suggest more diffuse dysfunction in bipolar
illness. For instance, Baxter et al. (1985) assessed resting
brain activity of manic, depressed, and mixed-episode bi-
polar patients with positron emission tomography. The de-
pressed and mixed-episode patients showed lower overall
brain glucose metabolism than the manic and control pa-
tients, and the uptake rate increased as these patients entered
euthymic or manic states. Other studies show that bipolar
disorder is associated with diffuse hypermetabolism
(Kennedy, Javanmard, & Vaccarino, 1997; Kishimoto et al.,
1987; Soares & Mann, 1997). Collectively, such outcomes
imply that manic and depressed episodes correspond with
diffuse patterns of cerebral dysfunction. The present find-
ings of nonspecific neuropsychological difficulties are con-
sistent with this suggestion. However, it should be acknowl-
edged that the battery of tests used in the present study is
relatively narrow in breadth. Other aspects of higher cog-
nitive function may be relatively spared in acutely ill bipolar
patients. As such, further research that uses a broader sam-
pling of neurobehavioral function would be necessary to
determine whether cognitive impairment is pervasive in
bipolar disorder.
Given the relatively similar level of deficit demonstrated
by the three bipolar groups on neuropsychological mea-
sures, these findings have potentially important implications
for clinical practice. In particular, because of their appar-
ently commensurate propensity for cognitive impairment,
patients with acute bipolar illnesses should be monitored
carefully regarding their activities of daily living and ca-
pacity for self-care; owing to neurobehavioral deficit, they
may be less able to care for themselves or manage their
treatment. For instance, bipolar patients frequently resist
medication, and there are some indications that poor treat-
ment adherence may contribute to increasing treatment re-
sistance across time (cf. Coryell, Keller, Lavori, & Endicott,
1990). Relative to this issue, several studies have demon-
strated that neuropsychological impairment corresponds
with worse treatment outcomes in individuals with mania
(cf. Atre-Vaidya et al., 1998; Silverstein, Harrow, & Bry-
son, 1994; Silverstein, Harrow, Mavrolefteros, & Close,
1997). Other research has shown that neuropsychological
abnormalities correspond with poor response to antidepres-
sant medication and cognitive–behavioral therapy in major
depression (Sotsky et al., 1991). Collectively, these findings
imply that the cognitive difficulties observed in the present
study may predict poor clinical outcomes among bipolar
patients.
A notable uncertainty raised by the current data concerns
the durability of neuropsychological deficits in bipolar dis-
order. In particular, the present findings show that neuro-
psychological abnormalities seem to occur during acute
mood disturbance. Nonetheless, the relative severity of neu-
ropsychological impairment during euthymic periods re-
mains unclear. In particular, existing data demonstrate that
euthymic patients show significant cognitive difficulties and
89NEUROPSYCHOLOGICAL IMPAIRMENT IN BIPOLAR DISORDER
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cerebral abnormalities (e.g., Atre-Vaidya et al., 1998;
Soares & Mann, 1997; van Gorp et al., 1998, 1999). Yet, it
is unknown whether impairment in a euthymic state is
comparable to that displayed during an acute manic, mixed,
or depressed episode. For example, bipolar patients in a
euthymic state may show significant neurobehavioral diffi-
culty but to a lesser extent than observed during acute mood
disturbance. Given the apparent implications of such neu-
robehavioral abnormalities for clinical and functional out-
comes, it may be worthwhile to address this issue within a
longitudinal research design.
Prior to concluding, it should be acknowledged that the
current data are limited in several respects. In particular, the
data indicate that acutely ill bipolar patients show impaired
neuropsychological function relative to a control group. In
addition to differing in diagnostic status, the patients differ
from the control group in medication status. Insofar as it
may influence neurobehavioral function, psychotropic med-
ication may further contribute to the differences between the
bipolar patients and control group. Furthermore, the diag-
noses were made by an attending board-certified psychia-
trist at a teaching hospital rather than with a structured
diagnostic interview. Although this diagnostic strategy is
considered relatively accurate (cf. Fennig et al., 1994; Ma-
ziade et al., 1992; Warner & Peabody, 1995), it is subopti-
mal, thereby introducing potential diagnostic error. More-
over, the current data are based entirely on a sample of
inpatients. The literature concerning neuropsychological
function in unipolar depression suggests that inpatients are
more severely impaired than outpatients (Burt, Zembar, &
Niederehe, 1995; Christensen, Griffiths, Mackinnon, & Ja-
comb, 1997; Kindermann & Brown, 1997; Veiel, 1997).
Granted, such data are concerned with unipolar depression
rather than bipolar disorder. Yet, it may be that patients with
acute bipolar disorder who do not require hospitalization
may display less impairment than those who do. This hy-
pothesis as yet remains untested, but doing so may provide
important information concerning the generalizability of
neuropsychological difficulties in bipolar disorder.
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Received December 18, 2000
Revision received May 1, 2001
Accepted July 25, 2001 䡲
91NEUROPSYCHOLOGICAL IMPAIRMENT IN BIPOLAR DISORDER
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