Journal of Affective Disorders 142 (2012) 150155

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Journal of Affective Disorders

journal homepage: www.elsevier.com/locate/jad

Research report

Reduced posterior corpus callosum area in suicidal and non-suicidal

patients with bipolar disorder
Fabiana Nery-Fernandes a,b,n,1, Marlos V. Rocha a,b,1, Andrea Jackowski c, Giovanna Ladeia d,
Jose Luiz Guimara~ es a, Lucas C. Quarantini a,b,e, Cesar A. Araujo-Neto d, Irismar R. De

Miranda-Scippa a,b,e
Oliveira e, Angela
a

Program of Mood and Anxiety Disorders (CETHA), Universidade Federal da Bahia, Salvador, Bahia, Brazil
s-Graduac- a~ o em Medicina e Sau
de (PPgMS), Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Bahia, Brazil
Programa de Po
c
rio Interdisciplinar de Neurociencias Clinicas (LiNC), Universidade Federal de Sa~ o Paulo, Brazil
Laborato
d
stica, Salvador, Bahia, Brazil
Image Memorial, Medicina Diagno
e
Department of Neuroscience and Mental Health, Universidade Federal da Bahia, Salvador, Bahia, Brazil
b

a r t i c l e i n f o

a b s t r a c t

Article history:
Received 20 February 2012
Accepted 1 May 2012
Available online 1 August 2012

Background: Impulsivity is a characteristic of bipolar disorder (BD) that can contribute to the risk for
suicidal behavior. Evidence suggests that gray and white matter abnormalities are linked with
impulsivity, but little is known about the association between corpus callosum (CC) and impulsivity
in BD. We examined the CC area and impulsivity in euthymic bipolar I patients, with and without
lifetime history of suicide attempts, and in healthy controls.
Methods: Nineteen bipolar patients with a suicide attempt history (BP-S), 21 bipolar patients without
suicide attempt history (BP-NS), and 22 healthy controls (HC) underwent clinical assessment by the
Structured Clinical Interview with the DSM-IV axis I (SCID-I), the Barratt Impulsiveness Scale (BIS-11),
and MRI scan.
Results: No differences were observed for any CC subregion between BP-S and BP-NS groups. There was
a signicant reduction in the genu (p 0.04) and isthmus areas (p 0.01), in bipolar patients compared
with HC. In the BP-S group, the BIS-11 total (p 0.01), attention (p 0.001) and non-planning (p 0.02)
impulsivity scores were signicantly higher than in the BP-NS and HC groups.
Limitations: These results cannot establish causality because of the cross-sectional nature of the study.
Conclusion: This report potentially provides evidence that a reduction in the CC area is present even in
non-symptomatic bipolar patients, which may be evidence of a biological trait marker for BD.
Furthermore, the study demonstrated that BP-S group had higher impulsivity even during euthymia,
which points to a sustained association between lifetime history of suicide attempts and impulsivity
in BD.
& 2012 Elsevier B.V. All rights reserved.

Keywords:
Bipolar disorder
Mood disorders
Attempted suicide
Corpus callosum
Magnetic resonance imaging
Impulsivity

1. Introduction
Numerous studies have documented a strong association
between suicidal behavior and bipolar disorder (BD). Individuals
with BD have lifetime suicide attempt rates of 20%56%, which
are almost 15 times higher than the rates found in the general
population (Harris and Barraclough, 1997). The Epidemiologic
Catchment Area Study demonstrated that the lifetime rate of
suicide attempts was 29.2% for those with BD compared with

n
Correspondence to: Hospital Universitario Professor Edgard Santos, terceiro
andar, Servic- o de Psiquiatria, 40110-909 Salvador, BA, Brazil.
Tel.: 55 71 9192 7186; fax: 55 71 3023 4111.
E-mail address: fabiana.nery@hotmail.com (F. Nery-Fernandes).
1
These authors contributed equally to this article.

0165-0327/$ - see front matter & 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jad.2012.05.001

15.9% for those with major depressive disorder and 4.2% for all
other DSM-III Axis I disorders combined (Chen and Dilsavier,
1996). Moreover, 15%19% of bipolar patients die as a result of
suicide (Valtonen et al., 2005; Goodwin and Jamison, 2007).
Unfortunately, most studies have evaluated only the clinical risk
factors for suicide attempts (Hawton et al., 2005; Marangell et al.,
2006), and knowledge about the neurobiology of suicide is still
limited. A recent review of neuroimaging studies of suicidal
patients showed involvement of the ventrolateral orbital, dorsomedial and dorsolateral prefrontal cortices, the anterior cingulate gyrus, and, to a lesser extent, the amygdala (Jollant et al.,
2011). In addition, alterations in white matter connections have
been suggested (Grangeon et al., 2010). These studies support the
concept of specic neuroanatomical alterations in suicidal behavior in patients with mental disorders. Considering that suicide is

F. Nery-Fernandes et al. / Journal of Affective Disorders 142 (2012) 150155

a potentially preventable cause of death, understanding the

neural correlates of suicidal behavior might be helpful in reducing
suicide rates among patients with BD and other psychiatric
disorders.
The neuroimaging evidence in BD has demonstrated that
region-specic abnormalities exist for several structures, such as
the amygdala, hippocampus, hypothalamus, basal ganglia, cerebellum and corpus callosum (Sublette et al., 2006; Baldac- ara et al.,
2011). However, one meta-analysis of 38 volumetric studies in
adults found no signicant structural differences between BD and
comparison subjects in any region, except for an enlarged right
lateral ventricle (McDonald et al., 2004). This discrepancy could be
explained by the small number of studies measuring each region
or by the considerable amount of variation in clinical samples,
mainly because a number of ndings appear to be related to the
phase of the bipolar illness, based on differential ndings across
different phases of the disease. Regarding suicide attempts in
bipolar patients, the data remain rare. Periventricular white
matter hyperintensities have been reported in patients with major
affective disorders who attempt suicide (Pompili et al., 2008;
Grangeon et al., 2010). Moreover, abnormalities in the structure
and function of the prefrontal cortex in bipolar patients who
attempt suicide have also been found, but these abnormalities
have been found in suicidal patients with other psychiatric
diagnoses as well (Sublette et al., 2006).
The corpus callosum (CC) is a white matter midline structure that
connects the two cerebral hemispheres, allowing interhemispheric
communication. It plays a crucial role in cognitive processes, such as
sensorymotor stimulations, attention, arousal, language, and memory (Phelps et al., 1991; Hellige et al., 1998). Subregions of the CC are
composed of approximately 180 million myelinated axons of different diameters that topographically map various cortical areas. Smalldiameter bers (o2 mm) are more common in the genu and the
splenium, which connect the prefrontal and higher-order temporoparietal processing areas (association area), whereas large-diameter
bers (42 mm) mainly constitute the body and isthmus, which
connect the visual, auditory and somatosensory areas (Aboitiz et al.,
1992).
In normal development, the CC increases in size into late
adolescence, primarily by the myelination of higher association
areas, which leads to increased speed in inter-hemispheric
information processing and related cognitive capacity (Giedd
et al., 1999; Keshavan et al., 2002a). Specically in bipolar
patients, CC alterations might lead to emotional and cognitive
decits (Bellani et al., 2009).
Few studies have examined the size of the CC in patients with
BD. A structural study on bipolar I patients in their rst episode of
mania (or in a mixed state) showed that these patients have
smaller total areas of the posterior body and isthmus regions
compared with healthy controls and that mania is inversely
correlated with the area of those regions (Atmaca et al., 2007).
Other structural studies have also shown that there are signicant
decreases in the total area of the genu, posterior body and
isthmus regions in BD patients compared with healthy controls
(Coffman et al., 1990; Brambilla et al., 2003). However, other
studies have failed to nd any differences in the area of the CC
between BD patients and healthy subjects (Hauser et al., 1989;
Yasar et al., 2006). Despite study variability, a meta-analysis
of these ve case-control studies showed reduced CC areas
in bipolar patients in comparison with healthy volunteers
(Arnone et al., 2008). One study also evaluated the magnetic
resonance imaging (MRI) signal intensity of the CC in bipolar
children and adolescent patients and demonstrated a signicantly lower signal intensity for all callosal sub-regions in the
BD group compared with healthy subjects (Caetano et al., 2008).
These MRI ndings suggest that a failure to integrate information

151

across the hemispheres might contribute to the pathophysiology

of BD.
Regarding the CC and suicide attempts, two recent studies
have been reported. The rst study found a reduced area in the
posterior third of the CC in elderly suicidal patients when
compared to elderly patients with current or lifetime major
depressive disorder or anxiety disorder and healthy controls
(Cyprien et al., 2011). Another important report from Matsuo
and colleagues showed that suicidal patients with BD were more
impulsive than the comparison groups and that suicidal BD
patients showed a signicant inverse partial correlation between
the Barratt Impulsiveness Scale (BIS-11) total score and the
anterior genu area. That study supports the hypothesis that a
smaller anterior CC area predicts higher impulsivity among
suicidal BD patients. Although there were no signicant differences among suicidal BD patients, non-suicidal BD patients and
healthy subjects for any region of the CC area, these ndings
suggest that in suicidal BD patients, the medial anterior regions of
the brain may participate in neural circuits relevant to impulsiveness and suicidal behaviors (Matsuo et al., 2010).
Impulsivity is a prominent and measurable characteristic of BD
that can contribute to risk for suicidal behavior (Swann et al.,
2005; Perround et al., 2011). Subjects with a history of suicide
attempts had more impulsivity assessed by the Barratt Impulsiveness Scale (BIS-11); this scale is intended to measure impulsivity as a stable trait but has been reported to be inuenced by
the clinical state as well (Swann et al., 2007). Most studies have
been cross-sectional, so it is not possible to differentiate whether
the differences in BIS-11 scores across clinical states are due to true
state dependence, differential characteristics of subjects with predominately depressive or manic courses of bipolar disorder, or
differences among patients with bipolar disorder who are predisposed to having more severe or recurrent illness and, therefore,
more likely to be symptomatic when they were studied (Najt et al.,
2007; Peluso et al., 2007).
Our aim was to examine CC structural abnormalities and
impulsivity in euthymic bipolar I patients with and without a
lifetime history of attempting suicide compared to healthy controls. We hypothesized that BD patients with a history of
attempting suicide would have higher impulsivity and a smaller
CC area than BD patients without a history of attempting suicide
and healthy subjects. Furthermore, we hypothesized that BD
patients without a history of attempting suicide would have no
differences in these parameters compared with healthy subjects.
The neuroimaging ndings in bipolar patients suggest that there
are structural variations associated with the different phases of
the disease (McDonald et al., 2004), so it was important to assess
the bipolar patients in euthymia, unlike previous studies, to try to
prevent mood-state-related ndings.

2. Methods
2.1. Subjects
We screened a total of 48 right-handed bipolar I patients, and
8 patients were excluded (5 because of a history of neurological
illness or head trauma with a loss of consciousness and 3 because
they could not undergo an MRI exam). Twenty-ve right-handed
healthy controls were evaluated, and 3 patients were excluded (1
because of previous head trauma and 2 because they could not
complete the MRI exam). Nineteen bipolar I euthymic patients
with a lifetime history of suicide attempts (BP-S) (6 males and 13
females, mean age39.8, SD11.4), 21 bipolar I patients without a
lifetime history of suicide attempts (BP-NS) (5 males and 16
females, mean age42.0, SD8.6), and 22 healthy controls (HC)

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F. Nery-Fernandes et al. / Journal of Affective Disorders 142 (2012) 150155

(10 males and 12 females, mean age37.7, SD13.5) underwent a

clinical assessment and an MRI scan. All BD patients were on
medication (mostly mood stabilizers).
All BD patients were referred to this study from an outpatient
clinic and were seen consecutively through the Program of Mood
and Anxiety Disorders (CETHA). All BD patients were interviewed
using the Structured Clinical Interview with DSM-IV axis I (SCIDI) (First et al., 1997), the Hamilton Depression Rating Scale (HDRS)
(Hamilton, 1960), the Young Mania Rating Scale (YMRS) (Young
et al., 1978) and the BIS-11 (Barrat, 2000). The BIS-11 was used to
evaluate trait impulsivity and is a self-report questionnaire containing 30 4-point Likert-type items. Scoring yields a total score and
three subscale scores derived by factor analysis: attention, motor
and non-planning (Barrat, 2000). Once both the BD diagnosis and
the euthymic state (YMRS and HDRSo7, for at least 2 months)
were conrmed, a questionnaire was administered to gather clinical
and socio-demographic characteristics. All evaluation instruments
were administered by trained experts in psychiatry. Patients were
classied as having a positive suicidal history if they reported one
or more self-injurious acts committed with the intent to die.
Healthy controls were recruited among the patients companions and were interviewed using the same evaluation instruments. The choice of patients companions as a control group was
to try to prevent bias associated with differences in socio-demographic data between groups. None of the healthy subjects had a
current or past Axis I DSM-IV psychiatric disorder or a rst-degree
relative with an Axis I psychiatric disorder.
The exclusion criteria were as follows: a history of neurological illness, a history of head trauma with a loss of consciousness,
substance abuse at any time and medical problem within the
preceding 6 months.
The study was approved by the local Medical Review Ethics
Committee and was performed in accordance with the ethical
standards of the Declaration of Helsinki. All patients had provided
written informed consent prior to their inclusion in the study.
2.2. MRI data processing and analysis
MRI scans were acquired with a 1.5T Sigma scanner (Symphony
Master/Class Siemens, Enlanger, German). Three-dimensional-gradient echo imaging (SPGR) was performed in the sagittal plane
(TR1850 ms, TE3.45 ms, ip angle131, FOV24 cm, slice
thickness1 mm, NEX1, matrix size256  256) to obtain 160
images covering the entire brain.
Initial image processing was performed using the ANALYZE
AVW 7.0 software platform and included mid-sagittal and ACPC
alignment. The CC was outlined on the midsagittal slice and semiautomatically segmented into seven sections using Witelsons
protocol. Briey, the maximal length of the CC was taken as the
line joining the most anterior and posterior points of the CC. This
line was used to divide the CC into anterior and posterior halves;
anterior, middle, and posterior thirds; and the posterior one-fth
region. Thus, the following seven regions were measured: rostrum,
region 1; genu, region 2; rostral body, region 3; anterior midbody,
region 4; posterior midbody, region 5; isthmus, region 6; and
splenium, region 7.
To adjust for brain size, we measured brain volume using VBM
methodology as implemented in the VBM Toolbox with SPM5
(http://dbm.neuro.uni-jena.de/vbm/) and previously described in
detail (Ashburner and Friston, 2005). The sum of all voxel values
within the segmented image approximates total volume within
the corresponding partition. Total brain volume was computed
from the sum of gray and white matter volumes (Ashburner and
Friston, 2005). Inter-rater reliability, performed on 10 randomly
selected independent ratings of total CC area and its subdivisions,
was 0.99 (Po0.0001). Intra-rater reliability performed on total CC

area, determined by 10 ratings, was 0.900.98 (P varying 0.0001

0.001). All reliability analyses were performed using a two-tailed
Pearsons correlation.

2.3. Statistics
Data were analyzed with SPSS 13.0 (SPSS, Chicago, IL). All
socio-demographic variables were analyzed by a chi-squared test,
Students T-test or a univariate analysis of variance, as appropriate. Group differences in the area of CC subregions were
assessed by a multivariate analyses of variance (MANOVA)
dened by two between-subject group factors [group (bipolar
patients with suicidal history, bipolar patients without suicidal
history and controls) and gender (males and females)] and eight
within-subject variables, i.e., rostrum, genu, rostral body, anterior
midbody, posterior midbody, isthmus, splenium and total callosal
area) followed by Bonferroni post-hoc tests. The CC subregions
were adjusted for total brain volume by dividing the area of each
callosal subregion by brain volume and multiplying this ratio
by 1000.
The MANOVA showed signicance, and follow-up univariate
analyses were conducted. An association between callosal measurements, BIS total score, attention, non-planning and impulsivity were examined by Pearsons correlation coefcient or
Spearmans rho, as appropriate. The level of statistical signicance
was set at p o0.05.

3. Results
In our sample, there were no signicant differences between
the BP-S, BP-NS, and HC groups regarding gender, age, and
educational level. There were also no signicant differences
between BP-S and BP-NS in age of BD onset, type of rst episode,
length of illness, history of psychiatric hospitalizations, number of
psychiatric hospitalizations, lifetime psychoses, or family history
of suicide or attempted suicide. However, the BP-S group had
signicantly more lifetime psychiatric co-morbidities than the
BP-NS group (x2 6.96; p 0.03). The demographics data for the
participants are presented in Table 1.
The independent samples test for the BIS scores demonstrated
that in the BP-S group, the BIS total score (F 4.58; p 0.01),
attention (F7.75; p0.001) and non-planning (F4.44; p0.02)
impulsivity subtype scores were signicantly higher than those in
the BP-NS and HC groups, but there were no differences among
the 3 groups for the motor impulsivity score. The clinical data for
the participants are presented in Table 1.
No correlations were observed between any subregion of the
CC and BIS total score, attention, motor, and non-planning
impulsivity in the BP-S and BP-NS groups (all were p 40.05).
There were also no signicant differences in total brain
(F 0.19; p 0.83), white matter (F 0.37; p 0.61) and gray
matter volumes (F 0.24; p 0.98) among the 3 groups. There
was a signicant reduction in the genu (F 4.12; p 0.04) and
isthmus area (F6.66; p 0.01) and a trend towards reduced total
CC area (F 3.52; p 0.06) in patients with BD (as one group) in
comparison with the healthy controls (Table 2). No differences for
any CC subregion were observed between BD patients who had
and had not had a lifetime history of suicide attempts.
A signicant gender effect, but no gender by group interaction,
was observed for the rostral body area (subregion 3) of the corpus
callosum, with females having a larger area (F(1)4.802;
p0.033). No gender or gender by group interaction effect was
observed for any other region of the corpus callosum (in all cases
p40.05).

F. Nery-Fernandes et al. / Journal of Affective Disorders 142 (2012) 150155

153

Table 1
Demographics and clinical data for the participants.
Bipolar patients

Healthy controls

Statistics

Suicidal (n 19)

Non-suicidal (n 21)

(n 22)

Gender (n)
male
female

6
13

5
16

10
12

x2 2.31, p 0.31

Age, mean 7 SD (years)

39.8 711.4

42.0 7 8.6

37.77 13.5

F 0.75, p 0.47

Educational level, mean 7SD (years)

12.0 73.0

11.2 7 3.7

11.27 2.7

F 0.37, p 0.69

Age of onset, mean 7 SD (years)

24.3 79.0

25.3 7 9.4

NA

t 0.34, p 0.73

Length of illness, mean 7SD (years)

15.6 77.2

16.5 7 10.7

NA

t 0.31, p 0.75

Hospitalizations (n)
Yes
No

13
6

18
3

NA
NA

x2 1.71, p 0.26

Number of hospitalizations, mean 7SD

6.07 5.8

3.1 7 2.8

NA

t  1.80, p 0.08

Type of rst episode

Depression
Mania
Unknown

11
7
1

10
11
0

NA
NA
NA

x2 1.84, p 0.39

Lifetime psychoses (n)

Yes
No

15
4

9
11

NA
NA

x2 2.77, p 0.96

Family history of suicide (n)

Yes
No

6
13

4
17

NA
NA

x2 0.83, p 0.47

Family history of attempted suicide (n)

Yes
No

2
17

4
17

NA
NA

x2 0.56, p 0.66

Psychiatric comorbidities (n)

Yes
No

10
9

4
19

NA
NA

x2 6.96, p 0.03*

BIS total score, mean 7 SD

67.3 714.8

58.3 7 8.6

58.57 9.0

F 4.58, p 0.01*

Attention score, mean 7SD

20.5 73.9

16.6 7 2.5

17.57 3.4

F 7.75, p 0.001**

Motor score, mean 7 SD

20.4 76.0

19.5 7 4.9

17.97 4.0

F 1.31, p 0.28

Non-planning score, mean 7SD

26.4 76.2

22.1 7 4.9

23.17 4.4

F 4.44, p 0.02*

Signicant at the 0.05 level (2-tailed).

Signicant at the 0.001 level (2-tailed).

nn

4. Discussion
In this report, we evaluated the relationship between impulsivity, a lifetime history of suicide attempts and the CC area in
patients with BD. This study is the rst that, to our knowledge,
has evaluated the CC area exclusively in euthymic bipolar I patients
with and without a lifetime history of attempting suicide. Although
no signicant differences for any CC subregion were observed
between BP-S and BP-NS groups, we demonstrated genu and
isthmus size reductions observed in BD patients as one group
compared with healthy controls, which is in agreement with
previous studies (Brambilla et al., 2004). The genu and the isthmus
could be important areas in the connection of different brain
structures, such as the frontal lobe, that are related to mood
regulation, and this nding may provide an initial explanation for
the mood dysregulation observed in bipolar patients (Wang et al.,
2008).
No correlations were observed between any subregions of the CC
and the BIS total and impulsivity subtype scores in the BP-S and BPNS groups. However, this study supports the data that showed that
the BP-S group has a higher impulsivity total score and higher
attention and non-planning impulsivity subtype scores than the BPNS and HC groups. This nding points to an association between

lifetime suicidal behavior and impulsivity in BD patients. Similar to

our report, Matsuo and colleagues evaluated the CC area, impulsivity
and suicidal behavior in BD patients and found no signicant
differences in the CC area between bipolar patients with and without
a history of suicide attempts. However, different from our ndings,
they demonstrated that BD patients with a history of suicide attempts
and with higher impulsivity had a smaller anterior genu area (Matsuo
et al., 2010). In contrast to our study, that study evaluated only
women in a non-euthymic phase, most often in depression, which
could lead to mood-state-related ndings.
Evidence regarding the role of the CC in BD pathology is still
rare, and the ndings are inconsistent. There is currently no
denitive explanation for the variable results observed among
studies examining the CC in patients with mood disorders;
however, the variability might be partly related to sample size
and the differences across studies in subject selection regarding
mean age, length of illness, age of onset, imaging access in
different phases of BD and different imaging methods.
In contrast to MRI studies, the signal intensity and diffusion
tensor imaging (DTI) studies of the CC have consistently shown
differences between BD patients and healthy controls (Brambilla
et al., 2004; Caetano et al., 2008). Two recent DTI studies on
euthymic bipolar patients demonstrated that callosal fractional

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F. Nery-Fernandes et al. / Journal of Affective Disorders 142 (2012) 150155

Table 2
Differences in the corpus callosum areas between bipolar patients and controls.
Corpus callosum area (mm2)

Bipolar patients (n40)

Healthy controls (n 22)

Statistics

CC total area
Male
Female
Total

457.427 79.11
496.527 58.53
485.777 66.16

507.70 7 74.20
524.697 104.53
516.977 90.32

F 3.52, p 0.06

CC1rostrum
Male
Female
Total

17.73 7 7.52
16.82 7 6.97
17.077 7.03

15.94 7 5.23
16.70 7 9.60
16.35 7 7.76

F 0.21, p 0.64

100.797 14.28
108.507 17.16
106.38 7 16.61

119.787 26.91
110.48 7 17.13
114.717 22.06

F 4.12, p 0.04*

CC3rostral body
Male
Female
Total

58.72 7 17.92
69.76 7 10.77
66.72 7 13.80

68.76 7 12.19
73.88 7 22.36
71.55 7 18.23

F 2.83, p 0.09

CC4anterior midbody
Male
Female
Total

56.79 7 10.68
61.27 7 9.29
60.047 9.76

63.11 7 12.34
65.72 7 13.05
64.53 7 12.50

F 3.19, p 0.07

CC5posterior midbody
Male
Female
Total

54.72 7 11.32
56.77 7 9.18
56.207 9.71

55.37 7 11.73
61.02 7 12.63
58.45 7 12.28

F 0.67, p 0.41

CC6isthmus
Male
Female
Total

42.81 7 9.02
45.37 7 6.71
44.66 7 7.39

50.017 10.82
53.05 7 16.82
51.67 7 14.17

F 6.66, p 0.01*

CC2genu
Male
Female
Total

CC7splenium
Male
Female
n

125.837 27.27
138.02 7 19.57

134.70 7 18.83
143.827 28.80

F 1.32, p 0.25

Signicant at the 0.05 level (2-tailed).

anisotropy was signicantly reduced compared with healthy

subjects, suggesting abnormalities in the structural integrity of
the CC (Chan et al., 2010; Macritchie et al., 2010).
A smaller CC has also been described in various other psychiatric
conditions, such as post-traumatic stress disorder (De Bellis et al.,
1999), schizophrenia (Keshavan et al., 2002b), and pathological
gambling (Yip et al., 2011). These ndings suggest that impaired
inter-hemispheric communication might be a common feature of
several neuropsychiatric disorders.
It is important to note that the current study evaluated only
euthymic patients. This nding suggests that the reductions, as well
as the abnormalities, shown in Macritchie et al. (2010) study of the CC
in BD patients were present even in non-symptomatic periods of the
disease. It is also necessary to highlight that there is a difference
between trait-related and state-related biomarkers (Lewis et al.,
2009). Therefore, trying to assess structural changes in euthymia
can lead to evidence of biological trait markers in BD disease,
regardless of mood state.
Some limitations of our study warrant consideration. First, there
was a small sample size, which leads to limitations in statistical
power. Second, this was a convenience sampling; therefore, the
sample size and the power of the study were not calculated. Third,
we did not evaluate co-morbidity with cluster B disorders or the
presence of family risk factors for suicidality. Fourth, the crosssectional design precluded examination of chronological relationships among BD, suicide attempts, and CC structural abnormalities.
Consequently, we cannot hypothesize about possible changes in CC
size secondary to the psychotropic medications taken by our
patients. Further studies with larger sample sizes of euthymic
patients and healthy controls, combining an evaluation of the CC

area with microstructure methods, should be performed to conrm

the reduction in size of specic areas of the CC in BD patients.
However, one of the strengths of our study is that it consisted of
well-characterized euthymic patients without any current clinical
co-morbidities.
In summary, this report adds to the evidence that BD patients
with a lifetime history of suicidal behavior exhibit higher impulsivity, even during euthymia, which points to a sustained association
between lifetime suicidal behavior and impulsivity in BD patients,
even during non-symptomatic periods. Moreover, the present study
may provide evidence that abnormalities in the CC area in BD are
present even in non-symptomatic patients, suggesting that a failure
to integrate information across the hemispheres might contribute to
the pathophysiology of BD. Furthermore, structural changes in
euthymic bipolar patients might be evidence of biological trait
markers of BD disease, regardless of mood state, which could play
a future role in bipolar disorder diagnoses, course and treatment.

Role of funding source

This project has been supported in part by the Mood and Anxiety Disorders
Program (CETHA), Salvador-Bahia, Brazil, and by the National Council of Technological and Scientic Development (CNPq), registered as no. 480918/2007-4.
CETHA and CNPq had no further role in the study design; in the collection,
analysis and interpretation of the data; in the writing of the report; or in the
decision to submit the paper for publication.

Conict of interest
The authors do not have any actual or potential conict of interest, including
any nancial, personal, or other relationships with other people or organizations,

F. Nery-Fernandes et al. / Journal of Affective Disorders 142 (2012) 150155

within three years of beginning the work submitted that could inappropriately
inuence, or be perceived to inuence, their work.

Acknowledgments
The authors would like to thank all of the patients who consented to be
included in this study for their cooperation and resilience in completing the
assessments. We also thank the Image Memorial Clinic for technical assistance.

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