Functional impairment in bipolar II disorder: is it as disabling as bipolar I?

Abstract

It is well established that patients with bipolar disorder experience functional impairment even in remission. Nevertheless, bipolar II disorder remains understudied because most investigations to date include only bipolar I patients or just a small sample of bipolar II patients, without explicitly comparing both subtypes of disorder. The main objective of the current report is to evaluate overall and multiple domains of functioning, specifically in bipolar II disorder compared to patients with bipolar I disorder and healthy subjects.
233 subjects from 3 groups were compared: bipolar I patients (n=106), bipolar II patients (n=66) and healthy controls (n=61). Bipolar patients meeting criteria of remission were recruited at the Hospital Clinic of Barcelona and at different study sites in Argentina. All participants were assessed with 17-item Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale (YMRS) and the Functioning Assessment Short Test (FAST). Clinical and sociodemographic data were also recorded.
Both subgroups of patients, bipolar I and bipolar II, showed lower overall functioning (p<0.001) and in each domain of the FAST scale (all, p<0.001) when compared to the healthy control group. Tukey post hoc test revealed that bipolar II patients scored worse in the cognitive domain compared to bipolar I patients. However, after controlling for potential confounding variables, this difference disappeared and only older age (p<0.005) and HAM-D scores (p<0.001) remained significant.
Our results suggest that bipolar II patients are as disabled as bipolar I patients. This may be explained, in part, because bipolar II patients experience greater lifetime residual depressive symptoms than the bipolar I subgroup, which may have particular impact on cognitive domains of functioning.

Full text

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Research report
Functional impairment in bipolar II disorder: Is it as disabling as bipolar I?
A.R. Rosaa, C.M. Bonnína, G.H. Vázquezb, M. Reinaresa, B. Soléa, R. Tabarés-Seisdedosc,
V. Balanzá-Martínezc, A. González-Pintod, J. Sánchez-Morenoa, E. Vietaa,⁎
aBipolar Disorders Program, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain
bDepartment of Neuroscience, University of Palermo, Buenos Aires, Argentina
cSection of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, CIBERSAM, Valencia, Spain
dDepartment of Psychiatry, Santiago Apóstol Hospital, University of the Basque, Country, CIBERSAM, Vitoria, Spain
a r t i c l e i n f oa b s t r a c t
Article history:
Received 15 February 2010
Received in revised form 18 May 2010
Accepted 18 May 2010
Available online 9 June 2010
Introduction: It is well established that patients with bipolar disorder experience functional
impairment even in remission. Nevertheless, bipolar II disorder remains understudied because
most investigations to date include only bipolar I patients or just a small sample of bipolar II
patients, without explicitly comparing both subtypes of disorder. The main objective of the
current report is to evaluate overall and multiple domains of functioning, specifically in bipolar
II disorder compared to patients with bipolar I disorder and healthy subjects.
Methods: 233 subjects from 3 groups were compared: bipolar I patients (n=106), bipolar II
patients (n=66) and healthy controls (n=61). Bipolar patients meeting criteria of remission
were recruited at the Hospital Clinic of Barcelona and at different study sites in Argentina. All
participants were assessed with 17-item Hamilton Depression Rating Scale (HAM-D), Young
Mania Rating Scale (YMRS) and the Functioning Assessment Short Test (FAST). Clinical and
sociodemographic data were also recorded.
Results: Both subgroups of patients, bipolar I and bipolar II, showed lower overall functioning
(pb0.001) and in each domain of the FAST scale (all, pb0.001) when compared to the healthy
control group. Tukey post hoc test revealed thatbipolar II patients scored worse in the cognitive
domain compared to bipolar I patients. However, after controlling for potential confounding
variables, this difference disappeared and only older age (pb0.005) and HAM-D scores
(pb0.001) remained significant.
Conclusions: Our results suggest that bipolar II patients are as disabled as bipolar I patients. This
may be explained, in part, because bipolar II patients experience greater lifetime residual
depressive symptoms than the bipolar I subgroup, which may have particular impact on
cognitive domains of functioning.
© 2010 Elsevier B.V. All rights reserved.
Keywords:
Bipolar subtype II
Functionality
Impairment
FAST
Disability
1. Background
A growing body of research has reported functional
impairment in acute phases of bipolar disorder which persists
even in remission (Calabrese et al., 2003; Tohen et al., 2005;
Goetz et al., 2007). These studies have described difficulties in
multiple areas of functioning such as work productivity,
cognitive functioning, and social relationships (Rosa et al.,
2008a, 2007; Weinstock and Miller, 2008; Tabares-Seisdedos
et al., 2008). However, almost all investigations evaluating
functional impairment in bipolar disorder are based on
patients with bipolar I disorder or include small groups of
subjects with bipolar II disorder, without explicitly compar-
ing the two groups (Altshuler et al., 2006; Fagiolini et al.,
2005; MacQueen et al., 2000).
Male sex, older age, low socio-economic level, number of
previous episodes, number of previous hospitalizations, longer
Journal of Affective Disorders 127 (2010) 71–76
⁎ Corresponding author. Bipolar Disorders Program, Clinical Institute of
Neuroscience, University Clinic Hospital of Barcelona, CIBERSAM, Villarroel,
170, 08036-Barcelona, Spain. Tel.: +34 932275401; fax: +34 932275794.
E-mail address: evieta@clinic.ub.es (E. Vieta).
0165-0327/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jad.2010.05.014
Contents lists available at ScienceDirect
Journal of Affective Disorders
journal homepage: www.elsevier.com/locate/jad

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duration of the illness, suicide attempts, and substance use
disorder have been reported to negatively influence on
psychosocial functioning (Rosa et al., 2009a, 2007; Keck et al.,
1998). Additionally, residual depressive symptoms have been
consistently related to functional impairment in bipolar
disorder (Simon et al., 2007; Kennedy et al., 2007; Kennedy
and Paykel, 2004). Neuropsychological deficits have also been
related to poor psychosocial functioning, in particular, impair-
ment in verbal memory and executive functions have been
found in both subtypes of bipolar disorder (Martinez-Aran
et al., 2007; Torrent et al., 2006; Robinson and Ferrier, 2006).
Despite all, it is not known whether the results above
mentioned can be applicable to the bipolar II subtype as well.
Withregardtopsychosocial functioning,again,bipolarIIis
not only understudied but also the scarce evidence is
inconsistent. For instance, using longitudinal data from the
National Institute of Mental Health Collaborative Depression
study, Judd et al. (2005) found that depressive symptoms
were more disabling than hypomanic and manic symptoms.
Curiously, after controlling the differences in depression
severity, no overall discrepancies in psychosocial disability
between bipolar I and II disorder were found. Another study
informed of similar scores of Global Assessment of Function-
ing (GAF)amongdepressivebipolarI andIIpatients,although
there was higher absenteeism from work in the bipolar I
group (Ruggero et al., 2007). Using SF-20 subscales, Cooke
et al. (1996) reported lower scores on social functioning and
poor mental health in the bipolar II group (n=13) than
bipolar I disorder (n=55). Robb et al. (1997) found greater
self-reported intrusiveness in bipolar II patients compared to
bipolar I, although these differences may have been due to
higher concurrent levels of depression in the bipolar II group.
The observed discrepancies between the studies are likely
related to the fact that some of them have examined bipolar
patients with current depressive symptoms which may
contribute to poor functioning (Ruggero et al., 2007). In
addition, not only the method of diagnosing, but also the
instruments used to assess functioning vary across studies
(Judd et al., 2003; Robb et al., 1997; Ruggero et al., 2007).
Finally, the lack of a healthy control group in the majority of
studies could also explain the inconsistency in the results
(Ruggero et al., 2007; Judd et al., 2003, 2005).
Taking into account these methodological considerations,
the present study was specifically focused on functional
impairment in patients with bipolar II disorder. As far as we
know, this is the first study to evaluate overall and multiple
domains of functioning specifically in bipolar II disorder,
involving two control groups: one comprising patients with
bipolar I disorder and the other one of healthy participants.
2. Method
2.1. Participants
The sample comprised a total of 233 participants, 172 of
whom were bipolar outpatients and 61 healthy controls. They
were enrolled from the Barcelona Bipolar Disorders Program
at the Hospital Clinic in Barcelona (Spain) and from
outpatient research programs of the Argentine Network for
Bipolar Disorders. Inclusion criteria were (a) age N18 years,
(b) fulfill DSM-IV criteria for bipolar I or bipolar II disorder,
and (c) meeting criteria of remission defined as a score ≤12
on the 17-HAM-D (Bobes et al., 2003; Hamilton, 1960), and a
score ≤9 on the YMRS (Colom et al., 2002; Young et al., 1978)
for at least three months previous to the assessment. All
enrolled patients received pharmacological treatment by
their psychiatrist according to the Program's protocols of
each center in a naturalistic manner.
A group of healthy controls with no psychiatric or
neurological history were screened from a pool of healthy
volunteers in Barcelona. It was also ensured that none in the
control group had a first-degree relative with bipolar
disorder. The control group included a representative sample
of students, employees, and houseworkers.
The study was approved by the Hospital Clinic of
Barcelona Ethics Committee and the institutional review
boards of the Argentinean study sites. All subjects gave
written informed consent to participate in this study.
2.2. Measures
2.2.1. Clinical and sociodemographic assessment
Diagnosis of bipolar I or II disorder was established by
means of the SCID for DSM-IV criteria (First et al., 1997). The
17-HAM-D and the YMRS were used to assess depressive and
manicsymptoms,respectively.Sociodemographicandclinical
information (age, gender, occupational status, age at onset,
age at first hospitalization, number of affective episodes,
number of hospitalizations, number of suicide attempts,
rapid cycling and chronicity) were collected through the
combination of an interview with the patient, the SCID and
complemented by clinical records.
2.2.2. Outcome measures
All participants were assessed with the FAST (Rosa et al.,
2007). The FAST is a valid and reliable instrument, easy to
apply and which requires a short period of time to administer
(3–6 min). The FAST evaluates functioning taking into
account the last 15 days. It was developed for the clinical
evaluation of the main difficulties presented by psychiatric
patients, and has been validated in several languages for
patients with bipolar disorder. The FAST scale consists of 24
items which allow the assessment of six specific areas of
functioning:
1) Autonomy refers to the patient's capacity to do things
alone and make his/her own decisions.
2) Occupational functioning refers to the capacity to main-
tain an employment, efficiency of performing tasks at
work, working in the field in which the patient was
educated and earning according to the level of the
employment position.
3) Cognitive functioning is related to the ability to concen-
trate, perform simple mental calculations, solving pro-
blems, learning and new information recall ability.
4) Financial issues involve the capacity of managing the
finances and spending in a balanced way.
5) Interpersonal relationships refer to relations with friends,
family, involvement in social activities; sexual relation-
ships and the ability to defend one's own interests.
6) Leisure time refers to the capability of performing physical
activities (sport, exercise) and maintaining hobbies.
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This scale provides a total score of functioning and also 6
specific subscores (one for each domain). Items are rated
using a 4-point scale, where (0)=no difficulty, (1)=mild
difficulty, (2)=moderate difficulty, and (3)=severe diffi-
culty. The overall FAST score ranges from 0 to 72, where
higher scores indicate greater disability, with a threshold
scoreabove11indicatingthepresenceofsignificantdisability.
2.3. Statistical analyses
All the data were analyzed with the Statistical Package for
Social Sciences (SPSS) software, version 16.0. The three
groups (bipolar I, bipolar II and healthy controls) were
compared on clinical and sociodemographic variables using
analysis of variance (ANOVA) and χ2tests. Group differences
between bipolar I, bipolar II and healthy controls in FAST
scores were tested with one-way ANOVA, followed by Tukey
post hoc comparison procedure when significant main effects
were present. The potential impact of sociodemographic and
clinical variables (that were found to be different in the
previous analyses) were controlled for in the analysis of
variancerunningan ANCOVAfor eachdomainof theFASTand
using group pertinence (bipolar I or bipolar II) as main factor.
3. Results
Thesamplecomprised106patientswithbipolarIdisorder,
66 patients with bipolar II disorder and 61 healthy controls.
The three groups did not differ with respect to gender
(Table 1). With regard to age, bipolar I patients were younger
than the other groups, but no significant difference was found
between bipolar II patients and healthy control group. The
patients groups (bipolar I and bipolar II) differed on age at
onset (p=0.001), which was higher in bipolar II disorder.
Patients with bipolar II disorder had higher HAM-D scores
(p=0.001), higher number of previous depressive episodes
(p=0.040) and lower number of previous hospitalizations
(p=0.001) than patients with bipolar I disorder.
Table 2 shows the total scores and subscores of the FAST
across the three groups. Both groups of patients with bipolar I
and bipolar II disorder showed lower overall functioning
compared with the healthy control group (pb0.001). Bipolar
patients also showed significantly lower functioning com-
pared with healthy control group across all domains of the
FAST (pb0.001), regardless disorder subtype. Large effect
sizes (Cohen's d values) were detected on all domains of FAST
comparing bipolar II patients with the healthy control group,
except for financial issues and leisure time (see Table 2). No
statistically significant differences between bipolar I and II
patients were found in autonomy, occupational functioning,
interpersonal relationships, financial issues, leisure time, and
overall functioning. Tukey post hoc analysis indicated that
subjects with bipolar II disorder experienced the highest
impairment on the cognitive domain, followed by the
patients with bipolar I disorder, and finally the healthy
control group (p=0.011). In this regard medium effect sizes
were observed (Cohen's d=0.34). Nevertheless, the ANCOVA
for the cognitive domain revealed no significant differences
between bipolar I and bipolar II groups after controlling for
three potential confounders such as age, HAM-D scores, and
number of depressive episodes. After controlling for those
factors, only age (F=8.30, df=1, p=0.005) and HAM-D
scores (F=12.56, df=1, p=0.001) remained statistically
significant.
4. Discussion
Bipolar II disorder is not just a “soft” form of manic-
depressive illness, but actually a highly recurrent and
burdensome condition, as reported elsewhere (Vieta et al.,
1997; Vieta and Suppes, 2008). Although several studies have
reported poor functioning in bipolar I disorder, few investiga-
tions have looked at functional impairment, specifically, in
the bipolar II subtype. The present study was carried out to
assess functional impairment in bipolar II patients involving
two control groups: one comprising patients with bipolar I
disorder and the other with healthy participants. In order to
avoid the interfering effects of acute mood symptoms on
functioning, only remitted patients were included in this
study. Our results reveal two main findings: 1) poor
functioning in bipolar disorder is not limited to the traditional
bipolar I subtype. When compared with healthy controls,
Table 1
Demographic and clinical characteristics of the study sample.
Bipolar I
(n=106)
Bipolar II
(n=66)
Controls
(n=61)
ANOVA
Fp
Age, years:mean (SD)
Age at onset, years:mean (SD)
Age at first hospitalization, years:mean (SD)
Chronicity, mean (SD)
HAM-D score, mean (SD)
YMRS score, mean (SD)
Number of depressive episodes, mean (SD)
Number of hypo(manic) episodes, mean (SD)
Number of hospitalizations, mean (SD)
Number of suicide attempts, mean (SD)
Gender, n (%)
Male
Poor work adaptation
Rapid cycling
42.73 (11.71)
23.88 (7.32)
28.50 (10.42)
18.77 (12.07)
1.90 (2.7)
1.54 (2.04)
5.23 (6.71)
5.51 (5.23)
2.64 (2.55)
0.53 (1.18)
47.74 (13.52)
30.19 (12.07)
33.89 (16.38)
17.94 (11.72)
3.68 (3.33)
1.89 (2.55)
8.30 (12.21)
7.95 (12.92)
0.79 (1.33)
0.43 (0.88)
49.16 (17.66) 4.6
17.41
3.09
0.191
14.57
0.973
4.28
2.85
24.33
0.21
0.008
0.001
0.082
0.663
0.001
0.325
0.040
0.093
0.001
0.649
52 (49.1)
39 (39.8)
9 (8.8)
26 (39.4)
26 (41.3)
9 (14.8)
26 (42.6)1.67
0.035
1.37
0.433
0.491
0.181
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bipolar II patients also experience greater functional impair-
ment in all domains. 2) Compared to bipolar I subtype,
patients with bipolar II disorder show a similar pattern of
functional impairment, except for the cognitive domain of the
FAST in which bipolar II patients scored even worse than
bipolar I patients. However, after controlling for age,
subsyndromal depressive symptoms and number of depres-
sive episodes, this statistical difference between patients
groups disappeared.
In the present study, both bipolar I and bipolar II patients
showed greater functional impairment than the healthy
control group. More specifically, large effect size differences
were observed between both bipolar groups and the healthy
control group, on distinct areas of functioning (occupational
functioning, cognitive functioning, interpersonal relation-
shipsandautonomy).Ourfindingsareconsistentwithseveral
previous studies where bipolar illness adversely affects
psychosocial functioning (Zarate et al., 2000; Strakowski
et al., 2000; Keck, 2006; Goldberg and Harrow, 2005;
Tabares-Seisdedos et al., 2008). In a study of first-episode
patients, Tohen et al. (2000) reported that almost all bipolar
patients achieved syndromal recovery at 24 months after
admission compared to only 37.6% achieving functional
recovery (defined as the proportion of patients who regained
occupational and living situations equivalent to those they
held prior to their first manic episode) (Tohen et al., 2000). In
another research, Judd et al. (2008) found higher work role
impairment(intermsofnumberofmonthsunabletowork)in
patientswithbipolarI disorder,followedbybipolarIIpatients
and finally patients with unipolar major depressive disorders.
Together with previous studies, our results support the
evidence that there is a gap between symptomatic recovery
and full functional recovery in both bipolar subtypes. Future
studies should include additional functioning assessment to
compliment symptomatic measures in the evaluation of
bipolar disorder. The assessment of psychosocial functioning
should, ideally, involve not only overall functioning but also
multiple domains of functioning.
Interestingly, we found that patients with bipolar II
disorder experienced the same functional impairment as
those with bipolar I disorder, except for the cognitive domain
of FAST. Specific sociodemographic and clinical differences
between the patients groups could partially explain this
finding. For instance, participants with bipolar II disorder had
higher HAM-D scores than patients with bipolar I disorder.
After adjusted analysis, HAM-D scores were strongly associ-
ated with poor cognitive functioning assessed by FAST. These
results point out the important role of residual depressive
symptoms on functioning, especially, on cognitive impair-
ment as assessed clinically. Overall, depressive symptomatol-
ogy at syndromal or subsyndromal levels appears to be
strongly associated with poor psychosocial functioning in
bipolar disorder (Simon et al., 2008, 2007; Kauer-Sant'anna
et al., 2009; Tabares-Seisdedos et al., 2008). In previous
studies, we found that residual depressive symptoms, albeit
minimal, were the best predictor of cognitive impairment and
occupational impairment in bipolar patients (Rosa et al.,
2009b; Bonnin et al., 2010). Similarly, a 20-year follow-up
study showed that each increase in depressive symptom
severity was associated with a strongly significant increase in
psychosocial disability, in bipolar I and II patients (Judd et al.,
2005). It has been reported that bipolar II patients experience
more severe, longer depressive episodes, and more persistent
residual depressive symptoms than subjects with bipolar I
disorder (Ayuso-Gutierrez and Ramos-Brieva, 1982; Cassano
and Savino, 1997; Benazzi, 2001) Considering that bipolar II
patients spend far more time with subsyndronal depressive
symptoms, there is a need of introducing therapeutic
interventions focused in residual depressive symptoms in
order to improve the psychosocial functioning, especially,
cognitive functioning. Furthermore, there is some evidence
suggesting that major depressive episodes, more common in
bipolar II patients, lead to greater functional impairment than
hypomanic or manic episodes (MacQueen et al., 2000).
Additionally, it has been demonstrated that depressive
episodes, especially, mixed depressive episodes increase the
risk of suicide attempts in bipolar patients, and particularly in
subjects with bipolar II disorder (Rihmer, 2005). The higher
risk of suicide attempts in subjects with bipolar II disorder
could explain, in part, why bipolar II patients tend to have
poor functioning, especially regarding cognitive and occupa-
tional domains (Rosa et al., 2008b).
Another potential factor that may explain poor cognitive
functioning assessed by the FAST in the bipolar II group is age.
In this context, previous studies have already identified older
age as a potential predictor of functional impairment
(Cacilhas et al., 2009; Rosa et al., 2009b). Depp et al. (2006)
also showed lower quality of well-being measures and lower
functioning parameters in middle-older bipolar patients.
Older patients often experienced more comorbid physical
illness and polypharmacy therapy which may be associated
with greater chronicity and dysfunction. In addition, emerg-
ing evidences suggest that ageing is associated with marked
neurocognitive deficits, which may also contribute to explain,
in part, functional impairment (Depp et al., 2007; Gildengers
et al., 2008).
Table 2
Functional impairment between bipolar I, bipolar II and control groups.
Bipolar I (A)
(n=106)
mean (SD)
Bipolar II (B)
(n=66)
mean (SD)
Controls (C)
(n=61)
mean (SD)
ANOVA
p
Tukey post
hoc tests
Cohen's d
AvBBvC A vC
FAST total
FAST autonomy
FAST occupational
FAST cognitive
FAST interpersonal rel.
FAST financial issues
FAST leisure time
17.67 (14.87)
2.23 (2.71)
5.50 (5.86)
3.26 (3.38)
4.08 (3.99)
1.00 (1.77)
1.77 (1.74)
20.43 (13.94)
2.37 (3.11)
5.84 (6.15)
4.53 (4.08)
4.59 (3.55)
0.84 (1.51)
2.26 (2.06)
5.93 (4.43)
0.38 (0.98)
1.16 (2.09)
1.00 (1.06)
1.82 (2.56)
0.18 (0.53)
1.39 (1.29)
23.69
12.99
16.38
19.73
11.22
6.25
4.03
0.0001
0.0001
0.0001
0.0001
0.0001
0.002
0.019
A=BNC
A=BNC
A=BNC
BNA,C; ANC
A=BNC
A=BNC
A=BNC
0.19
0.048
0.057
0.34
0.14
0.097
0.26
1.40
0.86
1.02
1.18
0.89
0.58
0.50
1.07
0.91
0.98
0.90
0.67
0.63
0.25
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5. Limitations
Several caveats bear consideration in interpreting our
results. First, although the FAST is an interviewer-adminis-
tered instrument and provides a clinical evaluation of the
functional impairment, we cannot rule out that the reported
subjective complaints of our patients, worsened by residual
depressive symptoms, may have contributed to a lower
psychosocial functioning. Second, albeit this is beyond the
scope of this article, a neuropsychological assessment would
have strengthened our results with the FAST scale, especially
in the cognitive domain, and could have validated the FAST as
an instrument for screening neurocognitive impairment in
bipolar disorder. However, the FAST cognitive domain does
not aim to replace neuropsychological assessment, but
actually could be used as a proxy to assess cognitive
functioning by a clinician. Third, all patients were recruited
from tertiary centres where the polypharmacy therapy is a
rule rather than the exception. We have not analysed the
effect of this polypharmacy on functioning, therefore we
could not determine its effect upon the results. Finally, this is
a cross-sectional study which does not allow us to determine
the direction of the relationship between bipolar subtypes
and functional impairment. Longitudinal studies are needed
to understand the cause-and-effect relationship between
specific domains of functioning and both bipolar I and II
disorders as well as other commonly used measures of
psychosocial functioning should be considered.
6. Conclusions
Our preliminary findings suggest that bipolar II patients are
at least so functionally disabled as bipolar I patients. This was
evident in all areas of functioning, except for cognitive domain,
where bipolar II patients performed unexpectedly worse.
However, specific demographic (age) and clinical (HAM-D
scores) differences between patients groups may explain the
poorer cognitive functioning observed in the bipolar II group,
pointing at the importance of treating depressive residual
(subthreshold) symptoms more aggressively. Prophylactic
treatments in bipolar II patients should be complemented
with psychosocial interventions in order to improve functional
outcomes. Finally, specific functioning measures in comple-
ment to symptomatic assessments should be included in the
comprehensive evaluation of bipolar disorder.
Role of funding source
Dr. Rosa would like to thank the support of the Spanish Ministry of
Science and Innovation, through a “Juan de la Cierva” postdoctoral contract
(JCI-2009-04329). The authors of this study would like to thank the support
of the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III
(PI080180 and PI08/90094), CIBERSAM and the support of the Generalitat de
Catalunya to the Bipolar Disorders Group (2009 SGR 1022). Another co-
author (Caterina M. Bonnín) is also funded by the Spanish Ministry of Science
and Innovation through a predoctoral grant “Formación Profesorado
Universitario” (FPU) (AP2008-01923).
Conflict of interest
Professor Eduard Vieta has served as consultant, advisor or speaker for
the following companies: Almirall, AstraZeneca, Bial, Bristol-Myers Squibb,
Eli Lilly, Forest Research Institute, Glaxo-Smith-Kline, Janssen-Cilag, Jazz,
Lundbeck, Merck-Sharp and Dohme, Novartis, Organon, Otsuka, Pfizer Inc,
Sanofi-Aventis, Servier, Shering-Plough, UBC, and Wyeth.
Dr. Gustavo H Vázquez is a consultant with AstraZeneca and Roche and
has received honoraria as speaker from AstraZeneca, Glaxo-Smith-Kline
(GSK), Pfizer and Eli Lilly Corporations.
Professor Ana González-Pinto has served as consultant, advisor or
speaker for the following companies: Almirall, AstraZeneca, Bristol-Myers
Squibb, Eli Lilly, Glaxo-Smith-Kline, Janssen-Cilag, Lundbeck, Novartis,
Otsuka, Pfizer Inc, Sanofi-Aventis, Shering-Plough, Boehringer-Ingelheim
and Wyeth. The other authors have no conflicts of interest.
Dr. Rafael Tabarés-Seisdedos has acted as consultant, advisor, or speaker
for the following companies: AstraZeneca, Eli Lilly and Company, Janssen
Pharmaceutica, Pfizer Inc.
Dr. Balanzá-Martínez has served as consultant, advisor or speaker for
AstraZeneca, Bristol-Myers Squibb, and Janssen-Cilag.
Dr. María Reinares has served as speaker for the following companies:
Astra Zeneca and Pfizer Inc.
The other authors have no conflicts of interest.
Acknowledgments
The authors of this report would like to thank the support
of the SpanishMinistry of Science and Innovation, Instituto de
Salud Carlos III, CIBERSAM, the Spanish Ministry of Education
and the Generalitat de Catalunya.
Dr. Vázquez would like to acknowledge the following
investigators in the Argentine Network for Bipolar Disorders:
Strejilevich S, M.D. and Cetkovich-Bakmas M, M.D. of Depart-
ment of Psychiatry INECO and Institute of Neurosciences
Favaloro Foundation, Buenos Aires; Aguayo S, M.D. Psychiatric
Department, Formosa Hospital, Formosa; Kahn C, M.D. and
Schiavo C, M.D. of Department of Mental Health, Teodoro
Alvarez Hospital, Buenos Aires; Zaratiegui R, M.D. and Lorenzo
L, M.D. of Psinapsys Psychiatric Private Center, La Plata;
Goldchluk A, M.D. and Herbst L, M.D. of Outpatient Service,
José T. Borda Hospital, Buenos Aires, Abraham E, M.D. of
Mendiondo Neurological Institute, Mar del Plata, García Bone-
tto G, M.D. of Center for Clinical Investigation, San Nicolás
Private Hospital, Córdoba; Padilla E, M.D. of Nestor Sequeiros
Psychiatric Hospital, San Salvador de Jujuy; Calvó M., M.D. and
Guerrero G, M.D. of Institute of Psychophatology, San Salvador
de Jujuy; Vilapriño J, M.D. and Vilapriño M, M.D. of Professor
Vilapriño Psychiatric Institute, Mendoza, Argentina.
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