The prevalence of psychopathology in offspring of
bipolar women from a Brazilian tertiary center
Prevalência de psicopatologia em filhos de mulheres
bipolares de um centro terciário brasileiro
Rua Dr. Nascimento, 709 - casa 10
96200-300 Rio Grande, RS, Brazil
Tel.: (+55 11) 3069-6648 – GRUDA/ (53) 3231-1788 - Sandra
Fax: (+55 11) 3069-6648
Sandra Petresco,1 Elisa Kijner Gutt,2 Renata Krelling,2 Francisco Lotufo Neto,2
Luis Augusto Paim Rohde,3 Ricardo Alberto Moreno1
1 Mood Disorders Unit, Department and Institute of Psychiatry, Clinical Hospital, Medical School, Universidade de São Paulo (USP), São Paulo (SP),
2 Department and Institute of Psychiatry, Clinical Hospital, Medical School, School of Medicine, Universidade de São Paulo (USP), São Paulo (SP),
3 Juvenile Bipolar Disorder Outpatient Program, Division of Child and Adolescent Psychiatry, Clinical Hospital of Porto Alegre (HCPA), Universidade
Federal do Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil
Objective: No previous study has assessed the occurrence of psychopathology in offspring of bipolar women from South America. The
objective of this study was to assess the prevalence of psychopathology in offspring of bipolar mothers from Brazil compared with two
control groups. Method: Children and adolescents aged 6 to 18 years of bipolar disorders mothers (n = 43), mothers with other mild to
moderate mental disorders (n = 53) and mothers without any psychiatric disorder (n = 53) were evaluated using the Kiddie Schedule
for Affective Disorders and Schizophrenia present and lifetime version, the Child Behavior Checklist and the Youth Self-Report. Raters
were blind to the mothers’ diagnoses, who were interviewed by means of the Structured Clinical Interview. Results: Bipolar offspring
had twice the chance of having one or more lifetime Axis I diagnoses [prevalence ratio = 2.11 (95% CI: 1.30-3.42) and p = 0.003]
and 2.8 higher risk of having a lifetime anxiety disorder [prevalence ratio = 2.83 (95% CI: 1.39-5.78) e p = 0.004] than the offspring
of mothers with no mental disorder. In addition, significantly higher scores on Child Behavior Checklist thought problems and Youth
Self-Report social problems, as well as anxiety/depression and internalizing problems were observed. Conclusion: Our results confirm
previous findings suggesting higher psychiatric problems in offspring of bipolar mothers and extend them to the Brazilian society
Descriptors: Bipolar disorder; Psychopathology; Risk factors; Children; Adolescent
Objetivo: Considerando-se a inexistência de estudos avaliando a ocorrência de psicopatologia em filhos de mães bipolares na América
do Sul, este se propõe a avaliar a prevalência de psicopatologia em filhos de mulheres bipolares comparado com dois grupos-controle.
Método: Crianças e adolescentes de 6 a 18 anos de idade, filhos de mães com transtorno bipolar (n = 43), filhos de mães com outros
transtornos psiquiátricos leve a moderados (n = 53) e filhos de mães sem nenhum diagnóstico psiquiátrico (n = 53) foram avaliados
usando o Kiddie Schedule for Affective Disorders and Schizophrenia present and lifetime version, o Child Behavior Checklist e o Youth
Self-Report por entrevistadores cegos ao diagnóstico das mães, as quais foram entrevistadas por meio do Structured Clinical Interview.
Resultados: Os filhos de mães bipolares tiveram duas vezes mais chance de ter um ou mais diagnósticos de Eixo I [Razão de Prevalência
= 2,11 (95% IC: 1,30-3,42) e p = 0,003] e 2,8 vezes maior risco de ter transtornos de ansiedade [Razão de prevalência = 2,83
(95% IC: 1,39-5,78) e p = 0,004] ao longo da vida do que os filhos de mulheres sem transtorno mental, além de maiores escores na
subescala de problemas de pensamento do Child Behavior Checklist e nas subescalas de problemas sociais, ansiedade/depressão e
problemas de internalização do Youth Self-Report. Conclusão: Nossos resultados confirmam os achados prévios da literatura internacional
que sugerem mais problemas psiquiátricos em filhos de mães bipolares e os estendem para a cultura brasileira
Descritores: Transtorno bipolar; Psicolopatologia; Fatores de risco; Crianças; Adolescentes
Submitted: January 10, 2009
Accepted: July 7, 2009
Rev Bras Psiquiatr. 2009;31(3):240-6
Petresco S et al.
Rev Bras Psiquiatr. 2009;31(3):240-6
There is growing recognition and interest in pediatric bipolar
disorder (PBD) since it is associated with severe life quality deficits,
causing great impairment in school performance, difficulty in
relationships with peers and relatives, and engagement in high-risk
behaviors.1,2 In addition, the disorder is associated with a high risk of
relapse and a low recovery index.3 Perlis et al. (2004) documented
in a clinical sample that subjects with onset of mood symptoms of
bipolar disorder (BD) at childhood will have a more severe course
associated with greater comorbidity.4
The study of bipolar probands is a remarkable opportunity to
understand early prodromal manifestations of BD, and might be
also useful in improving early diagnosis and fostering potential
preventive measures. A meta-analysis of 17 studies of bipolar
offspring found such individuals to be at a 2.7 times higher risk of
developing a mental disorder and 4.0 times more likely to develop
a mood disorder than are children of parents with no mental
disorders.5 Since 1997, cross-sectional studies have reported that
approximately 50% of bipolar offspring meet criteria for at least one
DSM-IV psychiatric disorder.6
Regarding specific psychiatric diagnoses besides mood disorders,
attention-deficit hyperactivity disorder (ADHD) or significant behavioral
or attentional problems have been reported in approximately 27% of
bipolar offspring studied.7 In children with strong family history of BD,
the diagnosis of ADHD can be the first sign of a BD.8 More recently,
Henin et al.9 documented a higher prevalence of anxiety disorders
in bipolar offspring (36%) compared to rates detected in children of
psychiatrically healthy parents (14%). These findings are concordant
with those suggesting that an anxiety disorder might be an alternative
pathway for the further development of BD.7 Hirshfeld-Becker et
al.10 studied a sample of children with a mean age of 6.8 years and
described significantly higher rates of disruptive behavior and anxiety
disorders in bipolar offspring than in offspring of both parents with
panic or major depression and parents with neither mood nor anxiety
disorders. Wals et al. found that daughters of bipolar parents obtained
significantly higher scores on the following CBCL scales: Total Problems,
Internalizing, Externalizing, Somatic Complaints, Anxious/Depressed,
Social problems, Delinquent Behavior and Aggressive Behavior; and
sons of bipolar parents obtained significantly higher scores on the Total
Problems, Externalizing, Thought Problems and Aggressive Behavior
scales than the normative sample.11
There has been extensive research on adult BD in Europe, the
USA and many other countries, although little research has been
accomplished on child and adolescent BD outside North America
and Europe. The international epidemiology and phenomenology
of pediatric BD is not well known.12,13 Nevertheless, current data
suggest that pediatric BD is either fairly rare or under diagnosed
outside the USA in epidemiological samples.14
The objective of this study was to assess the prevalence of
psychopathology in a high-risk child sample from Brazil. Our main
hypothesis was that bipolar offspring would present a higher rate of
categorical psychiatric diagnoses and dimensional psychiatric problems
than would both children of mothers without psychiatric disorders and
those with only mild disorders. To the best of our knowledge, this is the
first study to evaluate the prevalence of psychopathology in offspring of
a sample of South American women with BD.
This was a cross-sectional with a controlled group study assessing
bipolar mothers’ offspring aged between 6 and 18 years old. Mothers
were recruited between December 2004 and March 2006 from
the Mood Disorders Outpatient Unit at the Institute of Psychiatry,
Clinical Hospital, Medical School, Universidade de São Paulo,
Brazil. Of 211 patients undergoing treatment in the Mood Disorders
Outpatient Unit, 139 were females. We were able to contact 135
of these patients, 50 of whom had children aged between 6 and
18 years. We invited all eligible bipolar mothers who were under
treatment. All mothers had to live in São Paulo, had to have a
biological offspring between 6 and 18 years old and had to have a
reconfirmed DSM-IV15 diagnosis of BD I, II or NOS, according to the
DSM-IV Structured Clinical Interview (SCID).16 Only one randomly
selected proband from each family was assessed.
The control group comprised 106 offspring of women from the
General Gynecology Outpatient Service of the same University
Hospital, concomitantly recruited by consecutive sampling. For
psychiatric diagnosis, control group mothers were assessed using the
SCID.16 They had to live in São Paulo and had to have a biological
offspring between 6 and 18 years old. The presence of BD, severe
depressive episode, recurrent depressive disorder or any psychotic
disorder were the exclusion criteria for this control group. All mothers
signed a written informed consent and children and adolescents gave
their verbal assent to participate in study. The study was approved
by the hospital research ethics committee (number: 660/04).
2. Diagnostic procedures
Five extensively trained research psychiatrists and a PhD
psychologist made the diagnoses using the SCID16 for DSM-IV15
in both groups of mothers. The current version of the SCID was
translated into Portuguese17 and a previous version translated and
adapted into Portuguese had presented good reliability indices.18
Psychiatric disorders in children were assessed using the
Brazilian version19 of the K-SADS-PL,20 which is a semi-structured
interview allowing past and current diagnosis according to the
DSM-IV15 criteria in children and adolescents aged 6 to 18 years.
The Brazilian version has shown excellent psychometric properties
and similar content, along with inter-observer and test-retest
reliability (Kappa-agreement = 0.87-1.00).19 The interviews were
performed individually with the parent or guardian and with the
child or adolescent, and both answers were taken into account
for the decision about the diagnosis. In case of discrepancy, the
parent’s opinion had a major weight for externalizing disorders as
well as the child and adolescent’s impression for the internalizing
disorders. Different interviewers applied the SCID and the K-SADS-
PL in each family.
The CBCL21 was used to collect the dimensionality of symptoms
with parents and the YSR21 with adolescents (≥ 11 years old). The
CBCL21 is a questionnaire to be answered by parents or guardians
of children and adolescents aged 6 to 18 years. The instrument has
138 items: 20 items related to social skills and 118 items related to
behavioral problems. The behavioral problems are grouped into eight
scales: anxiety/depression, withdrawal, somatic complaints, social,
thought, and attention problems, and delinquent and aggressive
behavior. The first three scales comprise the internalizing dimension,
while the last two scales comprise the externalizing dimension. The
sum of scores on all eight scales constitutes the “total problems”.
The Brazilian version of the CBCL was previously validated showing
adequate psychometric properties.22 The YSR has similar format
and content to the CBCL, but was designed to be filled out as a
self report by adolescents aged 11 years or older.23 This instrument
was previously translated into Portuguese and culturally adapted
Psychopathology in bipolar offspring 242
Rev Bras Psiquiatr. 2009;31(3):240-6
In order to identify possible mania symptoms, the Young Mania
Rating Scale (YMRS) was used.25 The YMRS has proven useful
in evaluating mania symptoms in children.26 This instrument was
translated and adapted to Portuguese by Vilela et al. and also
showed adequate psychometric properties.27 Family socioeconomic
parameters were assessed using the Brazilian Criteria of Economic
Classification (Associação Brasileira de Empresas de Pesquisa -
ABEP).28 The lower the total score, the lower the purchasing power of
the family. The Global Assessment of Functioning (GAF)15 was used for
evaluating the mothers’ psychological functioning and the Child Global
Assessment Scale (CGAS)29 was used for children functioning.
Finally, trained research psychologists administered the four
subtests (Vocabulary, Block Design, Similarities, and Matrix
Reasoning) of the Wechsler Abbreviated Scale of Intelligence (WASI)
to estimate the IQs of the offspring.30
All interviewers were blind to the parents’ diagnostic status and
were under a child and adolescent psychiatrist’s supervision.
3. Statistical analysis
Since lifetime prevalence of other psychiatric disorders was very
common in mothers of the control group (50%), we decided not to
exclude this group during the analyses, thereby avoiding decreased
external validity and choosing a more realistic control group. Thus,
we split the control group into two subgroups: 1) mothers without
any psychiatric lifetime occurrence; 2) mothers with other psychiatric
At first, descriptive analyses were conducted, using means for continuous
variables and proportions for categorical variables. Comparisons
between the three groups were conducted through analysis of variance
(ANOVA) for continuous outcomes (differences among groups were
located by post-hoc analyses using Bonferroni) and the categorical
outcomes were assessed through Pearson’s Chi-square test, Pearson’s
Chi-square test with Yates correction and Fisher test, respecting
applicability conditions of each test.
Comparisons among the three groups regarding demographic
variables, and IQ scores were performed with one-way ANOVA.
Multivariate Poisson Regression31 was used to assess dichotomous
outcomes adjusted for potential confounders while the ANCOVA
assessed continuous outcomes. Potential confounders to be included
in models were defined based on a literature review (in this study
these confounders were gender, marital status, and mothers’ GAF) or
on a statistical definition (association with both the study factor and
outcome for p ≤ 0.20), where in the present case these confounders
were age, race, schooling, socioeconomic status, and intelligence
quotient of the offspring. A significance level of 0.05 was adopted
for all other analyses, where all tests were two-tailed.
As proposed by Achenbach23 and previously implemented by our
group in other investigations,32 we used the raw scores of both the
CBCL and the YSR.
The patient samples included three groups: a BD group with
43 patients from 50 eligible mothers (four patients, who had
the same demographic and psychiatric characteristics as the role
group, refused to participate and three were excluded – two had
adopted children and one did not meet DSM-IV criteria for BD
after reassessment). One hundred and six women without severe
psychiatric disorders were enrolled and subdivided into two control
groups: a) a control group without psychiatric disorder (w/o PD)
(n = 53, 50%) and b) a control group with other psychiatric
disorders (PD) (n = 53, 50%), including those who had one or
more mild or moderate psychiatric lifetime diagnoses according
to DSM-IV. The mean age of mothers w/o PD was 39.79 (SD =
5.59), with PD was 39.98 (SD = 4.44) and of bipolar mothers
was 38.26 (SD = 7.66). The mean Global Assessment Function
of mothers w/o PD was 91.48 (SD = 7.92), with PD was 78.45
(SD = 14.76) and of bipolar mothers was 61.74 (SD = 13.93)
with a one-way ANOVA Test p value less than 0.001. Demographic
characteristics and comorbidities of mothers from the three groups
are described in Table 1. The variable “others” presented in Table 1
Petresco S et al.
Rev Bras Psiquiatr. 2009;31(3):240-6
included separated, divorced, widows and singles.
The majority of the offspring of mothers with BD (69.8%)
did not live with their biological father, in contrast with offspring
from mothers with other PD (25.5%) and w/o PD (28.8%)
(p < 0.001).
The offspring gender distribution was 29 (54.7%) females on the
offspring of mothers w/o PD, 23 (43.4%) females on the offspring of
mothers with PD and 25 (58.1%) females on the bipolar offspring
group. The percentage of Caucasian offspring was 27 (50.9%) of
mothers w/o PD, 25 (47.2%) of mothers with PD and 30 (69.8%)
of bipolar mothers. Other offspring demographic characteristics are
described in Table 2. There was no significant difference among
groups in gender, age or ethnicity, although mothers and offspring
from both control groups (with and w/o PD) belonged to families
with significantly lower socioeconomic levels than did children from
the BD mothers group (p = 0.010).
The offspring’s DSM–IV prevalence of Lifetime Psychiatric
Diagnoses is shown in Table 3.
Bipolar offspring had higher prevalence ratios (Poisson Regression)
compared to those of mothers with and without PD in dichotomous
outcomes, adjusted for potential confounders (gender, marital
status, mothers’ GAF, age, race, schooling, socioeconomic status,
and intelligence quotient), in lifetime anxiety disorders and lifetime
Axis I disorders. These results are shown in Table 4.
Additionally, when compared with the whole control group,
the bipolar offspring group also had a higher prevalence ratio of
disruptive disorders (including ADHD) [prevalence ratio = 3.02
(95% CI: 1.02-8.91) and p = 0.045] and of lifetime Axis I disorders
[prevalence ratio = 1.67 (95% CI: 1.12-2.49) and p = 0.011].
Findings suggesting higher prevalence of anxiety disorders in
bipolar offspring remained significant even after adjustment for the
presence of comorbid anxiety disorder in bipolar mothers.
Considering CBCL outcomes adjusted for the same potential
confounders listed above using ANCOVA, we observed a significant
difference (p = 0.038) among groups in the CBCL thought problems
scale. Mean scores of all scales of CBCL are presented in Figure 1.
Regarding the YSR, we found a significant difference in Total
Problems, as well as a significant difference among the three
groups in social (p = 0.002), anxious/depressed (p = 0.026)
and internalizing problems (p = 0.046). Using Bonferroni test to
localize the differences among groups, the majority of the differences
were between the bipolar offspring and offspring of mothers without
PD group, except for social problems that show also a difference
between both offspring control groups (p = 0.005), with the highest
means in bipolar offspring group. Mean scores in all scales of YSR
are presented in Figure 2.
We did not find any relevant differences between groups in scores
of YMRS or in the CGAS.
Our findings suggest that bipolar offspring present a significantly
higher prevalence of lifetime Axis I disorders and more specifically a
higher prevalence of anxiety disorders than do offspring of mothers
without any PD. Similarly, significant differences in prevalence of
Psychopathology in bipolar offspring 244
Rev Bras Psiquiatr. 2009;31(3):240-6
lifetime Axis I disorders and in disruptive lifetime disorders were
found comparing bipolar offspring with the entire control group.
These findings corroborate those of Henin et al.9 that found a
huge prevalence of a myriad of mental disorders including disruptive
behavior disorders, separation anxiety disorder, generalized anxiety
disorder, social phobia, and depression in bipolar offspring in early
or middle childhood. In addition, Hirshfeld-Becker et al.10 reported
that offspring of bipolar parents had significantly higher rates of
disruptive behavior and anxiety disorders than did both offspring
of parents with panic or major depression disorders and offspring
of parents with neither mood or anxiety disorders. Singh et al.33
also found higher rates of psychopathology in bipolar offspring as
compared to controls’ offspring (respectively, 78% had at least one
DSM-IV Axis I diagnosis compared to only 24% in controls).
Whilst most studies have shown a prevalence of psychopathology
in bipolar offspring of around 50%,5 our study showed that
62.8% of bipolar offspring met criteria for at least one DSM-IV
lifetime diagnosis, compared to 58.5% of offspring from mothers
with mild psychiatric diagnoses and 41.5% of the offspring from
mothers without any psychiatric diagnosis. Of note, 9.3% of bipolar
offspring and 10.4% of children of mothers from both control groups
combined had a specific phobia as their sole diagnosis. Several
previous studies did not classify individuals as psychiatrically ill
based on the presence of simple phobia as the only diagnosis.
Remarkably, we found a high prevalence of psychiatric disorders
in our control group; it may be a limitation of our study but also
can reflect a less selected sample. Including only healthy controls
could raise differences but would not reflect a real population.
Besides, it is known that in developing countries the prevalence of
mental health problems is higher than in developed countries. Giel
et al.34 found that between 12% and 29% of children aged 5 to
15 years had mental health problems in four low-income countries
(Sudan, Philippines, Colombia and India). Paula et al.35 verified a
prevalence of mental health problems of 24.6% in a community
sample of children and adolescents aged 6 to 17 years in a city of
Anxiety disorders were the most prevalent diagnoses in our
study, and some authors have found similarly high rates of anxiety
disorders, particularly generalized anxiety disorder (GAD) and
separation anxiety disorder, in bipolar offspring.6,9 Recently, Bruckl
et al.36 have also documented that separation anxiety disorder
during adolescence is a risk factor for BD in adulthood in a
German community sample. Moreover, previous investigations have
suggested that adolescents with anxiety disorders have a higher risk
for BD than do those without anxiety disorders.37
We found a lifetime prevalence rate of mood disorders of 11.6%
among bipolar offspring, 11.3% in offspring of mothers with other
PD, and 5.7% in offspring of mothers without PD. In a meta-
analysis of 17 studies, Lapalme et al.5 reported a prevalence rate of
26.5% for mood disorders among bipolar offspring in comparison
with 8.3% in offspring of parents without PD with mild disorders.
The small prevalence of mood disorders found in our study might
be attributed to the lower overall age of our sample, given that the
onset of affective disorders frequently occurs during adolescence
or in early adulthood.5,11 The lifetime prevalence of ADHD among
bipolar offspring observed in our study was 11.6%, which lies
between the 5% found by Wals et al.11 and the rate of 27% found
by other studies in populations with similar characteristics.7 BD
offspring ADHD prevalence was high above the 4.7% found in the
sum of control groups in our study.
Regarding dimensional measures, we found significant differences
in thought problems on the CBCL, and anxious/depressed, social,
and internalizing problems on the YSR between bipolar offspring and
offspring of mothers without PD. Giles et al.38 verified that bipolar
offspring scored significantly higher than healthy controls on the
anxious/depressed, attention problems, aggression and withdrawal
subscales, and lower than bipolar youth on all scales of the CBCL
except for the somatic complaints and anxious/depressed subscales.
We found more internalizing symptoms in the YSR than in the
CBCL, which is in accordance with the literature. Children and
adolescents seem to be better informants of this kind of symptoms
than are their parents.
The number of separated bipolar mothers is almost two-fold
higher than that of mothers from the control groups in our sample,
and the mean GAF score of bipolar mothers was significantly lower
than the other mothers’. Since it is known that separated parents
might represent a risk factor for psychopathology in childhood
and adolescence,39 we used marital status and GAF as potential
Petresco S et al.
Rev Bras Psiquiatr. 2009;31(3):240-6
confounding factors in our analyses and the differences found
remained statistically significant.
Of note, the majority of the literature available on preadolescent
mania originates from North America. Thus, much could be learned
from cross-cultural studies on this group of children.40 This issue
is even more relevant considering the huge differences reported
in the prevalence of pediatric bipolar disorder between European
and American countries.13 Our study has the strength of applying
international validated measures of child psychopathology in a
sample from Brazil, a developing country. Other strength of our study
is the use of two dimensional diagnostic tools (CBCL and YSR) and
categorical diagnoses. In addition, we assessed psychopathology
from different information sources – parent and child – using the
However, this study must be interpreted in the context of
some limitations. First, the relatively small sample size for some
diagnoses made it difficult to exclude Type II errors when comparing
the groups. Second, reliability among raters was not checked,
although all were experienced clinicians with extensive training
in administering the instruments, being supervised by a child
psychiatrist. Third, unexpected high prevalence of mental disease
was found in the control group, probably due to the tertiary center
origin of the subjects or because of a possible selection bias. This
fact limits the generalizability of our findings. Finally, the Portuguese
translation of the WASI had not been validated yet when the study
was conducted. However, any assessment bias would have affected
all groups equally.
Our findings support that, in adult psychiatric settings, clinicians
should bear in mind that offspring of bipolar patients are at a high
risk for mental disorders. They should be prepared to refer suspect
children for evaluation, especially those presenting with anxiety
symptoms. It is important to adopt a more comprehensive approach
comprising the patient’s environment and family.
These subjects (offspring) should be prospectively followed-up
to the age of the most probable onset of psychiatric disorders,
particularly mood disorders, in order to verify prodromal signs of
such disorders and possibly minimize or prevent suffering.
We thank all interviewers involved in the study, Mario Renato de Azevedo
Júnior, the Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP),
the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES),
the teams from the Grupo de Estudos de Doenças Afetivas (GRUDA - Study
Group on Affective Diseases) and the PROMAM.
The authors Petresco, Gutt, Krelling and Lotufo-Neto have no conflict
Psychopathology in bipolar offspring 246 Download full-text
Rev Bras Psiquiatr. 2009;31(3):240-6
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