Five-year prospective outcome of psychopathology in the adolescent offspring of bipolar parents.
ABSTRACT For nearly 5 years a prospective high risk cohort study was carried out in the Netherlands among adolescent offspring of parents with bipolar disorder (BD). The purpose of this study was to determine the prevalence of psychopathology, specifically mood disorders, in adolescents and young adults with a bipolar parent.
At first and second measurement 140 and 132 children of bipolar parents, respectively, were psychiatrically evaluated with a semi-structured psychiatric interview (K-SADS-PL). At follow up (third measurement), nearly 5 years later, lifetime DSM IV diagnoses were obtained from the SCID interview for 129 subjects (aged 16--26 years).
Compared with the first measurement, the lifetime prevalence of BD increased from 3 to 10% at follow up. In addition, the lifetime prevalence of overall mood disorders increased to 40% and of overall psychopathology to 59%. All subjects except for one with BD, debuted with a unipolar mood disorder with a mean of 4.9 (SD 3.4) years prior to the first (hypo)manic episode.
At follow up, we noticed an increase in BD onset, while a further increase could be expected. In addition, we found that a unipolar depression in bipolar offspring is a risk factor for, and at the same time the first sign of, the development of BD.
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ABSTRACT: Objectives There is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder; however, their precise role remains unclear. In this study, we aimed to evaluate neuro-immune changes in a prospective study on children of patients with bipolar disorder.Methods Bipolar offspring, from the prospective Dutch bipolar offspring study (n = 140), were evaluated cross-sectionally within a longitudinal context at adolescence, young adulthood, and adulthood. We examined the expression of 44 inflammation-related genes in monocytes, the cytokines pentraxin 3 (PTX3), chemokine ligand 2 (CCL2), and interleukin-1β (IL-1β), and brain-derived neurotrophic factor (BDNF) and S100 calcium binding protein B (S100B) in the serum of bipolar offspring and healthy controls.ResultsDuring adolescence, bipolar offspring showed increased inflammatory gene expression in monocytes, high serum PTX3 levels, but normal CCL2 levels. BDNF levels were decreased, while S100B levels were normal. During young adulthood, monocyte activation remained, although to a lesser degree. Serum PTX3 levels remained high, and signs of monocyte migration became apparent through increased CCL2 levels. BDNF and S100B levels were not measured. At adulthood, circulating monocytes had lost their activation state, but CCL2 levels remained increased. Both BDNF and S100B were now increased. Abnormalities were independent of psychopathology state at all stages.Conclusions This study suggests an aberrant neuro-immune state in bipolar offspring, which followed a dynamic course from adolescence into adulthood and was present irrespective of lifetime or future mood disorders. We therefore assumed that the aberrant neuro-immune state reflects a general state of vulnerability for mood disorders rather than being of direct predictive value.Bipolar Disorders 07/2014; · 4.62 Impact Factor
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ABSTRACT: Background Severe mental illness (SMI), including schizophrenia, bipolar disorder and severe depression, is responsible for a substantial proportion of disability in the population. This article describes the aims and design of a research study that takes a novel approach to targeted prevention of SMI. It is based on the rationale that early developmental antecedents to SMI are likely to be more malleable than fully developed mood or psychotic disorders and that low-risk interventions targeting antecedents may reduce the risk of SMI.Methods/DesignFamilies Overcoming Risks and Building Opportunities for Well-being (FORBOW) is an accelerated cohort study that includes a large proportion of offspring of parents with SMI and embeds intervention trials in a cohort multiple randomized controlled trial (cmRCT) design. Antecedents are conditions of the individual that are distressing but not severely impairing, predict SMI with moderate-to-large effect sizes and precede the onset of SMI by at least several years. FORBOW focuses on the following antecedents: affective lability, anxiety, psychotic-like experiences, basic symptoms, sleep problems, somatic symptoms, cannabis use and cognitive delay. Enrolment of offspring over a broad age range (0 to 21 years) will allow researchers to draw conclusions on a longer developmental period from a study of shorter duration. Annual assessments cover a full range of psychopathology, cognitive abilities, eligibility criteria for interventions and outcomes. Pre-emptive early interventions (PEI) will include skill training for parents of younger children and courses in emotional well-being skills based on cognitive behavioural therapy for older children and youth. A sample enriched for familial risk of SMI will enhance statistical power for testing the efficacy of PEI.DiscussionFORBOW offers a platform for efficient and unbiased testing of interventions selected according to best available evidence. Since few differences exist between familial and ¿sporadic¿ SMI, the same interventions are likely to be effective in the general population. Comparison of short-term efficacy of PEI on antecedents and the long term efficacy for preventing the onset of SMI will provide an experimental test of the etiological role of antecedents in the development of SMI.BMC Psychiatry 12/2014; 14(1):344. · 2.24 Impact Factor
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ABSTRACT: Objectives It has been proposed that the offspring of parents with bipolar disorder (OBD), through genetic mechanisms and early family interactions, develop a heightened sensitivity to stress, maladaptive coping, and dysregulated behavior, which ultimately increases the risk for affective disorders. The current study tested certain predictions of this model by assessing different psychosocial and health-related outcomes in the OBD, including personality, coping style, smoking, suicidality, high-risk sexual behaviors, criminality, and mental health. Method The sample was composed of 74 OBD and 75 control offspring, who were between 14 and 27 years of age (mean: 19.38±3.56). Participants underwent a diagnostic interview and a structured interview to assess high-risk behavior and other maladaptive outcomes, and they completed the Revised NEO Personality Inventory and Coping in Stressful Situations questionnaire. Results The rates of affective (31.1%) and non-affective (56.8%) disorders were elevated in the OBD compared to controls (9.5% and 32.4%). Relative to controls, OBD endorsed fewer task-oriented and more distraction coping strategies [Wilk׳s λ=.83, F(1, 136) =6.92, p<.01], and were more likely to report engaging in high-risk sexual behavior (OR=2.37; Wald=4.13, 1 df, p<05). Importantly, OBD reported elevated high-risk sexual behavior relative to controls, irrespective of affective disorder diagnosis. Conclusion The results highlight a potential risk profile for the OBD, consisting of ineffective coping strategies and risky sexual behavior and are discussed in the context of current knowledge of stress and coping in this population. Limitations The present findings were based on cross-sectional data and relied on offspring self-report. It would be useful to corroborate these findings with biobehavioural and longitudinal measures.Journal of Affective Disorders 09/2014; 166:315–323. · 3.71 Impact Factor
Five-year prospective outcome of
psychopathology in the adolescent offspring of
Children of parents with bipolar disorder (BD;
bipolar offspring) are genetically at high risk of
developing BD, as well as other psychopathology
(1–3). Therefore, a greater understanding of the
development of BD can be gained through studying
bipolar offspring longitudinally. The prevalence of
mood disorders and in particular BD differs sub-
stantially in several offspring studies. In a meta-
analysis of 17 offspring studies, Lapalme et al. (1)
found that 52% of the bipolar offspring were
diagnosed with a psychiatric disorder according
to DSM-III (-R) criteria. Furthermore 5.4% of the
bipolar offspring were diagnosed with BD com-
pared with 0% of the control group. Several other
offspring studies have been conducted since. These
recent offspring studies reported various lifetime
prevalence numbers of bipolar spectrum disorder
and psychiatric disorders. One Canadian study
found 6 of 36 bipolar offspring subjects (17%) met
DSM-IV criteria for a bipolar spectrum disorder
and 19 children (53%) met DSM-IV criteria for at
least one psychiatric disorder during their lifetime
(4). Another study (5) found 9of 60 (15%) offspring
to have bipolar I or II disorder and 55% of the
sample had an Axis I disorder as determined by the
DSM-IV. Soutullo (6) reported that 50% of 24
bipolar offspring had a bipolar spectrum disorder,
Hillegers MHJ, Reichart CG, Wals M, Verhulst FC, Ormel J, Nolen
WA. Five-year prospective outcome of psychopathology in the
adolescent offspring of bipolar parents.
Bipolar Disord 2005: 7: 344–350. ª Blackwell Munksgaard, 2005
Objective: For nearly 5 years a prospective high risk cohort study was
carried out in the Netherlands among adolescent offspring of parents
with bipolar disorder (BD). The purpose of this study was to determine
the prevalence of psychopathology, specifically mood disorders, in
adolescents and young adults with a bipolar parent.
Method: At first and second measurement 140 and 132 children of
bipolar parents, respectively, were psychiatrically evaluated with a semi-
structured psychiatric interview (K-SADS-PL). At follow up (third
measurement), nearly 5 years later, lifetime DSM IV diagnoses were
obtained from the SCID interview for 129 subjects (aged 16–26 years).
Results: Compared with the first measurement, the lifetime prevalence
of BD increased from 3 to 10% at follow up. In addition, the lifetime
prevalence of overall mood disorders increased to 40% and of overall
psychopathology to 59%. All subjects except for one with BD, debuted
with a unipolar mood disorder with a mean of 4.9 (SD 3.4) years prior to
the first (hypo)manic episode.
Conclusion: At follow up, we noticed an increase in BD onset, while a
further increase could be expected. In addition, we found that a unipolar
depression in bipolar offspring is a risk factor for, and at the same time
the first sign of, the development of BD.
Manon HJ Hillegersa,
Catrien G Reichartb,
Marjolein Walsb, Frank C Verhulstb,
Johan Ormelcand Willem A Nolena,c
aAltrecht Institute for Mental Health Care, Utrecht,
bErasmus Medical Centre Rotterdam/Department
of Child and Adolescent Psychiatry, Sophia
Children’s Hospital, Rotterdam,cDepartment of
Psychiatry, University of Groningen Medical
Centre, Groningen, the Netherlands
Key words: bipolar – offspring – prevalence –
Received 24 June 2004, revised and accepted for
publication 7 March 2005
Corresponding author: Manon HJ Hillegers, MD,
Altrecht Institute for Mental Health Care,
Tolsteegsingel 2a, 3582 AC, Utrecht,
Fax: +31 30 2587495;
The authors of this paper do not have any commercial associations
that might pose a conflict of interest in connection with this manu-
Bipolar Disorders 2005: 7: 344–350
Copyright ª Blackwell Munksgaard 2005
compared with 9% of 13 healthy controls. In a
recent review Delbello and Geller (2) and Geller
et al. (7) concluded that the prevalence of mood
disorders in child and adolescent offspring of
bipolar parents ranges from 5 to 67% compared
with the prevalence of mood disorders in offspring
of healthy parents of 0–38%.
In 1997 we started a longitudinal study among
the adolescent offspring (aged 12–21 years) of
parents with a BD. In papers on the first and
second measurement after 1 year, we could not
confirm the previously established conclusion that
our adolescent bipolar offspring had a greater risk
for overall psychopathology, with 44% at the first
and 49% at the second measurement (8, 9). The
prevalence of mood disorder (27 and 33%, respec-
tively) but not of BD (3 and 4%, respectively) was
moderately higher in our sample than among
adolescents from the general population (10). In
this paper we report the third measurement of this
sample, almost 5 years after the first measurement.
We focus on the prevalence of mood disorders at
follow up and describe the onset and course of
these mood disorders.
Subjects and methods
The study presented here is part a of an ongoing
prospective high-risk cohort study among the
adolescent offspring of parents with BD in the
Netherlands. The Medical Ethical Review Com-
mittee of the University Medical Center Utrecht
approved the study. All the subjects of the study
were enrolled between November 1997 and March
1999. Sixty-two parent responders of the Dutch
12–21 years and 24 families with 38 children aged
12–21 years from outpatient clinics in nine psychi-
atric hospitals in the Netherlands agreed to par-
ticipate. After giving a complete description of the
study to all participating parents (86 bipolar
parents and their spouses) and offspring (n ¼
140), a written informed consent from both parents
were outpatients at the time of recruitment. Sixty-
four bipolar I and 22 bipolar II patients and their
offspring (72 males and 68 females) participated in
the study. The mean age of the participating
offspring was 16.1 years (SD ¼ 2.7; range 12–21).
Fifty-two of 86 proband parents were mothers
(60%). The mean age of the bipolar parents was
45.4 years. The study design, recruitment proce-
dure and study population have been described in
detail by Wals et al. (8). Fourteen months after the
first measurement, 132 subjects, aged 13–23 years,
were reassessed (9). At that time seven females and
one male from six families had dropped out. Two
families remained with siblings of the dropouts in
the study. As a result, at the second measurement
82 families were left in the study. At the third
measurement, 41 months (SD ¼ 5.2) after the
second measurement, 129 subjects from 80 families
were still participating (three further dropouts, one
refused only the SCID interview). One female
revised her decision to leave the study at second
measurement and participated again at follow up,
leaving the total number of subjects at 129.
Assessment of bipolar disorder in the parents
To include families in our cohort, DSM-IV bipolar
I or II diagnoses were confirmed by referring to the
mood disorders section of the International Diag-
nostic Check List (IDCL; 1993) in the interview
with bipolar parents. We compared the IDCL-
based diagnoses with the DSM-IV diagnoses made
by the treating psychiatrist and found no discrep-
During the first two measurements, diagnoses
according to DSM-IV criteria were assessed using
the Kiddie Schedule of Affective Disorders and
(K-SADS-PL) (11). The K-SADS-PL is an inter-
viewer-oriented diagnostic interview designed to
assess current and past DSM-IV symptoms in
diagnoses in children and adolescents, by inter-
viewing the parent(s) and the child separately. If
parents or children disagreed on the presence of a
symptom, greater weight was given to the parents?
reports of observable behavior rather than chil-
dren’s reports of subjective experiences (11).
Because of the increasing age of our subjects we
could not use the K-SADS-PL at the third meas-
urement. At this third measurement, the Structured
Clinical Interview for DSM-IV Axis I Disorders
(SCID I) (12) was used to determine current (last
month) and past (as of second measurement)
Because the SCID did not include all DSM-IV
diagnoses, the questionnaires for Attention Deficit
Hyperactivity Disorder (ADHD), Oppositional
Defiant Disorder, Conduct Disorder and Tic Dis-
orders originating from the K-SADS-PL were
added as a supplement to the SCID. The SCID
interview was conducted by two of the authors
viewers with graduate degrees in psychology. All
and Lifetime Version
three trained inter-
Psychopathology in the adolescent bipolar offspring
interviewers were intensively trained, and all inter-
view outcomes were evaluated with a child-and-
adolescent psychiatrist (CR). Lifetime DSM-IV
diagnoses at the third measurement were based on
the psychiatric interviews that took place during all
three measurements (time 1, time 2, and time 3)
adding up the incidence of psychopathology
between time 2 and time 3 to the incidence of
psychopathology between time 1 and time 2 and
the lifetime time 1 diagnoses. At the same time the
hierarchal rules of DSM-IV were taken into
account. For example, a subject with a lifetime
major depressive disorder at the first measurement,
who developed a manic episode between the second
and the third measurement, accounted lifetime
only for the diagnosis BD at third the measure-
ment, while the age of onset of BD was defined as
the age at which the subject first developed a mood
First, we assessed the number and percentages of
subjects with BD, any other mood disorder, and
any other non-mood disorder. Next, we assessed
the age of onset in all subjects with a mood
disorder, and performed standard Kaplan–Meier
(KM) survival analysis, taking into account the
time to onset of the first mood disorder (any mood
disorder or BD, respectively) as events in all
subjects with a mood disorder while censoring the
subjects reaching the end of the follow-up period of
the study without an event. Thus the KM analysis
resulted in an estimation of the probability of
remaining well for a given point of time.
The offspring cohort at the third measurement
consisted of 60 females and 69 males. Mean age
was 20.8 years (SD ¼ 2.7)
16–26 years. Further characteristics of the study
cohort are presented in Table 1.
The numbers and percentages of lifetime and
current DSM-IV diagnoses are
Table 2. The lifetime prevalence of BD in this
sample is 10%, the lifetime prevalence of mood
disorders 40% and of psychopathology in general
59%. At the third measurement there were only
nine subjects (7%) with a current (last month)
The mean ages of the 13 subjects with a BD
(21.5 years; SD ¼ 3.5), of the 38 subjects with a
unipolar mood disorder (21.2 years; SD ¼ 2.5)
and of the 78 subjects without a mood disorder
(20.5 years, SD ¼ 2.7) did not differ significantly.
In Table 3 characteristics of all 13 subjects with
BD are presented. Gender is equally distributed;
six female and seven male subjects developed BD.
The first mood disorder was a major depressive
disorder in five bipolar subjects and a mild mood
disorder in the remaining eight bipolar subjects. In
the period between the first mood episode meeting
DSM-IV criteria for a mild depression (Dep NOS,
Dysthymia, cyclothymia) and the first (hypo)manic
Table 1. Characteristics of the study population at the third measurement
(n ¼ 129)
Time interval (2–3 months)
Table 2. Number and percentages of bipolar offspring with lifetime and
current DSM-IV diagnoses at the third measurement (age 16–26; n ¼ 129)
Any mood disorder
Major depressive disorder
Depressive disorder NOS
(BP I, BP II)
with depressed mood
Attention deficit disorder
Substance abuse disorder
1 (1)0 (0)
NOS ¼ not otherwise specified; BP I ¼ bipolar I disorder; BP
II ¼ bipolar II disorder.
aConsists of enuresis, encopresis, pervasive developmental
disorder, tic, and eating disorders.
Hillegers et al.
episode, all eight subjects developed at least
one relapse depressive episode meeting DSM-IV
criteria for a major depressive disorder. The parent
of origin of BD in nine subjects is the mother
(70%). This does not differ significantly from the
distribution in the whole sample (mothers 60%)
since four of the 13 bipolar subjects are relatives:
two (half) sisters and one monozygotic twin. At the
third measurement nine subjects with BD were
receiving psychiatric treatment (pharmacologic
and/or counseling) of which five used lithium for
maintenance treatment. Only three of the bipolar
subjects received treatment with antidepressants
before (not during) the onset of the first (hypo)
manic episode for lifetime. One of these three
subjects additionally received temporarystimulants
because of comorbid ADHD. None of the bipolar
subjects received maintenance treatment with
Figure 1 shows the development of mood disor-
ders of all 51 subjects with any one lifetime mood
disorder. Twelve of thirteen subjects with BD
initially debuted with a unipolar (depressive)
disorder at a mean age of 13.4 years (SD 4.2), that
is, at a mean of 4.9 years (SD 3.4) prior to their
first (hypo)manic episode at a mean age of
Table 3. Characteristics of 13 subjects with bipolar disorder at the third measurement
MDD ¼ major mood disorder; Dep NOS ¼ depressive disorder not otherwise specified; BP I ¼ bipolar I disorder; BP II ¼ bipolar II
Treatment: pharmacologic and/or counseling.
aGender: F ¼ female; M ¼ male.
bParent of origin: M ¼ mother; F ¼ father.
cUse of antidepressant before switch to bipolar disorder.
dUse of stimulant before switch to bipolar disorder.
51 Mood Disorders
13 BD 38 UP
5 BPI 8 BPII 5 DYST
20 DEP NOS
2 DEP NOS 2 MDD
2 DEP NOS
Fig. 1. The course of lifetime mood disorders at the third measurement. BD ¼ bipolar disorder; BP I ¼ bipolar I disorder; BP II ¼
bipolar II disorder; MDD ¼ major depressive disorder; DEP NOS ¼ depressive disorder not otherwise specified; DYST ¼ dysthymic
disorder; CYCL ¼ cyclothymic disorder; UP ¼ unipolar disorder.
Psychopathology in the adolescent bipolar offspring
18.4 years (SD 2.9). Mean age of onset of 38
subjects with a unipolar mood disorder was
15.6 years (SD 4.1). There was no significant
difference in the age of onset between unipolar
and bipolar subjects.
In Fig. 2 the KM survival function is shown at
the onset of the first mood disorder episode among
all 129 bipolar offspring. The figure shows that the
first subject with a mood disorder in this cohort
debuted at age 8.6 years. At the third measurement
the youngest subject was 15.9 years old and there-
fore is first censored. At the age of 20.8 years
(mean age of the cohort) about 60% was still
without any lifetime mood disorder. The risk of
switching to (hypo)mania is substantial, as the
mean follow-up time to first (hypo) manic episode
is 4.9 years (SD 3.4; see Fig. 3) Therefore, we can
expect that in the coming years the proportion of
BD will increase as a consequence of switching
from unipolar to bipolar mood disorder.
In our study among children aged 16–26 years of
bipolar parents we found that the level of psycho-
pathology, mood disorders in general and BD in
particular, has increased compared with the first
two measurements 5 and 4 years earlier. Lifetime
increased from 44 to 49 to 59%, of any mood
disorder from 27 to 33 to 40% and of bipolar
spectrum disorder from 3 to 6 to 10%. Moreover,
we can expect a further increase of bipolar and
probably also unipolar mood disorders in the
coming years. The steep slope and absence of
flattening of the survival curves and of course the
age distribution of the cohort strongly predict a
further increase in the onset of mood disorder in
the near future. These results demonstrate the
advantages of follow-up studies over cross-sec-
Compared with our prior findings at the first
two measurements, our current findings are similar
to other studies that reported high percentages
of psychopathology in general and especially
mood disorders (1–7). Nevertheless, the lifetime
prevalence of 10% DSM-IV BDs in our study is
still moderate compared with other studies among
bipolar offspring in the older adolescent/young
adult age range. These studies show a range of
5–50% of lifetime BDs in bipolar offspring (13–16).
A possible explanation for the relatively late age of
onset of BD in our subjects might be the lack of
medication prior to their onset of BD (17). Only
three of the bipolar subjects had a history of
treatment with antidepressants before (not during)
the onset of the first (hypo) manic episode. One of
these three subjects additionally received stimu-
lants because of a comorbid ADHD. A US study
reported that bipolar adolescents with a history of
stimulant exposure were younger at the onset of
BD than those without prior stimulant exposure
(18). Another study concluded that children
exposed to antidepressants appear to be diagnosed
with BD earlier than those never exposed to these
medications (19). Treatment approaches between
the US and the Netherlands are different (17). The
Age at onset at first mood episode
Percent of subjects without a mood disorder
Fig. 2. Survival function of the first mood episode of 129
offspring of bipolar parents.
Time to first (hypo)mania
Percent of subjects without BSD
Fig. 3. Survival function of 51 subjects with a mood disorder;
time to first (hypo) mania (n ¼ 13).
Hillegers et al.
number of bipolar subjects of our sample receiving
treatment is limited when compared with bipolar
subjects described in other offspring studies (7). In
many US offspring studies subjects receive the
standard treatment as prescribed by their primary
treating team (7). However, this treatment is often
not reported in detail.
In terms of age distribution our study popula-
tion compares best with the study of Duffy (4).
They included 36 bipolar offspring subjects aged
10–25 years and found any psychiatric disorder in
53% and BD in 14%. In our cohort, 12 of the
13 subjects with a BD debuted with a unipolar
(depressive) mood disorder. Although illness starts
with one or more depressions in the majority of
bipolar patients (20, 21), our findings suggest that
this is probably the case in almost all patients.
When illness starts with a full-blown mania or
severe major depression, such episodes are easily
acknowledged, also retrospectively, as the debut of
the illness. However, minor/mild depression or a
hypomanic episode is often not recognized retro-
spectively, especially when they are overshadowed
by subsequent more severe episodes. In our study
because of careful diagnostics with its repeated
assessments, probably most (if not all) mild mood
disorders were detected. Therefore, our finding of a
debut of BD with a depression indicates that in the
bipolar offspring depression can be indicated as a
substantial risk factor for developing BD.
A limitation of the study is the change of the
diagnostic interview instrument. At the first and
the second measurement we used the K-SADS-
PL version, whereas at follow up we used the
SCID I interview. Because different instruments
may lead to different results, this might explain
the considerable increase in the prevalence of BD.
However, there are many similarities between
both instruments. The K-SADS-PL and the
SCID I are both semi-structured diagnostic psy-
chiatric interviews based on the DSM-IV. More-
over, they both first use screen questions to check
the presence of the main symptoms of the
disorder and then go on to the detailed questions
of the supplement. Both instruments provide
lifetime assessment; asking about past and cur-
rent episodes of the disorder. The K-SADS-PL is
administered by interviewing the parent(s) and
the adolescent, and finally achieving summary
ratings which include all sources of information.
The main difference between the K-SADS-PL
and the SCID I is the usage of more informants
in the K-SADS-PL, compared with only one
informant in the SCID. However, it is unlikely
that this is an explanation for more BDs at the
third measurement.Unlike mostdepressives,
hypomanic subjects seldom complain of, or suffer
from, their shifts in energy, activity and sleep
behavior and tend to experience them as positive.
Such changes are more likely first to be picked up
and recognized by family and friends (22).
Therefore, using only the child as an informant
may have led to relatively lower, but not higher,
rates of BD diagnoses.
A major limitation is that we had no control
group of children of parents without a BD while
there are no data on the prevalence of DSM-IV
16–25 years of the Dutch general population.
Therefore, we can only compare our results with
data of the Dutch population study (aged 18–
64 years) NEMESIS which has studied the preva-
lence of DSM-III-R diagnosis based on the fully
structured Composite International Diagnostic
Interview (CIDI) (23). Based on all three assess-
ments of NEMESIS (at baseline, after 1 year, and
after 2 years), 2.4% of the respondents were
identified with lifetime BD (DSM-III-R), while in
a reappraisal study based on the SCID a lifetime
prevalence of 5.2% (95% CI 2.2–8.1%) for DSM-
IV bipolar spectrum disorders was determined (24).
This percentage is about half of the 10% in our
sample, with an age range of 16–26 years.
Another limitation is the fact that the recruit-
ment of the study sample differed between our and
other studies. In our study more than two-thirds of
the patients (i.e., the parents of our cohort) were
recruited through the Dutch patients? association
(VMDB) and only one-third came from psychiatric
hospitals. Only patients with children who were
willing to participate were included. It is possible
that patients recruited through a patients? associ-
ation are relatively well-functioning compared with
those of the outpatient clinics.
In conclusion, in this study among bipolar
offspring aged 16–26 years we found high rates of
psychopathology, especially BDs and other mood
disorders. Moreover, we can anticipate that in our
subjects over the next few years the lifetime
prevalence of these disorders will further increase.
Finally, we also found that, to date, almost all
subjects with BD debuted with a depression at a
mean of 5 years prior to their first (hypo)manic
episode, indicating that depression in bipolar
offspring is a risk factor for the further develop-
ment of BD.
This study was financially supported by NWO (Dutch Organ-
ization for Scientific Research) and by the Stanley Medical
Psychopathology in the adolescent bipolar offspring
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