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The Dutch Bipolar Offspring Study: 12-Year Follow-Up
Esther Mesman, M.Sc.; Willem A. Nolen, M.D., Ph.D.; Catrien G. Reichart, M.D., Ph.D.; Marjolein Wals, Ph.D.; Manon H.J. Hillegers, M.D., Ph.D.
Am J Psychiatry 2013;170:542-549. doi:10.1176/appi.ajp.2012.12030401
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Presented in part at the joint annual meeting of the American Academy of Child Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry, Toronto, October 18–23, 2011; and at the fifth biennial conference of the International Society for Bipolar Disorders, Istanbul, Turkey, March 14–17, 2012.

Dr. Nolen has received grants from AstraZeneca, Eli Lilly, GlaxoSmithKline, and Wyeth and has received speaking fees from AstraZeneca, Pfizer, Servier, and Wyeth. Dr. Nolen has served on advisory boards for AstraZeneca and Servier. Dr. Hillegers has received speaking fees from Benecke, AstraZeneca, and Lundbeck. The other authors report no financial relationships with commercial interests.

Supported by grant 22963 from the 7FP of the European Commission and grant 9120818 from the Netherlands Organization for Scientific Research (NWO). Previous waves of this study were supported by the Stanley Medical Research Institute and NWO.

From the Department of Psychiatry, University Medical Center Utrecht, the Netherlands; Rudolf Magnus Institute for Neuroscience, Utrecht; Department of Psychiatry, University Medical Center Groningen, Groningen, the Netherlands; Department of Child and Adolescent Psychiatry, Curium-Leiden University Medical Center, Leiden, the Netherlands; and Institute of Psychology, Erasmus University, Rotterdam, the Netherlands.

Address correspondence to Dr. Hillegers (m.h.j.hillegers@umcutrecht.nl).

Copyright © 2013 by the American Psychiatric Association

Received March 28, 2012; Revised July 25, 2012; Revised September 04, 2012; Accepted October 05, 2012.


Objective  Offspring of bipolar parents have a genetically increased risk of developing mood disorders. In a longitudinal study, the authors followed a bipolar offspring cohort from adolescence into adulthood to determine the onset, prevalence, and early course of mood disorders and other psychopathology.

Method  The Dutch bipolar offspring cohort is a fixed cohort initiated in 1997 (N=140; age range at baseline, 12–21 years). Bipolar offspring were psychiatrically evaluated at baseline and at 1-, 5-, and 12-year follow-ups. Of the original sample, 77% (N=108) were followed for the full 12 years.

Results  Overall, 72% of the bipolar offspring developed a lifetime DSM-IV axis I disorder, 54% a mood disorder, and 13% bipolar spectrum disorders. Only 3% met DSM-IV criteria for bipolar I disorder. In 88% of the offspring with a bipolar spectrum disorder, the illness started with a depressive episode. In total, 24% of offspring with a unipolar mood disorder developed a bipolar spectrum disorder over time. Mood disorders were often recurrent (31%), were complex (comorbidity rate, 67%), and started before age 25.

Conclusions  Even after 12 years of follow-up, from adolescence into adulthood, bipolar I disorder was rare among bipolar offspring. Nevertheless, the risk of developing severe and recurrent mood disorders and other psychopathology was high. Future follow-up of this and other adult bipolar offspring cohorts is essential to determine whether recurrent mood disorders in bipolar offspring reflect the early stages of bipolar disorder.

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FIGURE 1. Survival Function of the Development of First Mood Disorders in the Dutch Bipolar Offspring Cohorta

a In panel A, the survival function is based on offspring developing their first manic or hypomanic episode (N=17), and censored cases are those who left the study with a lifetime unipolar mood disorder but without developing bipolar disorder (either as a dropout [N=7] or at the end of the study [N=44]). In panel B, the survival function is based on offspring who developed their first mood episode (N=68), and censored cases are those who left the study without a lifetime mood disorder (either as a dropout [N=22] or at the end of the study [N=50]).

FIGURE 2. Transition to Mood Disorders in the Dutch Bipolar Offspring Cohort (N=140)a

a Numbers in gray circles indicate the number of offspring in this category who left the study; a participant who left the study with a lifetime diagnosis at baseline, at 1 year, or at 5 years would remain in this category at follow-up and would be added to the gray circle. The mean age at baseline was 16.1 years (range=12–21); at the 1-year follow-up, 17.4 years (range=13–23); at the 5-year follow-up, 20.8 years (range=16–26); and at the 12-year follow-up, 28.0 years (range=22–32).

b Other disorders include any DSM-IV axis I disorder other than bipolar, unipolar mood, or anxiety disorders.

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TABLE 1.Demographic Characteristics of Offspring in the Dutch Bipolar Offspring Cohort at 12 Yearsa
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a There were no significant differences on any variable between offspring who participated in the 12-year assessment and those who dropped out of the study before that time.

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b A total of 16 complete families left the study; seven families have left the study partly.

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c Three bipolar parents have children from a previous marriage participating; therefore, 89 nonbipolar parents are presented here.

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d Socioeconomic status was measured on scale from 1 to 9, as described in Wals et al. (12).

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TABLE 2.Prevalence of Current and Lifetime DSM-IV Diagnoses in Bipolar Offspring at Baseline (N=140) and 12-Year Follow-Up (N=108)
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a Current diagnosis is defined as psychopathology in the past month. A current diagnosis of bipolar disorder does not imply a current episode.

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b Includes enuresis, encopresis, pervasive developmental disorder, tic disorder, body dysmorphic disorder, and eating disorders.

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TABLE 3.Clinical Characteristics of the 17 Bipolar Offspring Who Developed a Bipolar Spectrum Disorder
Table Footer Note

a Episode at first hospitalization: D=depression; M=mania; MM=mixed mania.

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b Use of antidepressants before onset of first hypomanic episode.

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c Use of stimulants before onset of first manic/hypomanic episode.



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