A high-risk study of bipolar disorder. Childhood clinical phenotypes as precursors of major mood disorders

Abstract

Context: The childhood precursors of adult bipolar disorder (BP) are still a matter of controversy.

Objective: To report the lifetime prevalence and early clinical predictors of psychiatric disorders in offspring from families of probands with DSM-IV BP compared with offspring of control subjects.

Design: A longitudinal, prospective study of individuals at risk for BP and related disorders. We report initial (cross-sectional and retrospective) diagnostic and clinical characteristics following best-estimate procedures.

Setting: Assessment was performed at 4 university medical centers in the United States between June 1, 2006, and September 30, 2009.

Participants: Offspring aged 12 to 21 years in families with a proband with BP (n = 141, designated as cases) and similarly aged offspring of control parents (n = 91).

Main outcome measure: Lifetime DSM-IV diagnosis of a major affective disorder (BP type I; schizoaffective disorder, bipolar type; BP type II; or major depression).

Results: At a mean age of 17 years, cases showed a 23.4% lifetime prevalence of major affective disorders compared with 4.4% in controls (P = .002, adjusting for age, sex, ethnicity, and correlation between siblings). The prevalence of BP in cases was 8.5% vs 0% in controls (adjusted P = .007). No significant difference was seen in the prevalence of other affective, anxiety, disruptive behavior, or substance use disorders. Among case subjects manifesting major affective disorders (n = 33), there was an increased risk of anxiety and externalizing disorders compared with cases without mood disorder. In cases but not controls, a childhood diagnosis of an anxiety disorder (relative risk = 2.6; 95% CI, 1.1-6.3; P = .04) or an externalizing disorder (3.6; 1.4-9.0; P = .007) was predictive of later onset of major affective disorders.

Conclusions: Childhood anxiety and externalizing diagnoses predict major affective illness in adolescent offspring in families with probands with BP.

Figure 1

Onset of major affective disorders in cases (n=141) and controls (n=91). The 2 groups are significantly different by log-rank test (P<.001).

Figure 2

Onset of anxiety disorders (A) and externalizing disorders (B) in cases with major affective disorders (n=33), minor affective disorders (n=21), and no affective disorder (n=87). The 3 groups are significantly different by log-rank test (P<.001).

Figure 3

Onset of major affective disorders in cases with an externalizing diagnosis by 12 years of age (n=19), an anxiety diagnosis by 12 years of age (n=25), and neither early-onset behavioral nor anxiety disorders (n=97). The 3 groups are significantly different by log-rank test (P=.007).