Diagnostic Precursors to Bipolar Disorder in Offspring of Parents With Bipolar Disorder: A Longitudinal Study

Am J Psychiatry. 2015 Jul;172(7):638-46. doi: 10.1176/appi.ajp.2014.14010035. Epub 2015 Mar 3.


Objective: The authors sought to identify diagnostic risk factors of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder ("high-risk offspring").

Method: High-risk offspring 6-18 years old (N=391) and demographically matched offspring (N=248) of community parents without bipolar disorder were assessed longitudinally with standardized diagnostic instruments by staff blind to parental diagnoses. Follow-up assessments were completed in 91% of the offspring (mean follow-up interval, 2.5 years; mean follow-up duration, 6.8 years).

Results: Compared with community offspring, high-risk offspring had significantly higher rates of subthreshold mania or hypomania (13.3% compared with 1.2%), manic, mixed, or hypomanic episodes (9.2% compared with 0.8%), and major depressive episodes (32.0% compared with 14.9%). They also had higher rates of attention deficit hyperactivity disorder (30.7% compared with 18.1%), disruptive behavior disorders (27.4% compared with 15.3%), anxiety disorders (39.9% compared with 21.8%), and substance use disorders (19.9% compared with 10.1%), but not unipolar major depressive disorder (major depression with no bipolarity; 18.9% compared with 13.7%). Multivariate Cox regressions showed that in the high-risk offspring, subthreshold manic or hypomanic episodes (hazard ratio=2.29), major depressive episodes (hazard ratio=1.99), and disruptive behavior disorders (hazard ratio=2.12) were associated with subsequent manic, mixed, or hypomanic episodes. Only subthreshold manic or hypomanic episodes (hazard ratio=7.57) were associated when analyses were restricted to prospective data.

Conclusions: Subthreshold manic or hypomanic episodes were a diagnostic risk factor for the development of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder and should be a target for clinical assessment and treatment research. Major depressive episodes and disruptive behavior disorders are also indications for close clinical monitoring of emergent bipolarity in high-risk offspring.

MeSH terms

  • Adolescent
  • Bipolar Disorder / diagnosis*
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / psychology
  • Child
  • Child of Impaired Parents / psychology*
  • Comorbidity
  • Cross-Sectional Studies
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / genetics
  • Depressive Disorder, Major / psychology
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Mental Disorders / diagnosis
  • Mental Disorders / genetics
  • Mental Disorders / psychology
  • Pennsylvania
  • Psychiatric Status Rating Scales
  • Risk Factors