The predictive value of childhood subthreshold manic symptoms for adolescent and adult psychiatric outcomes

Background Childhood subthreshold manic symptoms may represent a state of developmental vulnerability to Bipolar Disorder (BD) and may also be associated with other adverse psychiatric outcomes. To test this hypothesis we examined the structure and predictive value of childhood subthreshold manic symptoms for common psychiatric disorders presenting by early adulthood. Methods Subthreshold manic symptoms at age 11 years and lifetime clinical outcomes by age 19 years were ascertained in the TRacking Adolescents’ Individual Lives Survey (TRAILS), a prospective Dutch community cohort. We used latent class analysis to identify subthreshold manic symptom profiles at baseline. The association between class membership and subsequent clinical diagnoses of BD (comprising BD-I, BD-II, mania and hypomania), depressive, anxiety and substance abuse disorders was determined using Cox proportional-hazard ratio (HR) models. Results At age 11 years, we identified a normative (n=916; 47%), a mildly symptomatic (n=843; 43%) and a highly symptomatic class (n=198; 10%). Referenced to the normative class, the sex- and age-adjusted risk of new-onset BD by the age of 19 years was significantly increased in the mildly (HR=2.01, 95%CI 1.13–3.59) and highly symptomatic classes (HR=5.02, 95%CI 2.48–10.16). These estimates remained significant after further adjustments for cognitive and family function, parental socioeconomic status, parental psychiatric morbidity, and comorbid disorders at baseline (p-value for linear trend across classes<0.01). Class membership did not show significant associations with incident depressive, anxiety and substance abuse disorders in the fully adjusted regression models. Limitations The period of risk for adult-onset BD extends beyond the observational period of the study. Conclusions Elevated childhood subthreshold manic symptoms are associated with increased risk of BD by early adulthood and are therefore a potentially useful phenotype for the early identification of at-risk individuals.