Objective Identify diagnostic risk factors of mania/hypomania in the offspring of parents with bipolar disorder (“high-risk offspring”). Method High-risk offspring aged 6-18 years (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 interval 2.5 years; mean duration 6.8 years). Results High-risk offspring, as compared to community offspring, had significantly higher rates of subthreshold (hypo)manic (13.3% vs. 1.2%, p<.0001), manic/hypomanic (9.2% vs. 0.8%, p=.0003) and major depressive episodes (32.0% vs. 14.9%, p<.0001). They also had higher rates of attention-deficit hyperactivity (30.7% vs. 18.2%, p=.01), disruptive behavior (27.4% vs. 15.3%, p=.03), anxiety (39.9% vs. 21.8%, p=.0002), and substance use disorders (20.0% vs. 10.1%, p=.008), but not unipolar major depressive disorder (major depression with no bipolarity; 18.9% vs. 13.7%; p=.10). Multivariate Cox regressions in the high-risk offspring showed that subthreshold (hypo)manic episodes (Hazard Ratio 2.29, p=.03), major depressive episodes (Hazard Ratio 1.99, p=.05), and disruptive behavior disorders (Hazard Ratio 2.12, p=.03) were associated with subsequent mania/hypomania. Only subthreshold (hypo)manic episodes (Hazard Ratio 7.57, p<.0001) were associated when analyses were restricted to prospective data. Conclusions Subthreshold (hypo)manic episodes were a diagnostic risk factor for the development of mania/hypomania in the offspring of parents with bipolar disorder, and should be a target for clinical assessment and future treatment research. Major depressive episodes and disruptive behavior disorders are also indications for close clinical monitoring of emergent bipolarity in high-risk offspring.

Objective We aimed to assess dimensional symptomatic predictors of new-onset bipolar spectrum disorder in youth at familial risk of bipolar disorder (“at-risk” youth). Method Offspring aged 6–18 of parents with bipolar-I/II disorder (n=391) and offspring of community controls (n=248) were recruited without regard to non-bipolar psychopathology. At baseline, 8.4% (33/391) of offspring of bipolar parents had bipolar spectrum; 14.7% (44/299) of offspring with follow-up developed new-onset bipolar spectrum (15 with bipolar-I/II) over eight years. Scales collected at baseline and follow-up were reduced using factor analyses; factors (both at baseline and visit proximal to conversion or last contact) were then assessed as predictors of new-onset bipolar spectrum. Results Relative to community control offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsydromal manic, and affective lability symptoms (p<.05). The strongest predictors of new-onset bipolar spectrum were: baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms (p<.05). While affective lability and anxiety/depression were elevated throughout follow-up in those who later developed bipolar spectrum, manic symptoms increased up to the point of conversion. A path analysis supported the hypothesized model that affective lability at baseline predicted new-onset bipolar spectrum, in part, through increased manic symptoms at the visit prior to conversion; earlier parental age of mood disorder onset also significantly increased risk of conversion (p<.001). While youth without anxiety/depression, affective lability, and mania (and with a parent with older age of mood disorder onset) had a 2% predicted chance of conversion to bipolar spectrum, those with all risk factors had a 49% predicted chance of conversion. Conclusions Dimensional measures of anxiety/depression, affective lability, and mania are important predictors of new-onset bipolar spectrum in this population of at-risk youth. These symptoms emerged from among numerous other candidates, underscoring the potential clinical and research utility of these findings.

The data from this study provide robust evidence that supports the efficacy of midday bright light therapy for bipolar depression.