Toward the definition of a bipolar prodrome: Dimensional predictors of bipolar spectrum disorders in at-risk youths

Abstract

Objective: The authors sought to assess dimensional symptomatic predictorsofnew-onset bipolar spectrumdisorders in youths at familial risk of bipolar disorder ("at-risk" youths). Method: Offspring 6-18 years old of parents with bipolar I or II disorder (N=359) and community comparison offspring (N=220) were recruited. At baseline, 8.4% of the offspring of bipolarparentshadabipolar spectrumdisorder.Over8years,14.7% of offspring for whom follow-up data were available (44/299) developed a new-onset bipolar spectrum disorder (15 with bipolar I or II disorder).Measures collected at baseline and followup were reduced using factor analyses, and factors (both at baseline and at the visit prior to conversion or last contact) were assessed as predictors ofnew-onset bipolar spectrum disorders. Results: Relative to comparison offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsyndromal manic, and affective lability symptoms. The strongest predictors of new-onset bipolar spectrum disorders were baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms (p,0.05). While affective lability and anxiety/depressionwere elevated throughout follow-up in those who later developed a bipolar spectrumdisorder,manic symptoms increased up to the point of conversion. A path analysis supported the hypothesis that affective lability at baseline predicts a new-onset bipolar spectrumdisorder in part through increasedmanic symptoms at the visit prior to conversion; earlier parental age at mood disorder onset was also significantly associated with an increased risk of conversion. While youths without anxiety/ depression, affective lability, and mania (and with a parent with older age at mood disorder onset) had a 2% predicted chance of conversion to a bipolar spectrum disorder, those with all risk factorshada49%predicted chanceof conversion. Conclusions: Dimensional measures of anxiety/depression, affective lability, and mania are important predictors of newonset bipolar spectrum disorders in at-risk youths. These symptoms emerged from among numerous other candidates, underscoring the potential clinical and research utility of these findings.