Clinical predictors of conversion to bipolar disorder in a prospective longitudinal familial high-risk sample : focus on depressive features

Background: Identifying clinical features that predict conversion to bipolar disorder (BD) in those at high familial risk (HR) would assist in identifying a more focused population for early intervention. Method: In total 287 participants aged 12-30 (163 HR with a first-degree relative with BD and 124 controls (CONs)) were followed annually for a median of 5 years. We used the baseline presence of DSM-IV depressive, anxiety, behavioural and substance use disorders, as well as a constellation of specific depressive symptoms (as identified by the Probabilistic Approach to Bipolar Depression) to predict the subsequent development of hypo/manic episodes. Results: At baseline, HR participants were significantly more likely to report ≥4 Probabilistic features (40.4%) when depressed than CONs (6.7%; p <.05). Nineteen HR subjects later developed either threshold (n = 8; 4.9%) or subthreshold (n = 11; 6.7%) hypo/mania. The presence of ≥4 Probabilistic features was associated with a seven-fold increase in the risk of 'conversion' to threshold BD (hazard ratio = 6.9, p <.05) above and beyond the fourteen-fold increase in risk related to major depressive episodes (MDEs) per se (hazard ratio = 13.9, p <.05). Individual depressive features predicting conversion were psychomotor retardation and ≥5 MDEs. Behavioural disorders only predicted conversion to subthreshold BD (hazard ratio = 5.23, p <.01), while anxiety and substance disorders did not predict either threshold or subthreshold hypo/mania. Conclusions: This study suggests that specific depressive characteristics substantially increase the risk of young people at familial risk of BD going on to develop future hypo/manic episodes and may identify a more targeted HR population for the development of early intervention programs.