PREDICTING CONVERSION TO BIPOLAR DISORDER IN A PROSPECTIVE LONGITUDINAL GENETICALLY HIGH-RISK SAMPLE

Abstract

ObjectiveOur group has previously reported differences in the clinical, genetic and neuroimaging (structural and functional MRI, DTI) profiles of young people at increased genetic risk of bipolar disorder, compared to control subjects from families without mental illness. Identification of clinical, genetic and neuroimaging features that predict later ‘conversion’ to bipolar disorder (BD) in those at high genetic risk (HR) would assist in early intervention. This study aimed to investigate whether clinical features (such as lifetime depressive, anxiety or behavioural disorders) or genetic/neuroimaging findings predict later development of hypo/mania. Method287 12-30 year-old participants (163 HR with a first-degree relative with DSM-IV BD, and 124 controls) were assessed at baseline and 12-monthly follow-ups for up to six years. ResultsNineteen HR subjects later developed either threshold (n=8; 4.9%) or sub-threshold (n=11; 6.7%) hypo/manic episodes. A prior history of MDEs was associated with an increased risk of later conversion to threshold BD (hazard ratio=13.9, p<.05). Anxiety disorders did not predict later occurrence of hypo/mania. Behavioural disorders (including ADHD) predicted sub-threshold but not threshold episodes. After accounting for this risk, the presence of >4 ׳Probabilistic׳ depressive features was associated with a further seven-fold increase in the risk of conversion to threshold BD (hazard ratio=6.9, p<.05). Those features most strongly associated with such conversion were psychomotor retardation and > 5 MDEs. Data on the predictive capacity of genetic (polygenic risk scores) and neuroimaging findings will be presented. ConclusionsIn one of few prospective studies of predictors of conversion to BD in HR subjects, both a history of MDEs and >4 ׳Probabilistic׳ features predicted later development of threshold episodes of hypo/mania, and hence may constitute ‘targets’ for early intervention.