TRACKING THE LONGITUDINAL COURSE IN YOUNG PEOPLE AT HIGH RISK OF BIPOLAR DISORDER

Young people with a first-degree relative with bipolar disorder (BD) have a 10-15% risk of developing this illness, but currently we have little understanding of the specific clinical and/or biological features which predict such an outcome. Our group in Sydney established the Bipolar Disorder Kids and Sibs high-risk cohort over a decade ago (with 170 high risk young people, 130 controls and 65 who had already developed BD) and have collaborated closely with the US multi-site consortium led by John Nurnberger. We have followed this Australian sample regularly over time, with particular interest in neuroimaging, genetic (including epigenetic), neuropsychological and clinical findings. We have scanned subjects on 3 occasions (baseline, 2 and 10 years), having already published on changes over the first two years. We reported significant weakening in the high-risk subjects of structural connectivity in a network encompassing the left inferior and middle frontal areas, left striatal and thalamic structures, the left fusiform, and right parietal and occipital regions. These findings were more pronounced in those who had developed a first episode of hypo(mania) over those two years. We have also explored for clinical predictors of hypo(mania) onset, finding particular depressive features to be a strong predictor of this outcome. We will present clinical and biological findings of our 10-year follow-up. More studies of long-term biological and clinical changes over time, and predictors of the onset of hypo(mania) are needed to enable rational development of early intervention studies in those at increased familial risk of BD.