There is growing interest internationally in elucidating the clinical and biological profile of those at high genetic risk to bipolar disorder (BD) so as to enable the development of targeted early intervention programs. This presentation will focus on the emerging findings from our group and others – highlighting both prospective and cross-sectional reports. Clinical studies are now converging in finding increased rates of both anxiety and behavioural disorders in this group, with three sites reporting that these disorders increase the risk of later development of affective disorders. Cross-sectional neuropsychological studies of first degree relatives of those with BD have previously suggested impairments in verbal learning and working memory, but prospective studies such as our own have not confirmed such findings, suggesting that the well-documented impairments in those with established BD may represent sequelae of the illness. Molecular genetic studies from our own work and a UK group have demonstrated an enrichment of BD polygenic risk alleles in young high risk individuals. Neuroimaging studies – both structural and functional – are now indicating differences compared to controls without any family history of mental illness. Our own initial fMRI study reported reduced inferior frontal gyrus (IFG) activation during response inhibition to emotional stimuli, suggesting a potential trait marker of vulnerability to BD. We have subsequently found, using dynamic causal modelling, that this impaired IFG activation appears to be due to a specific network disturbance suggesting dysfunction in the processes that support hierarchical relationships between emotion and cognitive control. Other groups have also reported functional and structural evidence implicating the IFG in those at high risk of BD. Our preliminary functional and structural (DTI) connectivity analyses are also indicating impaired connections between the IFG and other relevant brain regions.