Intermediate pathways from genetic risk to bipolar disorder: Effects of early adversity in the offspring of bipolar parents

Bipolar disorder (BD) is a severe, psychiatric illness that emerges in adolescence or early adulthood and continues lifelong. Specific early exposures and influences can increase the likelihood of illness in genetically susceptible individuals; however, the pathways linking genetic risk to illness onset are not yet known. There is substantial evidence suggesting that stress or early adversity (EA) may increase the risk of depressive episodes later in life. Hypothalamic pituitary adrenal (HPA) dysregulation has been shown to mediate the stress response and is one of the most robust biological correlates of mood episodes. Longitudinal prospective research in genetically sensitive offspring is necessary to understand the effects of early adversity on later outcomes, and to clarify the influences of other risk factors such as temperament, stress and HPA axis function. I intend to build upon a funded longitudinal study of the offspring of parents with bipolar disorder and examine the influence of EA on the risk of developing psychopathology. For this research, I will define a novel variable of EA, exposure to active parental illness during the first decade of life, along with a self-report measure of EA including abuse and neglect. I will also include systematic measures of temperament, recent life stress and will sample early morning cortisol, a stress sensitive hormone. This project is aimed at understanding a more comprehensive model of the onset of mood disorders in offspring at risk. Furthermore, this research would for the first time in this population measure EA comprehensively using prospectively captured data at a critical time of development. Results from this research will inform us about the influence of EA on illness outcome in genetically vulnerable offspring, and will facilitate early diagnoses as well as identify novel targets for treatments and most importantly preventative strategies for this debilitating disorder.