THE DEVELOPING BRAIN DEVELOPING PSYCHOPATHOLOGY

Abstract

Overall Abstract Psychiatric disorders emerge over time and frequently the initial manifestations are apparent in early life. The early signs of psychopathology in childhood are often related but not identical to the clinical presentation during the adult years. Among individuals who develop classical bipolar disorder there is often a history of anxiety and / or behavioral disorders. Further, there have been hypotheses about a causal relationship between attention and cognitive disorders that begin in childhood and lead to or become bipolar disorder in adulthood. This symposium addresses clinical and cellular mechanisms of development in bipolar disorder. John Nurnberger will present and review data from an extensive “at risk” study in the USA inwhich offspring of parents with Bipolar disorder type I have been followed clinically for the emergence of psychiatric illness over time. The appearance of multiple types of psychopathology in the background of an elevated risk for bipolar suggests a causal mechanism in the evolution of adult psychopathology. Philip Mitchell, Australia, will present prospective findings on clinical and neurobiological predictors of ‘conversion’ to bipolar disorder. Detailed clinical, imaging, and genetic data from “at risk offspring” for bipolar disorder provide clear support of biological mechanisms that drive the increased risk for psychopathology in these individuals. Functional and structural neuroimaging connectivity studies from the Australian group reveal reduced connectivity in circuits responsible for emotion, and in particular implicate the inferior frontal gyrus. Research at the University of Michigan (McInnis & O’Shea) identified cellular models of neurons and astrocytes that are derived from induced pluripotent stem cells made from fibroblasts of bipolar individuals demonstrate differential patterning in early development and respond differently to patterning factors. Models that examine patterns of expression of mitochondrial genes among patients with schizophrenia demonstrate differential patterns among these genes that suggest there are intrinsic differences at very early stages of development. This symposium will integrate clinical and laboratory based models with the goals of identifying strategic time periods, psychopathology patterns, and biologically based models to study molecular mechanisms underlying the trajectory individuals at risk for and ultimately develop bipolar disorder.