Fragmented early-life experiences, aberrant circuit maturation, emotional vulnerabilities

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Project 3, integrated with the Center, investigates the processes and mechanisms by which a novel type of early adversity influences the development of psychopathology. Early adversity is one of the strongest and most widely reproduced determinants of subsequent mental illness. Novel findings from the current Center award period identify fragmented and unpredictable early life experiences (FRAG), especially unpredictable maternal signals, as altering trajectories of brain circuit maturation and influencing subsequent mental health. In addition to several emotional and cognitive consequences, we recently discovered anhedonia, a transdiagnostic risk factor for psychopathology, as resulting from exposure to FRAG. Project 3 will capitalize on a carefully characterized longitudinal cohort followed from early fetal life through adolescence, coupled with cutting-edge longitudinal neuroimaging techniques and computational network analyses and recently validated novel assessment tools to uncover the mechanisms by which unpredictable prenatal and postnatal maternal and environmental signals influence neurodevelopmental trajectories and underlying circuit development that contribute to mental health through young adulthood. Sex-specific susceptibilities to the effects of early-life FRAG on trajectories of neural circuit maturation and emotional and cognitive functions will be addressed in all 3 Aims. With Projects 1, 2, 4 and the BCDM and Imaging Cores, we will determine the consequences of early-life FRAG on neural circuits and behavioral trajectories that predict psychopathology with an emphasis on anhedonia during adolescence and young adulthood.