The Effects of Early Life Stress on the Development of Brain Networks: Predicting Risk for Depression and Suicidal Ideation in Adolescence

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Project Summary/Abstract Early life stress (ELS), including abuse, neglect, and loss, is associated with dramatic increases in lifelong risk for the development of mental health difficulties, such as depression and suicidal thoughts. In addition, depressed adolescents exhibit anomalies in networks of the brain that are involved in affective, cognitive, reward, and self-referential processing. Alterations in many of these networks are also associated with ELS and suicidal ideation (SI). Thus, it is possible that ELS affects the development of depression-related brain networks and contributes to risk for depressive episodes and SI. The neurodevelopmental mechanisms through which ELS might confer risk for these negative outcomes, however, are not well understood. In the proposed study, we will examine, for the first time, brain network development in adolescents with varying levels of ELS, in order to characterize trajectories that are associated with emergence of major depressive disorder (MDD) and SI. To this end, we will assess the effects of ELS on the development of brain networks longitudinally through adolescence to elucidate risk-related neurobiological mechanisms. In addition, we will examine concurrent and longitudinal associations of network development, depressive symptoms, and SI in youth with varying levels of ELS. Finally, we will determine whether developmental trajectories of networks predict the onset of MDD and SI. The results of this study will not only increase our understanding of the relations among ELS, brain network development, and mental health outcomes of MDD and SI, but will also provide insight into neuromarkers of depression and SI during the critical period of adolescence, a stage of increased risk for the onset of mental health difficulties. In addition, this research will advance our understanding of neuroprotective mechanisms in adolescents who have been exposed to ELS and yet do not develop depression and/or suicidal symptoms. Familial- and individual-level mediators between early life stress and the emergence of MDD and SI will also be examined in relation to brain network development. Thus, we anticipate that the current study will contribute to our understanding both of models of the onset of psychopathology following ELS and of neurobiological mechanisms by which ELS confers heightened risk for negative mental health outcomes. Findings from the proposed study will increase our knowledge of the developmental neurobiology of depression and SI, and will provide insight into the onset and progression of disorder following early adversity.