Adolescence is a high-risk period for the emergence of depression. Early identification and prevention are critical to reducing incidence and impact, and to aid these efforts research has begun to examine fundamental neural systems and mechanisms that underlie risk. Adolescence is a key period for reward circuit development, and abnormalities in the reward system are central to many etiological models of depression. [Event-related potential (ERP) and functional MRI (fMRI) measures of reward sensitivity are promising biomarkers of risk for depression. However, supporting evidence has primarily been cross-sectional, relied on a single neural measure, and/or not examined whether neural measures have predictive value above other risk factors (e.g., maternal history of depression, prior symptoms). Research on reward circuit development has largely not examined within-subjec t trajectories of change. This is a critical gap in the literature as three assessments are suggested for growth curve modeling, and four assessments allow for a better examination of non-linear changes. Trajectories of reward circuit development may provide a more sensitive measure of individual differences compared to a single assessment, particularly in relation to risk for psychopathology, and may help identify optimal points of intervention.] The proposed study is a competitive renewal of the trajectories of reward sensitivity across adolescence project (R01MH097767) that involved 317 8 to 14 year-old girls and a biological parent. The project is a multimodal neuroimaging study of reward sensitivity (ERPs and fMRI) and depressive symptoms that included a baseline (T1; ages 8 to 14) and follow-up assessment two years later (T2; ages 10 to 16). At T2, the majority of girls were just entering adolescence and had not completely traversed this pivotal period for reward system development and increased risk for depression. The proposed study will involve two additional assessments (T3; ages 12 to 18, and T4: ages 14 to 20) of neural reward sensitivity and psychopathology in girls, and [the addition of self-report and physiological measures of stress accumulation], which may impact reward trajectories and the emergence of depression. This study has three primary aims. First, we will examine whether maternal risk predicts developmental trajectories of reward in adolescent girls (Aim 1). These analyses will be conducted in adolescent girls who had no lifetime history of a depressive disorder at the baseline (T1) assessment (N=301). Maternal risk will be determined using two approaches: maternal history of depression and maternal reward sensitivity (measured via ERPs and fMRI). We will test the novel possibility that maternal reward sensitivity, compared to maternal history of depression, will better account for developmental trajectories of the adolescent girls? reward system. Second, we will examine whether developmental trajectories of reward predict depression in adolescent girls (Aim 2). Finally, we will examine the impact of stress on developmental trajectories of reward and depression in adolescent girls (Aim 3). Across Aims 1-3, we will test whether the ERP and fMRI measures exhibit similar or non-overlapping relationships with maternal risk and the development of depression.

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In a sample of 317 adolescent girls, this proposed study will use a longitudinal multimethod neuroimaging (ERPs and fMRI) approach to examine within-subject trajectories of reward sensitivity across adolescence in relation to depression risk (maternal lifetime history of depression, maternal reward sensitivity, and adolescent stress) and the development of depressive symptoms and syndromes.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Child Psychopathology and Developmental Disabilities Study Section (CPDD)
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Murphy, Eric Rousseau
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State University New York Stony Brook
Schools of Arts and Sciences
Stony Brook
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