Despite advances in the understanding of alterations in brain and behavior in adult affective psychopathology, and the more recent conceptualization of these illnesses as neurodevelopmental in origin, there is a dearth of early developmental data to inform this trajectory. The current proposal aims to fill this gap using data from a unique 13 year prospective longitudinal study, which started in the preschool period and contains three waves of functional and structural scan data: the Preschool Depression Study [PDS]. The proposed extension of this PDS study will focus on three constructs/RDoC domains encompassing specific aspects of emotion reactivity and regulation thought to be central to the development of affective psychopathology: 1) Negative Emotion Reactivity (NER), 2) Reward Reactivity (RR), and 3) Cognitive Emotion Re-appraisal (CER). Data from this sample has already shown that children who were depressed as preschoolers show similar alterations in brain structure and function relevant to the three constructs of interest as established in depressed adults. Brain markers of later recurrence, over and above behavioral symptoms have also been identified. Importantly, both hormonal and psychosocial factors influenced behavior and brain structure/function in the data to date. Follow-up of this unique sample with two additional waves of imaging and comprehensive assessment of these constructs, including measures of hormones, as they pass through adolescence represents an unprecedented, but time limited, opportunity to investigate early developmental antecedents and predictors of adolescent affective psychopathology. The proposed study will directly target the constructs of interest using parent and child report, direct behavioral assessments, and reward and emotion reappraisal tasks during fMRI scanning, as well as structural imaging and resting state functional connectivity, using tools developed in the Human Connectome Project. Using latent growth curve modeling approaches, we will test the hypotheses that specific patterns of individual differences in trajectories of the neural circuitry supporting NER (e.g., insula, hippocampus, amygdala), CER (e.g., dorsolateral prefrontal cortex and dorsal anterior cingulate and RR (e.g., striatum, insula) measured during preschool, school age and/or early adolescence predict: (1a) measures of the same constructs in mid to late adolescence; and (1b) risk for reoccurrence or new onset of affective psychopathology in adolescence, over key phenomenological and psychosocial variables assessed from preschool to school age. We will also test the hypothesis that pubertal timing and hormonal factors interact with both adaptive and impaired forms of NER, RR and CER to contribute to the emergence of sex differences in affective psychopathology during the high-risk phase of adolescence. This work will allow an investigation of the role of early childhood emotion and brain function in the course and trajectory of adolescent affective psychopathology, identification of potential markers of risk and pathways for early intervention, as well as potential mechanisms driving sex differences that emerge at this period.
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NIH ExPorter