Childhood adversity and central visceral circuits: mechanisms of affective risk

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DESCRIPTION (provided by applicant): Childhood adversity is a risk factor for developing recurrent and chronic mood and anxiety disorders. Further, childhood adversity is associated with dysregulated stress reactivity, which also underlies mood and anxiety disorders. However, the mechanisms by which childhood adversity shapes stress reactivity and confers vulnerability to stress-related affective disorders are unclear. Central visceral circuits (CVCs) comprise a candidate neural mechanism that may underlie both dysregulated stress reactivity and affective disorders. These circuits are the neural basis of brain-body connections, and are responsible for the reciprocal relationship between affect and physiology and the control of stress responses. CVCs encompass descending preautonomic circuits that orchestrate physiological outflow, and ascending viscerosensory circuits that relay information regarding body state from the brainstem to higher order brain areas. Early life experience differentially influences the structure and function of CVCs, as evidenced by studies in rat. While childhood adversity is associated with gross variations (e.g., in volume) within emotion-related brain regions and tracts in humans, littl is known regarding how childhood adversity specifically influences CVCs. To test the central hypothesis that childhood adversity influences later stress reactivity and vulnerability to affectie disorders via changes in the structure and function of CVCs, three aims will be evaluated in a representative community sample of 120 young adults. These participants will be well characterized for childhood adversity (e.g., emotional and physical abuse or neglect, parental arguing) and affective disorder symptoms (i.e., depressive and anxious symptoms). Participants will complete one MRI scanner session in order to gain multimodal neuroimaging data, including: 1. High-resolution structural connectivity (measures derived from a diffusion spectrum imaging sequence and subsequent detailed tractography), 2. Structural integrity (measures derived from a diffusion tensor imaging sequence), and 3. Stressor-evoked functional connectivity (psychophysiological interaction analyses performed with blood-oxygen-level dependent time-series data). Aim 1 tests the hypothesis that childhood adversity will be associated with the structural and functional connectivity of CVCs. Aim 2 tests the hypothesis that childhood adversity will be associated with both stress reactivity (derived from psychophysiological data acquired within the MRI scanner) and affective disorder symptoms. Aim 3 (Exploratory) tests the extent to which CVC structure/function represents a part of the path between childhood adversity and stress reactivity or affective disorder symptoms. Significance: Uncovering adversity-related changes in the structure and function of CVCs has the potential to provide methods of early detection of risk for affective disorders and of assessing the effectiveness of interventions in treating affective disorders.