Reward, pathophysiologic dimensions and psychological distress in young adults

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DESCRIPTION (provided by applicant): 18% of 18-25 year-olds seek help for psychological distress (e.g., depressive/anxiety symptoms, failing to cope with everyday stressors and interpersonal relationships). Yet unfortunately, there are few or no previous psychiatric history, and no biological, measures to predict future functional outcome and guide treatment choice for these vulnerable individuals. Two dimensions of behaviors and experiences that are common in these individuals, with potentially deleterious consequences for psychosocial function, are: impulsive sensation seeking, the tendency and willingness to seek, and take risks for, novel and intense sensations and experiences; and anhedonia, the inability to experience pleasure. The Research Domain Criteria is a dimensional approach to psychiatric illness that includes neural circuitry and self-report (SR) measures of behaviors related to dimensional constructs in core domains that are agnostic to DSM diagnoses. We have identified in non-help seeking (unaffected) and help-seeking (affected) adults significant relationships among neuroimaging measures of reward neural circuitry function and SR measures of the above two behaviors, that are in turn related to two positive valence systems domain constructs: reward expectancy and sustained responsiveness to reward attainment. We will recruit 150 affected 18-25 year-olds seeking help for psychological distress, irrespective of DSM diagnosis (>1 visit to student counseling/ emergency room psychiatrist/ Pittsburgh Youth and Family Training Institute (YFTI); referred to primary care/psychiatric services, continuing counseling/YFTI; unmedicated or SRI antidepressant/stimulants <2 weeks); and 125 age-, gender-, ethnicity-, SES- and IQ-matched unaffected individuals. We hypothesize: 1. Reward expectancy: greater reward circuitry activity and functional connectivity (FC) (in ventral striatum (VS), lateral orbitofrontal cortex) to monetay reward expectancy will be associated with higher scores on standardized measures of impulsive sensation seeking. Sustained responsiveness to reward attainment: greater medial prefrontal cortical activity and medial prefrontal cortical-VS FC to happy faces/monetary reward receipt will be associated with higher scores on standardized measures of anhedonia. Neuroimaging-SR relationships may differ between affected and unaffected individuals. 2. We will identify underlying factors among these neuroimaging and SR measures in all individuals, and separately in affected and unaffected individuals. 3. In affected individuals, the magnitude of many of these measures and factor scores will be significant predictors of poor outcome: no. days' hospitalization/intensive outpatient care; worsening psychological distress, affective/anxiety/ADHD symptoms, psychosocial function, quality of life; developing suicide ideation/attempt, psychosis, substance abuse/dependence. The proposed study aims to identify measures reflecting dimensions of pathophysiology in 18-25 year-olds seeking help for psychological distress, to ultimately provide neurobiological targets to guide personalized treatment, and optimize functional outcome for these vulnerable young people.