Reward, pathophysiologic dimensions and psychological distress in young adults

描述（由申请人提供）：18%的18-25岁的年轻人寻求心理困扰的帮助（例如，抑郁/焦虑症状，无法应对日常压力源和人际关系）。然而，不幸的是，很少或没有以前的精神病史，也没有生物学指标来预测未来的功能结果，并指导这些易感个体的治疗选择。在这些个体中常见的行为和经历的两个维度，对社会心理功能有潜在的有害影响，是：冲动的感觉寻求，倾向和意愿寻求，并承担风险，新奇和强烈的感觉和经历；快感缺乏症，无法体验快乐。研究领域标准是一种精神疾病的维度方法，包括神经回路和自我报告（SR）的行为测量，这些行为与DSM诊断不可知的核心领域的维度结构有关。我们发现，在非寻求帮助（未受影响）和寻求帮助（受影响）的成年人中，奖励神经回路功能的神经成像测量和上述两种行为的SR测量之间存在显著关系，这两种行为反过来又与两个正效价系统域结构相关：奖励期望和对奖励获得的持续反应。我们将招募150名受影响的18-25岁寻求心理困扰帮助的年轻人，无论他们是否被诊断为DSM（1次访问学生咨询/急诊室精神病学家/匹兹堡青年和家庭培训研究所）；转介至初级保健/精神科服务、持续辅导/青少年精神健康服务；未用药或SRI抗抑郁/兴奋剂<2周)；以及125名年龄、性别、种族、社会经济地位和智商匹配的未受影响的个体。我们假设：1。奖励预期：更大的奖励回路活动和功能连接（FC）（在腹侧纹状体（VS），外侧眶额皮质）与金钱奖励预期将与更高的冲动感觉寻求的标准化测量得分相关。对获得奖励的持续反应：更大的内侧前额叶皮层活动和内侧前额叶皮层vs FC对快乐的面孔/金钱奖励的接收将与更高的快感缺乏症标准化测量得分相关。神经成像- sr关系在受影响和未受影响的个体之间可能有所不同。2. 我们将在所有个体中，并在受影响和未受影响的个体中分别确定这些神经影像学和SR测量中的潜在因素。3. 在受影响的个体中，许多这些措施和因素得分的大小将是不良结果的重要预测因素：不。住院天数/门诊重症护理天数；心理困扰、情感/焦虑/ADHD症状、社会心理功能、生活质量恶化；产生自杀意念/企图、精神错乱、药物滥用/依赖。本研究旨在确定18-25岁青少年因心理困扰寻求帮助时反映病理生理维度的指标，最终为这些脆弱的年轻人提供神经生物学靶点，指导个性化治疗，并优化功能结果。

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.