Reward, pathophysiologic dimensions and psychological distress in young adults

描述（由申请人提供）：18%的18-25岁的人寻求心理困扰的帮助（例如，抑郁/焦虑症状，无法科普日常压力和人际关系）。然而，不幸的是，很少或根本没有以前的精神病史，也没有生物学的措施来预测未来的功能结果，并指导这些脆弱的个人的治疗选择。在这些个体中常见的两个方面的行为和经验，对心理社会功能具有潜在的有害后果，是：冲动的感觉寻求，寻求和冒险的倾向和意愿，新奇和强烈的感觉和经验;和快感缺乏，无法体验快乐。研究领域标准是精神疾病的维度方法，包括神经回路和与DSM诊断不可知的核心领域中的维度结构相关的行为的自我报告（SR）测量。我们已经确定在非寻求帮助（未受影响）和寻求帮助（受影响）的成年人之间的显着关系的神经影像学措施的奖励神经回路功能和SR措施的上述两种行为，这反过来又涉及到两个积极的效价系统域结构：奖励预期和持续的反应，以奖励的实现。我们将招募150名受影响的18-25岁寻求心理困扰帮助的青少年，无论DSM诊断如何（>1次访问学生咨询/急诊室精神科医生/匹兹堡青年和家庭培训研究所（YFTI）;转介到初级保健/精神病服务，继续咨询/YFTI;未用药或SRI抗抑郁药/兴奋剂<2周）;和125名年龄、性别、种族、SES和IQ匹配的未受影响的个体。我们假设：1.期望奖励：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）到货币奖励期望将与冲动感觉寻求的标准化测量的更高分数相关。对获得奖励的持续反应：内侧前额叶皮层活动和内侧前额叶皮层-VS FC对快乐面孔/金钱奖励的接受程度越高，则快感缺乏的标准化测量得分越高。神经成像SR关系可能会有所不同，受影响和未受影响的个人。2.我们将确定这些神经影像学和SR措施中的潜在因素，在所有个人，并分别在受影响和未受影响的个人。3.在受影响的个体中，许多这些指标和因子评分的大小将是不良结局的重要预测因素：住院天数/重症门诊护理;心理困扰、情感/焦虑/ADHD症状、心理社会功能、生活质量恶化;出现自杀意念/企图、精神病、药物滥用/依赖。该研究旨在确定反映18-25岁寻求心理困扰帮助的病理生理学维度的措施，最终提供神经生物学目标以指导个性化治疗，并优化这些弱势年轻人的功能结果。

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.