Anhedonia as a Risk Factor and Consequence of Substance Use

描述（由申请人提供）：物质使用是可预防的死亡和残疾的主要原因。药物使用通常在青春期开始和发展。因此，确定青少年药物使用开始和发展的新风险因素可能为制定创新性预防干预措施提供信息，从而减轻药物使用的公共卫生负担。快感缺乏症是一种情感维度，表明对奖励的兴趣和愉悦感减弱，最近已被确定为与物质使用有关。然而，现有文献中的关键空白阻止了对快感缺乏与物质使用关系的研究对该领域产生实质性影响。例如，现有的研究完全是横断面的，未能解析出共同的前因和背景因素的作用，使得这种联系的偶然特征不清楚。此外，过去的工作主要是研究成年人，只有三篇发表的关于青少年快感缺乏与物质使用关系的研究；每一项研究都有严重的局限性。此外，之前的每项研究都只使用了一种基于主观报告的快感缺乏症测量方法，而忽略了快感缺乏症结构的多面性。阐明快感缺乏症在物质使用中的不同方面的相对作用，对于设计新的预防方案至关重要，这些方案可以提高对健康替代非药物强化的兴趣的快感反应。此外，这些文献在很大程度上是脱节的和理论性的，以前没有努力将研究结果整合到一个更大的风险概念化的统一模型中。然而，重要的是要建立模型，以确定在从使用开始到发展的发展途径中，快感缺乏增加物质使用风险的理论机制，以推进基础理论和为干预开发提供信息。这样的研究对于开发针对快感缺乏的物质使用预防干预措施至关重要。因此，我们提出了一项纵向研究，以检验基于一个新的综合模型的假设，该模型预测快感缺乏会产生因果风险途径，通过正强化机制影响物质使用的开始和进展。该模型认为，快感缺乏症较高的个体对物质产生积极作用有预期，愿意使用物质，从而促进物质使用起始。一旦开始使用，高快感缺乏症个体可能对药物的急性主观奖励效应更敏感，这可能进一步降低非药物奖励的相对重要性，并导致替代强化的参与度下降。这两个因素可能会在药物相关强化与替代强化的价值之间造成强烈的不平衡，这可能会推动再次使用的动机，并增加物质使用进展的可能性。这些途径对于那些伴随特征的人来说可能特别突出，这些特征促进了快感缺乏对开始和进展物质使用动机的影响的表达。一旦建立了持续的使用，重复的药物暴露可能会导致心理生物学适应，进一步加剧快感缺乏，重复这个循环，并导致更多的使用。在本研究中，我们将招募2007名高中生参加一项纵向研究，每半年进行8次自我报告评估（9 - 12年级）。评估将在学校环境中进行，这将促进高效和有效的数据收集，并将涵盖自我报告测量和快感缺乏症的客观行为测量。该研究的主要目的是验证以下假设：(1)快感缺乏症将前瞻性地预测那些没有药物使用史的人开始使用药物；(2)快感缺乏症将前瞻性地预测药物使用的进展；(3)随着时间的推移，更频繁的使用将前瞻性地预测快感缺乏症的增加。第二个目标是积极的强化机制，调解和缓和快感缺乏对源自该模型的物质使用风险的影响。从这项研究中获得的信息可能对开发新的，更有效的预防策略具有重要价值，这些策略可以增强体验愉悦和积极强化，以防止物质使用。这些努力最终可以减轻药物使用障碍造成的巨大公共卫生负担。

DESCRIPTION (provided by applicant): Substance use is a leading cause of preventable death and disability. Substance use typically onsets and progresses during adolescence. Thus, identifying novel risk factors for adolescent substance use initiation and progression may inform the development of innovative preventive interventions that reduce the public health burden of substance use. Anhedonia-an affective dimension indicative of diminished interest and pleasure in rewarding-has been recently identified as a correlate of substance use. However, critical gaps in the extant literature prevent research on anhedonia's relation with substance use from having a substantial impact on the field. For example, existing research has been entirely cross-sectional and has failed to parse out the role of common antecedents and contextual factors, leaving the casual features of this association unclear. Also, past work has primarily studied adults, with only three published studies of anhedonia-substance use relations in adolescents; each of these studies are subject to critical limitations. Furthermore, each prior study has used only a single measure anhedonia based on subjective report, which ignores multi-faceted nature of the anhedonia construct. Elucidating the relative roles of distinct facets of anhedonia in substance use is critical for designing novel prevention programs that raise hedonic response to an interest in healthy alternative non-drug reinforces. Additionally, this literature has been greatly disjointed and theoretical, with no previous effort to integrate findings into a unifying model within larger conceptualization of risk. Yet, it is important for models to identify theoretial mechanisms by which anhedonia increases substance use risk in a developmental pathway from use initiation to progression in order to advance basic theory and inform intervention development. Such research is critical in order to move forward with developing substance use preventive interventions that target anhedonia. Accordingly, we propose a longitudinal study to test hypotheses based on a novel integrative model, which predicts that anhedonia gives rise to a causal risk pathway that influences both substance use initiation and progression via positive reinforcement mechanisms. This model purports that individuals with higher anhedonia have expectations that substances will produce positive effects and are willing to use substances, which could promote substance use initiation. Once use is initiated, high-anhedonia individuals may be more sensitive to the acute subjective rewarding effects of drugs, which may further devalue the relative salience of non-drug rewards and result in declining engagement in alternative reinforces. These two factors may create a strong imbalance between the value of drug-related versus alternative reinforces, which may drive motivation to use again and increase likelihood of substance use progression. These pathways may be particularly prominent for those with concomitant characteristics that facilitate the expression of anhedonia's influence on motivation to initiation and progress substance use. Once consistent use is established, repeated drug exposure may cause psychobiological adaptations that further escalate anhedonia, recapitulate this cycle, and lead to more use. In this study, we will recruit a cohort f 2007 high school students to participate in a longitudinal study with 8 semiannual waves of self-report assessment (9th - 12th grades). Assessments will take place in the school setting, which will facilitate efficient and effective data collection, and will span both self-report measures an objective behavioral measures of anhedonia. The primary aims of the study are to test the hypotheses that: (1) anhedonia will prospectively predict substance use initiation among those with no prior history of use, (2) anhedonia will prospectively predict substance use progression, and (3) Greater frequency of use will prospectively predict increases in anhedonia over time. Secondary aims will positive reinforcement mechanisms that mediate and moderate the effects of anhedonia on substance use risk that are derived from the model. The information gained from this study could be of significant value to developing novel, more effective prevention strategies that enhance experiential pleasure and positive reinforcement to prevent substance use. Such efforts could ultimately allay the substantial public health burden caused by substance use disorders.