物质滥用和抑郁症经常同时发生。青春期似乎是两种现象增长的一个脆弱的发展阶段，通常归因于奖赏和动机系统的快速成熟。另一个促成因素可能是炎症信号，它与物质使用障碍和抑郁症都有关联。先前的研究表明，炎症活动的增加会引起身体和情绪的疲劳，类似于抑郁症，而缺乏愉悦感和身体症状则可能导致物质使用。这种认为物质使用是一种自我药疗的观点，尚未得到以前的研究。为了测试这些联系，我们使用路径分析来研究老年青少年多个亚临床样本中三种前炎症标志物、特定的抑郁症状和物质使用频率之间的同步和前瞻性关联。参与者完成了重复的特定抑郁症状的自我报告措施（即情绪低落、缺乏愉悦感、身体问题、消极认知和功能困难）和物质使用频率的自我报告措施。采集血样来定量循环白细胞介素（IL）-6、肿瘤坏死因子-α（TNF-α）和C-反应蛋白（CRP）的水平。这项分析显示，IL-6和TNF-α水平对未来的物质使用有间接影响，但是只通过功能困难来实现。物质使用也预测未来的功能困难。只有缺乏愉悦感直接预测未来物质使用频率。这些发现有助于更精细地确定炎症生理和特定抑郁症状如何协同作用，增加物质使用的风险。 版权所有© 2023 Elsevier Inc.。保留所有权利。

Substance use and depression frequently co-occur. Adolescence appears to be a vulnerable developmental period for increases in both substance use and depressive symptoms, often attributed to rapid maturation of reward and motivation systems. Another contributing factor could be inflammatory signaling, which has been associated with both substance use disorder and depression. Prior research indicates that an increase in inflammatory activity can cause physical and emotional malaise, which resembles depression, and the anhedonia and somatic symptoms could lead to substance use. This perspective that substance use is a type of self-medication in response to anhedonia and subjective experiencing of increased inflammatory physiology has not been investigated previously. To test these associations, we used path analysis to examine concurrent and prospective associations between three pro-inflammatory markers, specific depressive symptoms, and substance use frequency in a diverse sample of older adolescents. Participants completed repeated self-report measures of specific depressive symptoms (i.e., dysphoria, anhedonia, somatic concerns, negative cognitions, and functional difficulties) and substance use frequency. Blood was collected to quantify circulating levels of interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). This analysis showed an indirect effect of IL-6 and TNF-α levels on future substance use, but only via functional difficulties. Substance use also predicted future functional difficulties. Only anhedonia directly predicted future substance use frequency. These findings help to more precisely identify pathways through which inflammatory physiology and specific depressive symptoms synergistically confer risk for substance use.Copyright © 2023 Elsevier Inc. All rights reserved.