RISK FOR SUBSTANCE ABUSE IN DEPRESSED ADOLESCENTS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。青少年时期物质使用障碍（SUD）的发展是一个重大的公共卫生问题，不仅关系到青少年群体，而且关系到成年人的长期心理健康。在青少年中，抑郁常与抑郁同时发生，在一些青少年中，抑郁可能是SUD的前兆。合并抑郁和SUD与显著增加的社会心理和经济负担相关，因此强调有必要确定增加这些疾病风险的因素。一些研究提出了关于抑郁症、SUD、社会心理压力和下丘脑-垂体-肾上腺（HPA）系统之间关系的假设。为了支持这一假设，在两项初步研究中，我们已经表明，皮质醇升高，或高水平的生活压力，与抑郁青年患SUD的风险增加有关。采用纵向设计，本研究旨在通过在抑郁青少年出现这些问题之前招募他们来研究抑郁青少年发展出抑郁障碍的风险。该研究还旨在评估该队列中HPA失调与SUD风险之间的关系。心理社会压力在预测SUD风险中的作用将在有和没有HPA失调的人群中进行评估。除了估计HPA失调和/或社会心理压力患者发生SUD的风险程度外，还将确定这些易感个体预防SUD的因素。该项目还旨在评估SUD对抑郁症临床病程和社会适应的影响。如果我们的初步结果显示高皮质醇与SUD风险之间的关系，在更大的抑郁青少年样本中得到重复，这一发现可能有助于确定可能从抗抑郁药或抗糖皮质激素治疗策略中获益最多的青少年亚组。有证据表明，抗抑郁药物的良好反应可能是由于下丘脑轴的正常调节。如果压力增加了某些抑郁青年患SUD的风险，他们可能会从辅助心理社会干预中受益。更集中和有效的治疗可能有助于降低抑郁青年患SUD的风险。此外，这种治疗策略可以扩展到非抑郁青年的测试中。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The development of substance use disorder (SUD) during adolescence is a major public health problem which not only relates to the younger population, but also for the long-term mental health of adults. SUD often co-occurs with depression in adolescents and in some youth, depression may be a precursor to SUD. Comorbid depression and SUD is associated with significant added psychosocial and economic burden, thus highlighting the need to identify factors that increase the risk for these disorders. Several lines of investigation suggest hypotheses for examining the associations among depression, SUD, psychosocial stress and hypothalamic-pituitary-adrenal (HPA) system. In support of this hypothesis, in two preliminary studies, we have shown that elevated cortisol, or high level of life stress, is associated with increased risk for SUD in depressed youth. Using a longitudinal design, this investigation aims to examine the risk for development of SUD in depressed adolescents by recruiting you th before they develop these problems. The study also aims to evaluate the association between HPA dysregulation and risk for SUD in this cohort. The contribution of psychosocial stress in predicting risk for SUD will be assessed in those with and without HPA dysregulation. In addition to estimating the magnitude of risk for SUD in those with HPA dysregulation and/or psychosocial stress, factors that confer protection against SUD in such vulnerable individuals will be identified. The project is also designed to assess the effects of SUD on clinical course of depression and on social adjustment. If our initial results, showing a relationship between high cortisol and risk for SUD, are replicated in a larger sample of depressed adolescents, the findings potentially might be helpful in identifying the subgroup of youth who might benefit most from antidepressant or anti-glucocorticoid treatment strategies. Evidence suggests that a good response to antidepressant agents may be due to the do wn-regulation of the HPA axis. If stress contributes to the risk for SUD in some depressed youth, they might benefit from adjunctive psychosocial interventions. More focused and effective treatments potentially might be helpful in reducing the risk for SUD in depressed youth. Moreover, such treatment strategies can be extended for testing in non-depressed youth.