Cocaine and HIV-mediated disruptions of hypothalamic signaling in hypothyroidism

描述(由申请者提供)：低社会经济背景、失业和环境低迷对求职者的观点和行为有重要影响。同样，一些患有情绪障碍的人可能会推迟寻求医疗保健，或者可能没有医疗福利，而转向药物滥用(SA)作为替代方案。一些与SA和/或HIV感染相关的共病直接影响行为和认知，并对生活质量、坚持抗逆转录病毒治疗和成功的药物成瘾治疗方案产生重大影响。在这种情况下，甲状腺激素水平的变化已经成为一些SA障碍和/或艾滋病毒感染患者的并发症，尽管这种联系的分子基础尚不清楚。我们的广泛假设是，SA和HIV CNS疾病导致下丘脑-垂体-甲状腺(HPT)反馈环路中断，并可能导致或加剧甲状腺功能减退。我们认为，这些干扰部分发生在下丘脑信号水平，并可能部分导致在许多滥用可卡因和HIV阳性的人中观察到的HPT综合征。我们拟议的探索性研究的结果将提供设计更详细研究所需的宝贵信息，以解决以下问题： 可卡因、HIV、HAART和CNS HPT信号的分子相互作用 对认知功能障碍、行为和疾病进展的影响 存在甲状腺疾病风险的SA障碍HIV患者的治疗策略。 我们的研究旨在解决可卡因和/或艾滋病毒是否会影响先前存在的亚临床或显性 提高治疗药物滥用者和/或艾滋病毒患者的医疗保健提供者的认识。如果不加以控制，这些疾病的组合可能会导致SA增加和更快的疾病进展。拟议研究的结果将增加我们对SA障碍和/或HIV感染患者下丘脑信号改变如何导致认知能力下降和疾病进展，和/或治疗失败的理解。 公共卫生相关性：甲状腺激素水平的变化已经成为一些SA障碍和/或艾滋病毒感染患者的并发症，尽管这种联系的分子基础尚不清楚。如果不加以控制，这些疾病的组合可能会导致SA增加和更快的疾病进展。我们的研究将为解决可卡因、艾滋病毒和中枢神经系统甲状腺信号之间的分子相互作用提供信息。

DESCRIPTION (provided by applicant): Low socio-economic background, unemployment and depressed environmental surroundings play significant roles in outlook and behavior. Likewise, some individuals suffering from mood disorders may delay seeking healthcare or may not have healthcare benefits and turn to substance abuse (SA) as an alternative. Some comorbidities associated with SA and/or HIV infection directly affect behavior and cognition, and impact significantly on quality of life, adherence to anti-retroviral therapy and successful drug addiction treatment programs. In this context, alterations in thyroid hormone levels have emerged as a complication among some individuals with SA disorders and/or HIV infection, although the molecular basis for the connection is unknown. Our broad hypothesis is that SA and HIV CNS disease contribute to disruptions in the hypothalamic pituitary thyroid (HPT) feedback loop and may lead to or exacerbate hypothyroidism. We propose that these disruptions occur, in part, at the level of hypothalamic signaling and may contribute, in part, to HPT syndrome observed in many individuals who abuse cocaine and are HIV positive. Results from our proposed exploratory study will provide valuable information needed to design more detailed studies addressing: molecular interactions among cocaine, HIV, HAART and CNS HPT signaling impact on cognitive dysfunction, behavior and disease progression treatment strategies for HIV patients with SA disorder at risk for thyroid disease. Our studies are designed to address if cocaine and/or HIV affect pre-existing subclinical or overt hypothyroidism to provide increased awareness among healthcare providers treating substance abuser and/or HIV patients. Left unchecked, the combination of these disorders could lead to increased SA and more rapid disease progression. Results from the proposed studies will increase our understanding of how altered hypothalamic signaling in patients suffering from SA disorders and/or HIV infection may contribute to declining cognition and disease progression, and/or treatment failure. PUBLIC HEALTH RELEVANCE: Alterations in thyroid hormone levels have emerged as a complication among some individuals with SA disorders and/or HIV infection, although the molecular basis for the connection is unknown. Left unchecked, the combination of these disorders could lead to increased SA and more rapid disease progression. Our study will provide information to address molecular interactions among cocaine, HIV, and CNS thyroid signaling.