Stress-Related Psychobiology and Inflammation in Diabetic African-American Women

描述（由申请人提供）：少数民族人口暴露于高水平的创伤，并有最低限度的获得精神和一般医疗保健。本申请中提出的研究试图调查导致具有2型糖尿病（T2 DM）和创伤相关精神病理学（创伤后应激障碍[PTSD]和/或重度抑郁症[MDD]）的较低社会经济地位（SES）的非裔美国妇女的心脏代谢疾病风险升高的心理生物学机制。特别是PTSD，以及某些形式的情绪和焦虑障碍通常反复与神经、神经内分泌和免疫系统的失调相关，其通常特征在于循环去甲肾上腺素增加和副交感神经张力降低、皮质醇分泌异常和全身炎症明显升高。在PTSD、MDD或PTSD/MDD患者中发现了与心理健康受试者不同的应激反应的自主神经、神经内分泌和炎性先天免疫介质产生的定量差异。因此，应激介质可能通过诊断依赖性生物学途径差异性地影响受PTSD和/或MDD影响的患者中肥胖、血脂异常、碳水化合物不耐受和内皮功能受损的发展和进展。尽管在试图了解心脏代谢疾病和创伤相关精神疾病的病理生理机制时，许多报告表明自主神经、神经内分泌和免疫因素之间存在关系，但迄今为止，还没有研究全面研究这些系统的相互作用方式。因此，本项目旨在利用我们在低SES、非裔美国人、初级保健人群中的丰富经验，以及母项目（MH 071537）的完善研究和招募基础设施，在（N=140）女性、非裔美国人T2 DM初级保健患者样本中检验以下三个假设：1.）将在创伤暴露的对照和诊断为PTSD、MDD或PTSD+MDD的受试者之间鉴定在心理社会应激挑战（Trier社会应激测试）之前、期间和之后评估的自主神经和神经内分泌功能的测量的显著差异; 2）在心理社会应激挑战之前、期间和之后收集的自主功能和神经内分泌介质的测量将预测在心理社会应激挑战之前、期间和之后收集的炎症介质的测量; 3.）在心理社会应激挑战之前、期间和之后收集的先天性炎症介质将预测心脏代谢功能标准测量的差异（例如葡萄糖耐量试验、血流介导的血管舒张）。本申请中提出的实验所获得的知识将增加我们对T2 DM女性压力心理生物学和创伤相关心理病理学的理解。

DESCRIPTION (provided by applicant): Minority populations are exposed to high levels of trauma and have minimal access to psychiatric and general medical care. The studies proposed in the current application seek to investigate the psychobiological mechanisms responsible for elevated cardiometabolic illness risk in African-American women of lower socioeconomic status (SES) with type 2 diabetes mellitus (T2DM) and trauma-related psychopathology (post- traumatic stress disorder [PTSD] and/or major depressive disorder [MDD]). PTSD in particular, and certain forms of mood and anxiety disorders in general, have been repeatedly associated with dysregulation of the nervous, neuroendocrine, and immune systems that is generally characterized by increased circulating norepinephrine and reduced parasympathetic tone, abnormal secretion of cortisol, and variably elevated systemic inflammation. Quantitative differences in the production of autonomic, neuroendocrine, and inflammatory innate immune mediators of the stress response, distinct from those observed in psychologically healthy subjects, are found in patients with PTSD, MDD, or PTSD/MDD. As a consequence, stress mediators may differentially influence the development and progression of obesity, dyslipidemia, carbohydrate intolerance, and impaired endothelial function in patients affected by PTSD and/or MDD through diagnosis- dependent biological pathways. Although a number of reports suggest a relationship between autonomic, neuroendocrine, and immune factors when attempting to understand the pathophysiological mechanisms linking cardiometabolic illnesses and trauma-related psychiatric disorders, to date no studies have examined in a comprehensive manner the ways by which these systems interact. Accordingly, this project seeks to leverage our extensive experience with a low SES, African-American, primary care population with the well-developed research and recruiting infrastructure of the parent project (MH071537) to test the following three hypotheses in a sample of (N=140) female, African-American primary care patients with T2DM: 1.) Significant differences in measures of autonomic and neuroendocrine function assessed before, during, and after psychosocial stress challenge (Trier Social Stress Test) will be identified between trauma- exposed controls and subjects diagnosed with PTSD, MDD, or PTSD+MDD; 2.) Measurements of autonomic function and neuroendocrine mediators collected before, during, and after psychosocial stress challenge will predict measurements of inflammatory mediators collected before, during, and after the psychosocial stress challenge; 3.) Innate inflammatory mediators collected before, during, and after psychosocial stress challenge will predict differences in standard measures of cardiometabolic function (e.g. glucose tolerance test, flow mediated vasodilatation). Knowledge gained by the experiments proposed in this application will increase our understanding of the psychobiology of stress in women with T2DM and trauma-related psychopathology.