Depression/Metabolic Syndrome in Mexican-American Women.

描述（由申请人提供）：本资助申请旨在验证胰岛素抵抗和高血糖趋势与重度抑郁症（MDD）血浆皮质醇水平平行的假设。我们还将测试更集中的假设，即抑郁症状的治疗改善胰岛素抵抗的状态。我们将通过研究墨西哥裔美国女性抑郁症患者来验证这些假设，这些患者来自于我们nigms资助的抗抑郁药物基因组学研究项目（GM61394）。这个应用程序建立在前瞻性研究提供的巨大资源的基础上，它提供了招募和治疗这些个体的机会。该项目是一项精心设计的前瞻性临床IIA期随机纵向研究，使用两种药理学药物（地西帕明和氟西汀）治疗墨西哥裔美国人的重度抑郁症。临床状态通过临床访谈和汉密尔顿抑郁评定量表、贝克抑郁量表和汉密尔顿焦虑评定量表等评定。这些工具已在西班牙语中得到广泛验证。该项目是一项治疗研究，采用单屏蔽和双屏蔽，随机分配治疗，并通过临床措施评估结果。所有受试者将接受全面的入学评估，然后进行后续评估。治疗将按照我们批准的方案进行。我们建议对体重正常的墨西哥裔美国妇女进行详细的内分泌、营养和代谢研究，这些妇女在医学上是健康的，并将广泛地用于我们的药物基因组学研究。该建议将允许通过评估治疗前后的内分泌（HPA轴和瘦素测量）、营养、身体成分和代谢功能（胰岛素敏感性将通过口服葡萄糖耐量试验、葡萄糖钳和精氨酸刺激试验评估）来确定MDD患者的胰岛素抵抗程度。治疗结果数据将与内分泌和代谢终点相关。一些证据表明，糖尿病通常与抑郁症有关，而抑郁症会增加患糖尿病的风险。这项工作将通过研究一个在以患者为导向的调查中明显不足的人群来解决这一重要领域。

DESCRIPTION (provided by applicant): This grant application has been developed to test the hypothesis that insulin resistance and hyperglycemic trends parallel plasma cortisol levels in major depressive disorder (MDD). We will also test the more focused hypothesis that treatment of depressive symptoms ameliorates state of insulin resistance. We will approach these hypotheses by studying depressed Mexican-American women from a rigorously characterized cohort of patients who have been recruited into our NIGMS-funded project in pharmacogenomics of antidepressant treatment response (GM61394). This application builds on the enormous resource provided by that prospective study, which provides the opportunity to recruit and treat these individuals. That project is a carefully designed, prospective clinical phase IIA randomized longitudinal study, using two pharmacological agents (desipramine and fluoxetine) with demonstrated efficacy in the treatment of MDD in the Mexican-American population. Clinical status is assessed with clinical interview and ratings such as the Hamilton Ratings Scale for Depression, Beck Depression Inventory, and Hamilton Anxiety Rating Scale. These instruments have been extensively validated in Spanish. That project is a treatment study with single- and double-masking, with random assignment of treatment, and with outcomes assessed with clinical measures. All subjects will undergo comprehensive intake assessments, and will then have follow-up assessments. Treatment will be provided according to our approved protocol. We propose to conduct detailed endocrine, nutritional, and metabolic studies in normal-weight Mexican-American women, who are otherwise medically healthy and who will be extensively characterized for our pharmacogenomic study. This proposal will permit the ascertainment of degree of insulin resistance in MDD through the assessment of endocrine (HPA axis and leptin measurements), nutritional, body composition, and metabolic function (insulin sensitivity will be assessed by oral glucose tolerance test, glucose clamp and arginine stimulation test) before and after treatment. Treatment outcome data will be correlated with endocrine and metabolic endpoints. Several lines of evidence suggest diabetes mellitus is often associated with depression and that depression increases the risk of developing diabetes. This work will address this important area by the study of an population group who is markedly under represented in patient-oriented investigation.