Depression/Metabolic Syndrome in Mexican-American Women.

描述（由申请人提供）：本资助申请旨在验证以下假设：重度抑郁症（MDD）患者的胰岛素抵抗和高血糖趋势与血浆皮质醇水平平行。我们还将测试更集中的假设，即治疗抑郁症状改善胰岛素抵抗状态。我们将通过研究抑郁症的墨西哥裔美国妇女来接近这些假设，这些妇女来自一个严格特征化的患者队列，这些患者已被招募到我们的NIGMS资助的抗抑郁治疗反应的药物基因组学项目（GM61394）中。该应用程序建立在前瞻性研究提供的巨大资源的基础上，该研究提供了招募和治疗这些人的机会。该项目是一项精心设计的前瞻性临床IIA期随机纵向研究，使用两种药物（地昔帕明和氟西汀），在墨西哥裔美国人人群中治疗MDD具有疗效。临床状态通过临床访谈和评分进行评估，如汉密尔顿抑郁评分量表、贝克抑郁量表和汉密尔顿焦虑评分量表。这些文书已在西班牙文中得到广泛验证。该项目是一项单盲和双盲治疗研究，随机分配治疗，并通过临床措施评估结局。所有受试者将接受全面的摄入评估，然后进行随访评估。将根据我们批准的方案提供治疗。我们建议在体重正常的墨西哥裔美国妇女中进行详细的内分泌、营养和代谢研究，这些妇女在其他方面都是健康的，并且将在我们的药物基因组学研究中进行广泛的表征。该提案将允许通过评估治疗前后的内分泌（HPA轴和瘦素测量）、营养、身体组成和代谢功能（将通过口服葡萄糖耐量试验、葡萄糖钳夹和精氨酸刺激试验评估胰岛素敏感性）来确定MDD的胰岛素抵抗程度。治疗结局数据将与内分泌和代谢终点相关。几条证据表明糖尿病通常与抑郁症有关，抑郁症会增加患糖尿病的风险。这项工作将解决这一重要领域的人口群体谁是明显代表面向病人的调查研究。

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.