Pioglitazone for Treatment of Unremitted Depression in Insulin Resistant Patients

描述(由申请人提供)：严重抑郁障碍(MDD)和II型糖尿病(DM2)具有许多共同的病理生理特征，反映了中枢神经系统(CNS)和内分泌稳态之间的双向联系。患有DM2的患者有很高的抑郁发生率，反过来，患有抑郁症的患者患DM2的风险也更高。胰岛素抵抗(IR)或“糖尿病前期”通常伴有抑郁症状，抑郁症患者有提示高IR的生物标记物。对这些相互联系的更多了解可能会导致抑郁症的概念化和治疗方式的戏剧性转变，更多地关注适当的代谢功能。目前的应用旨在通过安慰剂对照设计研究PPAR激动剂(吡格列酮)治疗改善胰岛素抵抗对情绪的影响。这项研究将招募80名抑郁症患者，其中一半患有胰岛素抵抗，另一半没有胰岛素抵抗。受试者将在12周的双盲治疗前后接受临床内分泌学评估(包括口服葡萄糖耐量测试)和神经心理测试。在整个研究过程中，患者的情绪和代谢功能将受到监测。我们建议识别和治疗抑郁症患者的胰岛素抵抗可能会降低与抑郁症相关的发病率、死亡率和经济负担。此外，使用胰岛素敏感型药物治疗抑郁症，使我们对如何治疗情绪障碍的看法发生了显著的转变。 与公共健康相关：肥胖症在美国的流行大大增加了总体发病率和死亡率的上升。国家胆固醇教育计划ATPIII(成人治疗小组)指南将糖尿病确定为相当于心血管疾病(CVD)的死亡风险，而不是之前将糖尿病概念化为CVD的风险因素。抑郁症患者患心血管疾病的风险显著增加。该协会既有男性也有女性，跨越不同的年龄段，并在世界各地的一系列国家发生。抑郁症患者的全因死亡率也明显更高。这项研究的结果可能进一步确立识别和治疗抑郁症患者胰岛素抵抗的重要性，以减少与抑郁症相关的发病率、死亡率和经济负担。此外，使用胰岛素敏感型药物治疗抑郁症，使我们对如何治疗情绪障碍的看法发生了显著的转变。。

DESCRIPTION (provided by applicant): Major depressive disorder (MDD) and type II diabetes (DM2), share numerous pathophysiological characteristics that reflect bidirectional links between the central nervous system (CNS) and endocrine homeostasis. Patients with DM2 have a high incidence of depression, and reciprocally, patients with depression are at increased risk of developing DM2. Insulin resistance (IR) or "pre-diabetes" is often accompanied by depressive symptomatology, and patients with depression have biomarkers suggestive of high IR. Greater understanding of these reciprocal links may lead to a dramatic shift in the way in which depression is conceptualized and treated, with a greater focus on proper metabolic function. The current application aims to investigate the effect of improved insulin resistance on mood upon treatment with a PPAR -agonist (pioglitazone) in a placebo-controlled design. Eighty patients with depression will be recruited in the study; half with insulin resistance and half without insulin resistance. Subjects will undergo clinical endocrinological evaluation (including oral glucose tolerance testing) and neuropsychological testing before and after 12 weeks of double-blind treatment. Patients' mood and metabolic function will be monitored throughout the study. We propose Identifying and treating insulin resistance in patients with depression may reduce the morbidity, mortality, and economic burden associated with depression. Further, the use of an insulin-sensitizing medication for the treatment of depression offers a remarkable shift in our view of how mood disorders can be treated. PUBLIC HEALTH RELEVANCE: The epidemic of obesity in the U.S. adds substantially to rise in overall morbidity and mortality. The National Cholesterol Education Program ATPIII (Adult Treatment Panel) Guidelines identify diabetes as a mortality risk equivalent to cardiovascular disease (CVD), in contrast to the previous conceptualization of diabetes as a risk factor for CVD. Patients with depression have significantly increased risk for CVD. The association exists for both men and women, spans various age groups, and occurs in a range of countries throughout the world. Patients with depression also have a significantly higher all-cause mortality rate. The results of this study may further establish the importance of identifying and treating insulin resistance in patients with depression to reduce the morbidity, mortality, and economic burden associated with depression. Further, the use of an insulin-sensitizing medication for the treatment of depression offers a remarkable shift in our view of how mood disorders can be treated. .