Pioglitazone for Treatment of Unremitted Depression in Insulin Resistant Patients

描述（由申请人提供）：重度抑郁症（MDD）和II型糖尿病（DM2）具有许多共同的病理生理学特征，反映了中枢神经系统（CNS）和内分泌稳态之间的双向联系。2型糖尿病患者抑郁症的发病率很高，而且抑郁症患者患2型糖尿病的风险增加。胰岛素抵抗（IR）或“糖尿病前期”往往伴随着抑郁症，抑郁症患者的生物标志物提示高IR。更好地了解这些相互联系可能会导致显着的转变，抑郁症的概念化和治疗的方式，更注重适当的代谢功能。本申请旨在以安慰剂对照设计研究在用PPAR激动剂（吡格列酮）治疗后改善的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周双盲治疗前后接受临床内分泌学评价（包括口服葡萄糖耐量试验）和神经心理学测试。在整个研究期间将监测患者的情绪和代谢功能。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发病率，死亡率和与抑郁症相关的经济负担。此外，使用胰岛素增敏药物治疗抑郁症为我们如何治疗情绪障碍提供了一个显着的转变。

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.