Insulin resistance is associated with depression risk in polycystic ovary syndrome
Article In Press
Eleni A. Greenwood, M.D., M.Sc., Lauri A. Pasch, Ph.D., Marcelle I. Cedars, M.D., Richard S. Legro, M.D., Esther Eisenberg, M.D., M.P.H., Heather G. Huddleston, M.D. for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Reproductive Medicine Network
To test the hypothesis that insulin resistance is associated with depression risk in polycystic ovary syndrome (PCOS).
Secondary analysis of data from a multicenter randomized trial.
Multicenter university-based clinical practices.
Seven hundred thirty-eight women with PCOS by modified Rotterdam criteria seeking pregnancy enrolled in a randomized clinical trial comparing clomiphene citrate versus letrozole.
The Primary Care Evaluation of Mental Disorders Patient Health Questionnaire was self-administered to identify depression using a validated algorithm at enrollment. Demographic and anthropometric data were collected, and serum assays were performed. Insulin resistance was estimated using the homeostatic model of insulin resistance (HOMA-IR), with a cutoff of >2.2 considered abnormal.
Main Outcome Measure(s)
Demographic, endocrine, and metabolic parameters associated with depression.
In a univariate logistic regression analysis, elevated HOMA-IR was associated with 2.3-fold increased odds of depression (odds ratio [OR] = 2.32; 95% confidence interval [CI], 1.28–4.21). This association remained significant after controlling for age and body mass index (adjusted OR [aOR] = 2.23; 95% CI, 1.11–4.46) and in a model including additional potential confounders (aOR = 2.03; 95% CI, 1.00–4.16).
Insulin resistance has a strong and independent association with depression in PCOS and may serve as a physiologic mediator. Our findings corroborate a growing body of evidence linking insulin resistance to depressed mood. The association between insulin resistance and depressed mood warrants further investigation to elucidate mechanisms and identify potential therapeutic targets.