The relationship of changes in leptin, neuropeptide Y and reproductive hormones to antipsychotic induced weight gain

Objectives Weight gain is an important side effect of antipsychotic (AP) treatment. Weight is regulated by multiple systems, including leptin, neuropeptide Y (NPY) and gonadal steroids. The aim was to investigate whether AP-induced weight gain was related to leptin and NPY abnormalities and whether these were associated with a disruption of gonadal steroid production. Methods Twenty two female patients with schizophrenia receiving standard AP treatment were studied over a 3-month period. Plasma leptin, NPY, gonadal steroids and their regulators were measured along with weight and BMI. Results Weight, leptin and testosterone levels increased over time. There were significant relationships between a change in oestrogen levels and both a change in NPY levels and a change in BMI. Change in BMI, weight and leptin all correlated strongly with a change in the testosterone/luteinizing hormone ratio. Conclusions AP treatment results in increase in weight over time and this increase is accompanied by increased leptin levels. AP-induced weight gain is also associated with disruption of the hypothalamic-pituitary-gonadal axis. Altered regulation of NPY, either through abnormal leptin control or serotonin blockade, is a possible explanation for the effects of AP medication on both weight and gonadal steroid levels. Copyright (C) 2003 John Wiley Sons, Ltd.