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

Abstract

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.