Meltzer, Herbert Y.

ObjectivesWe tested the hypothesis that a common functional variant in brain‐derived neurotrophic factor (BDNF), Val66Met, which has been shown to be associated with increased body mass index (BMI) in schizophrenia (SCZ) and schizoaffective disorder (SAD), is also associated with antipsychotic‐induced weight gain in bipolar disorder (BPD). Association of Val66Met with other metabolic measures, including high‐ and low‐density cholesterol, triglycerides, total cholesterol, fasting blood glucose, and hemoglobin A1c, was also tested.MethodsThis was a 12‐month, prospective, randomized trial of two atypical antipsychotic drugs (APDs) with moderate (risperidone) or high (olanzapine) risk to cause weight gain. Subjects were diagnosed as having BPD (n = 90) and SCZ or SAD (n = 76).ResultsBMI was significantly greater in all diagnoses for Met66 allele carriers at six months (p = 0.01). Met66 carriers with BPD showed a greater increase in the triglycerides/high‐density (HDL) cholesterol ratio (p = 0.01), a key marker for metabolic syndrome related to insulin resistance, and log‐triglycerides (p = 0.04), after three or six months of treatment. Met66 carriers had the greatest increase in log‐triglycerides (p = 0.03) and triglycerides/HDL cholesterol ratio after three months of treatment with risperidone (p = 0.003), and the highest BMI at six months (p = 0.01).ConclusionsThe positive association of BNDF Val66Met with high BMI values replicates previous findings in patients with SCZ and indicates the BDNF Val66Met genotype as a potential risk factor for obesity and insulin resistance measures in patients with BPD receiving antipsychotics as well.