The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with increased body mass index and insulin resistance measures in bipolar disorder and schizophrenia

Stefania Bonaccorso, Monsheel Sodhi, Jiang Li, William V Bobo, Yuejin Chen, Mevhibe Tumuklu, Christos Theleritis, Karuna Jayathilake, Herbert Y. Meltzer

Research output: Contribution to journalArticle

31 Scopus citations


Objectives: We 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. Methods: This 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). Results: BMI 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). Conclusions: The 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.

Original languageEnglish (US)
Pages (from-to)528-535
Number of pages8
JournalBipolar Disorders
Issue number5
StatePublished - Aug 1 2015



  • Antipsychotic drugs
  • Bipolar disorder
  • Body mass index
  • Brain-derived neurotrophic factor (BDNF) val66Met
  • Glucose
  • Lipids
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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