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


Authors: Bonaccorso, S.; Sodhi, M.; Li, J; Bobo, W. V.; Chen, Y; Tumuklu, M.; Theleritis, C.; Jayathilake, K.; Meltzer, H. Y.
Article Title: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with increased body mass index and insulin resistance measures in bipolar disorder and schizophrenia
Abstract: 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.
Keywords: Adult; Female; Humans; Middle Aged; Prospective Studies; Male; Risk Factors; Body Mass Index; Genotype; Alleles; Polymorphism, Single Nucleotide; Bipolar Disorder/drug therapy; Blood Glucose/metabolism; Lipids; Brain-Derived Neurotrophic Factor/genetics; Polymorphism, Genetic; Antipsychotic Agents/adverse effects; Benzodiazepines/adverse effects; Cholesterol, HDL/metabolism; Cholesterol, LDL/metabolism; Dyslipidemias/chemically induced/genetics/metabolism; Hemoglobin A, Glycosylated/metabolism; Insulin Resistance/genetics; Obesity/chemically induced/genetics/metabolism; Psychotic Disorders/drug therapy; Risperidone/adverse effects; Schizophrenia/drug therapy; Triglycerides/metabolism; antipsychotic drugs; bipolar disorder; brain-derived neurotrophic factor (BDNF) Val66Met; glucose; schizophrenia
Journal Title: Bipolar disorders
Volume: 17
Issue: 5
ISSN: 1399-5618; 1398-5647
Publisher: Wiley Periodicals, Inc  
Journal Place: Denmark
Date Published: 2015
Start Page: 528
End Page: 535
Language: ENG
DOI/URL:
Notes: LR: 20150804; CI: (c) 2015; JID: 100883596; 0 (Antipsychotic Agents); 0 (Blood Glucose); 0 (Brain-Derived Neurotrophic Factor); 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 0 (Hemoglobin A, Glycosylated); 0 (Triglycerides); 0 (brain-derived neurotrophic factor, human); 0 (hemoglobin A1c protein, human); 12794-10-4 (Benzodiazepines); 132539-06-1 (olanzapine); L6UH7ZF8HC (Risperidone); OTO: NOTNLM; 2014/04/07 [received]; 2014/12/17 [accepted]; ppublish