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: OBJECTIVE
  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.
authors: Department of Psychosis Studies, Institute of Psychiatry at the Maudsley, King's College London, London, UK.
authors: Stefania
authors: S
authors: Bonaccorso
authors: Department of Pharmacy Practice, University of Illinois, Chicago, IL, USA.
authors: Monsheel
authors: M
authors: Sodhi
authors: Department of Psychiatry and Behavioural Sciences, Northwestern University, Chicago, IL, USA.
authors: Jiang
authors: J
authors: Li
authors: Mayo Clinic, Rochester, MN, USA.
authors: William V
authors: WV
authors: Bobo
authors: Southern Arizona VA Health Care System, Tucson, AZ, USA.
authors: Yuejin
authors: Y
authors: Chen
authors: Faculty of Medicine, Department of Psychiatry, Gaziosmanpasa University, Tokat, Turkey.
authors: Mevhibe
authors: M
authors: Tumuklu
authors: Department of Psychosis Studies, Institute of Psychiatry at the Maudsley, King's College London, London, UK.
authors: Christos
authors: C
authors: Theleritis
authors: Department of Psychiatry and Behavioural Sciences, Northwestern University, Chicago, IL, USA.
authors: Karuna
authors: K
authors: Jayathilake
authors: Department of Psychiatry and Behavioural Sciences, Northwestern University, Chicago, IL, USA.
authors: Herbert Y
authors: HY
authors: Meltzer
mesh_terms: D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects; D001714:Bipolar Disorder / Q000188:drug therapy*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D050171:Dyslipidemias / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D000077152:Olanzapine; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000188:drug therapy*; D012307:Risk Factors; D018967:Risperidone / Q000009:adverse effects; D012559:Schizophrenia / Q000188:drug therapy*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D000077152:Olanzapine; D018967:Risperidone; D014280:Triglycerides; C517652:hemoglobin A1c protein, human; C579455:BDNF protein, human
keywords: antipsychotic drugs; bipolar disorder; body mass index; brain-derived neurotrophic factor (BDNF) Val66Met; glucose; lipids; schizophrenia