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

27 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)528-535
Number of pages8
JournalBipolar Disorders
Volume17
Issue number5
DOIs
StatePublished - Aug 1 2015

Fingerprint

Brain-Derived Neurotrophic Factor
Bipolar Disorder
Insulin Resistance
Schizophrenia
Triglycerides
Body Mass Index
Antipsychotic Agents
Risperidone
olanzapine
Psychotic Disorders
HDL Cholesterol
Weight Gain
Cholesterol
Blood Glucose
Fasting
Hemoglobins
Obesity
Alleles
Genotype
Therapeutics

Keywords

  • 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

Cite this

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with increased body mass index and insulin resistance measures in bipolar disorder and schizophrenia. / Bonaccorso, Stefania; Sodhi, Monsheel; Li, Jiang; Bobo, William V; Chen, Yuejin; Tumuklu, Mevhibe; Theleritis, Christos; Jayathilake, Karuna; Meltzer, Herbert Y.

In: Bipolar Disorders, Vol. 17, No. 5, 01.08.2015, p. 528-535.

Research output: Contribution to journalArticle

Bonaccorso, Stefania ; Sodhi, Monsheel ; Li, Jiang ; Bobo, William V ; Chen, Yuejin ; Tumuklu, Mevhibe ; Theleritis, Christos ; Jayathilake, Karuna ; Meltzer, Herbert Y. / The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with increased body mass index and insulin resistance measures in bipolar disorder and schizophrenia. In: Bipolar Disorders. 2015 ; Vol. 17, No. 5. pp. 528-535.
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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.",
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AU - Bonaccorso, Stefania

AU - Sodhi, Monsheel

AU - Li, Jiang

AU - Bobo, William V

AU - Chen, Yuejin

AU - Tumuklu, Mevhibe

AU - Theleritis, Christos

AU - Jayathilake, Karuna

AU - Meltzer, Herbert Y.

PY - 2015/8/1

Y1 - 2015/8/1

N2 - 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.

AB - 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.

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