Association between the brain-derived neurotrophic factor Val66Met polymorphism and therapeutic response to olanzapine in schizophrenia patients

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a major role in neurogenesis and neuroplasticity, and in the modulation of several neurotransmitter systems including the dopaminergic system. There are mixed reports about the association between the BDNF Val66Met polymorphism, schizophrenia, and treatment response to antipsychotic drugs. The present study evaluated the association of the BDNF Val66Met polymorphism with treatment response to atypical antipsychotic olanzapine in schizophrenia and the possible predictive value of the BDNF Val66Met genotype status in treatment response to antipsychotic medication. The study included 590 ethnically homogenous Caucasian patients with schizophrenia (diagnosed using the SCID), 40.2 +/- 12.0 years old, treated with olanzapine monotherapy (10-20 mg/day), or with other antipsychotics such as risperidone (3-6 mg/day), clozapine (100-500 mg/day), haloperidol (3-115 mg/day), fluphenazine (4-25 mg/day), and quetiapine (50-800 mg/day). Patients were subdivided into responders and non-responders according to a 50 % reduction in the Positive and Negative Syndrome Scale (PANSS) total and subscale scores after 8 weeks of treatment. The results, corrected for possible effects of gender and age, showed a significant association between the BDNF Val66Met polymorphism and treatment response to olanzapine in patients. The Val/Val genotype was observed more frequently in treatment responders to olanzapine, and this genotype was associated with an improvement in clinical symptoms. Our results suggest that BDNF Val66Met variants might influence the response to 8 weeks of monotherapy with olanzapine, in a relatively large sample of patients with schizophrenia.