Gender-specific Associations of the Brain-derived Neurotrophic Factor Val66Met Polymorphism with Neurocognitive and Clinical Features in Schizophrenia

Objective: To explore associations of the brain derived neurotrophic factor (BDNF) Val66Met polymorphism with cognitive functioning and psychopathology in patients with schizophrenia. Methods: We included 133 subjects meeting the DSM-IV criteria for schizophrenia who were in the post acute stage of the disease. BDNF Val66Met genotypes were identified via polymerase chain reaction. The computerized neurocognitive function battery, Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Social and Occupational Functioning Scale (SOFAS), and the Subjective Well being under Neuroleptic Treatment (SWN-K) were administered. Gender-stratified sub-analysis was also conducted to identify gender-specific patterns in the findings. Results: In male patients, no significant difference in any measure by BDNF genotype was evident, In female patients, scores on the CDSS and total PANSS and all subscales were significantly higher in valine (Val) carriers. In addition, scores on the SOFAS and SWN-K were significantly lower in Val carriers. In terms of neurocognitive measures, female patients with the Val allele had significantly poorer reaction times and fewer correct responses on the Continuous Performance Test (CPT) and the Trail Making Test (Parts A and B), After adjustment of PANSS total scores and log transformed CDSS scores, CPT outcomes were significantly poorer in female patients with than in those without the Val allele. Conclusion: Gender-specific associations of the Val allele with poor neurocognitive function and more severe psychopathology were evident. Further studies are required to explore the mechanisms of these differences and the potential utility of the BDNF genotype as a predictor of outcome in patients with schizophrenia.