Abstract: Introduction: Functional gene polymorphisms modulating neuroplasticity might mediate brain longitudinal structural changes in schizophrenia. The present study aimed to explore possible effects of BDNF Val66Met polymorphism variations on progressive structural brain changes after 3 years from the first episode of psychosis. Method: Patients were part of a large epidemiological and longitudinal intervention program of first-episode psychosis, carried out at the University Hospital Marqués de Valdecilla, Cantabria, Spain. Eighty first-episode patients and 54 healthy controls were included in the final analyses. Brain magnetic resonance imaging (baseline and 3-year follow-up) and BDNF genotype, and clinical and functional outcome were investigated. Results: We did not detect significant association between brain changes and BDNF Val66Met polymorphism variations in patients and controls (all p > 0.060). At baseline, there were no significant associations between brain anomalies and BDNF genotype. Functional deficits were similar in Met-carrier and Val homozygote patients after 3-year follow-up (X2 = 0.66; p = 0.564); there was no relationship between significant volume change across time and functional outcome. Otherwise, Met-carrier controls had significant high rates of alcohol-consumption (p = 0.019) compared to Val homozygote controls. Conclusion: Our findings do not support the notion that BDNF genotype variations may mediate brain macroscopic morphological changes across time.

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