Accumulating evidence showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. Recent studies have reported that the Val66Met polymorphism of the BDNF gene may be associated with susceptibility for schizophrenia and age of onset of this disease, with mix results. In the present study, the BDNF Val66Met gene polymorphism was examined in 387 inpatients (259 men and 128 women) meeting the DSM-IV criteria for schizophrenia and unrelated 365 healthy controls (255 men and 110 women). The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS). Age of onset was defined as the age at which the psychotic symptoms first appeared. Our results showed that genotype frequency distributions and allelic frequencies did not differ between patients and controls. No interaction was found between sex and genotypes. Analysis of covariance (ANCOVA) showed a significance of the BDNF Val66Met genotypes on the age of onset (F=3.76, p<0.02), after adjusting sex, age and duration of illness. Furthermore, ANCOVA showed that the significance of the BDNFVal66Met genotypes on age of onset was increased comparing the Val66Met heterozygotes with the combination of Val66Val and Met66Met homozygotes (F=5.85, p<0.01). Our results suggest that the BDNF Val66Met polymorphism may not contribute directly to the susceptibility to schizophrenia, but to the onset of the disease. Furthermore, our results show the heterozygous effect of the BDNF Val66Met gene on the clinical variability of schizophrenia phenotype.
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