Influences of SNAP-25 polymorphisms on cognitive dysfunctions in schizophrenic patients during an atypical antipsychotic treatment

Introduction: The synaptosomal-associated-protein of 25kDa (SNAP-25)is part of the soluble NSF attachment receptor (SNARE), which mediates synaptic vesicle membrane docking and fusion in the central nervous system. In earlier studies a possible involvement of this protein in schizophrenia is indicated. As neurocognitive impairment is considered to be a putative endophenotype according to genetic linkage and association studies we investigated the influences of three different SNAP-25 polymorphisms (MnlI, TaiI and Ddel) on neuropsychological test results before and during treatment with atypical antipsychotics. Methods: We have genotyped 118 schizophrenic patients being treated with different atypical antipsychotics. Cognitive function was assessed at baseline, week 4 or 6 and week 8 or 12. Results: We observed an overall improvement of neuropsychological test results in all patients. The MnlI and TaiI polymorphisms showed no association to cognitive dysfunctions. Homozygote T/T allele carriers of the DdeI polymorphism exhibited significant better results in cognitive domains working, verbal and visual memory as well as executive functions than those with the combined T/C and C/C genotypes. Additionally, these patients exhibited significantly better results in general cognitive indices. Conclusions: We observed an influence of the DdeI polymorphism of the SNAP-25 gene on cognitive dysfunctions of schizophrenic patients before and during an atypical antipsychotic treatment.