title: Associations of SNAP-25 polymorphisms with cognitive dysfunctions in Caucasian patients with schizophrenia during a brief trail of treatment with atypical antipsychotics.
abstract: The synaptosomal-associated protein of 25 kDa (SNAP-25) is part of the soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment receptor (SNARE), which mediates synaptic neurotransmission. In earlier studies a possible involvement of this protein in schizophrenia has been shown. As neurocognitive impairment is a core feature in the pathology of schizophrenia and considered to be a putative endophenotype according to genetic studies we investigated the influences of different SNAP-25 polymorphisms on neuropsychological test results before and during treatment with atypical antipsychotics. A total of 104 schizophrenic patients treated with atypical antipsychotics were genotyped for three different polymorphisms of the SNAP-25 gene (MnlI, TaiI and DdeI in the 3'-UTR). Cognitive function was assessed at baseline, week 4 or 6 and week 8 or 12. Results of individual neuropsychological tests were assigned to six cognitive domains (reaction time and quality; executive function; working, verbal and visual memory) and a general cognitive index. The MnlI and TaiI polymorphisms showed no associations to deficits on neuropsychological test results. In contrast, we observed a significant relation between the DdeI polymorphism of the SNAP-25 gene and cognitive dysfunctions. Homozygote T/T allele carriers of the DdeI polymorphism showed significant better neuropsychological test results in cognitive domains verbal memory and executive functions than those with the combined T/C and C/C genotypes (P < 0.01) at all three time points, but no differences in response to treatment with atypical antipsychotics. Additionally, TT carriers exhibited significantly better results in a general cognitive index (P < 0.05). As we observed an association between the DdeI polymorphism of the SNAP-25 gene and cognitive dysfunctions of schizophrenic patients our finding suggests that the SNAP-25 gene could play a role in the pathophysiology of neurocognitive dysfunctions in schizophrenia but is not predictive for treatment response with atypical antipsychotics.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University of Munich, Nussbaumstrasse 7, 80336, Munich, Germany. ilja.spellmann@med.uni-muenchen.de
authors.forename: Ilja
authors.initials: I
authors.lastname: Spellmann
authors.forename: Norbert
authors.initials: N
authors.lastname: Müller
authors.forename: Richard
authors.initials: R
authors.lastname: Musil
authors.forename: Peter
authors.initials: P
authors.lastname: Zill
authors.forename: Anette
authors.initials: A
authors.lastname: Douhet
authors.forename: Sandra
authors.initials: S
authors.lastname: Dehning
authors.forename: Anja
authors.initials: A
authors.lastname: Cerovecki
authors.forename: Brigitta
authors.initials: B
authors.lastname: Bondy
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.forename: Michael
authors.initials: M
authors.lastname: Riedel
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001288:Attention / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics*; D014706:Verbal Learning / Q000187:drug effects / Q000502:physiology; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D050825:Synaptosomal-Associated Protein 25