title: The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia.
abstract: The synaptosomal-associated protein of 25 kDa (SNAP-25) is an essential component of the core complex that mediates presynaptic vesicle trafficking. Thus, SNAP-25 is directly involved in the release of neurotransmitters. Quantitative alterations of SNAP-25 expression have been reported in brain regions and cerebrospinal fluid (CSF) of schizophrenics and in haloperidol treated rats. This observed altered expression may be influenced by genetic variants of SNAP-25. We hypothesized that polymorphisms of the SNAP-25 gene (sites DdeI, MnlI and TaiI in the 3'UTR) are associated with antipsychotic drug response and induced weight gain. A sample of 59 patients with prior suboptimal response to antipsychotic treatment and diagnosed with DSM-IV schizophrenia or schizoaffective disorder was examined. Patients were administered clozapine, haloperidol, olanzapine or risperidone for up to 14 weeks. Clinical response was defined as the difference between the baseline and the endpoint total scores on the Positive and Negative Syndrome Scale (PANSS). Weight was assessed at baseline and at study endpoint. ANOVA revealed that the MnlI and TaiI polymorphisms were associated with response (F[2,53] = 4.57, p = 0.01 and F[2,52] = 3.53, p = 0.03) and with weight gain (F[2,52] = 4.28, p = 0.01 and F[2,51] = 3.38, p = 0.04). When covariates were included, the MnlI polymorphism remained significantly associated with changes of PANSS scores, but not with weight gain. The DdeI polymorphism was not associated with response or weight gain. These findings suggest that SNAP-25 gene variants affect clinical response in patients with prior poor response to antipsychotics. Weight changes do not seem to be associated with polymorphism of the SNAP-25 gene, however, replication in independent samples is warranted.
authors.affiliation: Neurogenetics Section, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College Street R30, Toronto, Ont. M5T 1R8, Canada. daniel.mueller@charite.de
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.forename: Tim A
authors.initials: TA
authors.lastname: Klempan
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.forename: Tricia
authors.initials: T
authors.lastname: Sicard
authors.forename: Jan
authors.initials: J
authors.lastname: Volavka
authors.forename: Pal
authors.initials: P
authors.lastname: Czobor
authors.forename: Brian B
authors.initials: BB
authors.lastname: Sheitman
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lindenmayer
authors.forename: Leslie
authors.initials: L
authors.lastname: Citrome
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McEvoy
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: William G
authors.initials: WG
authors.lastname: Honer
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D050825:Synaptosomal-Associated Protein 25; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25