The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia

Daniel J. Müller, Tim A. Klempan, Vincenzo De Luca, Tricia Sicard, Jan Volavka, Pal Czobor, Brian B. Sheitman, Jean Pierre Lindenmayer, Leslie Citrome, Joseph Patrick McEvoy, Jeffrey A. Lieberman, William G. Honer, James L. Kennedy

Research output: Contribution to journalArticle

86 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)81-89
Number of pages9
JournalNeuroscience Letters
Volume379
Issue number2
DOIs
StatePublished - May 6 2005
Externally publishedYes

Fingerprint

Synaptosomal-Associated Protein 25
Antipsychotic Agents
Weight Gain
Schizophrenia
Genes
Haloperidol
olanzapine
Therapeutics
Weights and Measures
Risperidone
Clozapine
Diagnostic and Statistical Manual of Mental Disorders
Psychotic Disorders
Neurotransmitter Agents
Cerebrospinal Fluid
Analysis of Variance
Brain

Keywords

  • Antipsychotics
  • Genetics
  • Neurotransmitter
  • Response
  • SNAP-25
  • Schizophrenia
  • Side effects
  • Weight gain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Müller, D. J., Klempan, T. A., De Luca, V., Sicard, T., Volavka, J., Czobor, P., ... Kennedy, J. L. (2005). The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia. Neuroscience Letters, 379(2), 81-89. https://doi.org/10.1016/j.neulet.2004.12.037

The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia. / Müller, Daniel J.; Klempan, Tim A.; De Luca, Vincenzo; Sicard, Tricia; Volavka, Jan; Czobor, Pal; Sheitman, Brian B.; Lindenmayer, Jean Pierre; Citrome, Leslie; McEvoy, Joseph Patrick; Lieberman, Jeffrey A.; Honer, William G.; Kennedy, James L.

In: Neuroscience Letters, Vol. 379, No. 2, 06.05.2005, p. 81-89.

Research output: Contribution to journalArticle

Müller, DJ, Klempan, TA, De Luca, V, Sicard, T, Volavka, J, Czobor, P, Sheitman, BB, Lindenmayer, JP, Citrome, L, McEvoy, JP, Lieberman, JA, Honer, WG & Kennedy, JL 2005, 'The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia', Neuroscience Letters, vol. 379, no. 2, pp. 81-89. https://doi.org/10.1016/j.neulet.2004.12.037
Müller, Daniel J. ; Klempan, Tim A. ; De Luca, Vincenzo ; Sicard, Tricia ; Volavka, Jan ; Czobor, Pal ; Sheitman, Brian B. ; Lindenmayer, Jean Pierre ; Citrome, Leslie ; McEvoy, Joseph Patrick ; Lieberman, Jeffrey A. ; Honer, William G. ; Kennedy, James L. / The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia. In: Neuroscience Letters. 2005 ; Vol. 379, No. 2. pp. 81-89.
@article{3b61408e1e9b408e81cccff6d6ec2588,
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.",
keywords = "Antipsychotics, Genetics, Neurotransmitter, Response, SNAP-25, Schizophrenia, Side effects, Weight gain",
author = "M{\"u}ller, {Daniel J.} and Klempan, {Tim A.} and {De Luca}, Vincenzo and Tricia Sicard and Jan Volavka and Pal Czobor and Sheitman, {Brian B.} and Lindenmayer, {Jean Pierre} and Leslie Citrome and McEvoy, {Joseph Patrick} and Lieberman, {Jeffrey A.} and Honer, {William G.} and Kennedy, {James L.}",
year = "2005",
month = "5",
day = "6",
doi = "10.1016/j.neulet.2004.12.037",
language = "English (US)",
volume = "379",
pages = "81--89",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia

AU - Müller, Daniel J.

AU - Klempan, Tim A.

AU - De Luca, Vincenzo

AU - Sicard, Tricia

AU - Volavka, Jan

AU - Czobor, Pal

AU - Sheitman, Brian B.

AU - Lindenmayer, Jean Pierre

AU - Citrome, Leslie

AU - McEvoy, Joseph Patrick

AU - Lieberman, Jeffrey A.

AU - Honer, William G.

AU - Kennedy, James L.

PY - 2005/5/6

Y1 - 2005/5/6

N2 - 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.

AB - 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.

KW - Antipsychotics

KW - Genetics

KW - Neurotransmitter

KW - Response

KW - SNAP-25

KW - Schizophrenia

KW - Side effects

KW - Weight gain

UR - http://www.scopus.com/inward/record.url?scp=20144388485&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20144388485&partnerID=8YFLogxK

U2 - 10.1016/j.neulet.2004.12.037

DO - 10.1016/j.neulet.2004.12.037

M3 - Article

C2 - 15823421

AN - SCOPUS:20144388485

VL - 379

SP - 81

EP - 89

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

IS - 2

ER -