Effect of Catechol O-Methyltransferase Val158Met Polymorphism on the P50 Gating Endophenotype in Schizophrenia

Brett Y. Lu, Kimberly E. Martin, J. Christopher Edgar, Ashley K. Smith, Stephen Lewis, Michael A. Escamilla, Gregory A. Miller, Jose M. Cañive

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background: Studies have implicated prefrontal dopamine in cortical information filtering. Deficit in stimulus filtering, an endophenotype of schizophrenia, can be demonstrated using the auditory P50 paired-click gating paradigm. The role of prefrontal dopamine on P50 gating was investigated, using catechol-O-methyltransferase (COMT) valine (val)158methionine (met) polymorphism as a predictor of prefrontal dopamine activity. Methods: Twenty-five comparison and 42 schizophrenia subjects underwent P50 gating measurement and COMT genotyping. Results: In the combined sample, COMT polymorphism accounted for a unique 10% of gating variance (p = .02), after variance due to diagnosis, smoking status, and antipsychotic use was removed. Valine homozygous individuals exhibited the greatest gating deficit. Conclusions: Valine homozygous individuals are more likely to have gating deficits, supporting COMT as a genetic determinant of the P50 endophenotype, as well as a role for prefrontal dopamine in auditory filtering.

Original languageEnglish (US)
Pages (from-to)822-825
Number of pages4
JournalBiological Psychiatry
Volume62
Issue number7
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

Fingerprint

Endophenotypes
Catechol O-Methyltransferase
Dopamine
Schizophrenia
Valine
Antipsychotic Agents
Smoking

Keywords

  • Auditory gating
  • dopamine
  • electrophysiology
  • genetics
  • schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Effect of Catechol O-Methyltransferase Val158Met Polymorphism on the P50 Gating Endophenotype in Schizophrenia. / Lu, Brett Y.; Martin, Kimberly E.; Edgar, J. Christopher; Smith, Ashley K.; Lewis, Stephen; Escamilla, Michael A.; Miller, Gregory A.; Cañive, Jose M.

In: Biological Psychiatry, Vol. 62, No. 7, 01.10.2007, p. 822-825.

Research output: Contribution to journalArticle

Lu, Brett Y. ; Martin, Kimberly E. ; Edgar, J. Christopher ; Smith, Ashley K. ; Lewis, Stephen ; Escamilla, Michael A. ; Miller, Gregory A. ; Cañive, Jose M. / Effect of Catechol O-Methyltransferase Val158Met Polymorphism on the P50 Gating Endophenotype in Schizophrenia. In: Biological Psychiatry. 2007 ; Vol. 62, No. 7. pp. 822-825.
@article{71494d157e704c118e87bde21f0de605,
title = "Effect of Catechol O-Methyltransferase Val158Met Polymorphism on the P50 Gating Endophenotype in Schizophrenia",
abstract = "Background: Studies have implicated prefrontal dopamine in cortical information filtering. Deficit in stimulus filtering, an endophenotype of schizophrenia, can be demonstrated using the auditory P50 paired-click gating paradigm. The role of prefrontal dopamine on P50 gating was investigated, using catechol-O-methyltransferase (COMT) valine (val)158methionine (met) polymorphism as a predictor of prefrontal dopamine activity. Methods: Twenty-five comparison and 42 schizophrenia subjects underwent P50 gating measurement and COMT genotyping. Results: In the combined sample, COMT polymorphism accounted for a unique 10{\%} of gating variance (p = .02), after variance due to diagnosis, smoking status, and antipsychotic use was removed. Valine homozygous individuals exhibited the greatest gating deficit. Conclusions: Valine homozygous individuals are more likely to have gating deficits, supporting COMT as a genetic determinant of the P50 endophenotype, as well as a role for prefrontal dopamine in auditory filtering.",
keywords = "Auditory gating, dopamine, electrophysiology, genetics, schizophrenia",
author = "Lu, {Brett Y.} and Martin, {Kimberly E.} and Edgar, {J. Christopher} and Smith, {Ashley K.} and Stephen Lewis and Escamilla, {Michael A.} and Miller, {Gregory A.} and Ca{\~n}ive, {Jose M.}",
year = "2007",
month = "10",
day = "1",
doi = "10.1016/j.biopsych.2006.11.030",
language = "English (US)",
volume = "62",
pages = "822--825",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "7",

}

TY - JOUR

T1 - Effect of Catechol O-Methyltransferase Val158Met Polymorphism on the P50 Gating Endophenotype in Schizophrenia

AU - Lu, Brett Y.

AU - Martin, Kimberly E.

AU - Edgar, J. Christopher

AU - Smith, Ashley K.

AU - Lewis, Stephen

AU - Escamilla, Michael A.

AU - Miller, Gregory A.

AU - Cañive, Jose M.

PY - 2007/10/1

Y1 - 2007/10/1

N2 - Background: Studies have implicated prefrontal dopamine in cortical information filtering. Deficit in stimulus filtering, an endophenotype of schizophrenia, can be demonstrated using the auditory P50 paired-click gating paradigm. The role of prefrontal dopamine on P50 gating was investigated, using catechol-O-methyltransferase (COMT) valine (val)158methionine (met) polymorphism as a predictor of prefrontal dopamine activity. Methods: Twenty-five comparison and 42 schizophrenia subjects underwent P50 gating measurement and COMT genotyping. Results: In the combined sample, COMT polymorphism accounted for a unique 10% of gating variance (p = .02), after variance due to diagnosis, smoking status, and antipsychotic use was removed. Valine homozygous individuals exhibited the greatest gating deficit. Conclusions: Valine homozygous individuals are more likely to have gating deficits, supporting COMT as a genetic determinant of the P50 endophenotype, as well as a role for prefrontal dopamine in auditory filtering.

AB - Background: Studies have implicated prefrontal dopamine in cortical information filtering. Deficit in stimulus filtering, an endophenotype of schizophrenia, can be demonstrated using the auditory P50 paired-click gating paradigm. The role of prefrontal dopamine on P50 gating was investigated, using catechol-O-methyltransferase (COMT) valine (val)158methionine (met) polymorphism as a predictor of prefrontal dopamine activity. Methods: Twenty-five comparison and 42 schizophrenia subjects underwent P50 gating measurement and COMT genotyping. Results: In the combined sample, COMT polymorphism accounted for a unique 10% of gating variance (p = .02), after variance due to diagnosis, smoking status, and antipsychotic use was removed. Valine homozygous individuals exhibited the greatest gating deficit. Conclusions: Valine homozygous individuals are more likely to have gating deficits, supporting COMT as a genetic determinant of the P50 endophenotype, as well as a role for prefrontal dopamine in auditory filtering.

KW - Auditory gating

KW - dopamine

KW - electrophysiology

KW - genetics

KW - schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=34548478801&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548478801&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2006.11.030

DO - 10.1016/j.biopsych.2006.11.030

M3 - Article

C2 - 17448448

AN - SCOPUS:34548478801

VL - 62

SP - 822

EP - 825

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 7

ER -