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)(158)methionine (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.
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)(158)methionine (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.
Authors: Ann Olincy; David L Braff; Lawrence E Adler; Kristin S Cadenhead; Monica E Calkins; Dorcas J Dobie; Michael F Green; Tiffany A Greenwood; Raquel E Gur; Reuben C Gur; Gregory A Light; James Mintz; Keith H Nuechterlein; Allen D Radant; Nicholas J Schork; Larry J Seidman; Larry J Siever; Jeremy M Silverman; William S Stone; Neal R Swerdlow; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; Brandie D Wagner; Robert Freedman Journal: Schizophr Res Date: 2010-04-10 Impact factor: 4.939
Authors: J Christopher Edgar; Faith M Hanlon; Ming-Xiong Huang; Michael P Weisend; Robert J Thoma; Bruce Carpenter; Karsten Hoechstetter; José M Cañive; Gregory A Miller Journal: Psychophysiology Date: 2008-07-24 Impact factor: 4.016
Authors: S de la Salle; D Smith; J Choueiry; D Impey; T Philippe; H Dort; A Millar; P Albert; V Knott Journal: Neuroscience Date: 2013-03-25 Impact factor: 3.590
Authors: Randal G Ross; Sharon K Hunter; Lizbeth McCarthy; Julie Beuler; Amanda K Hutchison; Brandie D Wagner; Sherry Leonard; Karen E Stevens; Robert Freedman Journal: Am J Psychiatry Date: 2013-03 Impact factor: 18.112