RATIONALE: The common methionine (met) for valine (val) at codon 158 (val(158)met) polymorphism in the catechol-O-methyltransferase (COMT) gene has been associated with nicotine dependence, alterations in executive cognitive function, and abstinence-induced working memory deficits in smokers. OBJECTIVES: We sought to replicate the association of the COMT val allele with abstinence-induced alterations in working memory-related activity in task-positive (executive control) and task-negative (default mode network) regions. METHODS: Forty smokers (20 val/val and 20 met/met) performed an N-back task while undergoing blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) on two separate occasions: following 72 h of confirmed abstinence and during smoking as usual. An independent sample of 48 smokers who completed the identical N-back task during fMRI in smoking vs. abstinence for another study was used as a validation sample. RESULTS: Contrary to expectations, genotype by session interactions on BOLD signal in executive control regions (dorsolateral prefrontal cortex and dorsal cingulate/medial prefrontal cortex) revealed significant abstinence-induced reductions in the met/met group, but not the val/val group. Results also revealed that val/val smokers may exhibit less suppression of activation in task-negative regions such as the posterior cingulate cortex during abstinence (vs. smoking). These patterns were confirmed in the validation sample and in the whole-brain analysis, though the regions differed from the a priori regions of interest (ROIs) (e.g., precuneus, insula). CONCLUSIONS: The COMT val(158)met polymorphism was associated with abstinence-related working memory deficits in two independent samples of smokers. However, inconsistencies compared to prior findings and across methods (ROI vs. whole-brain analysis) highlight the challenges inherent in reproducing results of imaging genetic studies in addiction.
RATIONALE: The common methionine (met) for valine (val) at codon 158 (val(158)met) polymorphism in the catechol-O-methyltransferase (COMT) gene has been associated with nicotine dependence, alterations in executive cognitive function, and abstinence-induced working memory deficits in smokers. OBJECTIVES: We sought to replicate the association of the COMTval allele with abstinence-induced alterations in working memory-related activity in task-positive (executive control) and task-negative (default mode network) regions. METHODS: Forty smokers (20 val/val and 20 met/met) performed an N-back task while undergoing blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) on two separate occasions: following 72 h of confirmed abstinence and during smoking as usual. An independent sample of 48 smokers who completed the identical N-back task during fMRI in smoking vs. abstinence for another study was used as a validation sample. RESULTS: Contrary to expectations, genotype by session interactions on BOLD signal in executive control regions (dorsolateral prefrontal cortex and dorsal cingulate/medial prefrontal cortex) revealed significant abstinence-induced reductions in the met/met group, but not the val/val group. Results also revealed that val/val smokers may exhibit less suppression of activation in task-negative regions such as the posterior cingulate cortex during abstinence (vs. smoking). These patterns were confirmed in the validation sample and in the whole-brain analysis, though the regions differed from the a priori regions of interest (ROIs) (e.g., precuneus, insula). CONCLUSIONS: The COMTval(158)met polymorphism was associated with abstinence-related working memory deficits in two independent samples of smokers. However, inconsistencies compared to prior findings and across methods (ROI vs. whole-brain analysis) highlight the challenges inherent in reproducing results of imaging genetic studies in addiction.
Authors: E Pomarol-Clotet; M Fatjó-Vilas; P J McKenna; G C Monté; S Sarró; J Ortiz-Gil; C Aguirre; J J Gomar; A Guerrero; R Landin; A Capdevila; L Fañanás; R Salvador Journal: Neuroimage Date: 2010-04-14 Impact factor: 6.556
Authors: David M Cole; Christian F Beckmann; Christopher J Long; Paul M Matthews; Michael J Durcan; John D Beaver Journal: Neuroimage Date: 2010-05-02 Impact factor: 6.556
Authors: James Loughead; Riju Ray; E Paul Wileyto; Kosha Ruparel; Paul Sanborn; Steven Siegel; Ruben C Gur; Caryn Lerman Journal: Biol Psychiatry Date: 2010-03-06 Impact factor: 13.382
Authors: Freda Patterson; Christopher Jepson; James Loughead; Kenneth Perkins; Andrew A Strasser; Steven Siegel; Joseph Frey; Ruben Gur; Caryn Lerman Journal: Drug Alcohol Depend Date: 2009-09-05 Impact factor: 4.492
Authors: H Bowers; D Smith; S de la Salle; J Choueiry; D Impey; T Philippe; H Dort; A Millar; M Daigle; P R Albert; A Beaudoin; V Knott Journal: Genes Brain Behav Date: 2015-07-15 Impact factor: 3.449