Association of abstinence-induced alterations in working memory function and COMT genotype in smokers

作者：Ashare Rebecca L^*; Valdez Jeffrey N; Ruparel Kosha; Albelda Benjamin; Hopson Ryan D; Keefe John R; Loughead James; Lerman Caryn

来源：Psychopharmacology, 2013, 230(4): 653-662.

DOI：10.1007/s00213-013-3197-3

• Smoking
• Nicotine
• COMT
• Genetic
• fMRI
• Cognition
• Working memory

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.

• 出版日期2013-12