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Effect of abstinence challenge on brain function and cognition in smokers differs by COMT genotype.

ABSTRACT: The val allele of the catechol-O-methyltransferase (COMT) val(158)met polymorphism has been linked with nicotine dependence and with cognitive performance in healthy volunteers. We tested the hypothesis that the val allele is a risk factor for altered brain function and cognition during nicotine abstinence as compared with the normal smoking state. Chronic smokers (n=33) were genotyped prospectively for the COMT polymorphism for balanced selection of met/met, val/met and val/val groups. A visual N-back working memory task was performed during two separate blood oxygen level-dependent (BOLD) functional magnetic resonance imaging sessions in counterbalanced order: (1) smoking as usual, and (2)>or=14 h confirmed abstinence. Significant genotype by session interactions were observed for BOLD signal in right dorsolateral prefrontal cortex (DLPFC; (P=0.0005), left DLPFC (P=0.02) and dorsal cingulate/medial prefrontal cortex (P=0.01) as well as for task reaction time (P=0.03). Smokers with val/val genotypes were more sensitive to the abstinence challenge than carriers of the met allele, with the greatest effects on BOLD signal and performance speed at the highest working memory load. These data suggest a novel brain-behavior mechanism that may underlie the increased susceptibility to nicotine dependence and smoking relapse associated with the COMT val allele. Exploration of the effects of COMT inhibitors as a possible smoking cessation aid in this group may be warranted.

SUBMITTER: Loughead J

PROVIDER: S-EPMC3896978 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Effect of abstinence challenge on brain function and cognition in smokers differs by COMT genotype.

Loughead J J Wileyto E P EP Valdez J N JN Sanborn P P Tang K K Strasser A A AA Ruparel K K Ray R R Gur R C RC Lerman C C

Molecular psychiatry 20081209 8

The val allele of the catechol-O-methyltransferase (COMT) val(158)met polymorphism has been linked with nicotine dependence and with cognitive performance in healthy volunteers. We tested the hypothesis that the val allele is a risk factor for altered brain function and cognition during nicotine abstinence as compared with the normal smoking state. Chronic smokers (n=33) were genotyped prospectively for the COMT polymorphism for balanced selection of met/met, val/met and val/val groups. A visual ...[more]

PMID: 19065145

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Project description:The analysis of brain signal variability is a promising approach to understand pathological brain function related to chronic pain. This study investigates whether blood-oxygen-level-dependent signal variability (BOLDSV) in specific frequency bands is altered in temporomandibular disorder (TMD) and correlated to its clinical features. Twelve patients with chronic myofascial TMD and 24 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. The BOLDSV was measured as the standard deviation of the BOLD time series at each voxel and compared between groups. We also examined the potential relationship between the BOLDSV and the catechol-O-methyltransferase (COMT) Val158Met polymorphism. We assessed sensory-discriminative pain in the craniofacial region, pain sensitivity to sustained masseteric pain challenge, and TMD pain frequency for clinical correlation. Patients displayed reduced BOLDSV in the dorsolateral prefrontal cortex (dlPFC) as compared with HC in all frequency bands. In the slow-3 band, patients also showed reduced BOLDSV in the medial dorsal thalamus, primary motor cortex (M1), and primary somatosensory cortex (S1) and heightened BOLDSV in the temporal pole. Notably, we found a significant correlation between lower BOLDSV (slow-3) in the orofacial M1/S1 regions and higher clinical pain (intensity/area) and higher sensitivity of the masseter muscle pain. Moreover, lower BOLDSV (slow-3) in the dlPFC and ventrolateral PFC was associated with a higher TMD pain frequency. Participants who had the COMT 158Met substitution exhibited lower BOLDSV in the dlPFC and higher BOLDSV in the temporal pole as compared with participants without the COMT 158Met substitution. An increasing number of Met alleles was associated with lower dlPFC and greater temporal pole BOLDSV in both HC and TMD groups. Together, we demonstrated that chronic TMD patients exhibit aberrant BOLDSV in the top-down pain modulatory and sensorimotor circuits associated with their pain frequency and severity. COMT Val158Met polymorphism might affect clinical symptoms in association with regional brain signal variability, specifically involved in cognitive and emotional regulation of pain.

Dataset Information

Effect of abstinence challenge on brain function and cognition in smokers differs by COMT genotype.

Publications

Effect of abstinence challenge on brain function and cognition in smokers differs by COMT genotype.

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