Associations of cigarette smoking and polymorphisms in brain-derived neurotrophic factor and catechol-O-methyltransferase with neurocognition in alcohol dependent individuals during early abstinence
- 1Center for Imaging of Neurodegenerative Diseases, San Francisco VA Medical Center, San Francisco, CA, USA
- 2Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
- 3University of Colorado, Boulder, CO, USA
Chronic cigarette smoking and polymorphisms in brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) are associated with neurocognition in normal controls and those with various neuropsychiatric conditions. The influence of BDNF and COMT on neurocognition in alcohol dependence is unclear. The primary goal of this report was to investigate the associations of single nucleotide polymorphisms (SNPs) in BDNF Val66Met (rs6265) and COMT Val158Met (rs4680) with neurocognition in a treatment-seeking alcohol dependent cohort and determine if neurocognitive differences between non-smokers and smokers previously observed in this cohort persist when controlled for these functional SNPs. Genotyping was conducted on 70 primarily male treatment-seeking alcohol dependent participants (ALC) who completed a comprehensive neuropsychological battery after 33 ± 9 days of monitored abstinence. After controlling for COMT and BDNF genotypes, smoking ALC performed significantly worse than non-smoking ALC on the domains of auditory-verbal and visuospatial learning and memory, cognitive efficiency, general intelligence, processing speed, and global neurocognition. In smoking ALC, greater number of years of smoking over lifetime was related to poorer performance on multiple domains after controlling for genotypes and alcohol consumption. In addition, COMT Met homozygotes were superior to Val homozygotes on measures of executive skills and showed trends for higher general intelligence and visuospatial skills, while COMT Val/Met heterozygotes showed significantly better general intelligence than Val homozygotes. COMT Val homozygotes performed better than heterozygotes on auditory-verbal memory. BDNF genotype was not related to any neurocognitive domain. The findings are consistent with studies in normal controls and neuropsychiatric cohorts that reported COMT Met carriers demonstrated better performance on measures of executive skills and general intelligence. Results also indicated that the poorer performance of smoking compared to non-smoking ALC across multiple neurocognitive domains was not mediated by COMT or BDNF genotype. Overall, the findings lend support to the expanding clinical movement to make smoking cessation programs available to smokers at the inception of treatment for alcohol/substance use disorders.
Keywords: cigarette smoking, brain-derived neurotrophic factor, catechol-O-methyltransferase, neurocognition, alcohol dependence
Citation: Durazzo TC, Hutchison KE, Fryer SL, Mon A and Meyerhoff DJ (2012) Associations of cigarette smoking and polymorphisms in brain-derived neurotrophic factor and catechol-O-methyltransferase with neurocognition in alcohol dependent individuals during early abstinence. Front. Pharmacol. 3:178. doi: 10.3389/fphar.2012.00178
Received: 17 July 2012; Accepted: 16 September 2012;
Published online: 11 October 2012.
Copyright: © 2012 Durazzo, Hutchison, Fryer, Mon and Meyerhoff. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Timothy C. Durazzo, Center for Imaging of Neurodegenerative Diseases (114M), San Francisco VA Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA. e-mail: firstname.lastname@example.org