Abstract
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.
Highlights
A number of premorbid and/or comorbid factors may contribute to the pattern and magnitude of neurocognitive abnormalities demonstrated by those with alcohol use disorders (AUD; Parsons and Nixon, 1993; Oscar-Berman, 2000; Sher et al, 2005; Rourke and Loberg, 2009)
The primary findings from this cohort of primarily male, treatment-seeking alcohol dependent individuals with approximately 1 month of abstinence from alcohol were as follows: (1) smoking alcohol dependent participants (ALC) demonstrated significantly poorer performance than non-smoking ALC on multiple domains of neurocognition after controlling for COMT and brain-derived neurotrophic factor (BDNF) genotypes and medical, psychiatric, and substance abuse comorbidities; (2) in smoking ALC, greater number of lifetime years of smoking was associated with worse performance on multiple neurocognitive domains; (3) COMT genotype was significantly associated with measures of executive skills, general intelligence, and visuospatial memory; and (4) the BDNF Val66Met polymorphism was not a significant predictor of any neurocognitive domain
Chronic cigarette smoking in this cohort of alcohol dependent individuals in early recovery was a robust predictor of performance in multiple domains of neurocognition after controlling for BDNF and COMT genotypes, lifetime alcohol consumption, age, and AMNART
Summary
A number of premorbid and/or comorbid factors may contribute to the pattern and magnitude of neurocognitive abnormalities demonstrated by those with alcohol use disorders (AUD; Parsons and Nixon, 1993; Oscar-Berman, 2000; Sher et al, 2005; Rourke and Loberg, 2009). In our previous work assessing the neurocognitive consequences of AUD, we investigated the influence of chronic cigarette smoking, sociodemographic factors, alcohol consumption levels, as well as comorbid substance abuse, psychiatric and medical conditions (Durazzo et al, 2006, 2007b,c, 2008, 2010a). Among these variables, chronic cigarette smoking was the sole factor that consistently and robustly predicted neurocognition in our AUD participants. For COMT, studies with controls and individuals with various neuropsychiatric conditions reported that Met homozygosity was related to better performance on measures of executive skills, working memory, and general intellectual functioning.
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