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COMT Val158Met modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers.

Herman AI, Jatlow PI, Gelernter J, Listman JB, Sofuoglu M - Pharmacogenomics J. (2013)

Bottom Line: This study examined the influence of the COMT Val158Met polymorphism on subjective, physiological and cognitive effects of intravenous (IV) nicotine use in African Americans (AAs; n=56) and European Americans (EAs; n=68) smokers.Smokers with valine (Val)/Val genotype, compared with methionine (Met) carriers, had greater negative subjective effects from IV nicotine and had more severe withdrawal severity following overnight abstinence from smoking.The Val/Val genotype was associated with better performance on the math task and in AA smokers it was associated with greater systolic blood pressure.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and VA Connecticut Healthcare System, Yale University, School of Medicine, West Haven, CT, USA.

ABSTRACT
The catechol-O-methyltransferase (COMT) Val158Met polymorphism may be a risk factor for nicotine addiction. This study examined the influence of the COMT Val158Met polymorphism on subjective, physiological and cognitive effects of intravenous (IV) nicotine use in African Americans (AAs; n=56) and European Americans (EAs; n=68) smokers. Overnight abstinent smokers received saline followed by 0.5 and 1.0 mg per 70 kg doses of nicotine, administered 30 min apart. Smokers with valine (Val)/Val genotype, compared with methionine (Met) carriers, had greater negative subjective effects from IV nicotine and had more severe withdrawal severity following overnight abstinence from smoking. Women with Val/Val genotype reported greater difficulty concentrating and irritability than men with Val/Val or Met carrier genotypes. The Val/Val genotype was associated with better performance on the math task and in AA smokers it was associated with greater systolic blood pressure. These results support the rationale of pharmacologically inhibiting COMT to aid with smoking cessation among Val/Val genotype smokers.

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Related in: MedlinePlus

Mean±SEM of selected DEQ domains A) Feel Down B) Feel Bad C) Sedated D) Drug Strength E) Like the Drug, and F) Want More as functions of COMT genotype and nicotine dose.
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Figure 2: Mean±SEM of selected DEQ domains A) Feel Down B) Feel Bad C) Sedated D) Drug Strength E) Like the Drug, and F) Want More as functions of COMT genotype and nicotine dose.

Mentions: For all the DEQ assessments, the rating for the 1.0 mg nicotine or 0.5 mg nicotine does were > than for saline (all p values<0.05). For the rating of “Stimulated,” “High,” “Feel Drug Strength,” the ratings for the 1.0 mg nicotine> 0.5 mg nicotine (p<0.05). The NMR values were positively correlated with the ratings of “Stimulated” “High,” and “Feel Anxious” (p<0.05). The results for the DEQ items are summarized in Table 1 and Figure 2.


COMT Val158Met modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers.

Herman AI, Jatlow PI, Gelernter J, Listman JB, Sofuoglu M - Pharmacogenomics J. (2013)

Mean±SEM of selected DEQ domains A) Feel Down B) Feel Bad C) Sedated D) Drug Strength E) Like the Drug, and F) Want More as functions of COMT genotype and nicotine dose.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675163&req=5

Figure 2: Mean±SEM of selected DEQ domains A) Feel Down B) Feel Bad C) Sedated D) Drug Strength E) Like the Drug, and F) Want More as functions of COMT genotype and nicotine dose.
Mentions: For all the DEQ assessments, the rating for the 1.0 mg nicotine or 0.5 mg nicotine does were > than for saline (all p values<0.05). For the rating of “Stimulated,” “High,” “Feel Drug Strength,” the ratings for the 1.0 mg nicotine> 0.5 mg nicotine (p<0.05). The NMR values were positively correlated with the ratings of “Stimulated” “High,” and “Feel Anxious” (p<0.05). The results for the DEQ items are summarized in Table 1 and Figure 2.

Bottom Line: This study examined the influence of the COMT Val158Met polymorphism on subjective, physiological and cognitive effects of intravenous (IV) nicotine use in African Americans (AAs; n=56) and European Americans (EAs; n=68) smokers.Smokers with valine (Val)/Val genotype, compared with methionine (Met) carriers, had greater negative subjective effects from IV nicotine and had more severe withdrawal severity following overnight abstinence from smoking.The Val/Val genotype was associated with better performance on the math task and in AA smokers it was associated with greater systolic blood pressure.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and VA Connecticut Healthcare System, Yale University, School of Medicine, West Haven, CT, USA.

ABSTRACT
The catechol-O-methyltransferase (COMT) Val158Met polymorphism may be a risk factor for nicotine addiction. This study examined the influence of the COMT Val158Met polymorphism on subjective, physiological and cognitive effects of intravenous (IV) nicotine use in African Americans (AAs; n=56) and European Americans (EAs; n=68) smokers. Overnight abstinent smokers received saline followed by 0.5 and 1.0 mg per 70 kg doses of nicotine, administered 30 min apart. Smokers with valine (Val)/Val genotype, compared with methionine (Met) carriers, had greater negative subjective effects from IV nicotine and had more severe withdrawal severity following overnight abstinence from smoking. Women with Val/Val genotype reported greater difficulty concentrating and irritability than men with Val/Val or Met carrier genotypes. The Val/Val genotype was associated with better performance on the math task and in AA smokers it was associated with greater systolic blood pressure. These results support the rationale of pharmacologically inhibiting COMT to aid with smoking cessation among Val/Val genotype smokers.

Show MeSH
Related in: MedlinePlus