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

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.

[1]  A. Hofman,et al.  The effect of catechol-O-methyltransferase Met/Val functional polymorphism on smoking cessation: retrospective and prospective analyses in a cohort study , 2009, Pharmacogenetics and genomics.

[2]  D. Hatsukami,et al.  Signs and symptoms of tobacco withdrawal. , 1986, Archives of general psychiatry.

[3]  L. Cox,et al.  Evaluation of the brief questionnaire of smoking urges (QSU-brief) in laboratory and clinical settings. , 2001, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[4]  K. Z. Tang,et al.  Effect of abstinence challenge on brain function and cognition in smokers differs by COMT genotype , 2009, Molecular Psychiatry.

[5]  M. al’Absi,et al.  Psychophysiological effects of nicotine abstinence and behavioral challenges in habitual smokers , 2002, Pharmacology Biochemistry and Behavior.

[6]  Paul J. Harrison,et al.  Importance of the COMT gene for sex differences in brain function and predisposition to psychiatric disorders. , 2011, Current topics in behavioral neurosciences.

[7]  P. Willner,et al.  The Questionnaire of Smoking Urges is sensitive to abstinence and exposure to smoking-related cues. , 1999, Behavioural pharmacology.

[8]  M. Sofuoglu,et al.  Self-Administration of Intravenous Nicotine in Male and Female Cigarette Smokers , 2008, Neuropsychopharmacology.

[9]  M. Egan,et al.  Relative risk of neurological signs in siblings of patients with schizophrenia. , 2001, The American journal of psychiatry.

[10]  S. Hyman,et al.  Neural mechanisms of addiction: the role of reward-related learning and memory. , 2006, Annual review of neuroscience.

[11]  F. Luft,et al.  Differences in response to sodium administration in normotensive white and black subjects. , 1977, The Journal of laboratory and clinical medicine.

[12]  John A. Dani,et al.  Withdrawal from Chronic Nicotine Exposure Alters Dopamine Signaling Dynamics in the Nucleus Accumbens , 2012, Biological Psychiatry.

[13]  Ezio Tirelli,et al.  Selective effects of nicotine on attentional processes , 1999, Psychopharmacology.

[14]  Y. Kuepper,et al.  Genetic variants within the dopaminergic system interact to modulate endocrine stress reactivity and recovery , 2011, Behavioural Brain Research.

[15]  M. Sofuoglu,et al.  The reinforcement threshold for nicotine as a target for tobacco control. , 2012, Drug and alcohol dependence.

[16]  D. Hatsukami,et al.  Effects of three doses of transdermal nicotine on post-cessation eating, hunger and weight. , 1997, Journal of substance abuse.

[17]  W. Pickworth,et al.  Endocrine effects of nicotine administration, tobacco and other drug withdrawal in humans , 1998, Psychoneuroendocrinology.

[18]  P. Roussos,et al.  Tolcapone Effects on Gating, Working Memory, and Mood Interact with the Synonymous Catechol-O-methyltransferase rs4818C/G Polymorphism , 2009, Biological Psychiatry.

[19]  M. Munafo,et al.  Association of COMT Val108/158Met genotype with smoking cessation , 2008, Pharmacogenetics and genomics.

[20]  S. David,et al.  Genetic variation in the dopamine pathway and smoking cessation. , 2008, Pharmacogenomics.

[21]  P. Randall,et al.  COMT genotype influences the effect of alcohol on blood pressure: results from the COMBINE study. , 2009, American journal of hypertension.

[22]  Volker Arolt,et al.  Catechol-O-methyltransferase gene variation: Impact on amygdala response to aversive stimuli , 2012, NeuroImage.

[23]  D. Mant,et al.  Association between polymorphisms in dopamine metabolic enzymes and tobacco consumption in smokers. , 2000, Pharmacogenetics.

[24]  T. Kosten,et al.  Effects of tiagabine in combination with intravenous nicotine in overnight abstinent smokers , 2005, Psychopharmacology.

[25]  A. Waters,et al.  Minocycline reduced craving for cigarettes but did not affect smoking or intravenous nicotine responses in humans , 2009, Pharmacology Biochemistry and Behavior.

[26]  D. Murphy,et al.  Neuroendocrine, physiologic, and behavioral responses following intravenous nicotine in nonsmoking healthy volunteers and in patients with alzheimer's disease , 1990, Psychoneuroendocrinology.

[27]  T. Kosten,et al.  Effects of topiramate in combination with intravenous nicotine in overnight abstinent smokers , 2005, Psychopharmacology.

[28]  Hongyu Zhao,et al.  Characterization of a likelihood based method and effects of markers informativeness in evaluation of admixture and population group assignment , 2005, BMC Genetics.

[29]  J. Mendelson,et al.  Effects of Low- and High-Nicotine Cigarette Smoking on Mood States and the HPA Axis in Men , 2005, Neuropsychopharmacology.

[30]  P. Männistö,et al.  Are genetic variants of COMT associated with addiction? , 2010, Pharmacogenetics and genomics.

[31]  N. Benowitz,et al.  Nicotine metabolite ratio as an index of cytochrome P450 2A6 metabolic activity , 2004, Clinical pharmacology and therapeutics.

[32]  R. Weinshilboum,et al.  Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. , 1996, Pharmacogenetics.

[33]  S. Tiffany,et al.  The development and initial validation of a questionnaire on smoking urges. , 1991, British journal of addiction.

[34]  F. Luft,et al.  Racial differences in blood pressure in Evans County, Georgia: relationship to sodium and potassium intake and plasma renin activity. , 1980, Journal of chronic diseases.

[35]  Michael F Egan,et al.  Tolcapone Improves Cognition and Cortical Information Processing in Normal Human Subjects , 2007, Neuropsychopharmacology.

[36]  J. Axelrod.  Methylation reactions in the formation and metabolism of catecholamines and other biogenic amines. , 1966, Pharmacological reviews.

[37]  L. Stovner,et al.  High systolic blood pressure is associated with Val/Val genotype in the catechol-o-methyltransferase gene. The Nord-Trøndelag Health Study (HUNT). , 2007, American journal of hypertension.

[38]  J. Detre,et al.  Nicotine abstinence-induced cerebral blood flow changes by genotype , 2008, Neuroscience Letters.

[39]  R. Straub,et al.  Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[40]  O. Selnes.  A Compendium of Neuropsychological Tests , 1991, Neurology.

[41]  J. Sanjuán,et al.  Heterozygosity at catechol-O-methyltransferase Val158Met and schizophrenia: new data and meta-analysis. , 2011, Journal of psychiatric research.

[42]  T. Rebbeck,et al.  Association of catechol-O-methyltransferase with smoking cessation in two independent studies of women , 2005, Pharmacogenetics and genomics.

[43]  K. Danisa,et al.  Racial Differences in Pressure, Volume and Renin Interrelationships in Essential Hypertension , 1979, Hypertension.

[44]  W. Velicer,et al.  Biochemical verification of tobacco use and cessation. , 2002, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[45]  P. Donnelly,et al.  Inference of population structure using multilocus genotype data. , 2000, Genetics.

[46]  Robert Vlietinck,et al.  The Catechol-O-Methyl Transferase Val158Met Polymorphism and Experience of Reward in the Flow of Daily Life , 2008, Neuropsychopharmacology.

[47]  Xiang Yang Zhang,et al.  Association of functional catechol O-methyl transferase (COMT) Val108Met polymorphism with smoking severity and age of smoking initiation in Chinese male smokers , 2007, Psychopharmacology.

[48]  Ezio Tirelli,et al.  Effects of nicotine administered via a transdermal delivery system on vigilance: a repeated measure study , 1999, Psychopharmacology.

[49]  A. Grace,et al.  The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic–Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes , 2004, Neuropsychopharmacology.

[50]  B. Kolachana,et al.  COMT genotype predicts cortical-limbic D1 receptor availability measured with [11C]NNC112 and PET , 2008, Molecular Psychiatry.

[51]  George C Patton,et al.  Association between the COMT Val158Met polymorphism and propensity to anxiety in an Australian population-based longitudinal study of adolescent health , 2005, Psychiatric genetics.

[52]  A. Veronica Witte,et al.  Effects of COMT polymorphisms on brain function and behavior in health and disease , 2012, Brain Research Bulletin.

[53]  M. Muramatsu,et al.  Association of the catechol-O-methyl transferase gene Val158Met polymorphism with blood pressure and prevalence of hypertension: interaction with dietary energy intake. , 2011, American journal of hypertension.

[54]  J. Axelrod,et al.  Enzymatic O-methylation of epinephrine and other catechols. , 1958, The Journal of biological chemistry.

[55]  L. Landini,et al.  Molecular and biochemical changes of the cardiovascular system due to smoking exposure. , 2009, Current pharmaceutical design.

[56]  J. Henningfield,et al.  Effects of nicotine administration following 12 h of tobacco deprivation: assessment on computerized performance tasks , 2004, Psychopharmacology.

[57]  S J Heishman,et al.  Smoking after nicotine deprivation enhances cognitive performance and decreases tobacco craving in drug abusers. , 1999, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[58]  B. Kolachana,et al.  Variation in dopamine genes influences responsivity of the human reward system , 2009, Proceedings of the National Academy of Sciences.

[59]  R. Weinshilboum,et al.  Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. , 1999, Annual review of pharmacology and toxicology.

[60]  P. Jatlow,et al.  Rapid Nicotine Clearance is Associated with Greater Reward and Heart Rate Increases from Intravenous Nicotine , 2012, Neuropsychopharmacology.

[61]  N. Benowitz,et al.  Nicotine chemistry, metabolism, kinetics and biomarkers. , 2009, Handbook of experimental pharmacology.

[62]  André Aleman,et al.  Depression and the role of genes involved in dopamine metabolism and signalling , 2010, Progress in Neurobiology.

[63]  R. Kerwin,et al.  Pharmacogenetic studies of change in cortisol on ecstasy (MDMA) consumption , 2012, Journal of psychopharmacology.

[64]  D. Watson,et al.  Development and validation of brief measures of positive and negative affect: the PANAS scales. , 1988, Journal of personality and social psychology.