The Role of the CHRNA4 Gene in Internet Addiction: A Case-control Study

Recent studies from Asia provided first evidence for a molecular genetic link between serotonergic and dopaminergic neurotransmission and Internet addiction. The present report offers data on a new candidate gene in the investigation of Internet addiction—the gene coding for the nicotinic acetylcholine receptor subunit alpha 4 (CHRNA4). A case-control study was carried out. The participants were recruited from a large gene data bank, including people from the general population and from a university setting. A total of 132 participants with problematic Internet use and 132 age- and sex-matched controls participated in the study. Participants provided DNA samples and filled in the Internet Addiction Test Questionnaire. The T- variant (CC genotype) of the rs1044396 polymorphism on the CHRNA4 gene occurred significantly more frequently in the case group. Further analyses revealed that this effect was driven by females. Combined with the findings from other studies, the present data point in the direction that rs1044396 exerts pleiotropic effects on a vast range of behaviors, including cognition, emotion, and addiction.

[1]  R. A. Davis,et al.  A cognitive-behavioral model of pathological Internet use , 2001, Comput. Hum. Behav..

[2]  Eric Turkheimer,et al.  Beyond Heritability , 2009, Current directions in psychological science.

[3]  N. Saitou,et al.  Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. , 2003, Human molecular genetics.

[4]  P. Renshaw,et al.  Depression like characteristics of 5HTTLPR polymorphism and temperament in excessive internet users. , 2008, Journal of affective disorders.

[5]  K. Shokat,et al.  Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure , 2006, Science.

[6]  Tianhua Niu,et al.  A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is associated with vulnerability to nicotine addiction in men. , 2004, American journal of human genetics.

[7]  J. Kennedy,et al.  Genetic aspects of pathological gambling: a complex disorder with shared genetic vulnerabilities. , 2009, Addiction.

[8]  J. Reggers,et al.  The short allele of the serotonin transporter promoter polymorphism influences relapse in alcohol dependence , 2007, European Psychiatry.

[9]  J. Changeux,et al.  Effects of nicotine in the dopaminergic system of mice lacking the alpha4 subunit of neuronal nicotinic acetylcholine receptors , 2003, The European journal of neuroscience.

[10]  Jeffrey H. Meyer,et al.  Smoking-induced ventral striatum dopamine release. , 2004, The American journal of psychiatry.

[11]  M. K. Horne,et al.  Mice Lacking the α4 Nicotinic Receptor Subunit Fail to Modulate Dopaminergic Neuronal Arbors and Possess Impaired Dopamine Transporter Function , 2005, Molecular Pharmacology.

[12]  Raja Parasuraman,et al.  Both a Nicotinic Single Nucleotide Polymorphism (SNP) and a Noradrenergic SNP Modulate Working Memory Performance when Attention is Manipulated , 2009, Journal of Cognitive Neuroscience.

[13]  Kimberly Young,et al.  Internet Addiction: The Emergence of a New Clinical Disorder , 1998, Cyberpsychology Behav. Soc. Netw..

[14]  I. Scheffer,et al.  Phenotypic Characterization of an α4 Neuronal Nicotinic Acetylcholine Receptor Subunit Knock-Out Mouse , 2000, The Journal of Neuroscience.

[15]  Christian Montag,et al.  The Association between Dopamine DRD2 Polymorphisms and Working Memory Capacity Is Modulated by a Functional Polymorphism on the Nicotinic Receptor Gene CHRNA4 , 2010, Journal of Cognitive Neuroscience.

[16]  Christian Montag,et al.  Does excessive play of violent first-person-shooter-video-games dampen brain activity in response to emotional stimuli? , 2012, Biological Psychology.

[17]  Christian Montag,et al.  Internet Addiction and Personality in First-Person-Shooter Video Gamers , 2011, J. Media Psychol. Theor. Methods Appl..

[18]  F. Weiss,et al.  The dopamine hypothesis of reward: past and current status , 1999, Trends in Neurosciences.

[19]  E. Hardie,et al.  Excessive internet use: the role of personality, loneliness and social support networks in internet addiction , 2007 .

[20]  May R. Berenbaum,et al.  Caught in the Net , 2001 .

[21]  D. Comings,et al.  A study of the dopamine D2 receptor gene in pathological gambling. , 1996, Pharmacogenetics.

[22]  C. Ko,et al.  Brain activities associated with gaming urge of online gaming addiction. , 2009, Journal of psychiatric research.

[23]  L. Brown,et al.  Shared brain vulnerabilities open the way for nonsubstance addictions: Carving addiction at a new joint? , 2010, Annals of the New York Academy of Sciences.

[24]  R. Parasuraman,et al.  Beyond Heritability , 2005, Psychological science.

[25]  M. Munafo,et al.  Association of the DRD2 gene Taq1A polymorphism and alcoholism: a meta-analysis of case–control studies and evidence of publication bias , 2007, Molecular Psychiatry.

[26]  J. Homberg,et al.  Serotonin transporter dosage modulates long-term decision-making in rat and human , 2008, Neuropharmacology.

[27]  P. Renshaw,et al.  Dopamine Genes and Reward Dependence in Adolescents with Excessive Internet Video Game Play , 2007, Journal of addiction medicine.

[28]  R. Tao,et al.  Proposed diagnostic criteria for internet addiction. , 2010, Addiction.

[29]  Christian Montag,et al.  The nicotinic acetylcholine receptor gene CHRNA4 is associated with negative emotionality. , 2011, Emotion.

[30]  I. Reinvang,et al.  Nicotine receptor gene CHRNA4 modulates early event-related potentials in auditory and visual oddball target detection tasks , 2007, Neuroscience.

[31]  Yan Zhou,et al.  Gray matter abnormalities in Internet addiction: a voxel-based morphometry study. , 2011, European journal of radiology.

[32]  U. Maskos.  Role of endogenous acetylcholine in the control of the dopaminergic system via nicotinic receptors , 2010, Journal of neurochemistry.

[33]  A. Lajtha,et al.  Effect of nicotine on extracellular levels of neurotransmitters assessed by microdialysis in various brain regions: Role of glutamic acid , 1992, Neurochemical Research.

[34]  Mary McMurran,et al.  The Psychometric Properties of the Internet Addiction Test , 2004, Cyberpsychology Behav. Soc. Netw..

[35]  Christian Montag,et al.  Low self-directedness is a better predictor for problematic internet use than high neuroticism , 2010, Comput. Hum. Behav..

[36]  Christian Montag,et al.  Evidence for the modality independence of the genetic epistasis between the dopaminergic and cholinergic system on working memory capacity , 2011, European Neuropsychopharmacology.

[37]  Chih-Hung Ko,et al.  The Association between Internet Addiction and Problematic Alcohol Use in Adolescents: The Problem Behavior Model , 2008, Cyberpsychology Behav. Soc. Netw..

[38]  A. Yang,et al.  Association of CHRNA4 polymorphism with depression and loneliness in elderly males , 2012, Genes, brain, and behavior.