Download PDF
Pharmacopsychiatry 2005; 38(4): 158-160
DOI: 10.1055/s-2005-871237
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Serotonergic Effects of Smoking are Independent from the Human Serotonin Transporter Gene Promoter Polymorphism: Evidence from Auditory Cortical Stimulus Processing

J. Gallinat1*, D. Kunz1*, U. E. Lang2 , P. Kalus1 , G. Juckel1 , J. Eggers4 , R. Mahlberg1 , M. Staedtgen1 , C. Wernicke2 , H. Rommelspacher2 , M. N. Smolka3
  • 1Clinic for Psychiatry and Psychotherapy, Charité University Medicine, Campus Mitte, Berlin, Germany
  • 2Clinic for Psychiatry and Psychotherapy, Charité University Medicine, Campus Benjamin Franklin, Berlin, Germany
  • 3Central Institute of Mental Health, Mannheim, Germany
  • 4Clinic for Neurology, University Clinic Schleswig-Holstein Campus, Luebeck, Germany
Further Information

Publication History

Received: 27.7.2004 Revised: 5.10.2004

Accepted: 10.1.2005

Publication Date:
18 July 2005 (online)

Also available at
    Permissions and Reprints

Background: Cigarette smoking has been associated with mood enhancing properties and modulating effects on serotonin activity. The loudness dependence (LD) of the auditory-evoked N1/P2-component has been related to serotonergic neurotransmission, i. e. the allelic variants in the promoter of the 5-hydroxytryptamine-transporter (5-HTT) gene (SCL6A4). Moreover, smoking behavior has been associated to the 5-HTT-genotype. It was hypothesized that cigarette smoking modulates the LD and this effect was expected to interact with the 5-HTT-genotype. Methods: 5-HTT-genotype and LD were determined in 63 healthy smokers and 114 nonsmokers. Results: LD was significantly affected by smoking status (p = 0.008) and 5-HTT-genotype (p = 0.045) but not by smoking*genotype-interaction or daily cigarette consumption. Current smokers exhibited a significantly weaker LD compared to nonsmokers. 5-HTT-genotype showed no significant effect on smoking behavior. Discussion: The results indicate a higher serotonergic activity in smokers as compared to nonsmokers independent of 5-HTT-genotype. Since former smokers and never smokers showed similar LDs, the serotonin enhancing effect of smoking seems to be a characteristic state, which may contribute to the maintenance of smoking behavior.

References

  • 1 Cheeta S, Irvine E E, Kenny P J, File S E. The dorsal raphe nucleus is a crucial structure mediating nicotine’s anxiolytic effects and the development of tolerance and withdrawal responses.  Psychopharmacology. 2001;  155 78-85
    CrossrefPubMedSearch in Google Scholar
  • 2 Gallinat J, Bottlender R, Juckel G, Munke-Puchner A, Stotz G, Kuss H J. et al . The loudness dependency of the auditory evoked N1/P2-component as a predictor of the acute SSRI response in depression.  Psychopharmacology (Berl). 2000;  148 404-411
    CrossrefPubMedSearch in Google Scholar
  • 3 Gallinat J, Senkowski D, Wernicke C, Juckel G, Becker I, Sander T. et al . Allelic Variants of the Functional Promoter Polymorphism of the Human Serotonin Transporter Gene is Associated with Auditory Cortical Stimulus Processing.  Neuropsychopharmacology. 2003;  28 530-532
    CrossrefPubMedSearch in Google Scholar
  • 4 Glassman A H, Covey L S, Stetner F, Rivelli S. Smoking cessation and the course of major depression: a follow-up study.  Lancet. 2001;  357 1929-1932
    CrossrefPubMedSearch in Google Scholar
  • 5 Greenberg B D, Tolliver T J, Huang S J, Li Q, Bengel D, Murphy D L. Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets.  Am J Med Genet. 1999;  88 83-87
    CrossrefPubMedSearch in Google Scholar
  • 6 Haro R, Drucker-Colin R. A two-year study on the effects of nicotine and its withdrawal on mood and sleep.  Pharmacopsychiatry. 2004;  37 221-227
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Heinz A, Jones D W, Bissette G, Hommer D, Ragan P, Knable M. et al . Relationship between cortisol and serotonin metabolites and transporters in alcoholism.  Pharmacopsychiatry. 2002;  35 127-134
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Heinz A, Jones D W, Mazzanti C, Goldman D, Ragan P, Hommer D. et al . A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity.  Biol Psychiatry. 2000;  47 643-649
    Search in Google Scholar
  • 9 Hoffman B J. Expression cloning of a serotonin transporter: a new way to study antidepressant drugs.  Pharmacopsychiatry. 1994;  27 16-22
    PubMedSearch in Google Scholar
  • 10 Ishikawa H, Ohtsuki T, Ishiguro H, Yamakawa-Kobayashi K, Endo K, Lin Y L. et al . Association between serotonin transporter gene polymorphism and smoking among Japanese males.  Cancer Epidemiol Biomarkers Prev. 1999;  8 831-833
    PubMedSearch in Google Scholar
  • 11 Juckel G, Hegerl U, Molnar M, Csepe V, Karmos G. Auditory evoked potentials reflect serotonergic neuronal activity - a study in behaving cats administered drugs acting on 5-HT1A autoreceptors in the dorsal raphe nucleus.  Neuropsychopharmacology. 1999;  21 710-716
    CrossrefPubMedSearch in Google Scholar
  • 12 Juckel G, Mavrogiorgou P, Bredemeier S, Gallinat J, Frodl T, Schulz C. et al . Loudness dependence of primary auditory-cortex-evoked activity as predictor of therapeutic outcome to prophylactic lithium treatment in affective disorders - a retrospective study.  Pharmacopsychiatry. 2004;  37 46-51
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 Lang U E, Hellweg R, Gallinat J. Association of BDNF serum concentrations with central serotonergic activity: Evidence from auditory signal processing. Neuropsychopharmacology 2005; in press
    Search in Google Scholar
  • 14 Lerman C, Shields P G, Audrain J, Main D, Cobb B, Boyd N R. et al . The role of the serotonin transporter gene in cigarette smoking.  Cancer Epidemiol Biomarkers Prev. 1998;  7 253-255
    PubMedSearch in Google Scholar
  • 15 Lesch K P, Bengel D, Heils A, Sabol S Z, Greenberg B D, Petri S. et al . Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.  Science. 1996;  274 1527-1531
    CrossrefPubMedSearch in Google Scholar
  • 16 Miller M M, Abplanalp H, Goto R. Genotyping chickens for the B-G subregion of the major histocompatibility complex using restriction fragment length polymorphisms.  Immunogenetics. 1988;  28 374-379
    CrossrefPubMedSearch in Google Scholar
  • 17 Miyata G, Meguid M M, Fetissov S O, Torelli G F, Kim H J. Nicotine’s effect on hypothalamic neurotransmitters and appetite regulation.  Surgery. 1999;  126 255-263
    CrossrefPubMedSearch in Google Scholar
  • 18 Murphy J M, Horton N J, Monson R R, Laird N M, Sobol A M, Leighton A H. Cigarette smoking in relation to depression: historical trends from the Stirling County Study.  Am J Psychiatry. 2003;  160 1663-1669
    CrossrefPubMedSearch in Google Scholar
  • 19 Racke K, Schworer H, Simson G. Effects of cigarette smoking or ingestion of nicotine on platelet 5-hydroxytryptamine (5-HT) levels in smokers and nonsmokers.  Clin Investig. 1992;  70 201-204
    PubMedSearch in Google Scholar
  • 20 Sander T, Harms H, Dufeu P, Kuhn S, Hoehe M, Lesch K P. et al . Serotonin transporter gene variants in alcohol-dependent subjects with dissocial personality disorder.  Biol Psychiatry. 1998;  43 908-912
    CrossrefPubMedSearch in Google Scholar
  • 21 Sparrow D, O’Connor G T, Young J B, Rosner B, Weiss S T. Relationship of urinary serotonin excretion to cigarette smoking and respiratory symptoms. The Normative Aging Study.  Chest. 1992;  101 976-980
    CrossrefPubMedSearch in Google Scholar
  • 22 Staley J K, Krishnan-Sarin S, Zoghbi S, Tamagnan G, Fujita M, Seibyl J P. et al . Sex differences in [123I]beta-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers.  Synapse. 2001;  41 275-284
    CrossrefPubMedSearch in Google Scholar

Jürgen Gallinat, MD

Psychiatrische Universitätsklinik der Charité im St. Hedwig Krankenhaus

Turmstr. 21

10559 Berlin

Germany

Phone: +49 30 2311 2895

Fax: +49 30 2311 2903

Email: juergen.gallinat@charite.de