title: Tobacco use is associated with reduced amplitude and intensity dependence of the cortical auditory evoked N1-P2 component.
abstract: Tobacco use is linked to cerebral atrophy and reduced cognitive performance in later life. However, smoking-related long-term effects on brain function remain largely uncertain. Previous studies suggest that nicotine affects serotonergic signaling, and the intensity dependence (alias loudness dependence) of the auditory evoked N1-P2 potential has been proposed as a marker of serotonergic neurotransmission.
  
  
  
  In the present study, we assesed the effects of chronic smoking on amplitude and intensity dependence of the auditory evoked N1-P2 potential.
  
  
  
  Subjects underwent a 15-min intensity dependence of auditory evoked potentials (IAEP) paradigm. From N = 1739 eligible subjects (40-79 years), we systematically matched current smokers, ex-smokers, and never-smokers by sex, age, alcohol and caffeine consumption, and socioeconomic status. Between-group differences and potential dose-dependencies were evaluated.
  
  
  
  Analyses revealed higher N1-P2 amplitudes and intensity dependencies in never-smokers relative to ex- and current smokers, with ex-smokers exhibiting intermediate intensity dependencies. Moreover, we observed pack years and number of cigarettes consumed per day to be inversely correlated with amplitudes in current smokers.
  
  
  
  According to the IAEP serotonin hypothesis, our results suggest serotonin activity to be highest in current smokers, intermediate in ex-smokers, and lowest in never-smokers. To our knowledge, the present study is the first providing evidence for a dose-dependent reduction in N1-P2 amplitudes. Further, we extend prior research by showing reduced amplitudes and intensity dependencies in ex-smokers even 25 years, on average, after cessation. While we can rule out several smoking-related confounders to bias observed associations, causal inferences remain to be established by future longitudinal studies.
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany. philippe.jawinski@medizin.uni-leipzig.de.|Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany. philippe.jawinski@medizin.uni-leipzig.de.|Depression Research Center of the German Depression Foundation, Leipzig, Germany. philippe.jawinski@medizin.uni-leipzig.de.
authors.forename: Philippe
authors.identifier: http://orcid.org/0000-0002-2994-3075
authors.initials: P
authors.lastname: Jawinski
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mauche
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Depression Research Center of the German Depression Foundation, Leipzig, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Ulke
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany.
authors.forename: Jue
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany.|Depression Research Center of the German Depression Foundation, Leipzig, Germany.
authors.forename: Janek
authors.initials: J
authors.lastname: Spada
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Enzenbach
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany.|Depression Research Center of the German Depression Foundation, Leipzig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sander
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany.|Depression Research Center of the German Depression Foundation, Leipzig, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hegerl
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Hensch
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D000368:Aged; D001143:Arousal / Q000187:drug effects; D001303:Auditory Cortex / Q000503:physiopathology*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012701:Serotonin / Q000378:metabolism; D012907:Smoking / Q000503:physiopathology; D012959:Socioeconomic Factors; D014029:Tobacco Use Disorder / Q000503:physiopathology*
chemical_list: D012701:Serotonin
keywords: Addiction; Auditory evoked potentials; EEG; Intensity dependence; Loudness dependence; N1-P2; N100; P200; Smoking