title: nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: Current trends and perspectives.
abstract: BACKGROUND
  The prevalence of tobacco use in the population with schizophrenia is enormously high. Moreover, nicotine dependence is found to be associated with symptom severity and poor outcome in patients with schizophrenia. The neurobiological mechanisms that explain schizophrenia-nicotine dependence comorbidity are not known. This study systematically reviews the evidence highlighting the contribution of nicotinic acetylcholine receptors (nAChRs) to nicotine abuse in schizophrenia.
  
  
  METHODS
  Electronic data bases (Medline, Google Scholar, and Web of Science) were searched using the selected key words that match the aims set forth for this review. A total of 276 articles were used for the qualitative synthesis of this review.
  
  
  RESULTS
  Substantial evidence from preclinical and clinical studies indicated that dysregulation of α7 and β2-subunit containing nAChRs account for the cognitive and affective symptoms of schizophrenia and nicotine use may represent a strategy to remediate these symptoms. Additionally, recent meta-analyses proposed that early tobacco use may itself increase the risk of developing schizophrenia. Genetic studies demonstrating that nAChR dysfunction that may act as a shared vulnerability factor for comorbid tobacco dependence and schizophrenia were found to support this view. The development of nAChR modulators was considered an effective therapeutic strategy to ameliorate psychiatric symptoms and to promote smoking cessation in schizophrenia patients.
  
  
  CONCLUSIONS
  The relationship between schizophrenia and smoking is complex. While the debate for the self-medication versus addiction vulnerability hypothesis continues, it is widely accepted that a dysfunction in the central nAChRs represent a common substrate for various symptoms of schizophrenia and comorbid nicotine dependence.
authors.affiliation: Department of Psychology and Neuroscience Program, Temple University, Philadelphia, PA 19112, United States. Electronic address: vinay.parikh@temple.edu.
authors.forename: Vinay
authors.initials: V
authors.lastname: Parikh
authors.affiliation: Department of Psychology and Neuroscience Program, Temple University, Philadelphia, PA 19112, United States.
authors.forename: Munir Gunes
authors.initials: MG
authors.lastname: Kutlu
authors.affiliation: Department of Psychology and Neuroscience Program, Temple University, Philadelphia, PA 19112, United States.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Gould
mesh_terms: D000342:Affective Symptoms / Q000209:etiology; D000818:Animals; D003072:Cognition Disorders / Q000209:etiology; D016208:Databases, Factual / Q000706:statistics & numerical data; D006801:Humans; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012559:Schizophrenia / Q000150:complications / Q000453:epidemiology* / Q000378:metabolism*; D014029:Tobacco Use Disorder / Q000150:complications / Q000453:epidemiology* / Q000378:metabolism
chemical_list: D011978:Receptors, Nicotinic
keywords: Cognition; Comorbidity; Reward; Schizophrenia; Smoking; nAChRs