title: Minimal effects of prolonged smoking abstinence or resumption on cognitive performance challenge the "self-medication" hypothesis in schizophrenia.
abstract: One prominent, long-standing view is that individuals with schizophrenia smoke cigarettes more than the general population to "self-medicate" cognitive deficits and other symptoms. This study tested the self-medication hypothesis by examining the effects of smoking abstinence and resumption on cognition in patients with schizophrenia. Nicotine-dependent smokers with schizophrenia (n=26) were trained on a cognitive battery and then hospitalized to achieve and maintain confirmed abstinence from smoking for ~1 week. Cognition was tested while smoking as usual (baseline), one day after smoking cessation (early abstinence), ~1 week later (extended abstinence), and within ~3 weeks of resuming smoking (resumption). The test battery included measures of processing speed, attention, conflict resolution, verbal memory, working memory, verbal fluency, and executive function to evaluate multiple cognitive domains affected by schizophrenia. Positive and negative symptoms of schizophrenia, depressive symptoms, and dyskinesia were also measured at baseline and after prolonged abstinence. There were no significant changes in global cognitive test performance with smoking cessation, abstinence, or resumption. There were small decreases in a measure of processing speed and delayed verbal recall with abstinence, but these findings failed to survive adjustments for multiple comparisons. Surprisingly, in this within subject "On-Off-Off-On" design, there were no significant effects of early or prolonged abstinence from smoking on cognitive and behavioral measures in smokers with schizophrenia. The results of this study challenge the widely held "self-medication" hypothesis of smoking and schizophrenia, question the extent of pro-cognitive effects of smoking and nicotine in schizophrenia, and support encouraging smoking cessation in schizophrenia.
authors.affiliation: Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Boggs
authors.affiliation: Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Toral S
authors.initials: TS
authors.lastname: Surti
authors.affiliation: Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06519, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06519, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.affiliation: Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06519, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Cosgrove
authors.affiliation: Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06519, USA.
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Sewell
authors.affiliation: Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06519, USA.
authors.forename: Mohini
authors.initials: M
authors.lastname: Ranganathan
authors.affiliation: Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06519, USA. Electronic address: deepak.dsouza@yale.edu.
authors.forename: Deepak Cyril
authors.initials: DC
authors.lastname: D'Souza
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage; D003071:Cognition; D003072:Cognition Disorders / Q000150:complications; D005260:Female; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D009483:Neuropsychological Tests; D009538:Nicotine / Q000008:administration & dosage; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy; D012565:Schizophrenic Psychology; D012651:Self Medication; D012907:Smoking / Q000523:psychology*; D016540:Smoking Cessation
chemical_list: D014150:Antipsychotic Agents; D009538:Nicotine
keywords: Abstinence; Cognition; Nicotine; Schizophrenia; Smoking; Tobacco; Withdrawal