title: Smoking status as a potential confounder in the study of brain structure in schizophrenia.
abstract: Several but not all MRI studies have reported volume reductions in the hippocampus and dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia. Given the high prevalence of smoking among schizophrenia patients and the fact that smoking has also been associated with alterations in brain morphology, this study evaluated whether a proportion of the known gray matter reductions in key brain regions may be attributed to smoking rather than to schizophrenia alone. We examined structural MRI data of 112 schizophrenia patients (53 smokers and 59 non-smokers) and 77 healthy non-smoker controls collected by the MCIC study of schizophrenia. An automated atlas based probabilistic method was used to generate volumetric measures of the hippocampus and DLPFC. The two patient groups were matched with respect to demographic and clinical variables. Smoker schizophrenia patients showed significantly lower hippocampal and DLPFC volumes than non-smoker schizophrenia patients. Gray matter volume reductions associated with smoking status ranged between 2.2% and 2.8%. Furthermore, we found significant volume differences between smoker patients and healthy controls in the hippocampus and DLPFC, but not between non-smoker patients and healthy controls. Our data suggest that a proportion of the volume reduction seen in the hippocampus and DLPFC in schizophrenia is associated with smoking rather than with the diagnosis of schizophrenia. These results may have important implications for brain imaging studies comparing schizophrenia patients and other groups with a lower smoking prevalence.
authors.affiliation: Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Schneider
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus Medical Centre, Rotterdam, Netherlands; Department of Psychiatry and the Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Tonya
authors.initials: T
authors.lastname: White
authors.affiliation: Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Hass
authors.affiliation: Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Geisler
authors.affiliation: Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA; Massachusetts General Hospital/Massachusetts Institute of Technology/Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA.
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Wallace
authors.affiliation: Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
authors.forename: Veit
authors.initials: V
authors.lastname: Roessner
authors.affiliation: Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA; Massachusetts General Hospital/Massachusetts Institute of Technology/Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA.
authors.forename: Daphne J
authors.initials: DJ
authors.lastname: Holt
authors.affiliation: Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA; The Mind Research Network, Image Analysis and MR Research, Albuquerque, NM, USA.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA; Massachusetts General Hospital/Massachusetts Institute of Technology/Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Gollub
authors.affiliation: Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany; Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA; Massachusetts General Hospital/Massachusetts Institute of Technology/Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA. Electronic address: transden.lab@gmail.com.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehrlich
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D009929:Organ Size; D017397:Prefrontal Cortex / Q000473:pathology; D012559:Schizophrenia / Q000473:pathology*; D012907:Smoking / Q000453:epidemiology / Q000473:pathology*
keywords: Brain volume; DLPFC; Hippocampus; MRI; Schizophrenia; Smoking