title: Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment.
abstract: Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity.
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: Dara M
authors.initials: DM
authors.lastname: Cannon
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: Cathy
authors.initials: C
authors.lastname: Scanlon
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: Laurena
authors.initials: L
authors.lastname: Holleran
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: Heike
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: McFarland
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: Camilla
authors.initials: C
authors.lastname: Langan
authors.affiliation: Department of Radiology, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: Peter
authors.initials: P
authors.lastname: McCarthy
authors.affiliation: Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Gareth J
authors.identifier: 0000000252147421
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Hallahan
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: Colm
authors.initials: C
authors.lastname: McDonald
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001284:Atrophy / Q000188:drug therapy / Q000209:etiology; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology*; D002675:Child, Preschool; D003024:Clozapine / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
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