title: First- and second-generation antipsychotic drug treatment and subcortical brain morphology in schizophrenia.
abstract: Antipsychotic medication may influence brain structure, but to what extent effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) differ is still not clear. Here we aimed to disentangle the effects of FGA and SGA on variation in volumes of subcortical structures in patients with long-term treated schizophrenia. Magnetic resonance images were obtained from 95 patients with schizophrenia and 106 healthy control subjects. Among the patients, 40 received only FGA and 42 received only SGA. FreeSurfer 5.3.0 was used to obtain volumes of 27 subcortical structures as well as total brain volume and estimated intracranial volume. Findings of reduced total brain volume, enlarged ventricular volume and reduced hippocampal volume bilaterally among patients were replicated, largely independent of medication class. In the basal ganglia, FGA users had larger putamen bilaterally and right caudate volume compared to healthy controls, and the right putamen was significantly larger than among SGA users. FGA and SGA users had similar and larger globus pallidus volumes compared to healthy controls. Post hoc analyses revealed that the difference between FGA and SGA could be attributed to smaller volumes in the clozapine users specifically. We therefore conclude that basal ganglia volume enlargements are not specific to FGA.
authors.affiliation: Department of Psychiatric Research, Diakonhjemmet Hospital, P.O. Box 85, 0319, Vinderen, Oslo, Norway. k.n.jorgensen@medisin.uio.no.|NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. k.n.jorgensen@medisin.uio.no.
authors.forename: Kjetil N
authors.identifier: http://orcid.org/0000-0002-5751-4809
authors.initials: KN
authors.lastname: Jørgensen
authors.affiliation: Department of Psychiatric Research, Diakonhjemmet Hospital, P.O. Box 85, 0319, Vinderen, Oslo, Norway.|Department of Genetics, Environment and Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Ragnar
authors.initials: R
authors.lastname: Nesvåg
authors.affiliation: Department of Psychiatric Research, Diakonhjemmet Hospital, P.O. Box 85, 0319, Vinderen, Oslo, Norway.
authors.forename: Sindre
authors.initials: S
authors.lastname: Gunleiksrud
authors.affiliation: Department of Psychiatric Research, Diakonhjemmet Hospital, P.O. Box 85, 0319, Vinderen, Oslo, Norway.|NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Andrea
authors.initials: A
authors.lastname: Raballo
authors.affiliation: NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Clinical Neuroscience, HUBIN Project, Karolinska Institutet and Hospital, Stockholm, Sweden.
authors.forename: Erik G
authors.initials: EG
authors.lastname: Jönsson
authors.affiliation: Department of Psychiatric Research, Diakonhjemmet Hospital, P.O. Box 85, 0319, Vinderen, Oslo, Norway.|NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Clinical Neuroscience, HUBIN Project, Karolinska Institutet and Hospital, Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Agartz
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D014150:Antipsychotic Agents
keywords: Antipsychotic medication; Basal ganglia; Clozapine; Magnetic resonance imaging; Schizophrenia; Subcortical brain structures