title: Longitudinal regional brain volume loss in schizophrenia: Relationship to antipsychotic medication and change in social function.
abstract: BACKGROUND
  Progressive brain volume loss in schizophrenia has been reported in previous studies but its cause and regional distribution remains unclear. We investigated progressive regional brain reductions in schizophrenia and correlations with potential mediators.
  
  
  METHODS
  Participants were drawn from the Northern Finland Birth Cohort 1966. A total of 33 schizophrenia individuals and 71 controls were MRI scanned at baseline (mean age=34.7, SD=0.77) and at follow-up (mean age=43.4, SD=0.44). Regional brain change differences and associations with clinical mediators were examined using FSL voxelwise SIENA.
  
  
  RESULTS
  Schizophrenia cases exhibited greater progressive brain reductions than controls, mainly in the frontal and temporal lobes. The degree of periventricular brain volume reductions were predicted by antipsychotic medication exposure at the fourth ventricular edge and by the number of days in hospital between the scans (a proxy measure of relapse duration) at the thalamic ventricular border. Decline in social and occupational functioning was associated with right supramarginal gyrus reduction.
  
  
  CONCLUSIONS
  Our findings are consistent with the possibility that antipsychotic medication exposure and time spent in relapse partially explain progressive brain reductions in schizophrenia. However, residual confounding could also account for the findings and caution must be applied before drawing causal inferences from associations demonstrated in observational studies of modest size. Less progressive brain volume loss in schizophrenia may indicate better preserved social and occupational functions.
authors.affiliation: Department of Psychiatry, Cambridge Biomedical Campus, University of Cambridge, Box 189 CB2 0QQ, United Kingdom; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 0SZ, United Kingdom.
authors.forename: Joyce Y
authors.initials: JY
authors.lastname: Guo
authors.affiliation: Department of Psychiatry, Research Group for Clinical Neuroscience, University of Oulu, Oulu, Finland; Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Huhtaniska
authors.affiliation: Department of Psychiatry, Research Group for Clinical Neuroscience, University of Oulu, Oulu, Finland; Institute of Health Sciences, University of Oulu, Oulu, Finland; Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Jouko
authors.initials: J
authors.lastname: Miettunen
authors.affiliation: Institute of Health Sciences, University of Oulu, Oulu, Finland; Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Erika
authors.initials: E
authors.lastname: Jääskeläinen
authors.affiliation: Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Vesa
authors.initials: V
authors.lastname: Kiviniemi
authors.affiliation: Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Nikkinen
authors.affiliation: Department of Psychiatry, Research Group for Clinical Neuroscience, University of Oulu, Oulu, Finland.
authors.forename: Jani
authors.initials: J
authors.lastname: Moilanen
authors.affiliation: Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Haapea
authors.affiliation: Department of Psychiatry, Research Group for Clinical Neuroscience, University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, Oulu, Finland; Department of Psychiatry, Länsi-Pohja Healthcare District, Finland; Department of Psychiatry, the Middle Ostrobothnia Central Hospital, Kiuru, Finland; Mental Health Services, Joint Municipal Authority of Wellbeing in Raahe District, Finland; Mental Health Services, Basic Health Care District of Kallio, Finland; Visala Hospital, the Northern Ostrobothnia Hospital District, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Mäki
authors.affiliation: Department of Psychiatry, Cambridge Biomedical Campus, University of Cambridge, Box 189 CB2 0QQ, United Kingdom.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jones
authors.affiliation: Department of Psychiatry, Research Group for Clinical Neuroscience, University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Veijola
authors.affiliation: Department of Psychiatry, Research Group for Clinical Neuroscience, University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, Oulu, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Isohanni
authors.affiliation: Department of Psychiatry, Cambridge Biomedical Campus, University of Cambridge, Box 189 CB2 0QQ, United Kingdom; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 0SZ, United Kingdom. Electronic address: gm285@cam.ac.uk.
authors.forename: Graham K
authors.initials: GK
authors.lastname: Murray
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy* / Q000473:pathology*; D012565:Schizophrenic Psychology; D018709:Statistics, Nonparametric
chemical_list: D014150:Antipsychotic Agents
keywords: Antipsychotic medication; Longitudinal MRI; Schizophrenia