title: Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication.
abstract: Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999-2001 at the age of 33-35 years. A follow-up was conducted 9 years later during 2008-2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.
authors.affiliation: Department of Psychiatry, Institute of Clinical Medicine, 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, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Joyce Y
authors.initials: JY
authors.lastname: Guo
authors.affiliation: Department of Psychiatry, Institute of Clinical Medicine, University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, Oulu, Finland.
authors.forename: Jani S
authors.initials: JS
authors.lastname: Moilanen
authors.affiliation: Department of Psychiatry, Institute of Clinical Medicine, University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, Oulu, Finland.
authors.forename: Erika
authors.initials: E
authors.lastname: Jääskeläinen
authors.affiliation: Department of Psychiatry, Institute of Clinical Medicine, University of Oulu, Oulu, Finland; Institute of Health Sciences, University of Oulu, Oulu, Finland; Unit of General Practice, Oulu University Hospital, Oulu, Finland.
authors.forename: Jouko
authors.initials: J
authors.lastname: Miettunen
authors.affiliation: Department of Psychiatry, Institute of Clinical Medicine, University of Oulu, Oulu, Finland.
authors.forename: Merja
authors.initials: M
authors.lastname: Kyllönen
authors.affiliation: Department of Psychiatry, Institute of Clinical Medicine, University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, Oulu, Finland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Haapea
authors.affiliation: Department of Psychiatry, Institute of Clinical Medicine, University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, Oulu, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Huhtaniska
authors.affiliation: Department of Psychiatry, Institute of Clinical Medicine, University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, Oulu, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Alaräisänen
authors.affiliation: Department of Psychiatry, Institute of Clinical Medicine, University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, Oulu, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Mäki
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 Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Tuomo
authors.initials: T
authors.lastname: Starck
authors.affiliation: Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Jukka J
authors.initials: JJ
authors.lastname: Remes
authors.affiliation: Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Päivikki
authors.initials: P
authors.lastname: Tanskanen
authors.affiliation: Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Osmo
authors.initials: O
authors.lastname: Tervonen
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom; VU University Medical Centre, Department of Radiology, Amsterdam, The Netherlands.
authors.forename: Alle-Meije
authors.initials: AM
authors.lastname: Wink
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Angie
authors.initials: A
authors.lastname: Kehagia
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom; Department of Neuropsychiatry, School of Medicine, Toho University, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom; Cambridge Cognition Ltd, Bottisham, Cambridge, United Kingdom.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Barnett
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom; Institute of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Barnes
authors.affiliation: University of Eastern Finland, Faculty of Health Sciences, Institute of Clinical Medicine and Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hannu J
authors.initials: HJ
authors.lastname: Koponen
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jones
authors.affiliation: Department of Psychiatry, Institute of Clinical Medicine, 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, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Graham K
authors.initials: GK
authors.lastname: Murray
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011379:Prognosis; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D014150:Antipsychotic Agents