title: Lifetime antipsychotic medication and cognitive performance in schizophrenia at age 43 years in a general population birth cohort.
abstract: This naturalistic study analysed the association between cumulative lifetime antipsychotic dose and cognition in schizophrenia after an average of 16.5 years of illness. Sixty participants with schizophrenia and 191 controls from the Northern Finland Birth Cohort 1966 were assessed at age 43 years with a neurocognitive test battery. Cumulative lifetime antipsychotic dose-years were collected from medical records and interviews. The association between antipsychotic dose-years and a cognitive composite score based on principal component analysis was analysed using linear regression. Higher lifetime antipsychotic dose-years were significantly associated with poorer cognitive composite score, when adjusted for gender, onset age and lifetime hospital treatment days. The effects of typical and atypical antipsychotics did not differ. This is the first report of an association between cumulative lifetime antipsychotic dose and global cognition in midlife schizophrenia. Based on these data, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance at age 43 years. Potential biases related to the naturalistic design may partly explain the results; nonetheless, it is possible that large antipsychotic doses harm cognition in schizophrenia in the long-term.
authors.affiliation: Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, P.O. Box 26, 90029 OYS, Oulu, Finland. Electronic address: anja.husa@student.oulu.fi.
authors.forename: Anja P
authors.initials: AP
authors.lastname: Husa
authors.affiliation: Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, P.O. Box 26, 90029 OYS, Oulu, Finland. Electronic address: jani.m.moilanen@student.oulu.fi.
authors.forename: Jani
authors.initials: J
authors.lastname: Moilanen
authors.affiliation: Department of Psychiatry, University of Cambridge, Box 189 Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Herchel Smith Building, Forvie Site, Cambridge Biomedical Campus, Cambridge CB2 0SZ, United Kingdom. Electronic address: gm285@cam.ac.uk.
authors.forename: Graham K
authors.initials: GK
authors.lastname: Murray
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland. Electronic address: riikka.e.marttila@gmail.com.
authors.forename: Riikka
authors.initials: R
authors.lastname: Marttila
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland; Department of Diagnostic Radiology, Oulu University Hospital, P.O. Box 50, 90029 OYS, Finland. Electronic address: marianne.haapea@oulu.fi.
authors.forename: Marianne
authors.initials: M
authors.lastname: Haapea
authors.affiliation: Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. Electronic address: irina@rannikko.org.
authors.forename: Irina
authors.initials: I
authors.lastname: Rannikko
authors.affiliation: Department of Psychiatry, University of Cambridge, Box 189 Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Cambridge Cognition Ltd., Tunbridge Court, Bottisham, Cambridge, United Kingdom. Electronic address: jhb32@cam.ac.uk.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Barnett
authors.affiliation: Department of Psychiatry, University of Cambridge, Herchel Smith Building, Cambridge CB2 0SZ, United Kingdom. Electronic address: pbj21@cam.ac.uk.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jones
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, P.O. Box 26, 90029 OYS, Oulu, Finland; Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland. Electronic address: matti.isohanni@oulu.fi.
authors.forename: Matti
authors.initials: M
authors.lastname: Isohanni
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland; Department of Neurology, Kuopio University Hospital, Kuopio, Finland. Electronic address: anne.remes@uef.fi.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Remes
authors.affiliation: University of Helsinki and Helsinki University Hospital - Psychiatry, P.O. Box 22, 00014 Helsinki, Finland. Electronic address: hannu.j.koponen@hus.fi.
authors.forename: Hannu
authors.initials: H
authors.lastname: Koponen
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland. Electronic address: jouko.miettunen@oulu.fi.
authors.forename: Jouko
authors.initials: J
authors.lastname: Miettunen
authors.affiliation: Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland; Oulu Occupational Health, Hallituskatu 36 B, 90100 Oulu, Finland. Electronic address: erika.jaaskelainen@oulu.fi.
authors.forename: Erika
authors.initials: E
authors.lastname: Jääskeläinen
mesh_terms: D000328:Adult; D000367:Age Factors; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D005387:Finland; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents
keywords: Adverse effect; Cognition; Cross-sectional; Psychosis; Treatment