University of Oulu

Sanna Huhtaniska, Iikka Korkala, Tuomas Heikka, Lassi Björnholm, Heli Lehtiniemi, Anja P. Hulkko, Jani Moilanen, Jussi Tohka, José Manjón, Pierrick Coupé, Vesa Kiviniemi, Matti Isohanni, Hannu Koponen, Graham K. Murray, Jouko Miettunen, Erika Jääskeläinen, Antipsychotic and benzodiazepine use and brain morphology in schizophrenia and affective psychoses – Systematic reviews and birth cohort study, Psychiatry Research: Neuroimaging, Volume 281, 2018, Pages 43-52, ISSN 0925-4927,

Antipsychotic and benzodiazepine use and brain morphology in schizophrenia and affective psychoses : systematic reviews and birth cohort study

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Author: Huhtaniska, Sanna1,2,3; Korkala, Iikka1,3; Heikka, Tuomas1;
Organizations: 1Center for Life Course Health Research, University of Oulu, Finland
2Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland
3Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, Finland
4AI Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
5Instituto de Aplicaciones de las Tecnologías de la Información y de las Comunicaciones Avanzadas (ITACA), Universitat Politècnica de València, Spain
6Laboratoire Bordelais de Recherche en Informatique, Unité Mixte de Recherche CNRS (UMR 5800), PICTURA Research Group, France
7Department of Diagnostic Radiology, Oulu University Hospital, Finland
8Department of Psychiatry, Oulu University Hospital, Finland
9University of Helsinki, Helsinki University Hospital, Psychiatry, Helsinki, Finland
10University of Cambridge, Department of Psychiatry, United Kingdom
11University of Cambridge, Behavioural and Clinical Neuroscience Institute, United Kingdom
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
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Language: English
Published: Elsevier, 2018
Publish Date: 2019-08-24


The aim of this paper was to investigate differences in brain structure volumes between schizophrenia and affective psychoses, and whether cumulative lifetime antipsychotic or benzodiazepine doses relate to brain morphology in these groups. We conducted two systematic reviews on the topic and investigated 44 schizophrenia cases and 19 with affective psychoses from the Northern Finland Birth Cohort 1966. The association between lifetime antipsychotic and benzodiazepine dose and brain MRI scans at the age of 43 was investigated using linear regression. Intracranial volume, sex, illness severity, and antipsychotic/benzodiazepine doses were used as covariates. There were no differences between the groups in brain structure volumes. In schizophrenia, after adjusting for benzodiazepine dose and symptoms, a negative association between lifetime antipsychotic dose and the nucleus accumbens volume remained. In affective psychoses, higher lifetime benzodiazepine dose associated with larger volumes of total gray matter and hippocampal volume after controlling for antipsychotic use and symptoms. It seems that in addition to antipsychotics, the severity of symptoms and benzodiazepine dose are also associated with brain structure volumes. These results suggest, that benzodiazepine effects should also be investigated also independently and not only as a confounder.

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Series: Psychiatry research. Neuroimaging
ISSN: 0925-4927
ISSN-E: 1872-7506
ISSN-L: 0925-4927
Volume: 281
Pages: 43 - 52
DOI: 10.1016/j.pscychresns.2018.08.015
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3112 Neurosciences
Funding: This work was supported by grants from the Academy of Finland (grant numbers 132 071, 278 286, 268 336), the Sigrid Jusélius Foundation, the Brain & Behavior Research Foundation, the Orion Research Foundation sr, the Foundation for Psychiatric Research, The scholarship Fund of the University of Oulu - Tyyni Tani Found, the University of Oulu Scholarship Foundation, the Jalmari and Rauha Ahokas Foundation, The Maud Kuistila Memorial Foundation, the Jane and Aatos Erkko Foundation, and the Oy H Lundbeck Ab. The funders had no role in the study design, data collection, data analysis, interpreting the results or the decision to publish the article.
Academy of Finland Grant Number: 132071
Detailed Information: 132071 (Academy of Finland Funding decision)
278286 (Academy of Finland Funding decision)
268336 (Academy of Finland Funding decision)
Copyright information: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license