University of Oulu

Aino I.L. Saarinen, Sanna Huhtaniska, Juho Pudas, Lassi Björnholm, Tuomas Jukuri, Jussi Tohka, Niklas Granö, Jennifer H. Barnett, Vesa Kiviniemi, Juha Veijola, Mirka Hintsanen, Johannes Lieslehto, Structural and functional alterations in the brain gray matter among first-degree relatives of schizophrenia patients: A multimodal meta-analysis of fMRI and VBM studies, Schizophrenia Research, Volume 216, 2020, Pages 14-23, ISSN 0920-9964,

Structural and functional alterations in the brain gray matter among first-degree relatives of schizophrenia patients : a multimodal meta-analysis of fMRI and VBM studies

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Author: Saarinen, Aino I.L.1,2,3; Huhtaniska, Sanna4; Pudas, Juho3;
Organizations: 1Research Unit of Psychology, University of Oulu, Finland
2Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Finland
3Research Unit of Clinical Neuroscience, Department of Psychiatry, University of Oulu, Finland
4Center for Life Course Health Research, University of Oulu, Finland
5A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
6Helsinki University Hospital, Department of Adolescent Psychiatry, Finland
7Cambridge Cognition, Cambridge, UK
8Department of Psychiatry, University of Cambridge, Cambridge, UK
9Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland
10Department of Psychiatry, Oulu University Hospital, Oulu, Finland
11Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
12Section for Neurodiagnostic Applications, Department of Psychiatry, Ludwig Maximilian University, Nussbaumstrasse 7, 80336 Munich, Bavaria, Germany
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
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Language: English
Published: Elsevier, 2020
Publish Date: 2021-01-07


Objective: We conducted a multimodal coordinate-based meta-analysis (CBMA) to investigate structural and functional brain alterations in first-degree relatives of schizophrenia patients (FRs).

Methods: We conducted a systematic literature search from electronic databases to find studies that examined differences between FRs and healthy controls using whole-brain functional magnetic resonance imaging (fMRI) or voxel-based morphometry (VBM). A CBMA of 30 fMRI (754 FRs; 959 controls) and 11 VBM (885 FRs; 775 controls) datasets were conducted using the anisotropic effect-size version of signed differential mapping. Further, we conducted separate meta-analyses about functional alterations in different cognitive tasks: social cognition, executive functioning, working memory, and inhibitory control.

Results: FRs showed higher fMRI activation in the right frontal gyrus during cognitive tasks than healthy controls. In VBM studies, there were no differences in gray matter density between FRs and healthy controls. Furthermore, multi-modal meta-analysis obtained no differences between FRs and healthy controls. By utilizing the BrainMap database, we showed that the brain region which showed functional alterations in FRs (i) overlapped only slightly with the brain regions that were affected in the meta-analysis of schizophrenia patients and (ii) correlated positively with the brain regions that exhibited increased activity during cognitive tasks in healthy individuals.

Conclusions: Based on this meta-analysis, FRs may exhibit only minor functional alterations in the brain during cognitive tasks, and the alterations are much more restricted and only slightly overlapping with the regions that are affected in schizophrenia patients. The familial risk did not relate to structural alterations in the gray matter.

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Series: Schizophrenia research
ISSN: 0920-9964
ISSN-E: 1573-2509
ISSN-L: 0920-9964
Volume: 216
Pages: 14 - 23
DOI: 10.1016/j.schres.2019.12.023
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Funding: This study was supported financially by the Academy of Finland (J.V., grant number 124257, 141042, 212818, 214273, and 308555; V.K., Terva grant; J.T., grant number 316258), the Sigrid Jusélius Foundation (J.V.), the Gyllenberg Foundation (J.V.), the Medical Research Council (MRC) (V.K.), the Jane and Aatos Erkko Foundation (V.K.), the Finnish Medical Association (JL), Yrjö Jahnsson Foundation (J.L.), and Jalmari and Rauha Ahokas Foundation (J.L.).
Academy of Finland Grant Number: 124257
Detailed Information: 124257 (Academy of Finland Funding decision)
141042 (Academy of Finland Funding decision)
214273 (Academy of Finland Funding decision)
308555 (Academy of Finland Funding decision)
Copyright information: © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license