Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia

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J Psychiatry Neurosci 2015;40(3):207-213

Jorien van der Velde, PhD; Paula M. Gromann, MSc; Marte Swart, PhD; Lieuwe de Haan, PhD; Durk Wiersma, PhD; Richard Bruggeman, PhD; Lydia Krabbendam, PhD; André Aleman, PhD

Abstract

Background: Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies.

Methods: We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results. Results: We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings.

Limitations: The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites.

Conclusion: These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia.


Submitted Feb. 27, 2014; Revised Aug. 31, 2014; Accepted Nov. 1, 2014; Early-released Mar. 17, 2015

Acknowledgements: The GROUP study is supported by a grant from ZonMw, with the Mental Health program (project number: 10.000.1002). The authors are grateful for the time and effort of the families who make the GROUP project possible. The authors acknowledge Anita Sibeijn- Kuiper, Judith Steurman, Edith Liemburg and Michelle Servaas for their assistance with MRI scanning and Drs. Jan-Bernard Marsman and Marie- José van Tol for their advice regarding VBM statistics.

Affiliations: From the Neuroimaging Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands (van der Velde, Aleman); Hanze University of Applied Sciences Groningen, Academy of Social studies, Groningen, The Netherlands (van der Velde); the Department of Educational Neuroscience, Faculty of Psychology and Education, VU University Amsterdam, Amsterdam, The Netherlands (Gromann, Krabbendam); Lentis, Center for Mental Healthcare, Groningen, The Netherlands (Swart); the Department of Psychiatry, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands (de Haan); and the Department of Neuroscience and Psychiatry, University Medical Center Groningen, Groningen, The Netherlands (Wiersma, Bruggeman).

Competing interests: None declared.

Contributors: L. de Haan, D, Wieisma, R. Bruggeman, L. Krabbendam and A. Aleman designed the study. J. van der Velde, P. Gromann and M. Swart acquired the data, which J. van der Velde and A. Aleman analyzed. J. van der Velde wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.140064

Correspondence to: J van der Velde, Department of Neuroscience, Neuroimaging Center, UMCG-O&O, P.O. Box 196, 9700 AD Groningen, The Netherlands; jorien.van.der.velde@umcg.nl