J Psychiatry Neurosci 2017;42(2):122-130
Marco M. Picchioni, MRCP, FRCPsych, PhD; Fruhling Rijsdijk, PhD; Timothea Toulopoulou, PhD; Christopher Chaddock, PhD; James H. Cole, PhD; Ulrich Ettinger, PhD; Ana Oses, MD; Hugo Metcalfe, MSc; Robin M. Murray, MD; Philip McGuire, MD, PhD
Background: Reductions in whole brain and grey matter volumes are robust features of schizophrenia, yet their etiological influences are unclear.
Methods: We investigated the association between the genetic and environmental risk for schizophrenia and brain volumes. Whole brain, grey matter and white matter volumes were established from structural MRIs from twins varying in their zygosity and concordance for schizophrenia. Hippocampal volumes were measured manually. We conducted between-group testing and full genetic modelling.
Results: We included 168 twins in our study. Whole brain, grey matter, white matter and right hippocampal volumes were smaller in twins with schizophrenia. Twin correlations were larger for whole brain, grey matter and white matter volumes in monozygotic than dizygotic twins and were significantly heritable, whereas hippocampal volume was the most environmentally sensitive. There was a significant phenotypic correlation between schizophrenia and reductions in all the brain volumes except for that of the left hippocampus. For whole brain, grey matter and the right hippocampus the etiological links with schizophrenia were principally associated with the shared familial environment. Lower birth weight and perinatal hypoxia were both associated with lower whole brain volume and with lower white matter and grey matter volumes, respectively.
Limitations: Scan data were collected across 2 sites, and some groups were modest in size.
Conclusion: Whole brain, grey matter and right hippocampal volume reductions are linked to schizophrenia through correlated familial risk (i.e., the shared familial environment). The degree of influence of etiological factors varies between brain structures, leading to the possibility of a neuroanatomically specific etiological imprint.
Submitted Sept. 24, 2014; Revised June 12, 2015; Revised Oct. 2, 2015; Accepted Oct. 15, 2015
Affiliations: From the St. Andrew’s Academic Department, Institute of Psychiatry Psychology and Neuroscience, King’s College London, UK (Picchioni); the Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King’s College London, UK (Picchioni, Toulopoulou, Chaddock, Murray, McGuire); the Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry Psychology and Neuroscience, King’s College London, UK (Picchioni, Metcalfe); the Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry Psychology and Neuroscience, King’s College London, UK (Rijsdijk); the Department of Psychology, The University of Hong Kong, Hong Kong (Toulopoulou); the Computational, Cognitive & Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK (Cole); the Department of Psychology, University of Bonn, Bonn, Germany (Ettinger); and the Centro de Salut Mental del Ripolles, Institut d’Assistencia Sanitaria de Girona, Girona, Spain (Oses).
Funding: The study was in part funded by a Wellcome Trust Research Training Fellowship to M. Picchioni (064971), a NARSAD Young Investigator Award to T. Toulopoulou and by the European Community’s Sixth Framework Programme through a Marie Curie Training Network called the European Twin Study Network on Schizophrenia (EUTwinsS). U. Ettinger was funded by the Deutsche Forschungsgemeinschaft (ET 31/2-1).
Competing interests: None declared.
Contributors: M. Picchioni, T. Toulopoulou, J. Cole, U. Ettinger, R. Muray and P. McGuire designed the study. M. Picchioni, T. Toulopoulou, U. Ettinger, R. Murray and P. McGuire acquired the data, which all authors analyzed. M. Picchioni, T. Toulopoulou, C. Chaddock, E. Ettinger, A. Oses, H. Metcalfe, R. Murray and P. McGuire wrote the article, which all authors reviewed and approved for publication.
Correspondence to: M. Picchioni, PO23 Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College, London, UK; firstname.lastname@example.org