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Transl Psychiatry. 2019 Jan 17;9(1):12. doi: 10.1038/s41398-018-0225-4.

Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder.

Author information

1
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. emanuel.schwarz@zi-mannheim.de.
2
Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
3
Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
4
Department of Psychology, University of Oslo, Oslo, Norway.
5
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
6
Donders Center for Cognitive Neuroimaging, Radboud University, Nijmegen, The Netherlands.
7
Maastricht University Medical Center, Maastricht, The Netherlands.
8
Cognitive Brain Research Unit, Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
9
Centre for Population Neuroscience and Stratified Medicine (PONS) and MRC-SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
10
Brain Innovation B.V., Maastricht, The Netherlands.
11
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm County Council, Stockholm, Sweden.
12
Department of Psychiatry Research, Diakonhjemmet Hospital, Oslo, Norway.
13
Section of Psychiatry, Azienda Ospedaliera Universitaria Integrata Verona, Verona, VR, Italy.
14
Department of Neurosciences, Biomedicine and Movements Sciences, University of Verona, Verona, VR, Italy.
15
Institute of Psichiatry, Policlinico Bari, Azienda Ospedaliero Universitaria Consorziale Policlinico Bari, Bari, BA, Italy.
16
Azienda Ospedaliero-Universitaria Consorziale Policlinico, Bari, Italy.
17
Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
18
Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, The Netherlands.
19
Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands.
20
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
21
Departments of Human Genetics and Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.
22
Neuroscience and Mental Health Research Institute, Cardiff University, Maindy Road, Cardiff, CF24 4HQ, UK.
23
Department of Cognitive Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
24
Department of Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
25
Bernstein Center for Computational Neuroscience Heidelberg-Mannheim, Mannheim, Germany.
26
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, UK.
27
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, George Square, Edinburgh, EH8 9JZ, UK.
28
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
29
Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
30
Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055, Basel, Switzerland.
31
Transfaculty Research Platform Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland.
32
Psychiatric University Clinics, University of Basel, CH-4055, Basel, Switzerland.
33
Department Biozentrum, Life Sciences Training Facility, University of Basel, CH-4056, Basel, Switzerland.
34
Division of Cognitive Neuroscience, Department of Psychology, University of Basel, CH-4055, Basel, Switzerland.
35
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
36
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
37
District Hospital Mittelfranken, Department of Psychiatry, Psychotherapy and Psychosomatics, Ansbach, Germany.
38
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. Andreas.Meyer-Lindenberg@zi-mannheim.de.

Abstract

Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.

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