Multi-center MRI prediction models: Predicting sex and illness course in first episode psychosis patients

ABSTRACT Structural Magnetic Resonance Imaging (MRI) studies have attempted to use brain measures obtained at the first‐episode of psychosis to predict subsequent outcome, with inconsistent results. Thus, there is a real need to validate the utility of brain measures in the prediction of outcome using large datasets, from independent samples, obtained with different protocols and from different MRI scanners. This study had three main aims: 1) to investigate whether structural MRI data from multiple centers can be combined to create a machine‐learning model able to predict a strong biological variable like sex; 2) to replicate our previous finding that an MRI scan obtained at first episode significantly predicts subsequent illness course in other independent datasets; and finally, 3) to test whether these datasets can be combined to generate multicenter models with better accuracy in the prediction of illness course. The multi‐center sample included brain structural MRI scans from 256 males and 133 females patients with first episode psychosis, acquired in five centers: University Medical Center Utrecht (The Netherlands) (n = 67); Institute of Psychiatry, Psychology and Neuroscience, London (United Kingdom) (n = 97); University of São Paulo (Brazil) (n = 64); University of Cantabria, Santander (Spain) (n = 107); and University of Melbourne (Australia) (n = 54). All images were acquired on 1.5‐Tesla scanners and all centers provided information on illness course during a follow‐up period ranging 3 to 7 years. We only included in the analyses of outcome prediction patients for whom illness course was categorized as either “continuous” (n = 94) or “remitting” (n = 118). Using structural brain scans from all centers, sex was predicted with significant accuracy (89%; p < 0.001). In the single‐ or multi‐center models, illness course could not be predicted with significant accuracy. However, when reducing heterogeneity by restricting the analyses to male patients only, classification accuracy improved in some samples. This study provides proof of concept that combining multi‐center MRI data to create a well performing classification model is possible. However, to create complex multi‐center models that perform accurately, each center should contribute a sample either large or homogeneous enough to first allow accurate classification within the single‐center. HighlightsMulti‐center neuroimaging data can be combined to classify clear biological outcome.Classification is only significant in centers with similar illness outcome definition.Multi‐center models can increase performance of smaller and heterogeneous samples.Multi‐center studies should use large samples and standardized clinical information.Multi‐center models have the potential to yield clinically useful predictions.

[1]  Karl J. Friston,et al.  Unified segmentation , 2005, NeuroImage.

[2]  P. Chue,et al.  Sex differences in schizophrenia, a review of the literature. , 2000, Acta psychiatrica Scandinavica. Supplementum.

[3]  Clifford R. Jack,et al.  Diagnostic neuroimaging across diseases , 2011, NeuroImage.

[4]  Mert R. Sabuncu,et al.  A Unified Framework for MR Based Disease Classification , 2009, IPMI.

[5]  Vladimir Vapnik,et al.  An overview of statistical learning theory , 1999, IEEE Trans. Neural Networks.

[6]  R. Kahn,et al.  Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. , 2002, Archives of general psychiatry.

[7]  Xiaohai He,et al.  An Efficient Approach for Differentiating Alzheimer's Disease from Normal Elderly Based on Multicenter MRI Using Gray-Level Invariant Features , 2014, PloS one.

[8]  N. Andreasen,et al.  Initial magnetic resonance imaging volumetric brain measurements and outcome in schizophrenia: a prospective longitudinal study with 5-year follow-up , 2003, Biological Psychiatry.

[9]  R. Buchanan,et al.  Gender differences in temporal lobe structures of patients with schizophrenia: a volumetric MRI study. , 1999, The American journal of psychiatry.

[10]  R. Murray,et al.  Individualized prediction of illness course at the first psychotic episode: a support vector machine MRI study , 2011, Psychological Medicine.

[11]  N C Andreasen,et al.  The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. , 1992, Archives of general psychiatry.

[12]  The Asymmetry Bias in Me, We–Others Distance Ratings. The Role of Social Stereotypes , 2016, Front. Psychol..

[13]  Patricia Desmond,et al.  Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals. , 2006, Archives of general psychiatry.

[14]  R. Kahn,et al.  Brain volumes in schizophrenia: a meta-analysis in over 18 000 subjects. , 2013, Schizophrenia bulletin.

[15]  L. Petrangeli,et al.  Schedules for Clinical Assessment in Neuropsychiatry , 1997, Epidemiologia e Psichiatria Sociale.

[16]  R. Murray,et al.  Grey matter abnormalities in Brazilians with first-episode psychosis. , 2007, The British journal of psychiatry. Supplement.

[17]  S. Costafreda,et al.  Neuroimaging-Based Biomarkers in Psychiatry: Clinical Opportunities of a Paradigm Shift , 2013, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[18]  L. Opler,et al.  The Positive and Negative Syndrome Scale (PANSS): Rationale and Standardisation , 1989, British Journal of Psychiatry.

[19]  Matcheri S. Keshavan,et al.  Dorsolateral prefrontal cortex morphology and short-term outcome in first-episode schizophrenia , 2005, Psychiatry Research: Neuroimaging.

[20]  Hilleke E. Hulshoff Pol,et al.  Brain volumes as predictor of outcome in recent-onset schizophrenia: a multi-center MRI study , 2003, Schizophrenia Research.

[21]  Klaus P. Ebmeier,et al.  Multi-centre diagnostic classification of individual structural neuroimaging scans from patients with major depressive disorder. , 2012, Brain : a journal of neurology.

[22]  Christos Davatzikos,et al.  Neuroanatomical pattern classification in a population-based sample of first-episode schizophrenia , 2013, Progress in Neuro-psychopharmacology and Biological Psychiatry.

[23]  R. Murray,et al.  Lateral ventricle differences between first-episode schizophrenia and first-episode psychotic bipolar disorder: A population-based morphometric MRI study , 2010, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[24]  Tyrone D. Cannon,et al.  Elucidating a Magnetic Resonance Imaging-Based Neuroanatomic Biomarker for Psychosis: Classification Analysis Using Probabilistic Brain Atlas and Machine Learning Algorithms , 2009, Biological Psychiatry.

[25]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[26]  Alan C. Evans,et al.  A nonparametric method for automatic correction of intensity nonuniformity in MRI data , 1998, IEEE Transactions on Medical Imaging.

[27]  Karsten Mueller,et al.  Meta-analysis based SVM classification enables accurate detection of Alzheimer's disease across different clinical centers using FDG-PET and MRI , 2013, Psychiatry Research: Neuroimaging.

[28]  J. Vázquez-Barquero,et al.  Specific brain structural abnormalities in first-episode schizophrenia. A comparative study with patients with schizophreniform disorder, non-schizophrenic non-affective psychoses and healthy volunteers. , 2009, Schizophrenia Research.

[29]  Karl J. Friston,et al.  Cerebral Asymmetry and the Effects of Sex and Handedness on Brain Structure: A Voxel-Based Morphometric Analysis of 465 Normal Adult Human Brains , 2001, NeuroImage.

[30]  M. Yücel,et al.  Mapping grey matter reductions in schizophrenia: An anatomical likelihood estimation analysis of voxel-based morphometry studies , 2009, Schizophrenia Research.

[31]  Helen S Mayberg,et al.  Neuroimaging and psychiatry: the long road from bench to bedside. , 2014, The Hastings Center report.

[32]  R. Kahn,et al.  Detecting Neuroimaging Biomarkers for Psychiatric Disorders: Sample Size Matters , 2016, Front. Psychiatry.

[33]  Chih-Jen Lin,et al.  LIBSVM: A library for support vector machines , 2011, TIST.

[34]  H. Möller,et al.  Internal capsule size associated with outcome in first-episode schizophrenia , 2009, European Archives of Psychiatry and Clinical Neuroscience.

[35]  J. Suvisaari,et al.  Lifetime prevalence of psychotic and bipolar I disorders in a general population. , 2007, Archives of general psychiatry.

[36]  V. Cropley,et al.  Using longitudinal imaging to map the ‘relapse signature’ of schizophrenia and other psychoses , 2014, Epidemiology and Psychiatric Sciences.

[37]  R. S. Kahn,et al.  Brain volume changes in the first year of illness and 5-year outcome of schizophrenia , 2006, British Journal of Psychiatry.

[38]  H. Engeland,et al.  Brain Volume Changes in First-Episode Schizophrenia , 2015 .

[39]  Vaughan J. Carr,et al.  Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia , 2012, Neuroscience & Biobehavioral Reviews.

[40]  Radford M. Neal Pattern Recognition and Machine Learning , 2007, Technometrics.

[41]  J. Lieberman,et al.  Longitudinal study of brain morphology in first episode schizophrenia , 2001, Biological Psychiatry.

[42]  T. Brugha,et al.  SCAN. Schedules for Clinical Assessment in Neuropsychiatry. , 1990, Archives of general psychiatry.

[43]  N. Makris,et al.  Impact of normal sexual dimorphisms on sex differences in structural brain abnormalities in schizophrenia assessed by magnetic resonance imaging. , 2002, Archives of general psychiatry.

[44]  Randy L. Gollub,et al.  Neuropsychological Testing and Structural Magnetic Resonance Imaging as Diagnostic Biomarkers Early in the Course of Schizophrenia and Related Psychoses , 2011, Neuroinformatics.

[45]  Hilleke E. Hulshoff Pol,et al.  Classification of schizophrenia patients and healthy controls from structural MRI scans in two large independent samples , 2012, NeuroImage.

[46]  R. Kahn,et al.  Sex differences in the risk of schizophrenia: evidence from meta-analysis. , 2003, Archives of general psychiatry.

[47]  M. Filippi,et al.  Robust Automated Detection of Microstructural White Matter Degeneration in Alzheimer’s Disease Using Machine Learning Classification of Multicenter DTI Data , 2013, PloS one.

[48]  Yasuhiro Kawasaki,et al.  Differentiation of first-episode schizophrenia patients from healthy controls using ROI-based multiple structural brain variables , 2010, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[49]  V. Molina,et al.  Voxel-based morphometry comparison between first episodes of psychosis with and without evolution to schizophrenia , 2010, Psychiatry Research: Neuroimaging.

[50]  H. Yamasue,et al.  Classification of First-Episode Schizophrenia Patients and Healthy Subjects by Automated MRI Measures of Regional Brain Volume and Cortical Thickness , 2011, PloS one.

[51]  James J Levitt,et al.  A selective review of volumetric and morphometric imaging in schizophrenia. , 2010, Current topics in behavioral neurosciences.

[52]  Claude Lepage,et al.  Mapping reliability in multicenter MRI: Voxel‐based morphometry and cortical thickness , 2010, Human brain mapping.

[53]  P. Falkai,et al.  Detecting Neuroimaging Biomarkers for Schizophrenia: A Meta-Analysis of Multivariate Pattern Recognition Studies , 2015, Neuropsychopharmacology.

[54]  J. Lieberman,et al.  Brain volume in first-episode schizophrenia , 2006, British Journal of Psychiatry.

[55]  A. Mechelli,et al.  Using Support Vector Machine to identify imaging biomarkers of neurological and psychiatric disease: A critical review , 2012, Neuroscience & Biobehavioral Reviews.