title: Using structural MRI to identify individuals at genetic risk for bipolar disorders: a 2-cohort, machine learning study.
abstract: BACKGROUND
  Brain imaging is of limited diagnostic use in psychiatry owing to clinical heterogeneity and low sensitivity/specificity of between-group neuroimaging differences. Machine learning (ML) may better translate neuroimaging to the level of individual participants. Studying unaffected offspring of parents with bipolar disorders (BD) decreases clinical heterogeneity and thus increases sensitivity for detection of biomarkers. The present study used ML to identify individuals at genetic high risk (HR) for BD based on brain structure.
  
  
  METHODS
  We studied unaffected and affected relatives of BD probands recruited from 2 sites (Halifax, Canada, and Prague, Czech Republic). Each participant was individually matched by age and sex to controls without personal or family history of psychiatric disorders. We applied support vector machines (SVM) and Gaussian process classifiers (GPC) to structural MRI.
  
  
  RESULTS
  We included 45 unaffected and 36 affected relatives of BD probands matched by age and sex on an individual basis to healthy controls. The SVM of white matter distinguished unaffected HR from control participants (accuracy = 68.9%, p = 0.001), with similar accuracy for the GPC (65.6%, p = 0.002) or when analyzing data from each site separately. Differentiation of the more clinically heterogeneous affected familiar group from healthy controls was less accurate (accuracy = 59.7%, p = 0.05). Machine learning applied to grey matter did not distinguish either the unaffected HR or affected familial groups from controls. The regions that most contributed to between-group discrimination included white matter of the inferior/middle frontal gyrus, inferior/middle temporal gyrus and precuneus.
  
  
  CONCLUSIONS
  Although we recruited 126 participants, ML benefits from even larger samples.
  
  
  CONCLUSIONS
  Machine learning applied to white but not grey matter distinguished unaffected participants at high and low genetic risk for BD based on regions previously implicated in the pathophysiology of BD.
authors: Department of Psychiatry, Dalhousie University, Halifax, NS, Canada (Hajek, Cooke, Alda); Prague Psychiatric Centre/ National Institute of Mental Health, Prague, Czech Republic (Hajek, Kopecek, Novak, Hoschl, Alda); Charles University, 3rd Faculty of Medicine, Prague, Czech Republic (Kopecek, Novak, Hoschl, Alda).
authors: Tomas
authors: T
authors: Hajek
authors: Department of Psychiatry, Dalhousie University, Halifax, NS, Canada (Hajek, Cooke, Alda); Prague Psychiatric Centre/ National Institute of Mental Health, Prague, Czech Republic (Hajek, Kopecek, Novak, Hoschl, Alda); Charles University, 3rd Faculty of Medicine, Prague, Czech Republic (Kopecek, Novak, Hoschl, Alda).
authors: Christopher
authors: C
authors: Cooke
authors: Department of Psychiatry, Dalhousie University, Halifax, NS, Canada (Hajek, Cooke, Alda); Prague Psychiatric Centre/ National Institute of Mental Health, Prague, Czech Republic (Hajek, Kopecek, Novak, Hoschl, Alda); Charles University, 3rd Faculty of Medicine, Prague, Czech Republic (Kopecek, Novak, Hoschl, Alda).
authors: Miloslav
authors: M
authors: Kopecek
authors: Department of Psychiatry, Dalhousie University, Halifax, NS, Canada (Hajek, Cooke, Alda); Prague Psychiatric Centre/ National Institute of Mental Health, Prague, Czech Republic (Hajek, Kopecek, Novak, Hoschl, Alda); Charles University, 3rd Faculty of Medicine, Prague, Czech Republic (Kopecek, Novak, Hoschl, Alda).
authors: Tomas
authors: T
authors: Novak
authors: Department of Psychiatry, Dalhousie University, Halifax, NS, Canada (Hajek, Cooke, Alda); Prague Psychiatric Centre/ National Institute of Mental Health, Prague, Czech Republic (Hajek, Kopecek, Novak, Hoschl, Alda); Charles University, 3rd Faculty of Medicine, Prague, Czech Republic (Kopecek, Novak, Hoschl, Alda).
authors: Cyril
authors: C
authors: Hoschl
authors: Department of Psychiatry, Dalhousie University, Halifax, NS, Canada (Hajek, Cooke, Alda); Prague Psychiatric Centre/ National Institute of Mental Health, Prague, Czech Republic (Hajek, Kopecek, Novak, Hoschl, Alda); Charles University, 3rd Faculty of Medicine, Prague, Czech Republic (Kopecek, Novak, Hoschl, Alda).
authors: Martin
authors: M
authors: Alda
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics*; D002170:Canada; D015331:Cohort Studies; D018153:Czech Republic; D005260:Female; D020022:Genetic Predisposition to Disease; D066128:Gray Matter / Q000033:anatomy & histology / Q000473:pathology; D006801:Humans; D000069550:Machine Learning; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D059906:Neuroimaging; D010296:Parietal Lobe / Q000033:anatomy & histology / Q000473:pathology; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000473:pathology; D012307:Risk Factors; D060388:Support Vector Machine; D013702:Temporal Lobe / Q000033:anatomy & histology / Q000473:pathology; D066127:White Matter / Q000033:anatomy & histology / Q000473:pathology*; D055815:Young Adult