title: Neuroimaging predictors of functional outcomes in schizophrenia at baseline and 6-month follow-up.
abstract: OBJECTIVE
  Studies show that deficit syndrome schizophrenia patients, characterized by primary negative symptoms and poor functional outcome, have impairment in specific neural circuits. We assessed whether these same neural circuits are directly linked to functional outcomes across schizophrenia patients.
  
  
  METHODS
  T1- and diffusion-weighted MR images were obtained for schizophrenia (n=30) and matched healthy control participants (n=30). Negative symptoms and functional outcome were assessed at baseline and 6-month follow-up. Cortical thickness and tract-wise fractional anisotropy (FA) were compared between groups. To assess relationships of neuroimaging measures with functional outcome, principal component analysis (PCA) was performed on tract-wise FA values and components were entered into a multiple regression model for schizophrenia participants.
  
  
  RESULTS
  Consistent with the literature, schizophrenia participants showed frontotemporal reductions in cortical thickness and tract-wise FA compared to controls. The top two components from PCA explained 71% of the variance in tract-wise FA values. The second component (associated with inferior longitudinal and arcuate fasciculus FA) was significantly correlated with functional outcome (baseline: β=0.54, p=0.03; follow-up: β=0.74, p=0.047); further analysis revealed this effect was mediated by negative symptoms. Post-hoc network analysis revealed increased cortical coupling between right inferior frontal and supramarginal gyri (connected by the arcuate fasciculus) in schizophrenia participants with poorer functional outcome.
  
  
  CONCLUSIONS
  Our findings indicate that impairment in the same neural circuitry susceptible in deficit syndrome schizophrenia predicts functional outcome in a continuous manner in schizophrenia participants. This relationship was mediated by negative symptom burden. Our findings provide novel evidence for brain-based biomarkers of longitudinal functional outcome in people with schizophrenia.
authors.affiliation: Kimel Family Translational Imaging-Genetics Research Lab, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Institute of Medical Science, University of Toronto, 27 King's College Circle, Toronto, ON M5S, Canada.
authors.forename: Tina
authors.initials: T
authors.lastname: Behdinan
authors.affiliation: Institute of Medical Science, University of Toronto, 27 King's College Circle, Toronto, ON M5S, Canada; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 27 King's College Circle, Toronto, ON, M5S, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Foussias
authors.affiliation: Kimel Family Translational Imaging-Genetics Research Lab, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Wheeler
authors.affiliation: Kimel Family Translational Imaging-Genetics Research Lab, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Stefanik
authors.affiliation: Kimel Family Translational Imaging-Genetics Research Lab, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Institute of Medical Science, University of Toronto, 27 King's College Circle, Toronto, ON M5S, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Felsky
authors.affiliation: Institute of Medical Science, University of Toronto, 27 King's College Circle, Toronto, ON M5S, Canada; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 27 King's College Circle, Toronto, ON, M5S, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.affiliation: Institute of Medical Science, University of Toronto, 27 King's College Circle, Toronto, ON M5S, Canada; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 27 King's College Circle, Toronto, ON, M5S, Canada.
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.affiliation: Cerebral Imaging Centre, Douglas Mental Health University Institute, Verdun, QC, Canada; Department of Psychiatry, McGill University, Montreal, QC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Mallar Chakravarty
authors.affiliation: Kimel Family Translational Imaging-Genetics Research Lab, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Institute of Medical Science, University of Toronto, 27 King's College Circle, Toronto, ON M5S, Canada; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 27 King's College Circle, Toronto, ON, M5S, Canada. Electronic address: Aristotle.Voineskos@camh.ca.
authors.forename: Aristotle N
authors.initials: AN
authors.lastname: Voineskos
mesh_terms: D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D016014:Linear Models; D008297:Male; D009434:Neural Pathways / Q000473:pathology; D009929:Organ Size; D025341:Principal Component Analysis; D011379:Prognosis; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
keywords: Arcuate fasciculus; Cortical thickness; Diffusion tensor imaging; Fractional anisotropy; Inferior longitudinal fasciculus; Network analysis