title: Globally Efficient Brain Organization and Treatment Response in Psychosis: A Connectomic Study of Gyrification.
abstract: Converging evidence suggests that patients with first-episode psychosis who show a poor treatment response may have a higher degree of neurodevelopmental abnormalities than good Responders. Characterizing the disturbances in the relationship among brain regions (covariance) can provide more information on neurodevelopmental integrity than searching for localized changes in the brain. Graph-based connectomic approach can measure structural covariance thus providing information on the maturational processes. We quantified the structural covariance of cortical folding using graph theory in first-episode psychosis, to investigate if this systems-level approach would improve our understanding of the biological determinants of outcome in psychosis.
  
  
  
  Magnetic Resonance Imaging data were acquired in 80 first-episode psychosis patients and 46 healthy controls. Response to treatment was assessed after 12 weeks of naturalistic follow-up. Gyrification-based connectomes were constructed to study the maturational organization of cortical folding.
  
  
  
  Nonresponders showed a reduction in the distributed relationship among brain regions (high segregation, poor integration) when compared to Responders and controls, indicating a higher burden of aberrant neurodevelopment. They also showed reduced centrality of key regions (left insula and anterior cingulate cortex) indicating a marked reconfiguration of gyrification. Nonresponders showed a vulnerable pattern of covariance that disintegrated when simulated lesions removed high-degree hubs, indicating an abnormal dependence on highly central hub regions in Nonresponders.
  
  
  
  These findings suggest that a perturbed maturational relationship among brain regions underlies poor treatment response in first-episode psychosis. The information obtained from gyrification-based connectomes can be harnessed for prospectively predicting treatment response and prognosis in psychosis.
authors.affiliation: Departments of Psychiatry, Neuroscience and Medical Biophysics & Robarts Research Institute, Western University, London, ON, Canada.|Lawson Health Research Institute, London, ON, Canada.
authors.forename: Lena
authors.initials: L
authors.lastname: Palaniyappan
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Tiago Reis
authors.initials: TR
authors.lastname: Marques
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Heather
authors.initials: H
authors.lastname: Taylor
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK.|National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK.
authors.forename: Valeria
authors.initials: V
authors.lastname: Mondelli
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
authors.forename: A A T Simone
authors.initials: AATS
authors.lastname: Reinders
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bonaccorso
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.|National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: DiForti
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.|National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: David
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK.|National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK.
authors.forename: Carmine M
authors.initials: CM
authors.lastname: Pariante
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.|National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK.
authors.forename: Paola
authors.initials: P
authors.lastname: Dazzan
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000002:abnormalities / Q000000981:diagnostic imaging*; D063132:Connectome / Q000379:methods*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017063:Outcome Assessment, Health Care; D011618:Psychotic Disorders / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents
keywords: connectome; cortical folding; first-episode psychosis; graph theory; neuroimaging; surface based morphometry