Dataset Information

Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study.

ABSTRACT: Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia's alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.

SUBMITTER: Georgiadis F

PROVIDER: S-EPMC11371638 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study.

Georgiadis Foivos F Larivière Sara S Glahn David D Hong L Elliot LE Kochunov Peter P Mowry Bryan B Loughland Carmel C Pantelis Christos C Henskens Frans A FA Green Melissa J MJ Cairns Murray J MJ Michie Patricia T PT Rasser Paul E PE Catts Stanley S Tooney Paul P Scott Rodney J RJ Schall Ulrich U Carr Vaughan V Quidé Yann Y Krug Axel A Stein Frederike F Nenadić Igor I Brosch Katharina K Kircher Tilo T Gur Raquel R Gur Ruben R Satterthwaite Theodore D TD Karuk Andriana A Pomarol-Clotet Edith E Radua Joaquim J Fuentes-Claramonte Paola P Salvador Raymond R Spalletta Gianfranco G Voineskos Aristotle A Sim Kang K Crespo-Facorro Benedicto B Tordesillas Gutiérrez Diana D Ehrlich Stefan S Crossley Nicolas N Grotegerd Dominik D Repple Jonathan J Lencer Rebekka R Dannlowski Udo U Calhoun Vince V Rootes-Murdy Kelly K Demro Caroline C Ramsay Ian S IS Sponheim Scott R SR Schmidt Andre A Borgwardt Stefan S Tomyshev Alexander A Lebedeva Irina I Höschl Cyril C Spaniel Filip F Preda Adrian A Nguyen Dana D Uhlmann Anne A Stein Dan J DJ Howells Fleur F Temmingh Henk S HS Diaz Zuluaga Ana M AM López Jaramillo Carlos C Iasevoli Felice F Ji Ellen E Homan Stephanie S Omlor Wolfgang W Homan Philipp P Kaiser Stefan S Seifritz Erich E Misic Bratislav B Valk Sofie L SL Thompson Paul P van Erp Theo G M TGM Turner Jessica A JA Bernhardt Boris B Kirschner Matthias M

Molecular psychiatry 20240209 6

Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with s ...[more]

PMID: 38336840

Similar Datasets

Project description:Convergent evidences have revealed that schizophrenia is associated with brain dysconnectivity, which leads to abnormal network organization. However, discrepancies were apparent between the structural connectivity (SC) and functional connectivity (FC) studies, and the relationship between structural and functional deficits in schizophrenia remains largely unknown. In this study, resting-state functional magnetic resonance imaging and structural diffusion tensor imaging were performed in 20 patients with schizophrenia and 20 matched healthy volunteers (patients/controls = 19/17 after head motion rejection). Functional and structural brain networks were obtained for each participant. Graph theoretical approaches were employed to parcellate the FC networks into functional modules. The relationships between the entries of SC and FC were estimated within each module to identify group differences and their correlations with clinical symptoms. Although five common functional modules (including the default mode, occipital, subcortical, frontoparietal, and central modules) were identified in both groups, the patients showed a significantly reduced modularity in comparison with healthy participants. Furthermore, we found that schizophrenia-related aberrations of SC-FC coupling exhibited complex patterns among modules. Compared with controls, patients showed an increased SC-FC coupling in the default mode and the central modules. Moreover, significant SC-FC decoupling was demonstrated in the occipital and the subcortical modules, which was associated with longer duration of illness and more severe clinical manifestations of schizophrenia. Taken together, these findings demonstrated that altered module-dependent SC-FC coupling may underlie abnormal brain function and clinical symptoms observed in schizophrenia and highlighted the potential for using new multimodal neuroimaging biomarkers for diagnosis and severity evaluation of schizophrenia. Hum Brain Mapp 38:2008-2025, 2017. © 2017 Wiley Periodicals, Inc.

Project description:Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.

Dataset Information

Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study.

Publications

Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets