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ObjectiveSchizophrenia is associated with widespread brain-morphological alterations, believed to be shaped by the underlying connectome architecture. This study tests whether large-scale structural reorganization in schizophrenia relates to normative network architecture, in particular regional centrality/hubness and connectivity patterns. We examine network effects in schizophrenia across different disease stages, and transdiagnostically explore consistency of such relationships in patients with bipolar and major depressive disorder.MethodsWe studied anatomical MRI scans from 2,439 adults with schizophrenia and 2,867 healthy controls from 26 ENIGMA sites. Case-control patterns of structural alterations were evaluated against two network susceptibility models: 1) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; 2) epicenter models, which identify regions whose typical connectivity profile most closely resembles the disease-related morphological alteration patterns. Both susceptibility models were tested across schizophrenia disease stages and compared to meta-analytic bipolar and major depressive disorder case-control maps.ResultsIn schizophrenia, regional gray matter reductions co-localized with interconnected hubs, in both the functional (r=0.58, pspinspin=0.01). Epicenters were identified in temporo-paralimbic regions, extending to frontal areas. We found unique epicenters for first-episode and early stages, and a shift from occipital to temporal-frontal epicenters in chronic stages. Transdiagnostic comparisons revealed shared epicenters in schizophrenia and bipolar, but not major depressive disorders.ConclusionsCortical reorganization over the course of schizophrenia closely reflects brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters. The observed overlapping epicenters for schizophrenia and bipolar disorder furthermore suggest shared pathophysiological processes within the schizophrenia-bipolar-spectrum.

Background: Social cognitive deficits are prominent across several dimensions of psychopathology that compose a variety of psychiatric diagnoses. The hierarchical structure of the dimensions of psychopathology appears related to general cognitive ability (GCA). Yet, the exact relations among social cognition, GCA, and psychopathology dimensions remain unclear. Effective targeting of interventions toward social-cognitive deficits in psychopathology likely depends on improved understanding of these relations.Methods: Data were collected from three samples totaling 976 participants that included psychosis spectrum patients, their first-degree biological relatives, and individuals from community sources. Participants completed dimensional psychopathology measures and social cognition tasks (e.g., emotion perception and mentalizing). Using combined-sample analysis, we computed bi-factor exploratory structural equation models to estimate general and specific psychopathology factors, as well as their associations with social cognition and GCA.Results: Higher levels of general psychopathology, suspiciousness, and psychoticism (positive schizotypy) were associated with worse social cognition, but GCA statistically accounted for these associations. Two specific factors—detachment (negative schizotypy) and callous aggression—were associated with worse social cognition, independent of GCA. Interestingly, greater Machiavellianism and eccentricity were associated with better social cognition and GCA.Conclusion: Findings underscore social cognitive deficits as key features of psychopathology that span traditional categorical classifications and are specifically related to schizotypal and antagonistic psychopathology. Future research should further explore how dimensional, hierarchical models of psychopathology can be incorporated into social-cognitive interventions.

A number of studies of posttraumatic stress disorder (PTSD) report thinner cerebral cortical gyri using gyrus-based analysis or thinner foci within the gyri using vertex-based analysis. However, the locations of these findings are inconsistent across studies, and the spatial transformations required during vertex-based analysis may affect the focal findings. A mega-analysis using a large number of subjects from multiple PTSD studies could potentially identify more reproducible cortical thickness abnormalities. Investigating both the vertex and gyral thicknesses simultaneously may verify the vertex-based focal findings using gyral data without imposing any spatial transformation. Here we aggregated data from 24 international laboratories using ENIGMA standardized procedures for 949 adult PTSD patients and 1493 controls without PTSD (age 18 to 65 years). We examined whether gyral and vertex cortical thickness are (a) different between subjects with PTSD and controls and (b) associated with PTSD symptom severity in trauma-exposed subjects. Regions with overlapping thinner cortical gyri and thinner vertex clusters were located in frontal, temporal, parietal, and occipital cortices. Thinner right lateral orbitofrontal and right lingual gyri and concomitantly thinner vertex clusters in the anterior portions of both gyri were associated with PTSD symptom severity. Convergent findings in these locations suggest focally thinner cortex in these gyri, which may be involved in altered processing and regulation of emotion and sensory inputs underlying posttraumatic stress symptoms.