Abstract
Background: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.Methods: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.Results: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.Conclusions: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.
Highlights
Response to antipsychotic medication is an important indicator of long-term outcome in psychosis[1]; understanding the neurobiological factors contributing to a favorable treatment response may be crucial to understanding the natural course of psychotic disorders
This is the first study that has used a connectomic approach with gyrification data to predict treatment response in psychosis
We found that first-episode psychosis (FEP) patients with poor response to treatment already show, at illness onset, abnormalities in the structural covariance patterns of the cortical folding, indicating a higher burden of abnormal neurodevelopment in this group
Summary
Response to antipsychotic medication is an important indicator of long-term outcome in psychosis[1]; understanding the neurobiological factors contributing to a favorable treatment response may be crucial to understanding the natural course of psychotic disorders. Presence of obstetric complications,[2] early age of onset,[3] and neurological soft signs[4] are all independently associated with poor response to treatment These observations have led to a notion that psychotic disorders associated with less favorable outcome are a form of neurodevelopmental disorders.[5,6]. 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. Results: 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 showed reduced centrality of key regions (left insula and anterior cingulate cortex) indicating a marked reconfiguration of gyrification. The information obtained from gyrification-based connectomes can be harnessed for prospectively predicting treatment response and prognosis in psychosis
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