Contracted anterior-posterior systematic covariance of cortical thickness in early-onset schizophrenia

Background and Hypothesis: Schizophrenia is a neurodevelopmental condition with alterations in both sensory and association cortical areas. These alterations have been reported to follow structural connectivity patterning, and to occur in a system-level fashion. Here, we investigated whether pathological alterations of schizophrenia originated from an early disruption of cortical organization by using 7−17-years-old individuals with early-onset schizophrenia (EOS). Study Design: We estimated cortical thickness using T1-weighted structural MRI data from 95 patients with antipsychotic-naive first-episode EOS and 99 typically developing (TD) controls. We then computed structural covariance of cortical thickness and estimated system-level organizational axes by performing nonlinear dimensionality reduction techniques on covariance matrices for the EOS and TD groups. Finally, we tested for group differences between EOS and TD individuals in terms of both structural covariance and covariance distances along the systematic axis. Study Results: The first covariance gradient differentiated motor regions from other cortical areas. Similar to the macrostructural axis in adults, the second gradient axis in young TD discriminated anterior from posterior regions and was compressed in EOS patients relative to TD controls. In addition, patients showed increased structural covariance between two ends of the systematic axis, with increased geodesic distance of covarying regions between two ends. Conclusion: Our findings revealed a contracted organizational axis of cortical thickness in EOS patients, which was attributed to excessive distally coordinated changes between anterior and posterior regions of the cortex. Taken together, our study suggests a possible early disruption of system-level neurodevelopment in schizophrenia.