Abstract
Schizophrenia has increasingly been considered a neurodevelopmental disorder, and the advancement of neuroimaging techniques and associated computational methods has enabled quantitative re-examination of this important theory on the pathogenesis of the disease. Inspired by previous findings from neonatal brains, we proposed that an increase in diffusion magnetic resonance imaging (dMRI) mean diffusivity (MD) should be observed in the cerebral cortex of schizophrenia patients compared with healthy controls, corresponding to lower tissue complexity and potentially a failure to reach cortical maturation. We tested this hypothesis using dMRI data from a Chinese Han population comprising patients from four different hospital sites. Utilizing data-driven methods based on the state-of-the-art tensor-based registration algorithm, significantly increased MD measurements were consistently observed in the cortex of schizophrenia patients across all four sites, despite differences in psychopathology, exposure to antipsychotic medication and scanners used for image acquisition. Specifically, we found increased MD in the limbic system of the schizophrenic brain, mainly involving the bilateral insular and prefrontal cortices. In light of the existing literature, we speculate that this may represent a neuroanatomical signature of the disorder, reflecting microstructural deficits due to developmental abnormalities. Our findings not only provide strong support to the abnormal neurodevelopment theory of schizophrenia, but also highlight an important neuroimaging endophenotype for monitoring the developmental trajectory of high-risk subjects of the disease, thereby facilitating early detection and prevention.
Highlights
Over the past two decades, the advancement of neuroimaging techniques and associated computational methods has provided us with insight into the causes, progression and even treatment of schizophrenia,[1] enabling quantitative re-examination of classical and popular theories on the pathogenesis of the disease.[2]
Inspired by the above-mentioned diffusion magnetic resonance imaging (dMRI) findings, we propose that in the context of abnormal neurodevelopment in schizophrenia, mean diffusivity (MD) in the cerebral cortex of schizophrenia patients should be increased relative to healthy controls, corresponding to decreased itself) based registration, which may considerably affect the reliability of results, has been detailed recently.[16]
Using dMRI of schizophrenia patients located at four different hospital sites, we observed significantly increased MD in the cortex compared with healthy controls, providing strong support to our hypothesis that schizophrenia patients exhibit an immature cortex resulting from abnormal neurodevelopment
Summary
Over the past two decades, the advancement of neuroimaging techniques and associated computational methods has provided us with insight into the causes, progression and even treatment of schizophrenia,[1] enabling quantitative re-examination of classical and popular theories on the pathogenesis of the disease.[2] the majority of previous findings have exhibited relatively poor consistency and replication,[3] likely due primarily to the relatively small sample size in each single study and the multitude of variables that can affect brain development.[4] The aim of this study is to investigate the ‘abnormal neurodevelopment’ theory of schizophrenia, using expertly collected and well-curated neuroimaging data. When considering schizophrenia as a deviation from normal neurodevelopment, a better understanding of normative brain development is essential to understand the processes underlying schizophrenia pathology
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