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      The Xi'an Schizophrenia Imaging Lab (SIL) data and ten years of MRI study on schizophrenia

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      Psychoradiology
      Oxford University Press (OUP)

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          Abstract

          The Schizophrenia Imaging Laboratory (SIL) data are based on a collaboration of >10 years studying the schizophrenic brain using magnetic resonance imaging (MRI) in Xi'an, China. Collection of SIL data (N = 665; 319 patients, 48 first-degree relatives, and 298 control participants) started in 2011, with the purpose of performing a trans-scale study focusing on schizophrenia, and this has since diversified into three datasets: pooling clinical assessment, neuroimaging and genetic data to answer clinical and preclinical questions in psychiatry. Most of them come from Fourth Military Medical University, and the rest of the data come from the Xi'an Mental Health Center. In the SIL data, all the participants underwent clinical assessments (clinical characteristics, e.g. Positive and Negative Syndrome Scale, and cognitive tests) and MRI scans, including T2-weighted imaging, high-resolution T1-weighted imaging, functional imaging, diffusion weighted imaging, and arterial spin labeling at baseline, and 103 participants had transcriptome-wide data of whole blood (mRNA, small RNA, lncRNA, and circRNA). Scanning machines included the GE Discovery MR750 3.0 T scanner and Siemens 3.0 T Magnetom Trio Tim MR scanner. Clinical assessment at discharge from the hospital was available for 188 patients whose episode resulted in hospitalization. Afterward, 148 participants completed the follow-up assessments and scans. The whole study had no influence on the therapy. It investigated different aspects of familial risk, neural mechanisms, symptoms, diagnosis, treatment, and clinical translation. Central to the success of these 10 years are the efforts of the dedicated staff at SIL. Importantly, this work was supported by the National Key Basic Research and Development Program (2011CB707805), National Natural Science Foundation (81571651, 81801675), project funding by the China Postdoctoral Science Foundation (2019TQ0130, 2020M683739), Fourth Military Medical University (2019CYJH, 2014D07), and the State Scholarship Fund, China Scholarship Council (201603170143). The data set has been a formidable force for innovation in neuroimaging of schizophrenia. SIL data support >50 active studies. Summaries of these key studies are listed in Table 1. SIL consistently contributes to the characterization of robust neuroimaging phenotype, objective diagnosis, and therapeutic effects on brain and prediction of treatment outcomes. First, targeting the biological phenotype, we discovered new evidence of neurodevelopmental disorders associated with a disrupted brain connectome throughout the course, and established a new phenotype of auditory verbal hallucinations. Second, we explored new strategies in biological psychiatry for objective diagnosis, and creatively applied radiomics to identify this disease without solid lesions. Furthermore, to optimize treatment levels, we revealed the mechanism for predicting brain age by improved brain structural networks after antipsychotic treatment, and constructed a new model for efficacy prediction. SIL has worked with researchers to publish evidence that advances psychiatry, neuroscience, and radiology, and improves schizophrenia patient care. Requests to access SIL data and further inquiries can be directed to us. Table 1: A selection of key findings using SIL data. Publications Total N from SIL data Main findings Xi et al., 2022 100 controls and 100 patients Early medication improves the brain aging of patients with schizophrenia. Li et al., 2020 54 controls and 90 patients A neuroimaging biomarker based on functional striatal abnormalities is developed for schizophrenia identification, prognosis, and subtyping. Cui et al., 2019 114 controls and 81 patients Disrupted rich club organization and functional dynamics might be an early feature in the pathophysiology of schizophrenia. Rozycki et al., 2018 24 controls and 18 patients Structural MRI provides a robust and reproducible imaging signature of schizophrenia. Cui et al., 2017 19 controls and 32 patients Dysfunction in brain regions in schizophrenia patients with auditory verbal hallucinations are involved in auditory processing, language production and monitoring, and sensory information filtering. Conflict of Interest The authors declare no conflict of interests.

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          Most cited references5

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          A neuroimaging biomarker for striatal dysfunction in schizophrenia

          Mounting evidence suggests that function and connectivity of the striatum is disrupted in schizophrenia1-5. We have developed a new hypothesis-driven neuroimaging biomarker for schizophrenia identification, prognosis and subtyping based on functional striatal abnormalities (FSA). FSA scores provide a personalized index of striatal dysfunction, ranging from normal to highly pathological. Using inter-site cross-validation on functional magnetic resonance images acquired from seven independent scanners (n = 1,100), FSA distinguished individuals with schizophrenia from healthy controls with an accuracy exceeding 80% (sensitivity, 79.3%; specificity, 81.5%). In two longitudinal cohorts, inter-individual variation in baseline FSA scores was significantly associated with antipsychotic treatment response. FSA revealed a spectrum of severity in striatal dysfunction across neuropsychiatric disorders, where dysfunction was most severe in schizophrenia, milder in bipolar disorder, and indistinguishable from healthy individuals in depression, obsessive-compulsive disorder and attention-deficit hyperactivity disorder. Loci of striatal hyperactivity recapitulated the spatial distribution of dopaminergic function and the expression profiles of polygenic risk for schizophrenia. In conclusion, we have developed a new biomarker to index striatal dysfunction and established its utility in predicting antipsychotic treatment response, clinical stratification and elucidating striatal dysfunction in neuropsychiatric disorders.
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            Multisite Machine Learning Analysis Provides a Robust Structural Imaging Signature of Schizophrenia Detectable Across Diverse Patient Populations and Within Individuals

            Past work on relatively small, single-site studies using regional volumetry, and more recently machine learning methods, has shown that widespread structural brain abnormalities are prominent in schizophrenia. However, to be clinically useful, structural imaging biomarkers must integrate high-dimensional data and provide reproducible results across clinical populations and on an individual person basis. Using advanced multi-variate analysis tools and pooled data from case-control imaging studies conducted at 5 sites (941 adult participants, including 440 patients with schizophrenia), a neuroanatomical signature of patients with schizophrenia was found, and its robustness and reproducibility across sites, populations, and scanners, was established for single-patient classification. Analyses were conducted at multiple scales, including regional volumes, voxelwise measures, and complex distributed patterns. Single-subject classification was tested for single-site, pooled-site, and leave-site-out generalizability. Regional and voxelwise analyses revealed a pattern of widespread reduced regional gray matter volume, particularly in the medial prefrontal, temporolimbic and peri-Sylvian cortex, along with ventricular and pallidum enlargement. Multivariate classification using pooled data achieved a cross-validated prediction accuracy of 76% (AUC = 0.84). Critically, the leave-site-out validation of the detected schizophrenia signature showed accuracy/AUC range of 72-77%/0.73-0.91, suggesting a robust generalizability across sites and patient cohorts. Finally, individualized patient classifications displayed significant correlations with clinical measures of negative, but not positive, symptoms. Taken together, these results emphasize the potential for structural neuroimaging data to provide a robust and reproducible imaging signature of schizophrenia. A web-accessible portal is offered to allow the community to obtain individualized classifications of magnetic resonance imaging scans using the methods described herein.
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              Disturbed Brain Activity in Resting-State Networks of Patients with First-Episode Schizophrenia with Auditory Verbal Hallucinations: A Cross-sectional Functional MR Imaging Study.

              Purpose To investigate auditory verbal hallucination (AVH)-specific patterns of brain activity within the resting-state networks (RSNs) that have been proposed to underpin the neural mechanisms of schizophrenia (SZ). Materials and Methods This cross-sectional study was approved by the local ethics committee, and written informed consent was obtained from all participants prospectively recruited. Independent component analysis was used to investigate RSNs in 17 patients with first-episode untreated SZ with AVHs, 15 patients with SZ without AVHs, and 19 healthy control subjects who underwent resting-state functional magnetic resonance imaging. Dual regression was implemented to perform between-group analysis. Regional brain function was then explored within RSNs by using the amplitude of low-frequency fluctuation. Two-sample t tests were used to compare regional brain function between the two patient groups, and Pearson correlation analysis was used to characterize the relationship between imaging findings and severity of AVHs. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of these brain function measures. Results Independent component analysis demonstrated symptom-specific abnormal disrupted coactivation within the auditory, default mode, executive, motor, and frontoparietal networks and was pronounced in the auditory cortex, supramarginal gyrus, insula, putamen, dorsolateral prefrontal cortex, angular gyrus, precuneus, and thalamus (P < .05 with false discovery rate correction). Amplitude of low-frequency fluctuation analysis demonstrated similar patterns within these RSNs (P < .05 with false discovery rate correction). Furthermore, a positive correlation between the degree of coactivation within the motor network and the severity of AVHs was observed in patients with SZ with AVHs (r = 0.67, P = .003). The area under the receiver operating characteristic curve was 0.76-0.90 for all RSNs. Conclusion These findings indicate that dysfunctional brain regions are involved in auditory processing, language production and monitoring, and sensory information filtering in patients with SZ with AVHs, which may be helpful in furthering the understanding of pathophysiological correlates of AVHs in SZ. Online supplemental material is available for this article.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Psychoradiology
                Oxford University Press (OUP)
                2634-4416
                June 2022
                August 11 2022
                June 2022
                August 11 2022
                August 11 2022
                : 2
                : 2
                : 54-55
                Article
                10.1093/psyrad/kkac008
                63147217-040d-409f-9ca1-50345cd71295
                © 2022

                https://creativecommons.org/licenses/by/4.0/

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