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However, the neurobiological basis of symptomatic diversity remains poorly understood. We hypothesized that schizophrenia\u2019s diverse symptoms arise from the interplay of structural and functional alterations across multiple brain regions, rather than isolated abnormalities in a single area.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>A total of 495 schizophrenia patients and 507 healthy controls from 8 sites were recruited. Five symptomatic dimensions of schizophrenia patients were derived from the Positive and Negative Syndrome Scale. Multivariate canonical correlation analysis was introduced to identify symptom-related multimodal magnetic resonance imaging composite indicators (MRICIs) derived from gray matter volume, functional connectivity strength, and white matter fractional anisotropy. The intergroup differences in MRICIs were compared, and the paired-wise correlations between symptom dimensions and MRICIs were resolved. Finally, K-means clustering was used to identify the underlying biological subtypes of schizophrenia based on MRICIs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Results<\/jats:title>\n                    <jats:p>Canonical correlation analysis identified 15 MRICIs in schizophrenia that were specifically contributed by the neuroimaging measures of multiple regions, respectively. These MRICIs can effectively characterize the complexity of symptoms, showing correlations within and across symptom dimensions, and were consistent across both first-episode and chronic patients. Additionally, some of these indicators could moderately differentiate schizophrenia patients from healthy controls. K-means clustering identified 2 schizophrenia subtypes with distinct MRICI profiles and symptom severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Symptom-guided multimodal and multivariate MRICIs could decode the symptom heterogeneity of schizophrenia patients and might be considered as potential biomarkers for schizophrenia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/schbul\/sbaf037","type":"journal-article","created":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T16:15:54Z","timestamp":1742055354000},"source":"Crossref","is-referenced-by-count":3,"title":["Deciphering the Heterogeneity of Schizophrenia: A Multimodal and Multivariate Neuroimaging Framework for Unveiling Brain-Symptom Relationships and Underlying Subtypes"],"prefix":"10.1093","volume":"52","author":[{"given":"Luli","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Radiology, Tianjin Key Lab of Functional Imaging, Tianjin Institute of Radiology and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital , Tianjin 300052 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, The First Affiliated Hospital of Harbin Medical University , Harbin 150001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology, Tianjin Key Lab of Functional Imaging, Tianjin Institute of Radiology and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital , Tianjin 300052 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Tianjin Key Lab of Functional Imaging, Tianjin Institute of Radiology and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital , Tianjin 300052 ,","place":["China"]},{"name":"Department of Radiology, Beijing Friendship Hospital, Capital Medical University , Beijing 100050 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Radiology, Tianjin Key Lab of Functional Imaging, Tianjin Institute of Radiology and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital , Tianjin 300052 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Laboratory of Experimental Hematology, Tianjin Medical University General Hospital , Tianjin 300052 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Radiology, Tianjin Key Lab of Functional Imaging, Tianjin Institute of Radiology and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital , Tianjin 300052 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Radiology, Tianjin Key Lab of Functional Imaging, Tianjin Institute of Radiology and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital , Tianjin 300052 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Radiology, Tianjin Key Lab of Functional Imaging, Tianjin Institute of Radiology and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital , Tianjin 300052 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Radiology, Tianjin Key Lab of Functional Imaging, Tianjin Institute of Radiology and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital , Tianjin 300052 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Medical Imaging, Tianjin Medical University , Tianjin 300070 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Radiology, Tianjin Key Lab of Functional Imaging, Tianjin Institute of Radiology and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital , Tianjin 300052 ,","place":["China"]},{"name":"School of Medical Imaging, Tianjin Medical University , Tianjin 300070 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Liu","sequence":"additional","affiliation":[{"name":"Psychiatric Clinical Laboratory, The First Psychiatric Hospital of Harbin , Harbin 150056, Heilongjiang Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xijin","family":"Wang","sequence":"additional","affiliation":[{"name":"Psychiatric Clinical Laboratory, The First Psychiatric Hospital of Harbin , Harbin 150056, Heilongjiang Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Tianjin Fourth Center 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