Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns
Abstract Background This study aimed to investigate the neuroanatomical subtypes among early-onset schizophrenia (EOS) patients by exploring the association between structural alterations and molecular mechanisms using a combined analysis of morphometric similarity network (MSN) changes and specific...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-023-03201-1 |
| _version_ | 1797397965791297536 |
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| author | Guanqun Yao Ting Zou Jing Luo Shuang Hu Langxiong Yang Jing Li Xinrong Li Yuqi Zhang Kun Feng Yong Xu Pozi Liu |
| author_facet | Guanqun Yao Ting Zou Jing Luo Shuang Hu Langxiong Yang Jing Li Xinrong Li Yuqi Zhang Kun Feng Yong Xu Pozi Liu |
| author_sort | Guanqun Yao |
| collection | DOAJ |
| description | Abstract Background This study aimed to investigate the neuroanatomical subtypes among early-onset schizophrenia (EOS) patients by exploring the association between structural alterations and molecular mechanisms using a combined analysis of morphometric similarity network (MSN) changes and specific transcriptional expression patterns. Methods We recruited 206 subjects aged 7 to 17 years, including 100 EOS patients and 106 healthy controls (HC). Heterogeneity through discriminant analysis (HYDRA) was used to identify the EOS subtypes within the MSN strength. The differences in morphometric similarity between each EOS subtype and HC were compared. Furthermore, we examined the link between morphometric changes and brain-wide gene expression in different EOS subtypes using partial least squares regression (PLS) weight mapping, evaluated genetic commonalities with psychiatric disorders, identified functional enrichments of PLS-weighted genes, and assessed cellular transcriptional signatures. Results Two distinct MSN-based EOS subtypes were identified, each exhibiting different abnormal MSN strength and cognitive functions compared to HC. The PLS1 score mapping demonstrated anterior–posterior gradients of gene expression in EOS1, whereas inverse distributions were observed in EOS2 cohorts. Genetic commonalities were identified in autistic disorder and adult schizophrenia with EOS1 and inflammatory bowel diseases with EOS2 cohorts. The EOS1 PLS1- genes (Z < -5) were significantly enriched in synaptic signaling-related functions, whereas EOS2 demonstrated enrichments in virtual infection-related pathways. Furthermore, the majority of observed associations with EOS1-specific MSN strength differences contributed to specific transcriptional changes in astrocytes and neurons. Conclusions The findings of this study provide a comprehensive analysis of neuroanatomical subtypes in EOS, shedding light on the intricate relationships between macrostructural and molecular aspects of the EOS disease. |
| first_indexed | 2024-03-09T01:17:51Z |
| format | Article |
| id | doaj.art-b33be2b65e054522bd37ffde22057e42 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-03-09T01:17:51Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-b33be2b65e054522bd37ffde22057e422023-12-10T12:21:32ZengBMCBMC Medicine1741-70152023-12-0121111810.1186/s12916-023-03201-1Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patternsGuanqun Yao0Ting Zou1Jing Luo2Shuang Hu3Langxiong Yang4Jing Li5Xinrong Li6Yuqi Zhang7Kun Feng8Yong Xu9Pozi Liu10School of Medicine, Tsinghua UniversitySchool of Life Sciences, University of Electronic Science and Technology of ChinaSchool of Medicine, Tsinghua UniversityShanghai Mental Health CenterSchool of Medicine, Tsinghua UniversityCollege of Humanities and Social Science, Shanxi Medical UniversityDepartment of Psychiatry, the First Hospital of Shanxi Medical UniversitySchool of Medicine, Tsinghua UniversitySchool of Medicine, Tsinghua UniversitySchool of Mental Health, Shanxi Medical UniversitySchool of Medicine, Tsinghua UniversityAbstract Background This study aimed to investigate the neuroanatomical subtypes among early-onset schizophrenia (EOS) patients by exploring the association between structural alterations and molecular mechanisms using a combined analysis of morphometric similarity network (MSN) changes and specific transcriptional expression patterns. Methods We recruited 206 subjects aged 7 to 17 years, including 100 EOS patients and 106 healthy controls (HC). Heterogeneity through discriminant analysis (HYDRA) was used to identify the EOS subtypes within the MSN strength. The differences in morphometric similarity between each EOS subtype and HC were compared. Furthermore, we examined the link between morphometric changes and brain-wide gene expression in different EOS subtypes using partial least squares regression (PLS) weight mapping, evaluated genetic commonalities with psychiatric disorders, identified functional enrichments of PLS-weighted genes, and assessed cellular transcriptional signatures. Results Two distinct MSN-based EOS subtypes were identified, each exhibiting different abnormal MSN strength and cognitive functions compared to HC. The PLS1 score mapping demonstrated anterior–posterior gradients of gene expression in EOS1, whereas inverse distributions were observed in EOS2 cohorts. Genetic commonalities were identified in autistic disorder and adult schizophrenia with EOS1 and inflammatory bowel diseases with EOS2 cohorts. The EOS1 PLS1- genes (Z < -5) were significantly enriched in synaptic signaling-related functions, whereas EOS2 demonstrated enrichments in virtual infection-related pathways. Furthermore, the majority of observed associations with EOS1-specific MSN strength differences contributed to specific transcriptional changes in astrocytes and neurons. Conclusions The findings of this study provide a comprehensive analysis of neuroanatomical subtypes in EOS, shedding light on the intricate relationships between macrostructural and molecular aspects of the EOS disease.https://doi.org/10.1186/s12916-023-03201-1Early-onset schizophreniaMorphometric similarity networkNeuroanatomical subtypesTranscriptional signaturesCell type-specific signatures |
| spellingShingle | Guanqun Yao Ting Zou Jing Luo Shuang Hu Langxiong Yang Jing Li Xinrong Li Yuqi Zhang Kun Feng Yong Xu Pozi Liu Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns BMC Medicine Early-onset schizophrenia Morphometric similarity network Neuroanatomical subtypes Transcriptional signatures Cell type-specific signatures |
| title | Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns |
| title_full | Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns |
| title_fullStr | Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns |
| title_full_unstemmed | Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns |
| title_short | Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns |
| title_sort | cortical structural changes of morphometric similarity network in early onset schizophrenia correlate with specific transcriptional expression patterns |
| topic | Early-onset schizophrenia Morphometric similarity network Neuroanatomical subtypes Transcriptional signatures Cell type-specific signatures |
| url | https://doi.org/10.1186/s12916-023-03201-1 |
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