Molecular mechanisms explaining sex-specific functional connectivity changes in chronic insomnia disorder
Abstract Background This study investigates the hypothesis that chronic insomnia disorder (CID) is characterized by sex-specific changes in resting-state functional connectivity (rsFC), with certain molecular mechanisms potentially influencing CID's pathophysiology by altering rsFC in relevant...
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BMC
2025-05-01
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| Online Access: | https://doi.org/10.1186/s12916-025-04089-9 |
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| author | Liyong Yu Zhifu Shen Wei Wei Zeyang Dou Yucai Luo Daijie Hu Wenting Lin Guangli Zhao Xiaojuan Hong Siyi Yu |
| author_facet | Liyong Yu Zhifu Shen Wei Wei Zeyang Dou Yucai Luo Daijie Hu Wenting Lin Guangli Zhao Xiaojuan Hong Siyi Yu |
| author_sort | Liyong Yu |
| collection | DOAJ |
| description | Abstract Background This study investigates the hypothesis that chronic insomnia disorder (CID) is characterized by sex-specific changes in resting-state functional connectivity (rsFC), with certain molecular mechanisms potentially influencing CID's pathophysiology by altering rsFC in relevant networks. Methods Utilizing a resting-state functional magnetic resonance imaging (fMRI) dataset of 395 participants, including 199 CID patients and 196 healthy controls, we examined sex-specific rsFC effects, particularly in the default mode network (DMN) and five insomnia-genetically vulnerable regions of interest (ROIs). By integrating gene expression data from the Allen Human Brain Atlas, we identified genes linked to these sex-specific rsFC alterations and conducted enrichment analysis to uncover underlying molecular mechanisms. Additionally, we simulated the impact of sex differences in rsFC with different sex compositions in our dataset and employed machine learning classifiers to distinguish CID from healthy controls based on sex-specific rsFC data. Results We identified both shared and sex-specific rsFC changes in the DMN and the five genetically vulnerable ROIs, with gene expression variations associated with these sex-specific connectivity differences. Enrichment analysis highlighted genes involved in synaptic signaling, ion channels, and immune function as potential contributors to CID pathophysiology through their influence on connectivity. Furthermore, our findings demonstrate that different sex compositions significantly affect study outcomes and higher diagnostic performance in sex-specific rsFC data than combined sex. Conclusions This study uncovered both shared and sex-specific connectivity alterations in CID, providing molecular insights into its pathophysiology and suggesting considering sex differences in future fMRI-based diagnostic and treatment strategies. |
| format | Article |
| id | doaj-art-7d31d3990bc343bda81f438bbeb90c99 |
| institution | DOAJ |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-7d31d3990bc343bda81f438bbeb90c992025-08-20T03:16:40ZengBMCBMC Medicine1741-70152025-05-0123111810.1186/s12916-025-04089-9Molecular mechanisms explaining sex-specific functional connectivity changes in chronic insomnia disorderLiyong Yu0Zhifu Shen1Wei Wei2Zeyang Dou3Yucai Luo4Daijie Hu5Wenting Lin6Guangli Zhao7Xiaojuan Hong8Siyi Yu9School of Acupuncture and Tuina, Chengdu University of Traditional Chinese MedicineDepartment of Traditional Chinese Medicine, the Affiliated Hospital of North Sichuan Medical CollegeSchool of Acupuncture and Tuina, Chengdu University of Traditional Chinese MedicineSchool of Acupuncture and Tuina, Chengdu University of Traditional Chinese MedicineSchool of Acupuncture and Tuina, Chengdu University of Traditional Chinese MedicineSchool of Acupuncture and Tuina, Chengdu University of Traditional Chinese MedicineSchool of Rehabilitation and Health Preservation, Chengdu University of Traditional Chinese MedicineSchool of Rehabilitation and Health Preservation, Chengdu University of Traditional Chinese MedicineSchool of Acupuncture and Tuina, Chengdu University of Traditional Chinese MedicineSchool of Acupuncture and Tuina, Chengdu University of Traditional Chinese MedicineAbstract Background This study investigates the hypothesis that chronic insomnia disorder (CID) is characterized by sex-specific changes in resting-state functional connectivity (rsFC), with certain molecular mechanisms potentially influencing CID's pathophysiology by altering rsFC in relevant networks. Methods Utilizing a resting-state functional magnetic resonance imaging (fMRI) dataset of 395 participants, including 199 CID patients and 196 healthy controls, we examined sex-specific rsFC effects, particularly in the default mode network (DMN) and five insomnia-genetically vulnerable regions of interest (ROIs). By integrating gene expression data from the Allen Human Brain Atlas, we identified genes linked to these sex-specific rsFC alterations and conducted enrichment analysis to uncover underlying molecular mechanisms. Additionally, we simulated the impact of sex differences in rsFC with different sex compositions in our dataset and employed machine learning classifiers to distinguish CID from healthy controls based on sex-specific rsFC data. Results We identified both shared and sex-specific rsFC changes in the DMN and the five genetically vulnerable ROIs, with gene expression variations associated with these sex-specific connectivity differences. Enrichment analysis highlighted genes involved in synaptic signaling, ion channels, and immune function as potential contributors to CID pathophysiology through their influence on connectivity. Furthermore, our findings demonstrate that different sex compositions significantly affect study outcomes and higher diagnostic performance in sex-specific rsFC data than combined sex. Conclusions This study uncovered both shared and sex-specific connectivity alterations in CID, providing molecular insights into its pathophysiology and suggesting considering sex differences in future fMRI-based diagnostic and treatment strategies.https://doi.org/10.1186/s12916-025-04089-9Chronic insomniaFunctional connectivityDefault mode networkSex-specific effectsTranscriptional signaturesMachine learning |
| spellingShingle | Liyong Yu Zhifu Shen Wei Wei Zeyang Dou Yucai Luo Daijie Hu Wenting Lin Guangli Zhao Xiaojuan Hong Siyi Yu Molecular mechanisms explaining sex-specific functional connectivity changes in chronic insomnia disorder BMC Medicine Chronic insomnia Functional connectivity Default mode network Sex-specific effects Transcriptional signatures Machine learning |
| title | Molecular mechanisms explaining sex-specific functional connectivity changes in chronic insomnia disorder |
| title_full | Molecular mechanisms explaining sex-specific functional connectivity changes in chronic insomnia disorder |
| title_fullStr | Molecular mechanisms explaining sex-specific functional connectivity changes in chronic insomnia disorder |
| title_full_unstemmed | Molecular mechanisms explaining sex-specific functional connectivity changes in chronic insomnia disorder |
| title_short | Molecular mechanisms explaining sex-specific functional connectivity changes in chronic insomnia disorder |
| title_sort | molecular mechanisms explaining sex specific functional connectivity changes in chronic insomnia disorder |
| topic | Chronic insomnia Functional connectivity Default mode network Sex-specific effects Transcriptional signatures Machine learning |
| url | https://doi.org/10.1186/s12916-025-04089-9 |
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