Individualized resting-state functional connectivity abnormalities unveil two major depressive disorder subtypes with contrasting abnormal patterns of abnormality
Abstract Modern neuroimaging research has recognized that major depressive disorder (MDD) is a connectome disorder, characterized by altered functional connectivity across large-scale brain networks. However, the clinical heterogeneity, likely stemming from diverse neurobiological disturbances, comp...
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Nature Publishing Group
2025-02-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03268-9 |
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| author | Keke Fang Lianjie Niu Baohong Wen Liang Liu Ya Tian Huiting Yang Ying Hou Shaoqiang Han Xianfu Sun Wenzhou Zhang |
| author_facet | Keke Fang Lianjie Niu Baohong Wen Liang Liu Ya Tian Huiting Yang Ying Hou Shaoqiang Han Xianfu Sun Wenzhou Zhang |
| author_sort | Keke Fang |
| collection | DOAJ |
| description | Abstract Modern neuroimaging research has recognized that major depressive disorder (MDD) is a connectome disorder, characterized by altered functional connectivity across large-scale brain networks. However, the clinical heterogeneity, likely stemming from diverse neurobiological disturbances, complicates findings from standard group comparison methods. This variability has driven the search for MDD subtypes using objective neuroimaging markers. In this study, we sought to identify potential MDD subtypes from subject-level abnormalities in functional connectivity, leveraging a large multi-site dataset of resting-state MRI from 1276 MDD patients and 1104 matched healthy controls. Subject-level extreme functional connections, determined by comparing against normative ranges derived from healthy controls using tolerance intervals, were used to identify biological subtypes of MDD. We identified a set of extreme functional connections that were predominantly between the visual network and the frontoparietal network, the default mode network and the ventral attention network, with the key regions in the anterior cingulate cortex, bilateral orbitofrontal cortex, and supramarginal gyrus. In MDD patients, these extreme functional connections were linked to age of onset and reward-related processes. Using these features, we identified two subtypes with distinct patterns of functional connectivity abnormalities compared to healthy controls (p < 0.05, Bonferroni correction). When considering all patients together, no significant differences were found. These subtypes significantly enhanced case-control discriminability and showed strong internal discriminability between subtypes. Furthermore, the subtypes were reproducible across varying parameters, study sites, and in untreated patients. Our findings provide new insights into the taxonomy and have potential implications for both diagnosis and treatment of MDD. |
| format | Article |
| id | doaj-art-dbff22f1061f4d2d8889e758d09745d6 |
| institution | Kabale University |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-dbff22f1061f4d2d8889e758d09745d62025-02-09T12:55:33ZengNature Publishing GroupTranslational Psychiatry2158-31882025-02-0115111010.1038/s41398-025-03268-9Individualized resting-state functional connectivity abnormalities unveil two major depressive disorder subtypes with contrasting abnormal patterns of abnormalityKeke Fang0Lianjie Niu1Baohong Wen2Liang Liu3Ya Tian4Huiting Yang5Ying Hou6Shaoqiang Han7Xianfu Sun8Wenzhou Zhang9Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalDepartment of Breast Disease, Henan Breast Cancer Center, the affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalDepartment of Magnetic Resonance Imaging, the First Affiliated Hospital of Zhengzhou University, Henan ProvinceDepartment of Magnetic Resonance Imaging, the First Affiliated Hospital of Zhengzhou University, Henan ProvinceDepartment of Magnetic Resonance Imaging, the First Affiliated Hospital of Zhengzhou University, Henan ProvinceDepartment of Magnetic Resonance Imaging, the First Affiliated Hospital of Zhengzhou University, Henan ProvinceDepartment of ultrasound, the affiliated cancer hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Magnetic Resonance Imaging, the First Affiliated Hospital of Zhengzhou University, Henan ProvinceDepartment of Breast Disease, Henan Breast Cancer Center, the affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalDepartment of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalAbstract Modern neuroimaging research has recognized that major depressive disorder (MDD) is a connectome disorder, characterized by altered functional connectivity across large-scale brain networks. However, the clinical heterogeneity, likely stemming from diverse neurobiological disturbances, complicates findings from standard group comparison methods. This variability has driven the search for MDD subtypes using objective neuroimaging markers. In this study, we sought to identify potential MDD subtypes from subject-level abnormalities in functional connectivity, leveraging a large multi-site dataset of resting-state MRI from 1276 MDD patients and 1104 matched healthy controls. Subject-level extreme functional connections, determined by comparing against normative ranges derived from healthy controls using tolerance intervals, were used to identify biological subtypes of MDD. We identified a set of extreme functional connections that were predominantly between the visual network and the frontoparietal network, the default mode network and the ventral attention network, with the key regions in the anterior cingulate cortex, bilateral orbitofrontal cortex, and supramarginal gyrus. In MDD patients, these extreme functional connections were linked to age of onset and reward-related processes. Using these features, we identified two subtypes with distinct patterns of functional connectivity abnormalities compared to healthy controls (p < 0.05, Bonferroni correction). When considering all patients together, no significant differences were found. These subtypes significantly enhanced case-control discriminability and showed strong internal discriminability between subtypes. Furthermore, the subtypes were reproducible across varying parameters, study sites, and in untreated patients. Our findings provide new insights into the taxonomy and have potential implications for both diagnosis and treatment of MDD.https://doi.org/10.1038/s41398-025-03268-9 |
| spellingShingle | Keke Fang Lianjie Niu Baohong Wen Liang Liu Ya Tian Huiting Yang Ying Hou Shaoqiang Han Xianfu Sun Wenzhou Zhang Individualized resting-state functional connectivity abnormalities unveil two major depressive disorder subtypes with contrasting abnormal patterns of abnormality Translational Psychiatry |
| title | Individualized resting-state functional connectivity abnormalities unveil two major depressive disorder subtypes with contrasting abnormal patterns of abnormality |
| title_full | Individualized resting-state functional connectivity abnormalities unveil two major depressive disorder subtypes with contrasting abnormal patterns of abnormality |
| title_fullStr | Individualized resting-state functional connectivity abnormalities unveil two major depressive disorder subtypes with contrasting abnormal patterns of abnormality |
| title_full_unstemmed | Individualized resting-state functional connectivity abnormalities unveil two major depressive disorder subtypes with contrasting abnormal patterns of abnormality |
| title_short | Individualized resting-state functional connectivity abnormalities unveil two major depressive disorder subtypes with contrasting abnormal patterns of abnormality |
| title_sort | individualized resting state functional connectivity abnormalities unveil two major depressive disorder subtypes with contrasting abnormal patterns of abnormality |
| url | https://doi.org/10.1038/s41398-025-03268-9 |
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