Neurodevelopmental trajectories, polygenic risk, and lipometabolism in vulnerability and resilience to schizophrenia
Abstract Background Schizophrenia (SZ) arises from a complex interplay involving genetic and molecular factors. Early intervention of SZ hinges upon understanding its vulnerability and resiliency factors in study of SZ and genetic high risk for SZ (GHR). Methods Herein, using integrative and multimo...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | BMC Psychiatry |
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| Online Access: | https://doi.org/10.1186/s12888-023-04597-z |
| _version_ | 1797863892608614400 |
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| author | Jia Duan Xiaohong Gong Fay Y. Womer Kaijin Sun Lili Tang Juan Liu Junjie Zheng Yue Zhu Yanqing Tang Xizhe Zhang Fei Wang |
| author_facet | Jia Duan Xiaohong Gong Fay Y. Womer Kaijin Sun Lili Tang Juan Liu Junjie Zheng Yue Zhu Yanqing Tang Xizhe Zhang Fei Wang |
| author_sort | Jia Duan |
| collection | DOAJ |
| description | Abstract Background Schizophrenia (SZ) arises from a complex interplay involving genetic and molecular factors. Early intervention of SZ hinges upon understanding its vulnerability and resiliency factors in study of SZ and genetic high risk for SZ (GHR). Methods Herein, using integrative and multimodal strategies, we first performed a longitudinal study of neural function as measured by amplitude of low frequency function (ALFF) in 21 SZ, 26 GHR, and 39 healthy controls to characterize neurodevelopmental trajectories of SZ and GHR. Then, we examined the relationship between polygenic risk score for SZ (SZ-PRS), lipid metabolism, and ALFF in 78 SZ, and 75 GHR in cross-sectional design to understand its genetic and molecular substrates. Results Across time, SZ and GHR diverge in ALFF alterations of the left medial orbital frontal cortex (MOF). At baseline, both SZ and GHR had increased left MOF ALFF compared to HC (P < 0.05). At follow-up, increased ALFF persisted in SZ, yet normalized in GHR. Further, membrane genes and lipid species for cell membranes predicted left MOF ALFF in SZ; whereas in GHR, fatty acids best predicted and were negatively correlated (r = -0.302, P < 0.05) with left MOF. Conclusions Our findings implicate divergence in ALFF alteration in left MOF between SZ and GHR with disease progression, reflecting vulnerability and resiliency to SZ. They also indicate different influences of membrane genes and lipid metabolism on left MOF ALFF in SZ and GHR, which have important implications for understanding mechanisms underlying vulnerability and resiliency in SZ and contribute to translational efforts for early intervention. |
| first_indexed | 2024-04-09T22:44:06Z |
| format | Article |
| id | doaj.art-bb73ca8042f64fca9ef4a705c62556af |
| institution | Directory Open Access Journal |
| issn | 1471-244X |
| language | English |
| last_indexed | 2024-04-09T22:44:06Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Psychiatry |
| spelling | doaj.art-bb73ca8042f64fca9ef4a705c62556af2023-03-22T12:00:43ZengBMCBMC Psychiatry1471-244X2023-03-0123111210.1186/s12888-023-04597-zNeurodevelopmental trajectories, polygenic risk, and lipometabolism in vulnerability and resilience to schizophreniaJia Duan0Xiaohong Gong1Fay Y. Womer2Kaijin Sun3Lili Tang4Juan Liu5Junjie Zheng6Yue Zhu7Yanqing Tang8Xizhe Zhang9Fei Wang10Department of Psychiatry. Early Intervention Unit, Affiliated Nanjing Brain Hospital, Nanjing Medical UniversityState Key Laboratory of Genetic Engineering and Human Phenome Institute, School of Life Sciences, Fudan UniversityDept of Psychiatry and Behavioral Sciences, Vanderbilt University Medical CenterDepartment of Psychiatry. Early Intervention Unit, Affiliated Nanjing Brain Hospital, Nanjing Medical UniversityDepartment of Psychiatry. Early Intervention Unit, Affiliated Nanjing Brain Hospital, Nanjing Medical UniversityDepartment of Psychiatry. Early Intervention Unit, Affiliated Nanjing Brain Hospital, Nanjing Medical UniversityDepartment of Psychiatry. Early Intervention Unit, Affiliated Nanjing Brain Hospital, Nanjing Medical UniversityDepartment of Psychiatry. Early Intervention Unit, Affiliated Nanjing Brain Hospital, Nanjing Medical UniversityDepartment of Psychiatry and Gerontology, The First Affiliated Hospital, China Medical UniversitySchool of Biomedical Engineering and Informatics, Nanjing Medical UniversityDepartment of Psychiatry. Early Intervention Unit, Affiliated Nanjing Brain Hospital, Nanjing Medical UniversityAbstract Background Schizophrenia (SZ) arises from a complex interplay involving genetic and molecular factors. Early intervention of SZ hinges upon understanding its vulnerability and resiliency factors in study of SZ and genetic high risk for SZ (GHR). Methods Herein, using integrative and multimodal strategies, we first performed a longitudinal study of neural function as measured by amplitude of low frequency function (ALFF) in 21 SZ, 26 GHR, and 39 healthy controls to characterize neurodevelopmental trajectories of SZ and GHR. Then, we examined the relationship between polygenic risk score for SZ (SZ-PRS), lipid metabolism, and ALFF in 78 SZ, and 75 GHR in cross-sectional design to understand its genetic and molecular substrates. Results Across time, SZ and GHR diverge in ALFF alterations of the left medial orbital frontal cortex (MOF). At baseline, both SZ and GHR had increased left MOF ALFF compared to HC (P < 0.05). At follow-up, increased ALFF persisted in SZ, yet normalized in GHR. Further, membrane genes and lipid species for cell membranes predicted left MOF ALFF in SZ; whereas in GHR, fatty acids best predicted and were negatively correlated (r = -0.302, P < 0.05) with left MOF. Conclusions Our findings implicate divergence in ALFF alteration in left MOF between SZ and GHR with disease progression, reflecting vulnerability and resiliency to SZ. They also indicate different influences of membrane genes and lipid metabolism on left MOF ALFF in SZ and GHR, which have important implications for understanding mechanisms underlying vulnerability and resiliency in SZ and contribute to translational efforts for early intervention.https://doi.org/10.1186/s12888-023-04597-zSchizophreniaGenetic high riskMRINeurodevelopmental trajectoriesPolygenic RiskLipometabolism |
| spellingShingle | Jia Duan Xiaohong Gong Fay Y. Womer Kaijin Sun Lili Tang Juan Liu Junjie Zheng Yue Zhu Yanqing Tang Xizhe Zhang Fei Wang Neurodevelopmental trajectories, polygenic risk, and lipometabolism in vulnerability and resilience to schizophrenia BMC Psychiatry Schizophrenia Genetic high risk MRI Neurodevelopmental trajectories Polygenic Risk Lipometabolism |
| title | Neurodevelopmental trajectories, polygenic risk, and lipometabolism in vulnerability and resilience to schizophrenia |
| title_full | Neurodevelopmental trajectories, polygenic risk, and lipometabolism in vulnerability and resilience to schizophrenia |
| title_fullStr | Neurodevelopmental trajectories, polygenic risk, and lipometabolism in vulnerability and resilience to schizophrenia |
| title_full_unstemmed | Neurodevelopmental trajectories, polygenic risk, and lipometabolism in vulnerability and resilience to schizophrenia |
| title_short | Neurodevelopmental trajectories, polygenic risk, and lipometabolism in vulnerability and resilience to schizophrenia |
| title_sort | neurodevelopmental trajectories polygenic risk and lipometabolism in vulnerability and resilience to schizophrenia |
| topic | Schizophrenia Genetic high risk MRI Neurodevelopmental trajectories Polygenic Risk Lipometabolism |
| url | https://doi.org/10.1186/s12888-023-04597-z |
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