Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression
Abstract Late-life depression (LLD) is a heterogenous mood disorder influenced by genetic factors. Cortical physiological processes such as cortical inhibition, facilitation, and plasticity may be markers of illness that are more strongly associated with genetic factors than the clinical phenotype....
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-06-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02532-0 |
| _version_ | 1797789596941025280 |
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| author | Rafae A. Wathra Xiaoyu Men Samar S. M. Elsheikh Victoria S. Marshe Tarek K. Rajji Jennifer I. Lissemore Benoit H. Mulsant Jordan F. Karp Charles F. Reynolds Eric J. Lenze Zafiris J. Daskalakis Daniel J. Müller Daniel M. Blumberger |
| author_facet | Rafae A. Wathra Xiaoyu Men Samar S. M. Elsheikh Victoria S. Marshe Tarek K. Rajji Jennifer I. Lissemore Benoit H. Mulsant Jordan F. Karp Charles F. Reynolds Eric J. Lenze Zafiris J. Daskalakis Daniel J. Müller Daniel M. Blumberger |
| author_sort | Rafae A. Wathra |
| collection | DOAJ |
| description | Abstract Late-life depression (LLD) is a heterogenous mood disorder influenced by genetic factors. Cortical physiological processes such as cortical inhibition, facilitation, and plasticity may be markers of illness that are more strongly associated with genetic factors than the clinical phenotype. Thus, exploring the relationship between genetic factors and these physiological processes may help to characterize the biological mechanisms underlying LLD and improve diagnosis and treatment selection. Transcranial magnetic stimulation (TMS) combined with electromyography was used to measure short interval intracortical inhibition (SICI), cortical silent period (CSP), intracortical facilitation (ICF), and paired associative stimulation (PAS) in 79 participants with LLD. We used exploratory genome-wide association and gene-based analyses to assess for genetic correlations of these TMS measures. MARK4 (which encodes microtubule affinity-regulating kinase 4) and PPP1R37 (which encodes protein phosphatase 1 regulatory subunit 37) showed genome-wide significant association with SICI. EGFLAM (which encodes EGF-like fibronectin type III and laminin G domain) showed genome-wide significant association with CSP. No genes met genome-wide significant association with ICF or PAS. We observed genetic influences on cortical inhibition in older adults with LLD. Replication with larger sample sizes, exploration of clinical phenotype subgroups, and functional analysis of relevant genotypes is warranted to better characterize genetic influences on cortical physiology in LLD. This work is needed to determine whether cortical inhibition may serve as a biomarker to improve diagnostic precision and guide treatment selection in LLD. |
| first_indexed | 2024-03-13T01:52:56Z |
| format | Article |
| id | doaj.art-d78d02dc81894ea1b973335339a307c6 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-13T01:52:56Z |
| publishDate | 2023-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-d78d02dc81894ea1b973335339a307c62023-07-02T11:27:30ZengNature Publishing GroupTranslational Psychiatry2158-31882023-06-011311810.1038/s41398-023-02532-0Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depressionRafae A. Wathra0Xiaoyu Men1Samar S. M. Elsheikh2Victoria S. Marshe3Tarek K. Rajji4Jennifer I. Lissemore5Benoit H. Mulsant6Jordan F. Karp7Charles F. Reynolds8Eric J. Lenze9Zafiris J. Daskalakis10Daniel J. Müller11Daniel M. Blumberger12Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental HealthCampbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthCampbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthCampbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthTemerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental HealthDepartment of Psychiatry and Behavioral Sciences, Stanford University Medical CenterDepartment of Psychiatry, Temerty Faculty of Medicine, University of TorontoDepartment of Psychiatry, University of Arizona College of MedicineDepartment of Psychiatry, University of Pittsburgh School of MedicineDepartment of Psychiatry, Washington University School of MedicineDepartment of Psychiatry, University of California San DiegoDepartment of Psychiatry, Temerty Faculty of Medicine, University of TorontoTemerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental HealthAbstract Late-life depression (LLD) is a heterogenous mood disorder influenced by genetic factors. Cortical physiological processes such as cortical inhibition, facilitation, and plasticity may be markers of illness that are more strongly associated with genetic factors than the clinical phenotype. Thus, exploring the relationship between genetic factors and these physiological processes may help to characterize the biological mechanisms underlying LLD and improve diagnosis and treatment selection. Transcranial magnetic stimulation (TMS) combined with electromyography was used to measure short interval intracortical inhibition (SICI), cortical silent period (CSP), intracortical facilitation (ICF), and paired associative stimulation (PAS) in 79 participants with LLD. We used exploratory genome-wide association and gene-based analyses to assess for genetic correlations of these TMS measures. MARK4 (which encodes microtubule affinity-regulating kinase 4) and PPP1R37 (which encodes protein phosphatase 1 regulatory subunit 37) showed genome-wide significant association with SICI. EGFLAM (which encodes EGF-like fibronectin type III and laminin G domain) showed genome-wide significant association with CSP. No genes met genome-wide significant association with ICF or PAS. We observed genetic influences on cortical inhibition in older adults with LLD. Replication with larger sample sizes, exploration of clinical phenotype subgroups, and functional analysis of relevant genotypes is warranted to better characterize genetic influences on cortical physiology in LLD. This work is needed to determine whether cortical inhibition may serve as a biomarker to improve diagnostic precision and guide treatment selection in LLD.https://doi.org/10.1038/s41398-023-02532-0 |
| spellingShingle | Rafae A. Wathra Xiaoyu Men Samar S. M. Elsheikh Victoria S. Marshe Tarek K. Rajji Jennifer I. Lissemore Benoit H. Mulsant Jordan F. Karp Charles F. Reynolds Eric J. Lenze Zafiris J. Daskalakis Daniel J. Müller Daniel M. Blumberger Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression Translational Psychiatry |
| title | Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression |
| title_full | Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression |
| title_fullStr | Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression |
| title_full_unstemmed | Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression |
| title_short | Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression |
| title_sort | exploratory genome wide analyses of cortical inhibition facilitation and plasticity in late life depression |
| url | https://doi.org/10.1038/s41398-023-02532-0 |
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