Metabolic features of treatment-refractory major depressive disorder with suicidal ideation
Abstract Peripheral blood metabolomics was used to gain chemical insight into the biology of treatment-refractory Major Depressive Disorder with suicidal ideation, and to identify individualized differences for personalized care. The study cohort consisted of 99 patients with treatment-refractory ma...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-12-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02696-9 |
| _version_ | 1797388063982223360 |
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| author | Lisa A. Pan Jane C. Naviaux Lin Wang Kefeng Li Jonathan M. Monk Sai Sachin Lingampelly Anna Maria Segreti Kaitlyn Bloom Jerry Vockley Mark A. Tarnopolsky David N. Finegold David G. Peters Robert K. Naviaux |
| author_facet | Lisa A. Pan Jane C. Naviaux Lin Wang Kefeng Li Jonathan M. Monk Sai Sachin Lingampelly Anna Maria Segreti Kaitlyn Bloom Jerry Vockley Mark A. Tarnopolsky David N. Finegold David G. Peters Robert K. Naviaux |
| author_sort | Lisa A. Pan |
| collection | DOAJ |
| description | Abstract Peripheral blood metabolomics was used to gain chemical insight into the biology of treatment-refractory Major Depressive Disorder with suicidal ideation, and to identify individualized differences for personalized care. The study cohort consisted of 99 patients with treatment-refractory major depressive disorder and suicidal ideation (trMDD-SI n = 52 females and 47 males) and 94 age- and sex-matched healthy controls (n = 48 females and 46 males). The median age was 29 years (IQR 22–42). Targeted, broad-spectrum metabolomics measured 448 metabolites. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) were measured as biomarkers of mitochondrial dysfunction. The diagnostic accuracy of plasma metabolomics was over 90% (95%CI: 0.80–1.0) by area under the receiver operator characteristic (AUROC) curve analysis. Over 55% of the metabolic impact in males and 75% in females came from abnormalities in lipids. Modified purines and pyrimidines from tRNA, rRNA, and mRNA turnover were increased in the trMDD-SI group. FGF21 was increased in both males and females. Increased lactate, glutamate, and saccharopine, and decreased cystine provided evidence of reductive stress. Seventy-five percent of the metabolomic abnormalities found were individualized. Personalized deficiencies in CoQ10, flavin adenine dinucleotide (FAD), citrulline, lutein, carnitine, or folate were found. Pathways regulated by mitochondrial function dominated the metabolic signature. Peripheral blood metabolomics identified mitochondrial dysfunction and reductive stress as common denominators in suicidal ideation associated with treatment-refractory major depressive disorder. Individualized metabolic differences were found that may help with personalized management. |
| first_indexed | 2024-03-08T22:35:20Z |
| format | Article |
| id | doaj.art-68ee96b7a9524fae9d5b610c0a3b414f |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-08T22:35:20Z |
| publishDate | 2023-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-68ee96b7a9524fae9d5b610c0a3b414f2023-12-17T12:30:41ZengNature Publishing GroupTranslational Psychiatry2158-31882023-12-0113111210.1038/s41398-023-02696-9Metabolic features of treatment-refractory major depressive disorder with suicidal ideationLisa A. Pan0Jane C. Naviaux1Lin Wang2Kefeng Li3Jonathan M. Monk4Sai Sachin Lingampelly5Anna Maria Segreti6Kaitlyn Bloom7Jerry Vockley8Mark A. Tarnopolsky9David N. Finegold10David G. Peters11Robert K. Naviaux12Department of Psychiatry, University of Pittsburgh School of MedicineThe Mitochondrial and Metabolic Disease Center, University of California, San Diego School of MedicineThe Mitochondrial and Metabolic Disease Center, University of California, San Diego School of MedicineThe Mitochondrial and Metabolic Disease Center, University of California, San Diego School of MedicineThe Mitochondrial and Metabolic Disease Center, University of California, San Diego School of MedicineThe Mitochondrial and Metabolic Disease Center, University of California, San Diego School of MedicineDepartment of Psychiatry, University of Pittsburgh School of MedicineDepartment of Pediatrics, University of Pittsburgh School of MedicineDepartment of Pediatrics, University of Pittsburgh School of MedicineDepartment of Pediatrics, McMaster UniversitySchool of Public Health, Department of Human Genetics, University of Pittsburgh School of MedicineDepartment of Psychiatry, University of Pittsburgh School of MedicineThe Mitochondrial and Metabolic Disease Center, University of California, San Diego School of MedicineAbstract Peripheral blood metabolomics was used to gain chemical insight into the biology of treatment-refractory Major Depressive Disorder with suicidal ideation, and to identify individualized differences for personalized care. The study cohort consisted of 99 patients with treatment-refractory major depressive disorder and suicidal ideation (trMDD-SI n = 52 females and 47 males) and 94 age- and sex-matched healthy controls (n = 48 females and 46 males). The median age was 29 years (IQR 22–42). Targeted, broad-spectrum metabolomics measured 448 metabolites. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) were measured as biomarkers of mitochondrial dysfunction. The diagnostic accuracy of plasma metabolomics was over 90% (95%CI: 0.80–1.0) by area under the receiver operator characteristic (AUROC) curve analysis. Over 55% of the metabolic impact in males and 75% in females came from abnormalities in lipids. Modified purines and pyrimidines from tRNA, rRNA, and mRNA turnover were increased in the trMDD-SI group. FGF21 was increased in both males and females. Increased lactate, glutamate, and saccharopine, and decreased cystine provided evidence of reductive stress. Seventy-five percent of the metabolomic abnormalities found were individualized. Personalized deficiencies in CoQ10, flavin adenine dinucleotide (FAD), citrulline, lutein, carnitine, or folate were found. Pathways regulated by mitochondrial function dominated the metabolic signature. Peripheral blood metabolomics identified mitochondrial dysfunction and reductive stress as common denominators in suicidal ideation associated with treatment-refractory major depressive disorder. Individualized metabolic differences were found that may help with personalized management.https://doi.org/10.1038/s41398-023-02696-9 |
| spellingShingle | Lisa A. Pan Jane C. Naviaux Lin Wang Kefeng Li Jonathan M. Monk Sai Sachin Lingampelly Anna Maria Segreti Kaitlyn Bloom Jerry Vockley Mark A. Tarnopolsky David N. Finegold David G. Peters Robert K. Naviaux Metabolic features of treatment-refractory major depressive disorder with suicidal ideation Translational Psychiatry |
| title | Metabolic features of treatment-refractory major depressive disorder with suicidal ideation |
| title_full | Metabolic features of treatment-refractory major depressive disorder with suicidal ideation |
| title_fullStr | Metabolic features of treatment-refractory major depressive disorder with suicidal ideation |
| title_full_unstemmed | Metabolic features of treatment-refractory major depressive disorder with suicidal ideation |
| title_short | Metabolic features of treatment-refractory major depressive disorder with suicidal ideation |
| title_sort | metabolic features of treatment refractory major depressive disorder with suicidal ideation |
| url | https://doi.org/10.1038/s41398-023-02696-9 |
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