Toni Ali-Sisto1, Tommi Tolmunen2, Heimo Viinamäki3, Pekka Mäntyselkä4, Minna Valkonen-Korhonen3, Heli Koivumaa-Honkanen5, Kirsi Honkalampi6, Anu Ruusunen7, Jatin Nandania8, Vidya Velagapudi8, Soili M Lehto9. 1. Institute of Clinical Medicine/Psychiatry, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland. Electronic address: tonial@student.uef.fi. 2. Department of Psychiatry, Kuopio University Hospital, P.O. Box 100, 70029 KYS, Finland. 3. Institute of Clinical Medicine/Psychiatry, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland; Department of Psychiatry, Kuopio University Hospital, P.O. Box 100, 70029 KYS, Finland. 4. Primary Health Care Unit, University of Eastern Finland and Kuopio University Hospital, P.O. Box 1627, 70211 Kuopio, Finland. 5. Institute of Clinical Medicine/Psychiatry, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland; Department of Psychiatry, Kuopio University Hospital, P.O. Box 100, 70029 KYS, Finland; Departments of Psychiatry, South-Savonia Hospital District, Mikkeli, Finland; Departments of Psychiatry, North Karelia Central Hospital, Joensuu, Finland; Departments of Psychiatry, SOTE, Iisalmi, Finland; Departments of Psychiatry, Lapland Hospital District, Rovaniemi, Finland. 6. Department of Education and Psychology, University of Eastern Finland, P.O. Box 111, 80101 Joensuu, Finland. 7. Department of Psychiatry, Kuopio University Hospital, P.O. Box 100, 70029 KYS, Finland; Deakin University, Geelong, IMPACT Strategic Research Centre, VIC, Australia. 8. Metabolomics Unit, Institute for Molecular Medicine Finland FIMM, University of Helsinki, P.O. Box 20, 00014, Finland. 9. Institute of Clinical Medicine/Psychiatry, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland; Department of Psychiatry, Kuopio University Hospital, P.O. Box 100, 70029 KYS, Finland; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, P.O. Box 9, 00014, Finland.
Abstract
BACKGROUND: Major depressive disorder (MDD) is characterized by increased oxidative and nitrosative stress. We compared nitric oxide metabolism, i.e., the global arginine bioavailability ratio (GABR) and related serum amino acids, between MDD patients and non-depressed controls, and between remitted and non-remitted MDD patients. METHODS: Ninety-nine MDD patients and 253 non-depressed controls, aged 20-71 years, provided background data via questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of ornithine, arginine, citrulline, and symmetric and asymmetric dimethylarginine. GABR was calculated as arginine divided by the sum of ornithine plus citrulline. We compared the above measures between: 1) MDD patients and controls, 2) remitted (n=33) and non-remitted (n = 45) MDD patients, and 3) baseline and follow-up within the remitted and non-remitted groups. RESULTS: Lower arginine levels (OR 0.98, 95% CI 0.97-0.99) and lower GABR (OR 0.13, 95% CI 0.03-0.50) were associated with the MDD vs. the non-depressed group after adjustments for potential confounders. The remitted group showed a decrease in GABR, arginine, and symmetric dimethylarginine, and an increase in ornithine after the follow-up compared with within-group baseline values. The non-remitted group displayed an increase in arginine and ornithine levels and a decrease in GABR. No significant differences were recorded between the remitted and non-remitted groups. LIMITATIONS: The MDD group was not medication-free. CONCLUSIONS: Arginine bioavailability may be decreased in MDD. This could impair the production of nitric oxide, and thus add to oxidative stress in the central nervous system.
BACKGROUND: Major depressive disorder (MDD) is characterized by increased oxidative and nitrosative stress. We compared nitric oxide metabolism, i.e., the global arginine bioavailability ratio (GABR) and related serum amino acids, between MDDpatients and non-depressed controls, and between remitted and non-remitted MDDpatients. METHODS: Ninety-nine MDDpatients and 253 non-depressed controls, aged 20-71 years, provided background data via questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of ornithine, arginine, citrulline, and symmetric and asymmetric dimethylarginine. GABR was calculated as arginine divided by the sum of ornithine plus citrulline. We compared the above measures between: 1) MDDpatients and controls, 2) remitted (n=33) and non-remitted (n = 45) MDDpatients, and 3) baseline and follow-up within the remitted and non-remitted groups. RESULTS: Lower arginine levels (OR 0.98, 95% CI 0.97-0.99) and lower GABR (OR 0.13, 95% CI 0.03-0.50) were associated with the MDD vs. the non-depressed group after adjustments for potential confounders. The remitted group showed a decrease in GABR, arginine, and symmetric dimethylarginine, and an increase in ornithine after the follow-up compared with within-group baseline values. The non-remitted group displayed an increase in arginine and ornithine levels and a decrease in GABR. No significant differences were recorded between the remitted and non-remitted groups. LIMITATIONS: The MDD group was not medication-free. CONCLUSIONS:Arginine bioavailability may be decreased in MDD. This could impair the production of nitric oxide, and thus add to oxidative stress in the central nervous system.
Authors: Jolyn Fernandes; Joshua D Chandler; Ken H Liu; Karan Uppal; Li Hao; Xin Hu; Young-Mi Go; Dean P Jones Journal: Toxicol Sci Date: 2019-05-01 Impact factor: 4.849
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Authors: Lulu Yao; Kun Cai; Fanghua Mei; Xiaohua Wang; Chuangang Fan; Hong Jiang; Fang Xie; Ying Li; Lu Bai; Kang Peng; Wenwen Deng; Shenghan Lai; Jun Wang Journal: Front Psychiatry Date: 2021-05-21 Impact factor: 4.157