Toni Ali-Sisto1, Tommi Tolmunen2, Elena Toffol3, Heimo Viinamäki2, Pekka Mäntyselkä4, Minna Valkonen-Korhonen2, Kirsi Honkalampi5, Anu Ruusunen2, Vidya Velagapudi6, Soili M Lehto2. 1. Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. Electronic address: tonial@student.uef.fi. 2. Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland; Department of Psychiatry, Kuopio University Hospital, P.O. Box 100, 70029 KYS, Finland. 3. Metabolomics Unit, Institute for Molecular Medicine, Finland. 4. Primary Health Care Unit, University of Eastern Finland and Kuopio University Hospital, P.O. Box 1627, 70211, Kuopio, Finland. 5. Department of Education and Psychology, University of Eastern Finland, P.O. Box 111, 80101 Joensuu, Finland. 6. Metabolomics Unit, Institute for Molecular Medicine, Finland; FIMM, P.O. Box 20, FI-00014, University of Helsinki, Finland.
Abstract
INTRODUCTION: The purine cycle and altered purinergic signaling have been suggested to play a role in major depressive disorder (MDD). Nevertheless, data on this topic are scarce. Based on previous studies, we hypothesized that compared with non-depressed controls, MDD patients have distinct purine metabolite profiles. METHODS: The samples comprised 99 MDD patients and 253 non-depressed controls, aged 20-71 years. Background data were collected with questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) to determine seven purine cycle metabolites belonging to the purine cycle. We investigated the levels of these metabolites in three settings: (1) MDD patients vs. non-depressed controls and (2) remitted vs. non-remitted MDD patients, and also (3) within-group changes in metabolite levels during the follow-up period. RESULTS: In logistic regression adjusted for age, gender, smoking, alcohol use, physical exercise, glycosylated hemoglobin, and high-density lipoprotein cholesterol, lower levels of inosine (OR 0.89, 95% CI 0.82-0.97) and guanosine (OR 0.32, 95% CI 0.17-0.59), and higher levels of xanthine (OR 2.21, 95% CI 1.30-3.75) were associated with MDD vs. the non-depressed group. Levels of several metabolites changed significantly during the follow-up period in the MDD group, but there were no differences between remitted and non-remitted groups. CONCLUSIONS: We observed altered purine metabolism in MDD patients compared with non-depressed controls. Furthermore, our observations suggest that circulating xanthine may accumulate in MDD patients.
INTRODUCTION: The purine cycle and altered purinergic signaling have been suggested to play a role in major depressive disorder (MDD). Nevertheless, data on this topic are scarce. Based on previous studies, we hypothesized that compared with non-depressed controls, MDDpatients have distinct purine metabolite profiles. METHODS: The samples comprised 99 MDDpatients and 253 non-depressed controls, aged 20-71 years. Background data were collected with questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) to determine seven purine cycle metabolites belonging to the purine cycle. We investigated the levels of these metabolites in three settings: (1) MDDpatients vs. non-depressed controls and (2) remitted vs. non-remitted MDDpatients, and also (3) within-group changes in metabolite levels during the follow-up period. RESULTS: In logistic regression adjusted for age, gender, smoking, alcohol use, physical exercise, glycosylated hemoglobin, and high-density lipoprotein cholesterol, lower levels of inosine (OR 0.89, 95% CI 0.82-0.97) and guanosine (OR 0.32, 95% CI 0.17-0.59), and higher levels of xanthine (OR 2.21, 95% CI 1.30-3.75) were associated with MDD vs. the non-depressed group. Levels of several metabolites changed significantly during the follow-up period in the MDD group, but there were no differences between remitted and non-remitted groups. CONCLUSIONS: We observed altered purine metabolism in MDDpatients compared with non-depressed controls. Furthermore, our observations suggest that circulating xanthine may accumulate in MDDpatients.
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