title: Purine metabolism is dysregulated in patients with major depressive disorder.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. Electronic address: tonial@student.uef.fi.
authors.forename: Toni
authors.initials: T
authors.lastname: Ali-Sisto
authors.affiliation: 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.
authors.forename: Tommi
authors.initials: T
authors.lastname: Tolmunen
authors.affiliation: Metabolomics Unit, Institute for Molecular Medicine, Finland.
authors.forename: Elena
authors.initials: E
authors.lastname: Toffol
authors.affiliation: 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.
authors.forename: Heimo
authors.initials: H
authors.lastname: Viinamäki
authors.affiliation: Primary Health Care Unit, University of Eastern Finland and Kuopio University Hospital, P.O. Box 1627, 70211, Kuopio, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Mäntyselkä
authors.affiliation: 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.
authors.forename: Minna
authors.initials: M
authors.lastname: Valkonen-Korhonen
authors.affiliation: Department of Education and Psychology, University of Eastern Finland, P.O. Box 111, 80101 Joensuu, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Honkalampi
authors.affiliation: 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.
authors.forename: Anu
authors.initials: A
authors.lastname: Ruusunen
authors.affiliation: Metabolomics Unit, Institute for Molecular Medicine, Finland; FIMM, P.O. Box 20, FI-00014, University of Helsinki, Finland.
authors.forename: Vidya
authors.initials: V
authors.lastname: Velagapudi
authors.affiliation: 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.
authors.forename: Soili M
authors.initials: SM
authors.lastname: Lehto
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000097:blood*; D005260:Female; D005387:Finland; D006151:Guanosine / Q000097:blood; D006801:Humans; D007288:Inosine / Q000097:blood; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D011687:Purines / Q000097:blood*; D011795:Surveys and Questionnaires; D019820:Xanthine / Q000097:blood
chemical_list: D011687:Purines; D006151:Guanosine; D019820:Xanthine; D007288:Inosine
keywords: Guanosine; Inosine; Major depressive disorder; Metabolomics; Purine metabolism; Xanthine