title: The one-carbon-cycle and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in recurrent major depressive disorder; influence of antidepressant use and depressive state?
abstract: BACKGROUND
  An important biological factor suggested in the pathophysiology of (recurrent) Major Depressive Disorder (MDD) concerns a polymorphism in a gene encoding for the MTHFR-enzyme of the one-carbon (1-C)-metabolism. Integratively investigating key 1-C-components (folate, homocysteine, vitamin B6 and B12), including the possible effects of antidepressant medication and depressive state, could provide more insight in the possible association between the MTHFR-polymorphism and recurrent MDD.
  
  
  METHODS
  We compared the MTHFR C677T-polymorphism together with the key 1-C-components in clinically ascertained patients with recurrent MDD (n=137) to age- and gender-matched healthy controls (n=73).
  
  
  RESULTS
  First, patients had lower folate (t=2.25; p=.025) as compared to controls; a difference that resolved after correction for demographics (t=1.22; p=.223). Second, patients that were depressed during sampling had lower vitamin B6 (t=-2.070; p=.038) and higher homocysteine (t=2.404; p=.016) compared to those in remission. Finally, current use of antidepressants had no influence on the 1-C-components.
  
  
  CONCLUSIONS
  Despite investigation of a specific recurrently depressed patient population, we found no clear associations with the 1-C-cycle, except for higher homocysteine and lower vitamin B6 during the depressed state. This suggests that 1-C-cycle alterations in MDD are state-associated, possibly resulting from high levels of acute (psychological) stress, and may provide a treatment target to reduce cardiovascular risk in this population.
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands. Electronic address: a.lok@amc.uva.nl.
authors.forename: A
authors.initials: A
authors.lastname: Lok
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands.
authors.forename: R J T
authors.initials: RJ
authors.lastname: Mocking
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Assies
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands.
authors.forename: M W
authors.initials: MW
authors.lastname: Koeter
authors.affiliation: Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands.
authors.forename: C L
authors.initials: CL
authors.lastname: Bockting
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: de Vries
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Visser
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: Derks
authors.affiliation: Department of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Kayser
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands; Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Schene
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D002244:Carbon / Q000378:metabolism*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012008:Recurrence; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood
chemical_list: D000928:Antidepressive Agents; D006710:Homocysteine; D002244:Carbon; D025101:Vitamin B 6; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12
keywords: Depressive disorder; Folate; Homocysteine; Methylenetetrahydrofolate Reductase (NADPH2)/genetics; Vitamin B6