title: Altered one-carbon metabolism in posttraumatic stress disorder.
abstract: BACKGROUND
  Posttraumatic stress disorder (PTSD) is associated with increased morbidity and mortality through somatic conditions, particularly cardiovascular disease. The one-carbon metabolism in connection with the hypothalamic-pituitary-adrenal (HPA)-axis may be an important mediator of this increased cardiovascular risk.
  
  
  METHODS
  In a mixed-gender sample of 49 PTSD patients and 45 healthy controls we therefore investigated: (1) alterations in the one-carbon metabolism as reflected in fasting plasma concentrations of homocysteine, folate, vitamins B6 and B12, and (2) associations of these one-carbon metabolites with the HPA-axis hormones cortisol, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S).
  
  
  RESULTS
  After correction for confounders, PTSD patients had significantly elevated homocysteine (z = 2.963, p = .003) compared to controls, but normal levels of folate, vitamin B6 and B12. Comorbid depression did not explain the observed higher homocysteine levels. Patients showed increased risk for moderate hyperhomocysteinemia (OR = 7.0, χ(2) = 7.436, p = .006). Additionally, homocysteine was associated with PTSD severity (z = 2.281, p = .005). Moreover, all HPA-axis hormones were associated with folate in both patients and controls (all p's ≤ .011), while DHEA-S influenced folate in patients (z = 2.089, p = .037).
  
  
  CONCLUSIONS
  Our clinical sample is relatively small and therefore small-sized effects may have remained undetected.
  
  
  CONCLUSIONS
  Our study indicates that: (1) the one-carbon metabolism is altered in PTSD patients, (2) earlier findings of higher homocysteine in male PTSD patients are generalized to female patients, (3) homocysteine is negatively associated with PTSD severity, and (4) HPA-axis alterations are associated with the one-carbon metabolism. Longitudinal studies are needed to determine whether elevated homocysteine levels reflect preexisting risk factors and/or consequences of psychological trauma.
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Giel-Jan
authors.initials: GJ
authors.lastname: de Vries
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands; Arq Psychotrauma Expert group, Diemen, The Netherlands.
authors.forename: Anja
authors.initials: A
authors.lastname: Lok
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Mocking
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Johanna
authors.initials: J
authors.lastname: Assies
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands; Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
authors.forename: Aart
authors.initials: A
authors.lastname: Schene
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands; Arq Psychotrauma Expert group, Diemen, The Netherlands. Electronic address: M.Olff@amc.nl.
authors.forename: Miranda
authors.initials: M
authors.lastname: Olff
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003687:Dehydroepiandrosterone / Q000097:blood; D003863:Depression / Q000097:blood / Q000150:complications; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000378:metabolism; D000067073:Psychological Trauma / Q000097:blood / Q000378:metabolism; D012307:Risk Factors; D013313:Stress Disorders, Post-Traumatic / Q000097:blood* / Q000150:complications / Q000378:metabolism*; D014805:Vitamin B 12 / Q000097:blood*; D025101:Vitamin B 6 / Q000097:blood*
chemical_list: D006710:Homocysteine; D003687:Dehydroepiandrosterone; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12; D006854:Hydrocortisone
keywords: HPA-axis; Homocysteine; One-carbon metabolism; PTSD