Altered one-carbon metabolism in posttraumatic stress disorder

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.

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).

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).

Our clinical sample is relatively small and therefore small-sized effects may have remained undetected.

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.