Figure 3.

Overview of current literature on ¹H MRS in PTSD by study design, hardware, and reported significant or null findings by metabolite and brain region. Currently published reports on ¹H MRS in PTSD cover a broad range of patient ages, with a smaller relative number of investigations into pediatric or geriatric participants, and generally demonstrate small disparities in age between groups under study for analyses reporting experimental group ages (random-effects standardized mean difference SMD 0.10, 95% confidence interval CI −0.02-0.23, P = .08; N = 33 comparisons from 28 studies) (A). The number of ¹H-MRS analyses examining male-only participants is higher than the reverse, with an additional skew toward more male-saturated control groups in the few studies that demonstrated uneven between-group sex-matching (B). The majority of existing ¹H-MRS investigations of PTSD have been conducted at 1.5 and 3T, field strengths that do not typically enable the straightforward separation of signals from neurotransmitter glutamate from those of its metabolic byproduct glutamine (C). Especially in hippocampus, for which voxel placement and size may contribute to challenging spectral quantification of lower-SNR metabolites, the ¹H-MRS literature on PTSD is currently dominated by N-acetyl aspartate (NAA), free cholines (Cho), and creatine (Cr), with fewer investigations on neurotransmitters glutamate (Glu) and GABA or endogenous antioxidant glutathione (GSH) despite putative roles in excitatory/inhibitory balance and oxidative stress potentially important to regional anatomical and functional alterations previously observed in PTSD (D). D based on data reported in Tables 3, 5, and 6; see Supplementary Information for data tables underlying A-C. Gln: glutamine; Glx: glutamate + glutamine. TEC: trauma-exposed control; HC: healthy control; VC: veteran control; AUD: alcohol use disorder.