Table 1.

Studies examining direct evidence of GABAergic and glutamatergic abnormalities

Study	Method	Target	N	ROIs	Additional Findings
Blood Serum and Plasma Analysis
Nishi et al. (2015) [34]	BSA	Glu, Gln	97 cTEC 8 cPTSD±	Serum	Elevated serum Glu in cPTSD±; Glu positively correlated with cPTSD severity; Gln/Glu ratio inversely correlated with PTSD severity.
Vaiva et al. (2006) [32]	BPA	GABA	6wks (1yr): 44(22) cPTSD± 34(7) cTEC	Plasma	Lower plasma GABA in PTSD± at 6 weeks and at 1 year posttrauma; Lower GABA at 6 weeks predicted higher cPTSD± at 1year.
Vaiva et al. (2004) [33]	BPA	GABA	57 cPTSD 51 cTEC 69 HC	Plasma	Lower plasma GABA in cPTSD compared to cTEC or HC.
Schur et al. (2016) [16]	BPA	GABA	731 TE/CD	Plasma	Increased GABA levels 6-months postdeployment positively correlated with onset of PTSD and other psychopathology
DNA / Candidate Gene Studies
Zhang et al. (2014) [37]	DNA	SLC1A1	264 mPTSD 154 mTEC	—	RS10739062 was associated with mPTSD diagnosis and severity.
1H-MRS
Meyerhoff et al. (2014) [25]	1H-MRS	GABA, Glu	27 mPTSD 18 mTEC	POC TEMP ACC	Lower GABA in POC and TEMP in mPTSD; reduced POC GABA & elevated POC Glu correlated with increasing insomnia severity; reduced ACC Glu correlated with increased arousal scores.
Michels et al. (2014) [28]	1H-MRS	GABA	12 cPTSD 17 cTEC	ACC DLPFC	Elevated GABA in ACC & DLPFC in cPTSD.
Pennington et al. (2014) [26]	1H-MRS	GABA, Glu, mI	10 xPAUD 28 xPTSD 20 xTEC	POC TC ACC	Lower POC GABA & higher TC Glu in xPTSD compared to xTEC; Lower ACC Glu and mI in xPAUD compared to xPTSD and xTEC; increased GABA and Glu correlated with improved neurocognition in xPAUD.
Rosso et al. (2014) [27]	1H-MRS	GABA	13 cPTSD 13 HC	Insula dACC	Lower insular GABA in cPTSD; reduced insular GABA associated with increased state and trait anxiety in the whole cohort.
Yang et al. (2015) [36]	1H-MRS	Glx	10 cPTSD-c 23 cPTSD-r 21 HC	rACC	ACC Glx: cPTSD-c < cPTSD-r < HC.
PET
Gueze et al. (2008) [30]	PET	GABA(A) BZD receptor	9 mPTSD 7 mTEC	Voxel-wise	Lower receptor binding in the cortex, HPC, and THAL in mPTSD.
SPECT
Bremner et al. (2000) [29]	SPECT	BZD receptor	13 mPTSD 13 HC	Voxel-wise	Lower PFC receptor binding in mPTSD
Fujita et al. (2004) [31]	SPECT	BZD receptor	19 mPTSD 19 HC	Voxel-wise	No difference between groups; Receptor binding negatively correlated with childhood trauma in right STG.

Abbreviations (methods): BPA = blood plasma analysis; BSA = blood serum analysis; DNA = candidate gene study/DNA isolation and genotyping; 1H-MRS = proton magnetic resonance spectroscopy; PET = positron emission tomography; SPECT = single-photon emission computed tomography. Abbreviations (metabolites/receptors): BZD = benzodiazepine; GABA = gamma-aminobutyric acid; Glu = glutamate; Glx = glutamate + glutamine; mI = Myo-inositol; SLC1A1 = glutamate transporter gene thought to be associated with PTSD; Abbreviations (population): cPTSD = civilian PTSD; cTEC = civilian trauma-exposed control; mPTSD = military PTSD; mTEC = military trauma-exposed control; PTSD = posttraumatic stress disorder; PTSD-c = PTSD current; HC = healthy control; xPAUD = mixed civilian and military PTSD with comorbid alcohol use disorder; PTSD± = full or subthreshold; PTSD-r = PTSD remission; TEC = trauma exposed control; TE/CD = trauma exposed/combat deployment; xPTSD = mixed military and civilian PTSD population; xTEC = mixed military and civilian trauma-exposed control population; Abbreviations (ROIs): ACC = anterior cingulate cortex; dACC = dorsal ACC; DLPFC = dorsolateral prefrontal cortex; HPC = hippocampus; POC = parietooccipital cortex; rACC = rostral ACC; STG = superior temporal gyrus; TEMP = temporal cortex/cortices; THAL = thalamus; Abbreviations (other): CAPS = clinician administered PTSD scale.