Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality

Abstract

Study objectives: To test if posttraumatic stress disorder (PTSD) is associated with low brain gamma-aminobutyric acid (GABA) levels and if reduced GABA is mediated by poor sleep quality.

Design: Laboratory study using in vivo proton magnetic resonance spectroscopy (1H MRS) and behavioral testing.

Setting: VA Medical Center Research Service, Psychiatry and Radiology.

Patients or participants: Twenty-seven patients with PTSD (PTSD+) and 18 trauma-exposed controls without PTSD (PTSD-), recruited from United States Army reservists, Army National Guard, and mental health clinics.

Interventions: None.

Measurements and results: 1H MRS at 4 Tesla yielded spectra from three cortical brain regions. In parieto-occipital and temporal cortices, PTSD+ had lower GABA concentrations than PTSD-. As expected, PTSD+ had higher depressive and anxiety symptom scores and a higher Insomnia Severity Index (ISI) score. Higher ISI correlated with lower GABA and higher glutamate levels in parieto-occipital cortex and tended to correlate with lower GABA in the anterior cingulate. The relationship between parieto-occipital GABA and PTSD diagnosis was fully mediated through insomnia severity. Lower N-acetylaspartate and glutamate concentrations in the anterior cingulate cortex correlated with higher arousal scores, whereas depressive and anxiety symptoms did generally not influence metabolite concentrations.

Conclusions: Low brain gamma-aminobutyric acid (GABA) concentration in posttraumatic stress disorder (PTSD) is consistent with most findings in panic and social anxiety disorders. Low GABA associated with poor sleep quality is consistent with the hyperarousal theory of both primary insomnia and PTSD. Our data demonstrate that poor sleep quality mediates low parieto-occipital GABA in PTSD. The findings have implications for PTSD treatment approaches.

Keywords: GABA; brain; glutamate; magnetic resonance spectroscopy; posttraumatic stress disorder; sleep.

Figure 1

Locations of the volumes of interest on T2-weighted magnetic resonance images (left: ACC; middle: POC; right: TEMP). Examples of stimulated echo spectrum (right, top) and GABA spectrum (right, bottom) analyzed. The GABA spectrum is shown on a different vertical scale than the stimulated echo spectrum. ACC, anterior cingulate cortex; Cho, choloine; Cr, creatine; GABA, gamma-aminobutyric acid; Glu, glutamate; Glx, a combination of signals from Glu and glutamine at 3.7 ppm; NAA, N-acetylaspartate; POC, parieto-occipital cortex; TEMP, medial temporal cortex.

Figure 2

Insomnia severity index (ISI) versus parieto-occipital cortex (POC) gamma-aminobutyric acid (GABA) concentration (i.u. = institutional units) in patients with PTSD (PTSD+). Spearman correlation (rho = -0.55, P = 0.008) and 95% confidence interval.