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


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


METHODS
VA Medical Center Research Service, Psychiatry and Radiology.


METHODS
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.


METHODS
None.


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.
Department of Radiology and Biomedical Imaging, Center for Imaging of Neurodegenerative Diseases, DVA Medical Center, and University of California San Francisco, San Francisco, CA.
Dieter J
DJ
Meyerhoff
Department of Radiology and Biomedical Imaging, Center for Imaging of Neurodegenerative Diseases, DVA Medical Center, and University of California San Francisco, San Francisco, CA.
Anderson
A
Mon
Psychiatry Research Service VAMC, and University of California San Francisco, San Francisco, CA.
Thomas
T
Metzler
Psychiatry Research Service VAMC, and University of California San Francisco, San Francisco, CA.
Thomas C
TC
Neylan
D001143:Arousal; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D057566:Self Report; D012890:Sleep / Q000502:physiology*; D007319:Sleep Initiation and Maintenance Disorders / Q000378:metabolism / Q000503:physiopathology; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism* / Q000503:physiopathology*; D014481:United States; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate
GABA; brain; glutamate; magnetic resonance spectroscopy; posttraumatic stress disorder; sleep