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Depress Anxiety. 2014 Feb;31(2):115-23. doi: 10.1002/da.22155. Epub 2013 Jul 16.

Insula and anterior cingulate GABA levels in posttraumatic stress disorder: preliminary findings using magnetic resonance spectroscopy.

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Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.



Increased reactivity of the insular cortex and decreased activity of the dorsal anterior cingulate cortex (ACC) are seen in functional imaging studies of posttraumatic stress disorder (PTSD), and may partly explain the persistent fear and anxiety proneness that characterize the disorder. A possible neurochemical correlate is altered function of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). We report results from what we believe is the first study applying proton magnetic resonance spectroscopy ((1) H-MRS) to measure brain GABA in PTSD.


Thirteen adults with DSM-IV PTSD and 13 matched healthy control subjects underwent single voxel (1) H-MRS at 4 Tesla. GABA was measured in the right anterior insula and dorsal ACC, using Mescher-Garwood Point-Resolved Echo Spectroscopy Sequence (MEGAPRESS) spectral editing. Subjects were interviewed with the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale, and also completed the State and Trait Anxiety Inventory.


Insula GABA was significantly lower in PTSD subjects than in controls, and dorsal ACC GABA did not differ significantly between the groups. Insula GABA was not significantly associated with severity of PTSD symptoms. However, lower insula GABA was associated with significantly higher state and trait anxiety in the subject sample as a whole.


PTSD is associated with reduced GABA in the right anterior insula. This preliminary evidence of the (1) H-MRS GABA metabolite as a possible biomarker of PTSD encourages replication in larger samples and examination of relations with symptom dimensions. Future studies also should examine whether insula GABA is a marker of anxiety proneness, cutting across clinical diagnostic categories.


GABA; anxiety; insular cortex; magnetic resonance spectroscopy; posttraumatic stress disorder

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