Abstract
Gamma-aminobutyric acid (GABA) metabolism is implicated in posttraumatic stress disorder (PTSD) and may be altered in prefrontal-limbic brain regions involved in arousal regulation. This study used proton magnetic resonance spectroscopy (MRS) to test the hypothesis that PTSD and trauma-exposed non-PTSD comparison (TENC) adults have significantly different GABA than healthy comparison (HC) subjects in two brain areas implicated in arousal (medial prefrontal cortex, insula) but not in a control brain area (posterior temporal cortex). We also examined whether GABA alterations correlated with hyperarousal and dissociation symptoms. One hundred and fourteen participants (39 PTSD, 34 TENC, 41 HC) underwent 3T MRS of the medial prefrontal, right insular, and right posterior temporal cortices, and the GABA plus macromolecule signal (GABA+) was normalized to creatine (Cr). The Clinician Administered PTSD Scale measured hyperarousal symptoms, including sleep disruption. The Dissociative Experiences Scale assessed dissociation symptoms. PTSD and TENC participants had significantly lower mPFC GABA+/Cr than HC participants, and this deficit was significantly correlated with greater dissociation. Compared with HC, PTSD patients but not TENC had significantly lower insula GABA+/Cr. Total hyperarousal symptoms and sleep disruption were not significantly associated with GABA+/Cr alterations in either region. Our findings point to lower GABA in cortical areas implicated in arousal regulation in PTSD and suggest that GABA alterations are associated with symptoms of trauma-related psychopathology but not always a biomarker of diagnosis. These findings also add to evidence that dissociation has distinct neural correlates within PTSD, including high excitability of medial prefrontal cortex.
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Acknowledgements
We thank all participants of this research study, and the technologists and staff of the McLean Imaging Center. A preliminary report of these data was presented as a poster presentation at the 2018 annual meeting of the American College for Neuropsychopharmacology (ACNP). No portion of these data has been previously published.
Funding
This research was supported by the National Institute of Mental Health (R01MH096987; IMR). IMR was also partially supported by R01MH120400 and P50MH115874. EAO was partially supported by K23MH112873. The authors have no conflicts of interest in relation to this work.
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IMR conceived the study and obtained funding. IMR, MMS, JEJ designed the study and protocol. IMR, MMS, EAO, JEJ contributed to data collection and processing, and BR assisted with statistical analysis and review. IMR wrote the initial draft of the manuscript. All authors provided critical input to the manuscript, contributed to revised drafts, and approved the final manuscript.
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Rosso, I.M., Silveri, M.M., Olson, E.A. et al. Regional specificity and clinical correlates of cortical GABA alterations in posttraumatic stress disorder. Neuropsychopharmacol. 47, 1055–1062 (2022). https://doi.org/10.1038/s41386-021-01197-x
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DOI: https://doi.org/10.1038/s41386-021-01197-x
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