Impaired GABA neuronal response to acute benzodiazepine administration in panic disorder

Andrew W. Goddard, Graeme F. Mason, Michael Appel, Douglas L. Rothman, Ralitza Gueorguieva, Kevin L. Behar, John H. Krystal

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Abstract

Objective: Disturbances in the metabolism of the brain amino acid transmitter γ-aminobutyric acid (GABA) may contribute to the pathophysiology of human anxiety disorders. Animal studies indicate that deletions or reductions in the expression of the gene for the GABA synthetic enzyme, glutamate decarboxylase 65 (GAD65), reduce basal cortical GABA levels or stress-induced release of GABA in the cerebral cortex and increase fear behaviors. Complementing these findings, the authors recently observed lower than normal cortical GABA levels in patients with panic disorder. In the current study, the authors tested the hypothesis that panic disorder patients have a deficient GABA neuronal response to benzodiazepine (clonazepam) administration. Method: In a parallel-group, repeated-measures design, occipital cortex GABA responses to acute oral, open-label benzodiazepine administration were tested in 10 panic disorder patients and nine healthy comparison subjects. Occipital cortex total GABA levels were measured before and after medication administration by means of a novel proton magnetic resonance spectroscopic technique. Results: Panic disorder patients had a deficient GABA neuronal response (blunted reduction of occipital cortex GABA level) to acute benzodiazepine administration, compared to the healthy subjects, who exhibited a significant decrease in occipital cortex GABA levels after this intervention. The patients also appeared to have persistently low occipital cortex GABA after chronic benzodiazepine treatment. Conclusions: Overall, these data are consistent with the hypothesis that a trait-like abnormality in GABA neuronal function contributes to the pathogenesis of human panic disorder. The data raise the possibility that GAD65 enzyme dysfunction could be a pathogenic factor in panic disorder.

Original languageEnglish (US)
Pages (from-to)2186-2193
Number of pages8
JournalAmerican Journal of Psychiatry
Volume161
Issue number12
DOIs
StatePublished - Dec 1 2004

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ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Goddard, A. W., Mason, G. F., Appel, M., Rothman, D. L., Gueorguieva, R., Behar, K. L., & Krystal, J. H. (2004). Impaired GABA neuronal response to acute benzodiazepine administration in panic disorder. American Journal of Psychiatry, 161(12), 2186-2193. https://doi.org/10.1176/appi.ajp.161.12.2186