The role of GABA in the pathophysiology and treatment of anxiety disorders.

Charles B. Nemeroff

Research output: Contribution to journalReview articlepeer-review

207 Scopus citations


Mechanisms underlying the pathological characteristics of the various anxiety disorders have yet to be fully elucidated. One of the most widely accepted mediators known to play a central role in the pathophysiology of anxiety disorders is the g-aminobutyric acid (GABA) system. Evidence supporting the role of a dysfunctional GABA system has resulted from clinical experience with the benzodiazepines, as well as subsequent determination of mechanism of action, genetic engineering, and neuroimaging studies of the GABA receptor. The concatenation of results suggests a relative deficiency in GABA neurotransmission, which can be augmented by agents acting on different components of the GABA system. Agents such as the benzodiazepines, neuroactive steroids, and barbiturates act as allosteric modulators of the GABAA receptor; b-carboline and the barbiturates function as direct GABA agonists. Valproate, gabapentin, pregabalin, and vigabatrin increase brain GABA levels or neurotransmission at least in part by targeting the metabolic pathways of GABA. Tiagabine selectively increases synaptic GABA availability by blocking the reuptake of GABA via transporter inhibition. Evidence exists, to a greater or lesser extent, that all of these agents possess anxiolytic properties, as would be expected by their mechanisms of action. This article reviews the findings implicating the GABA system in the pathophysiology of anxiety disorders and describes the potential role of agents that modulate GABA neurotransmission in the treatment of these disorders.

Original languageEnglish (US)
Pages (from-to)133-146
Number of pages14
JournalPsychopharmacology bulletin
Issue number4
StatePublished - 2003
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)


Dive into the research topics of 'The role of GABA in the pathophysiology and treatment of anxiety disorders.'. Together they form a unique fingerprint.

Cite this