GABAergic implications in anxiety and related disorders.

Evidence indicates that anxiety disorders arise from an imbalance in the functioning of brain circuits that govern the modulation of emotional responses to possibly threatening stimuli. The circuits under consideration in this context include the amygdala's bottom-up activity, which signifies the existence of stimuli that may be seen as dangerous. Moreover, these circuits encompass top-down regulatory processes that originate in the prefrontal cortex, facilitating the communication of the emotional significance associated with the inputs. Diverse databases (e.g., Pubmed, ScienceDirect, Web of Science, Google Scholar) were searched for literature using a combination of different terms e.g., "anxiety", "stress", "neuroanatomy", and "neural circuits", etc. A decrease in GABAergic activity is present in both anxiety disorders and severe depression. Research on cerebral functional imaging in depressive individuals has shown reduced levels of GABA within the cortical regions. Additionally, animal studies demonstrated that a reduction in the expression of GABAA/B receptors results in a behavioral pattern resembling anxiety. The amygdala consists of inhibitory networks composed of GABAergic interneurons, responsible for modulating anxiety responses in both normal and pathological conditions. The GABAA receptor has allosteric sites (e.g., α/γ, γ/β, and α/β) which enable regulation of neuronal inhibition in the amygdala. These sites serve as molecular targets for anxiolytic medications such as benzodiazepine and barbiturates. Alterations in the levels of naturally occurring regulators of these allosteric sites, along with alterations to the composition of the GABAA receptor subunits, could potentially act as mechanisms via which the extent of neuronal inhibition is diminished in pathological anxiety disorders.