Impairment of GABAergic transmission in depression: new insights from neuroimaging studies

Several lines of evidence suggest that abnormalities in GABAergic neurotransmission are associated with the neurobiology of depression. Animal studies demonstrate that GABA agonists and antagonists can modulate commonly used behavioral models of depression and that chronic administration of antidepressant drugs induce marked changes in GABAergic function. In humans, depressed patients have lower plasma and CSF GABA concentrations than nondepressed comparison subjects. The recent discovery that several anticonvulsant and GABA-mimetic agents possess mood stabilizing and antidepressant properties has further increased interest in these findings. Novel imaging techniques now allow investigation of the GABAergic contribution to affective disorder pathophysiology. Through the techniques of PET, SPECT, and MRS, GABAergic function can be evaluated in vivo. Preliminary studies employing these techniques are finding new evidence suggesting that GABAergic abnormalities are associated with stress, anxiety, and depression. This article reviews the existing literature investigating the possible involvement of GABA in the neurobiology of depression and briefly highlights how these novel neuroimaging techniques can be used to further assess this hypothesis.