Taken together with the recent findings that enhanced GABAergic transmission is associated with parvalbumin-expressing interneurones [168,169,170] and upregulation of NMDAR [53,146,147,148], the compounds that can establish GABAergic disinhibition of parvalbumin-expressing GABAergic interneurones by targeting the microcircuit between glutamatergic and GABAergic transmission systems hold promise as rapid-acting antidepressants and represent a breakthrough strategy for the treatment of depression. This evidence concerns the gene PVALB and major depressive disorder.