Peripheral GABAergic markers in late-life depression: Links to clinical outcomes

Late-life depression (LLD) is a debilitating condition, characterized by mood disturbance and cognitive decline. Gamma-aminobutyric acidergic (GABAergic) deficits are a hallmark of both aging and depression; however, few studies have examined the GABAergic system in LLD. We hypothesized that there would be significant decrease in peripheral GABA levels and γ-aminobutyric acid type A (GABA-A) receptor subunit expression in individuals with LLD compared to healthy controls (HC). In this study, we measured plasma GABA levels and the mRNA expression of four GABA-A receptor subunits (GABRA1, GABRA4, GABRA5, and GABRR2) in peripheral blood mononuclear cells (PBMCs) from 87 older adults (LLD, n = 46; HC, n = 41). Plasma GABA levels were quantified using enzyme-linked immunosorbent assay (ELISA), and receptor subunit expression was assessed by quantitative-real time (RT-qPCR). There were no significant differences between LLD and HC in plasma GABA levels or GABA-A receptor subunit expression. In LLD, within-group analyses showed GABRA5, GABRR2, GABRA4, GABRA1 expression were negatively correlated with cognitive performance on the Montreal Cognitive Assessment MoCA scores (ρ = -0.464, p = 0.045, ρ = -0.515, p = 0.041; ρ = -0.414, p = 0.078, and ρ = -0.477, p = 0.062 respectively). This is the first study that investigated GABA-A receptor subunit expression in the periphery of individuals with LLD. Our findings suggest that altered peripheral GABA-A receptor subunit expression, even in the absence of between-group differences, is associated with reduced cognitive function in LLD.