Systematic review of gamma-aminobutyric-acid inhibitory deficits across the reproductive life cycle

Simone N. Vigod, Kate Strasburg, Zafiris J. Daskalakis, Daniel M. Blumberger

Deficiencies in the inhibitory functioning of gamma-aminobutyric acid (GABA) have been implicated in the pathophysiology of depressive disorders. Reproductive life cycle events, including menstruation, pregnancy, and menopause, are consistently associated with increased psychopathology, in particular mood disorders. Given that GABA-inhibitory activity may be modulated directly or indirectly by estrogen, progesterone, and their metabolites receptors, it has been hypothesized that GABA deficits may be evident during these reproductive periods. We aimed to compare GABA function among women during these "high-risk" reproductive periods to GABA function among women at other time periods. We conducted a systematic review of studies comparing women during reproductive life stages associated with depressive disorder risk (luteal phase of the menstrual cycle, perinatal period, and menopausal transition) to women at other time periods. The study outcome was GABA function. The review included 11 studies, 9 focused on the menstrual cycle, and 2 focused on the perinatal period. GABA-inhibitory function fluctuated across the menstrual cycle, with differing patterns in women with and without depressive disorders. GABA-inhibitory function was reduced in pregnancy and early postpartum compared to the nonpregnant state. Key limitations were the absence of studies evaluating the menopausal transition, and the heterogeneity of GABA outcome measures. GABA-inhibitory function fluctuates across the menstrual cycle and is reduced perinatally. This has potential implications for a role of GABAergically mediated interventions in the prevention and treatment of menstrual cycle-related and perinatal depressive disorders.