Posterior cingulate GABA levels are associated with depression severity during the premenstrual phase in women

Fluctuations in depressive symptoms across the menstrual cycle occur in some women, with a pronounced intensification during the luteal phase. Given that the GABAergic system is modulated by neurosteroids, alterations within this system may contribute to mood regulation in women with Major Depressive Disorder (MDD). We investigated the association between gamma-aminobutyric acid (GABA) concentrations in the posterior and anterior cingulate cortex (PCC and ACC) and depressive symptoms in relation to menstrual cycle phase. Thirty-one unmedicated women diagnosed with MDD were evaluated. Clinical variables including depressive and anxiety symptomatology and prior depression history were assessed. GABA concentrations were quantified using proton magnetic resonance spectroscopy ( 1 H-MRS). PCC_GABA concentrations were significantly associated with the severity of the current depressive episode, with lower PCC_GABA concentrations in women with higher depression scores. When analyses were stratified by menstrual phase, this association was observed only among participants assessed during the premenstrual phase. These findings suggest that PCC_GABA concentrations are associated with depressive symptom severity in unmedicated women during the premenstrual phase of the menstrual cycle. Further research is warranted to elucidate the neurosteroid-mediated modulation of GABAergic neurotransmission in the pathophysiology of mood disorders. • Depressive symptoms increase during the premenstrual phase. • Hormonal modulation of GABA may drive symptom changes. • PCC_GABA levels were associated to depression severity in the premenstrual phase. • Findings link reproductive phase with mood regulation.