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Survey study, 2026

Does a brain chemical relate to depression that worsens before periods in women with major depression?

Yes, during the premenstrual phase. Women with worse depression had lower levels of GABA (a brain chemical) in a specific brain region, but only when tested just before their period.

Early or limited evidence 31 unmedicated women with major depressive disorder

What they did

Cross-sectional study of 31 unmedicated women with major depressive disorder. Researchers measured GABA levels in two brain regions using MRI scanning and assessed depression and anxiety symptoms at different points in the menstrual cycle.

What they found

Lower GABA concentrations in the posterior cingulate cortex (a brain region) were associated with more severe depression. This relationship was only observed when women were assessed during the premenstrual phase, not during other phases of the cycle.

What it means for you

Brain chemistry may help explain why some women's depression worsens before their period. However, this is a very small study of women not taking medication, so we cannot know if findings apply to women on antidepressants or other groups. The study is too preliminary to guide treatment.

31

Unmedicated women with major depression

2

Brain regions measured with MRI

About the study

Original title
Posterior cingulate GABA levels are associated with depression severity during the premenstrual phase in women
Authors
Flores-Ramos M, Osorio-Durán R, Saavedra EM et al.
Journal
Journal of affective disorders
Year
2026
Study design
Survey study
What was tested
None
Open access
Yes
Original abstract

Background: 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). Methods: 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). Results: 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. Conclusion: 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.

Reproduced under CC-BY.

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