fMRI shows decreased activation in anterior cingulate cortex and increased activation in amygdala in women with premenstrual dysphoric disorder

Photo by CDC / Unsplash

Frontiers in Medicine Published June 4, 2026 Medically reviewed June 4, 2026 DOI ↗ By Dr. Ji-eun Park, MD · Brain, Mind & Pain

Key Takeaway

Note decreased anterior cingulate cortex activation and increased amygdala activation in PMDD women.

This systematic review investigated functional brain alterations in women of reproductive age with premenstrual dysphoric disorder compared to healthy controls. The study included 598 participants, comprising 294 PMDD patients and 304 healthy controls. Functional magnetic resonance imaging was used to assess brain activity patterns associated with the condition. No specific medications were evaluated as part of the primary analysis in this review.

Women with premenstrual dysphoric disorder demonstrated decreased activation in the anterior cingulate cortex, dorsolateral prefrontal cortex, medial orbitofrontal cortex, and postcentral gyrus. Conversely, increased activation was observed in the amygdala and insula. Additionally, the review noted impairments in corticolimbic connectivity between these regions. Specific effect sizes, absolute numbers, and p-values were not reported for these outcomes.

The authors suggest that targeting these identified mechanisms may inform the development of novel interventions for symptom relief. No adverse events or tolerability data were reported in this review. The study setting was not reported, and follow-up duration was not reported. Funding or conflicts of interest were not reported. The review does not establish causality between these brain changes and the disorder itself.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

IntroductionPremenstrual Dysphoric Disorder (PMDD) affects approximately 1.6% of women of reproductive age and significantly impacts quality of life. Despite its prevalence, the underlying pathophysiology remains incompletely understood. First-line treatment typically involves selective serotonin reuptake inhibitors (SSRIs); however, approximately 40 percent of women with PMDD do not respond to these medications. This systematic review synthesizes current evidence on functional brain alterations in women with PMDD, as assessed using functional magnetic resonance imaging (fMRI), with the goal of identifying potential novel therapeutic strategies.MethodsData from 598 participants, including 294 PMDD patients and 304 healthy controls, were analyzed.ResultsThe findings suggest alterations in both topdown regulatory mechanisms and large-scale brain networks, including the salience network, default mode network, and executive control network. These alterations are characterized by decreased activation in the anterior cingulate cortex, dorsolateral prefrontal cortex, medial orbitofrontal cortex, and postcentral gyrus, alongside increased activation in the amygdala and insula, as well as impairments in corticolimbic connectivity.DiscussionThese results highlight the complexity of PMDD, implicating widespread neural circuits rather than a single localized dysfunction. Targeting these mechanisms may inform the development of novel interventions for symptom relief.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251174749.