Functional MRI evidence of brain alterations in premenstrual dysphoric disorder: a systematic review.

Introduction: Premenstrual 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. Methods: Data from 598 participants, including 294 PMDD patients and 304 healthy controls, were analyzed. Results: The 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. Discussion: These 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 registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251174749.