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Background: Premenstrual dysphoric disorder (PMDD) is characterized by symptoms of irritability, affective lability, anxiety, and depression, which occur only in the luteal phase of ovulatory menstrual cycles. This offers an ideal model to assess the neural correlates of the on and off switch of mood symptoms. Recently, we highlighted differences in grey matter volume between individuals with PMDD and healthy controls during the luteal phase, depicting smaller volumes in those diagnosed with the condition. However, it is unknown whether such alterations represent state-like changes specific to the symptomatic phase, or trait-like characteristics.

Methods: Here, 28 patients with PMDD and 26 controls underwent anatomical magnetic resonance imaging during the mid-follicular and the late-luteal phases of the menstrual cycle. For each time point, we assessed grey matter volumes over the whole brain using voxel-based morphometry.

Results: We found no group-by-phase interaction effect on grey matter volumes, but a main effect of group across menstrual cycle phases, suggesting trait rather than state structural markers of PMDD. Patients displayed smaller volumes compared to controls, primarily in the cerebellum and cuneus, and at a trend-level in ventral occipito-temporal, parietal, paracentral and orbitofrontal areas, as well as the putamen (Cohen’s d range: 0.4–1.1).

Conclusions: These findings suggest that the differences in grey matter volumes found in PMDD are stable across the menstrual cycle and could represent trait-like, vulnerability markers of PMDD.