Emotion generation and regulation in premenstrual dysphoric disorder: dysregulation of large-scale brain networks across the menstrual cycle.

Background: Emotion regulation deficits have been highlighted as a transdiagnostic feature of multiple psychiatric disorders, including premenstrual dysphoric disorder (PMDD). In this study, we hypothesize that deficient prefrontal "top-down" regulation of key nodes of the salience network (SN) is a characteristic of PMDD, driven by increased levels of progesterone-derived neuroactive steroids.

Methods: Functional magnetic resonance imaging (fMRI) was used to investigate menstrual-cycle related variations in brain activity and connectivity during two emotional tasks (emotion generation and regulation) in 29 women with PMDD and 27 controls. We also examined whether differential brain activation between groups is related to serum levels of progesterone-derived neuroactive steroids and premenstrual symptom severity.

Results: Women with PMDD showed increased reactivity in key nodes of the SN and - at subthreshold level - in the default mode network (DMN) during the luteal phase when passively viewing negative emotional stimuli. Intriguingly, SN hyperactivity in PMDD patients was apparent also during the follicular phase and related to premenstrual symptom severity. PMDD and control women had similar network connectivity patterns and activity in regions associated with the conscious control of emotion in PMDD. No link to progesterone-derived neuroactive steroids was found.

Conclusions: Multiple network aberrations during the luteal phase may explain the development of mood symptoms in the luteal phase. Furthermore, higher baseline (follicular) SN activity may render PMDD women more susceptible to severe mood symptoms in response to hormonal fluctuations. What drives increased SN activity in the follicular phase is unknown, but innate and neuroplastic mechanisms are proposed.