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Premenstrual dysphoric disorder (PMDD) is characterized by severe cyclic mood symptoms emerging in the luteal phase of the menstrual cycle. The variation in progesterone levels and its metabolites during the luteal phase seems critical to the occurrence of PMDD symptoms. Notably, the efficacy of selective progesterone receptor modulator (SPRM) treatment on the mental symptoms of PMDD has been recently demonstrated. In the present study, structural magnetic resonance imaging was used to assess the effects of SPRM treatment, compared with placebo, on grey matter morphology in women with PMDD. In total, 35 women were scanned during the luteal phase, before and after three months of treatment with SPRM or placebo. Symptom severity was assessed using the Daily Record of Severity of Problems (DRSP), while gonadal hormone levels were measured by liquid chromatography-tandem mass spectrometry. Region-of-interest and whole-brain approaches were employed to perform voxel-based morphometry analyses, subcortical volumetric analyses, and surface-based morphometry analyses. No interaction or main effects of treatment and time were observed on grey matter volume and cortical surface measures (cortical thickness, gyrification index, sulcal depth, and fractal dimension). The relationship between change in brain morphology and symptom severity was also explored but no treatment-dependant grey matter structure change was related to symptom severity change. These findings suggest that SPRM treatment does not impart macrostructural changes onto grey matter structure, at least in the short term., Competing Interests: Conflict of Interest RL received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR, Heel, and support from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. ISP has served occasionally on advisory boards or acted as invited speaker at scientific meetings for Asarina Pharma, Bayer Health Care, Gedeon Richter, Peptonics, Shire/Takeda, Sandoz, and Lundbeck A/S. All other authors declare that they have no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Premenstrual dysphoric disorder (PMDD) is a female-specific condition classified in the Diagnostic and Statical Manual-5th edition under depressive disorders. Alterations in grey matter volume, cortical thickness and folding metrics have been associated with a number of mood disorders, though little is known regarding brain morphological alterations in PMDD. Here, women with PMDD and healthy controls underwent magnetic resonance imaging (MRI) during the luteal phase of the menstrual cycle. Differences in grey matter structure between the groups were investigated by use of voxel- and surface-based morphometry. Machine learning and multivariate pattern analysis were performed to test whether MRI data could distinguish women with PMDD from healthy controls. Compared to controls, women with PMDD had smaller grey matter volume in ventral posterior cortices and the cerebellum (Cohen's d = 0.45-0.76). Region-of-interest analyses further indicated smaller volume in the right amygdala and putamen of women with PMDD (Cohen's d = 0.34-0.55). Likewise, thinner cortex was observed in women with PMDD compared to controls, particularly in the left hemisphere (Cohen's d = 0.20-0.74). Classification analyses showed that women with PMDD can be distinguished from controls based on grey matter morphology, with an accuracy up to 74%. In line with the hypothesis of an impaired top-down inhibitory circuit involving limbic structures in PMDD, the present findings point to PMDD-specific grey matter anatomy in regions of corticolimbic networks. Furthermore, the results include widespread cortical and cerebellar regions, suggesting the involvement of distinct networks in PMDD pathophysiology., (© 2022. The Author(s).)

Ovarian hormones fluctuations across the menstrual cycle are experienced by about 58% of women in their fertile age. Maladaptive brain sensitivity to these changes likely leads to the severe psychological, cognitive, and physical symptoms repeatedly experienced by women with Premenstrual Dysphoric Disorder (PMDD) during the late luteal phase of the menstrual cycle. However, the neuroanatomical correlates of these symptoms are unknown. The relationship between grey matter structure and PMDD symptom severity was delineated using structural magnetic resonance imaging during the late luteal phase of fifty-one women diagnosed with PMDD, combined with Voxel- and Surface-Based Morphometry, as well as subcortical volumetric analyses. A negative correlation was found between depression-related symptoms and grey matter volume of the bilateral amygdala. Moreover, the severity of affective and somatic PMDD symptoms correlated with cortical thickness, gyrification, sulcal depth, and complexity metrics, particularly in the prefrontal, cingulate, and parahippocampal gyri. The present findings provide the first evidence of grey matter morphological characteristics associated with PMDD symptomatology in brain regions expressing ovarian hormone receptors and of relevance to cognitive-affective functions, thus potentially having important implications for understanding how structural brain characteristics relate to PMDD symptomatology., (© 2022. The Author(s).)

Premenstrual disorder (PMDD) affects around 5% of women in childbearing ages. An increased sensitivity in emotion processing areas of the brain to variations in ovarian steroid levels has been suggested as part of the pathophysiology in PMDD, but prior neuroimaging studies of emotion processing are yet inconclusive. Previous behavioral studies of women with PMDD have, however, reported enhanced luteal phase startle responsivity during emotional anticipation. Here we used functional magnetic resonance imaging (fMRI) to investigate central neural circuitry activity during anticipation of, and exposure to, emotional stimuli across the menstrual cycle in women with and without PMDD. As compared to healthy controls, women with PMDD displayed significantly enhanced reactivity in the prefrontal cortex during anticipation of, but not exposure to, negative emotional stimuli during the luteal phase. In PMDD patients, BOLD reactivity during anticipation or viewing of negative emotional stimuli was not dependent on absolute levels of estradiol or progesterone. However, progesterone levels were positively correlated with emotion-induced reactivity in the dorsolateral prefrontal cortex to positive emotional stimuli. These findings suggest that cortical emotional circuitry reactivity during anticipation is altered in PMDD during the luteal phase, which might be part of the pathophysiology behind the emotional symptoms or lack of emotional control reported by women with PMDD., (© 2013 Elsevier B.V. and ECNP. All rights reserved.)

Background: Premenstrual dysphoric disorder (PMDD) has generally not been associated with impulsive behavior. However, some studies suggest that women with PMDD have higher impulsivity scores than healthy controls and that brain activity during response inhibition may vary across the menstrual cycle. Therefore, our aim was to unravel potentially important cognitive aspects of PMDD by investigating brain activity during response inhibition in women with PMDD and healthy controls in relation to menstrual cycle phase., Methods: Fourteen PMDD patients and 13 healthy controls performed a Go/NoGo task to measure brain activity during response inhibition by use of event-related functional magnetic resonance imaging., Results: Women with PMDD displayed decreased activity during both menstrual cycle phases compared to healthy controls in several task-related parietal areas. A significant group by phase interactions was found in the left insula, driven by enhanced activity among healthy controls in the follicular phase and by enhanced insula activity during the luteal phase among PMDD patients., Limitations: The limitations of the present study are the relatively limited sample size, the relatively small number of NoGo trials and the lack of a baseline contrast for the NoGo trials., Conclusions: During response inhibition women with PMDD have reduced activity in areas associated with attention and motor function which is unrelated to menstrual cycle phase. Insular cortex activity, involved in both affective and cognitive processing, was significantly activated during the luteal phase among PMDD women. These findings are relevant for the understanding of how ovarian steroids influence mood symptoms in women., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Premenstrual dysphoric disorder (PMDD) with luteal phase related anxiety and mood swings compromise quality of life in around 4% of reproductive women. While anxiety is related to amygdala function, prior studies on amygdala reactivity both in healthy controls and women with PMDD are inconsistent with respect to menstrual cycle effects. Here women with PMDD and healthy controls were exposed to emotional faces during the mid-follicular and late luteal phase, and mean blood-oxygen-level dependence (BOLD) signal changes in the amygdala were determined with functional magnetic resonance imaging (fMRI). Women with PMDD had enhanced bilateral amygdala reactivity in the follicular phase in comparison with healthy controls, but there was no difference between groups during the luteal phase. In contrast, healthy controls displayed higher left amygdala reactivity in the luteal than in their follicular phase. However, among women with PMDD follicular phase progesterone serum concentrations were positively correlated with bilateral amygdala reactivity while depression scores were positively correlated with right amygdala reactivity in the luteal phase. In addition, women with PMDD and high scores on trait anxiety had increased right amygdala reactivity in the luteal as compared to the follicular phase. Finally, amygdala reactivity was more prone to habituation in women with PMDD, as they had enhanced amygdala reactivity in comparison with controls at the first, but not the second scanning session. Thus, while the study failed to indicate increased luteal phase amygdala reactivity in women with PMDD, our findings suggest that anxiety proneness and progesterone levels modulate menstrual cycle related amygdala reactivity in women with PMDD., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The acoustic startle response (ASR) is a withdrawal reflex to sudden or noxious auditory stimuli and, most importantly, an unbiased measure of emotional processing of appetitive and aversive stimuli. By exposing subjects to fearful situations, such as aversive pictures, the ASR may be enhanced, suggesting that amygdala modulates the startle circuit during threat situations. As one previous study, investigating affective modulation of the ASR in women with premenstrual dysphoric disorder (PMDD), discovered no difference during picture viewing it is possible that the mood changes observed in PMDD relate to anxious anticipation rather than to direct stimulus responding. Hence we sought to examine the effects of PMDD on picture anticipation and picture response. Sixteen PMDD patients and 16 controls watched slide shows containing pleasant and unpleasant pictures and positive and negative anticipation stimuli during the follicular and luteal phase of the menstrual cycle. Simultaneously, semi-randomized startle probes (105 dB) were delivered and the ASR was assessed with electromyography. Compared with control subjects, PMDD patients displayed an enhanced startle modulation by positive and negative anticipation stimuli in the luteal phase of the menstrual cycle. This finding was mainly driven by increased modulation in the luteal phase in comparison to the follicular phase among PMDD patients but also by an increased modulation in patients compared to controls during luteal phase. This suggests that the neural circuits underlying response to emotional anticipation are more sensitive during this period and emphasize the need of examining the neural correlates of anticipatory processes in women with PMDD., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Premenstrual dysphoric disorder (PMDD) is a mood disorder for which selective progesterone receptor modulator (SPRM) treatment has been demonstrated to be beneficial. The neural signatures of this treatment have been so far identified as greater fronto-cingulate reactivity during aggressive response to provocation, but no changes in terms of gray matter structure. White matter has recently been found to differ between patients with PMDD and healthy controls. The present study thus sought to investigate the relationship between white matter volume and SPRM treatment in patients with PMDD. A pharmaco-neuroimaging study was conducted on patients with PMDD participating in a randomized controlled trial. Participants underwent magnetic resonance imaging before and after treatment randomization to ulipristal acetate (an SPRM), or placebo, for three months. The interaction effect of treatment by time on white matter volume (WMV) was assessed. Voxel based morphometry analyses were performed on both a whole brain exploratory level and on regions of interest. No treatment effect was observed on WMV in any region, including the anterior thalamic radiations, cingulum, forceps minor, fornix, inferior fronto-occipital fasciculus, superior cerebellar peduncle, superior longitudinal fasciculus, and uncinate fasciculus. This is the first finding to indicate that no white matter volume alterations follow three-month progesterone antagonism, suggesting that white matter volume does not participate in symptom relief upon SPRM treatment for PMDD. • No effect of three-month treatment with SPRM on WMV. • No significant time by treatment interaction effect on WMV. • No follow-up differences on WMV between treatment groups. [ABSTRACT FROM AUTHOR]