Introduction: Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are becoming common mental diseases in women impairing daily functioning. Estimation of the epidemiological burden of PMS/PMDD can serve as scientific basis for prevention and management of premenstrual disorders. Herein, we firstly provide a protocol to perform estimation on the prevalence and risk factors for PMS/PMDD in the general population globally and regionally. Methods/design: The PubMed, Web of Science, Chinese National Knowledge Infrastructure, the Cochrane Central Register of Controlled Trials (Cochrane Library), Chinese VIP Information, EMBASE, Wanfang Database, as well as the Chinese Biomedical Literature Database will be queried to find related studies containing information on the prevalence of PMDD (2011–2021). Two independent reviewers will comb the literature and abstract the data characteristics. Disparities will be reconciled via consents. The primary outcome will be the global prevalence. The random-effect model will be employed to pool the assessments. The standard χ 2 tests, as well as the I 2 statistic will be used to determine heterogeneity. Furthermore, the meta-regression analysis will be employed to estimate the differences in study-level characteristics. All the statistical analyses will be carried out in the software Stata v 15.0 (Stata Corporation, College Station, TX), as well as the R (v R 3.5.1, R Foundation for Statistical Computing, Vienna, Austria) software. Discussion: Based on existing evidence, our study will offer a high-quality synthesis for global and regional prevalence, burden, and risk factors of PMS/PMDD. Effective strategies will be made for prevention and management of epidemiological burden on the PMS/PMDD, even premenstrual disorders. Ethics and dissemination: This study does not involve the specific patients, and all research data comes from publicly available professional literature, so an ethics committee is not required to conduct an ethical review and approval of the study. INPLASY registration number: INPLASY2021120065.

BackgroundPerimenopausal depression (PMD) is characterized by affective symptoms as well as menopause-specific somatic complaints and has attracted increasing attention over the past few decades. Using a bibliometric tool, this study aims to evaluate the origin, current hotspots, and research trends on PMD.MethodsArticles with research on PMD were retrieved from Web of Science Core Collection (WoSCC). We used the bibliometric method to analyze publication years, journals, countries, institutions, authors, research hotspots, and trends. We plotted the reference co-citation network and used keywords to analyze the research hotspots and trends.ResultsA total of 209 publications related to PMD were identified from WoSCC on May 8, 2022. The number of publications concerning PMD every year shows an upward trend. Further analysis indicated that 209 articles were contributed by 45 countries, 288 institutions, and 501 authors. The United States contributed the most significant number of publications, followed by China. Harvard University is the core institution of PMD research, and Cohen’s work has had an important impact on another research. The occurrence and pathological mechanisms of depression during the menopausal transition from the knowledge base of PMD. All of them belong to the category of gynecology and psychosis, which reflects the focus of the research topics. Major depression, postmenopausal women, symptoms like hot flashes, and prevalence and risk factors are research hotspots in the PMD field. The frontiers in PMD field that will impact future research are anxiety, meta-analysis, association, and Beck Depression Inventory-II (BDI-II).ConclusionThese findings provide us with the core countries, institutions, and authors in PMD research and point out the direction of attention in this field. The current research focuses on depression, postmenopausal women, hot flashes, and other symptoms, as well as the prevalence and risk factors. The frontiers will be anxiety, meta-analysis, related factors, and depression assessment in future research.

Background: Premenstrual dysphoric disorder (PMDD) is a common mental health challenge among women of reproductive age. Allopregnanolone (3α, 5α-THP; ALLO) mediated functional alterations of GABAA receptors (GABAA-R) are involved in PMDD pathogenesis, however, the specific mechanism remains unknown. Therefore, we investigated the role of ALLO mediated GABAA-Rα4 in the pathophysiology of PMDD. Purpose: We determined whether the pathogenesis of PMDD is associated with ALLO mediated GABAA-Rα4 expression changes in different brain regions. Methods: Rat models of PMDD liver-qi invasion syndrome (PMDD-LIS) were established via the resident intruder paradigm. Behavioral changes of rats were assessed by aggressive behavior tests, EPM and OFT. The levels of progesterone and ALLO in serum as well as brain areas were determined by ELISA. Variations in GABAA-Rα4 levels in brain regions were assessed by immunofluorescence and RT-PCR. Medicated serum was used to interfere with rat hippocampal neurons, and changes in Clcurrent were recorded through electrophysiology. Results: Premenstrual anxiety and irritability of PMDD-LIS patients can be simulated in PMDD-LIS rat models. Exogenous ALLO significantly improved the anxiety behaviors of PMDD-LIS rats. Changes in ALLO among different brain regions varied. GABAA-Rα4 expressions were low in the amygdala and abnormally high in the hippocampus, however, ALLO alleviated these deviations. Whole-cell patch clamp recording technique showed a weaker Clcurrent intensity of PMDD-LIS rats, reduced neuroinhibitory functions and increased Clcurrent intensity in the ALLO group drug serum intervention and enhanced emotional inhibition function. Conclusion: We established that ALLO regulation of the GABAA-Rα4 subunit in the amygdala and hippocampus is involved in PMDD-LIS pathogenesis.

Background: Premenstrual dysphoric disorder (PMDD) is a severe mood disorder with pathological changes rooted in GABRB2 copy number variation. Here, we aimed to elucidate the gene dose effect and allopregnanolone binding mechanism of Gabrb2 on possible PMDD-like and comorbid phenotypes in knockout mice. Methods: PMDD-like behaviors of Gabrb2-knockout mice were measured through various tests. Western Blot and ELISA were used to detect changes in the GABAAR subunits and related neurotransmitter changes in mice respectively for the internal mechanism. The response of mice to allopregnanolone (ALLO) was examined through an exogenous ALLO injection, then validated by the patch-clamp technique to elaborate the potential mechanism of ALLO-mediated GABAAR. Results: Gabrb2-knockout mice displayed changes in anxiety-like and depression-like emotions opposite to PMDD symptoms, changes in social, learning, and memory capacities similar to PMDD symptoms, and pain threshold changes opposite to PMDD symptoms. GABAAR δ subunit expression in the brains of the Gabrb2knockout mice was significantly higher than that of Wild-type mice (P<0.05). Gabrb2-knockout mice demonstrated neurotransmitter metabolism disturbance of GABA, Glu, acetylcholine, DA, norepinephrine, and epinephrine. Moreover, Gabrb2-knockout mice did not display the expected phenotypic effect after ALLO injection. Relative to WT mice, the knockout of the β2 subunit gene enhanced the agonistic effect of ALLO on GABAA receptors in cortical neuronal cells. Conclusions: GABAAR β 2 regulates PMDD-like behaviors. The ALLO binding site may not be located on β two subunits, abnormal δ and ε subunit expression in the mouse brain and the disturbance of neurotransmitters may result in ALLO sensitivity.

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