Neuroendocrine pathogenesis of perimenopausal depression.
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ABSTRACT:
SUBMITTER: Han Y
PROVIDER: S-EPMC10098367 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
Neuroendocrine pathogenesis of perimenopausal depression.
Han Yuping Y Gu Simeng S Li Yumeng Y Qian Xin X Wang Fushun F Huang Jason H JH
Frontiers in psychiatry 20230330
With the development of social economics and the increase of working pressure, more and more women are suffering from long-term serious stress and showing symptoms of perimenopausal depression (PMD). The incidence rate of PMD is increasing, and the physical and mental health are seriously affected. However, due to the lack of accurate knowledge of pathophysiology, its diagnosis and treatment cannot be accurately executed. By consulting the relevant literature in recent years, this paper elaborat ...[more]
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Project description:ObjectiveTo systematically evaluate the risk factors for perimenopausal depression in Chinese women and to provide a basis for screening perimenopausal women at high-risk for depression.MethodsA computer search of seven databases, including SinoMed, PubMed, Web of Science, and so on, and two clinical trial registries on the risk factors for depression in Chinese women during perimenopause was conducted for meta-analysis. The search time limit was from the establishment of the database to December 2022. The included case-control and cross-sectional studies were evaluated using the Newcastle-Ottawa scale (NOS) and criteria developed by the Agency for Healthcare Research and Quality (AHRQ).ResultsA total of 15 papers with 12,168 patients and 18 risk factors were included. Meta-analysis results showed that the risk factors for depression in perimenopausal women were relationship quality [OR = 1.23, 95% confidence intervals (1.03, 1.46)], marital status [OR = 2.49, 95% CI (1.77, 3.50)], family income [OR = 1.48 95% CI (1.10, 2.00)], comorbid chronic diseases [OR = 2.39, 95% CI (1.93, 2.95)], exercise status [OR = 1.63, 95% CI (1.26, 2.11)], perimenopausal syndrome [OR = 2.36, 95% CI (2.11, 2.63)], age [OR = 1.04, 95% CI (1.01, 1.07)], and stressful events [OR = 12.14, 95% CI (6.48, 22.72)], and social support was a protective factor [OR = 0.76, 95% CI (0.63, 0.91), p < 0.05].ConclusionBased on the exploration of risk factors for perimenopausal depression in Chinese women, we aimed to provide guidance for the screening of risk factors for depression in perimenopausal women and thereby reduce the incidence of depression.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#myprospero, CRD42023403972.
| S-EPMC10598844 | biostudies-literature
Project description:BackgroundThe issues related to the treatment of perimenopausal depression (PMD) are the side effects of antidepressants and hormone replacement therapy. The aim of this study was to assess the efficiency and safety of acupuncture and moxibustion in PMD patients.MethodsDatabases, namely PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, CBM, VIP, and WanFang, were reviewed for related randomized controlled trials dated between database inception and November 22, 2022. The primary outcomes were the efficacy rate and the Hamilton Depression Scale score. The secondary outcomes were the levels of follicle-stimulating hormone, luteinizing hormone, and estradiol and the Kupperman score. Odds ratios (ORs) were generated as the effect size for dichotomous outcomes, while the standard mean difference (SMD) ± standard deviation was used for continuous outcomes. Matrices were developed to demonstrate pairwise comparisons of regimens related to each endpoint. Utilizing Review Manager (RevMan) 5.3, Stata 16.0 and SPSS 21, data were analyzed.ResultsIn total, 27 studies involving 2269 PMD patients and 8 therapeutic measures were incorporated into the network meta-analysis (NMA). The NMA showed that warm acupuncture (OR = 1.55, 95% CI: 1.00-2.44), electroacupuncture (OR = 1.34, 95% CI: 1.00-1.8), abdominal acupuncture (OR = 1.19, 95% CI: 0.73-1.96), and common acupuncture (OR = 1.4, 95% CI: 0.9-2.17) were more effective than fluoxetine + menopausal hormone treatment in the treatment of PMD. The NMA also showed that, based on the Hamilton Depression Scale score, warm acupuncture was more effective than the other 4 acupuncture-related treatments, i.e., electroacupuncture (SMD = -1.22, 95% CI: -2.34 to -0.09), thread embedding (SMD = -1.31, 95% CI: -2.21 to -0.40), abdominal acupuncture (SMD = -1.33, 95% CI: -2.42 to -0.24), and common acupuncture (SMD = -1.46, 95% CI: -2.26 to -0.66). The cumulative ranking probability (SUCRA) showed that warm acupuncture (99.6%) was the best treatment method.ConclusionsThe findings of this network meta-analysis may help patients and therapists choose the best acupuncture therapy for treating perimenopausal depression patients and furnish reliable evidence for guidelines.
| S-EPMC10443772 | biostudies-literature
Project description:The development of natural membranes as coatings for nanoparticles to traverse the blood-brain barrier (BBB) presents an effective approach for treating central nervous system (CNS) disorders. In this study, we have designed a nanogel loaded with PACAP and estrogen (E2), sheathed with exosomes and responsive to reactive oxygen species (ROS), denoted as HA NGs@exosomes. The objective of this novel design is to serve as a potent drug carrier for the targeted treatment of perimenopausal depression. The efficient cellular uptake and BBB penetration of HA NGs@exosomes has been demonstrated in vitro and in vivo. Following intranasal intervention with HA NGs@exosomes, ovariectomized mice under chronic unpredictable mild stress (CUMS) have shown improved behavioral performance, indicating that HA NGs@exosomes produced a rapid-onset antidepressant effect. Moreover, HA NGs@exosomes exhibit notable antioxidant and anti-inflammatory properties and may regulate the expression of pivotal proteins in the PACAP/PAC1 pathway to promote synaptic plasticity. Our results serve as a proof-of-concept for the utility of exosome-sheathed ROS-responsive nanogel as a promising drug carrier for the treatment of perimenopausal depression.
| S-EPMC10408189 | biostudies-literature
Project description:The estimated 20-30% of women who develop perimenopausal depression (PMD) are at an increased risk of cardiovascular and all-cause mortality. The therapeutic benefits of estradiol (E2) and symptom-provoking effects of E2-withdrawal (E2-WD) suggest that a greater sensitivity to changes in E2 at the cellular level contribute to PMD. We developed an in vitro model of PMD with lymphoblastoid cell lines (LCLs) derived from participants of a prior E2-WD clinical study. LCLs from women with past PMD (n = 8) or control women (n = 9) were cultured in three experimental conditions: at vehicle baseline, during E2 treatment, and following E2-WD. Transcriptome analysis revealed significant differences in transcript expression in PMD in all experimental conditions, and significant overlap in genes that were changed in PMD regardless of experimental condition. Of these, chemokine CXCL10, previously linked to cardiovascular disease, was upregulated in women with PMD, but most so after E2-WD (p < 1.55 × 10-5). CYP7B1, an enzyme intrinsic to DHEA metabolism, was upregulated in PMD across experimental conditions (F(1,45) = 19.93, p < 0.0001). These transcripts were further validated via qRT-PCR. Gene networks dysregulated in PMD included inflammatory response, early/late E2-response, and cholesterol homeostasis. Our results provide evidence that differential behavioral responsivity to E2-WD in PMD reflects intrinsic differences in cellular gene expression. Genes such as CXCL10, CYP7B1, and corresponding proinflammatory and steroid biosynthetic gene networks, may represent biomarkers and molecular targets for intervention in PMD. Finally, this in vitro model allows for future investigations into the mechanisms of genes and gene networks involved in the vulnerability to, and consequences of, PMD.
| S-EPMC7878574 | biostudies-literature
Project description:To identify the principal targets associated with depression in perimenopausal mice, an unbiased quantitative proteomic screening was conducted in the hippocampus of perimenopausal depression and normal mice
2024-10-22 | PXD057078 |
Project description:The menopause transition is a time when women experience an increased risk for new onset depression, as well as relapse of depression. While there are overlapping symptoms between major depression and depression during menopause, differences suggest 'perimenopausal depression' may be a unique subtype of depression associated with characteristic symptoms. There is currently no validated scale designed to measure perimenopausal depression. The aim of the current study was to develop and validate the 'Meno-D', a self-reporting or clinician rated questionnaire, designed to rate the severity of symptoms of perimenopausal depression. The development phase of the Meno-D involved literature review, clinical observation, and focus groups. A 12-item questionnaire was developed and clinically reviewed for face validity for content. The Meno-D was administered to women experiencing symptoms of perimenopausal depression as part of a larger baseline assessment battery. Validation involved confirmatory factor analysis (CFA). The development of the Meno-D resulted in 12 items. A total of 93 participants with perimenopausal depression were involved in the baseline assessments, 82 completed the Meno-D. Factor analysis identified five sub-scales of the Meno-D "somatic; cognitive; self; sleep; sexual" with high-internal consistency; discriminant validity and a good construct and convergent validity. The Meno-D provides a unique tool for clinicians and researchers to measure the presence of perimenopausal depression.
| S-EPMC6023883 | biostudies-literature
Project description:ObjectiveWe examined the short-term efficacies of three estrogen-like compounds under placebo-controlled conditions in women with perimenopause-related depression (PMD).MethodsWomen with PMD were randomized in a double-blind parallel design to one of four treatments: transdermal 17-beta estradiol (TE) (100 mcg/d); oral raloxifene (60 mg/d); a proprietary phytoestrogen compound, Rimostil (1,000 mg twice/d); or placebo for 8 weeks. The main outcome measures were the Center for Epidemiology Studies Depression Scale, 17-item Hamilton Rating Scale for Depression (HRSD), and the Beck Depression Inventory completed at each clinic visit. Secondary outcomes included a visual analogue self-rating completed at each clinic visit, and daily self-ratings of hot flush severity. Cognitive tests were performed at pretreatment baseline and at the end of the trial. In the primary analysis, we obtained four repeated measures in each woman in the four treatment arms. Analyses were done with SAS Version 9.4 software (SAS Institute, Inc, Cary, NC), using PROC MIXED (for mixed models). All models included the following four explanatory variables, regardless of whether they were statistically significant: 1) treatment group (TE, raloxifene, Rimostil, placebo); 2) week (W2, W4, W6, W8); 3) treatment group-by-week interaction; and 4) baseline value of the measure being analyzed. The inclusion of additional variables was evaluated individually for each outcome measure.ResultsSixty-six women were randomized into the trial, four women dropped out of the trial, and 62 women were included in the final data analysis. No effect of treatment group was observed in either the Center for Epidemiology Studies Depression Scale (P = 0.34) or Beck Depression Inventory (P = 0.27) scores; however, there was a difference in HRSD scores between treatment groups (P = 0.0037) that pair-wise comparisons of the combined weekly scores in each treatment demonstrated TE's beneficial effects on HRSD scores compared with Rimostil (P = 0.0005), and less consistently with placebo (P = 0.099). The average (SD) of the baseline scores for each treatment group on the HRSD was as follows: TE-15.3 (4.5), raloxifene-16.0 (3.7), Rimostil-14.0 (2.7), and placebo-15.2 (3.0). Whereas the HRSD scores after 8 weeks of treatment (least-square means) were TE-5.2(1.1), raloxifene-5.8(1.2), Rimostil-11.2(1.4), and placebo-7.8(1.1). No differences were observed between raloxifene and either TE or placebo in any scale score. HRSD scores in women assigned to TE were improved compared with those on Rimostil during weeks 6 and 8 (P values = 0.0008, 0.0011, respectively). Cognitive testing at week 8 showed that none of the three active treatment groups performed better than placebo.ConclusionsThis study did not identify significant therapeutic benefits of TE, Rimostil, or raloxifene compared with placebo in PMD. However, improvements in depression ratings were observed between TE compared with Rimostil. Thus, our findings do not support the role of ERbeta compounds in the treatment of PMD (and indeed could suggest a more important role of ERalpha).
| S-EPMC9022873 | biostudies-literature
Project description:ImportancePerimenopause is accompanied by an increased risk of new and recurrent depression. The coincidence of declining ovarian function with the onset of depression led to the inference that "withdrawal" from physiologic estradiol levels underpinned depression in perimenopause. To our knowledge, this is the first controlled systematic study to directly test the estrogen withdrawal theory of perimenopausal depression (PMD).ObjectiveTo examine the role of estradiol withdrawal in PMD.Design, setting, and participantsInitial open-label treatment with estradiol followed by randomized, double-blind, placebo-controlled, parallel-design evaluation of continued estradiol treatment was evaluated at an outpatient research facility at the National Institutes of Health Clinical Center. An intent-to-treat analysis was performed between October 2003 and July 2012. Participants included asymptomatic postmenopausal women with past PMD responsive to hormone therapy (n = 26) and asymptomatic postmenopausal women with no history of depression (n = 30) matched for age, body mass index, and reproductive status who served as controls. Data were analyzed between November 2012 and October 2013 by repeated-measures analysis of variance.InterventionsAfter 3 weeks of open-label administration of transdermal estradiol (100 µg/d), participants were randomized to a parallel design to receive either estradiol (100 µg/d; 27 participants) or matched placebo skin patches (29 participants) for 3 additional weeks under double-blind conditions.Main outcomes and measuresCenter for Epidemiologic Studies-Depression Scale and 17-item Hamilton Depression Rating Scale (completed by raters blind to diagnosis and randomization status), self-administered visual analog symptom ratings, and blood hormone levels obtained at weekly clinic visits.ResultsNone of the women reported depressive symptoms during open-label use of estradiol. Women with past PMD who were crossed over from estradiol to placebo experienced a significant increase in depression symptom severity demonstrated using the Center for Epidemiologic Studies-Depression Scale and 17-item Hamilton Depression Rating Scale, with mean (SD) scores increasing from estradiol (ie, 2.4 [2.0] and 3.0 [2.5]) to placebo (8.8 [4.9] and 6.6 [4.5], respectively [P = .0004 for both]). Women with past PMD who continued estradiol therapy and all women in the control group remained asymptomatic. Women in both groups had similar hot-flush severity and plasma estradiol levels during use of placebo.Conclusions and relevanceIn women with past PMD that was previously responsive to hormone therapy, the recurrence of depressive symptoms during blinded hormone withdrawal suggests that normal changes in ovarian estradiol secretion can trigger an abnormal behavioral state in these susceptible women. Women with a history of PMD should be alert to the risk of recurrent depression when discontinuing hormone therapy.Trial registrationclinicaltrials.gov Identifier: NCT00060736.
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Project description:Bone represents a common site of metastases for several solid tumors. However, the ability of neuroendocrine neoplasms (NENs) to localize to bone has always been considered a rare and late event. Thanks to the improvement of therapeutic options, which results in longer survival, and of imaging techniques, particularly after the introduction of positron emission tomography (PET) with gallium peptides, the diagnosis of bone metastases (BMs) in NENs is increasing. The onset of BMs can be associated with severe skeletal complications that impair the patient's quality of life. Moreover, BMs negatively affect the prognosis of NEN patients, bringing out the lack of curative treatment options for advanced NENs. The current knowledge on BMs in gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) NENs is still scant and is derived from a few retrospective studies and case reports. This review aims to perform a critical analysis of the evidence regarding the role of BMs in GEP- and BP-NENs, focusing on the molecular mechanisms underlining the development of BMs, as well as clinical presentation, diagnosis, and treatment of BMs, in an attempt to provide suggestions that can be used in clinical practice.
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Project description:Major depressive disorder (MDD) is a major health concern with alarming rates of completed suicide. Thus, it is important to understand the pathophysiology of this disorder. In addition, disturbingly high rates of relapse and low rates of recovery make it urgent not only to develop targeted treatments but to identify biomarkers that can predict treatment response for individual patients. MicroRNAs (miRNAs) are a class of small non-coding RNAs that control gene expression by modulating translation, mRNA degradation or stability of mRNA targets. The role of miRNAs in disease pathophysiology is emerging rapidly. Several recent studies have suggested the possible role of miRNAs in synaptic plasticity, neurogenesis, and stress response, all implicated in MDD. Emerging studies showthe direct role of miRNAs in the development of depression phenotype. More recently, the role of miRNAs in prognosis and treatment response is being considered for various disease pathophysiology, including MDD. The review discusses the recent studies demonstrating the role of miRNAs in MDD and whether miRNA can be used as a biomarker for MDD pathogenesis and treatment response.
| S-EPMC4755329 | biostudies-literature