Perimenopausal Depression Research Articles

Investigating Differential Gene Expression in Response to Ovarian Steroid Manipulation in Vitro in Perimenopausal and Postpartum Depression

Affective disorders like perimenopausal depression (PMD) or postpartum depression (PPD) can be distinguished by their appearance during reproductive endocrine-related change. Clinical evidence (Bloch, 2000; Schmidt, 2015) demonstrates that women with these disorders have a heightened behavioral sensitivity to changes in ovarian steroids like estradiol (E2) and progesterone (P), suggesting a genetic predisposition towards abnormal affective responses to normal hormonal events.

Therapeutic effect of acupuncture combined with wheat-grain moxibustion on perimenopausal depression with kidney deficiency and liver depression

To compare the therapeutic effect of acupuncture combined with wheat-grain moxibustion and oral fluoxetine hydrochloride capsule on perimenopausal depression with kidney deficiency and liver depression. A total of 60 patients of perimenopausal depression with kidney deficiency and liver depression were randomized into an observation group and a control group, 30 cases in each one. Acupuncture combined with wheat-grain moxibustion were adopted in the observation group. Acupuncture was applied at Baihui (GV 20), Yintang (GV 29), Fengchi (GB 20), etc. for 30 min. Wheat-grain moxibustion was applied at Ganshu (BL 18), Shenshu (BL 23), Mingmen (GV 4) and Yongquan (KI 1), 3 moxa-cones for each acupoint. The treatment in the observation group was given once every 2 days, 3 times a week. Fluoxetine hydrochloride capsule was given orally in the control group, 20 mg each time, once a day. Treatment for 8 weeks was required in the both groups. The scores of Hamilton depression scale (HAMD) and modified Kupperman scale were observed in the both groups before and after treatment, and at 1, 3, 6-month follow-up. The therapeutic efficacy was evaluated after treatment. Compared before treatment, the scores of HAMD and modified Kupperman scale after treatment and at each time point of follow-up were decreased in the both groups (P<0.01), and the HAMD scores in the observation group were lower than the control group (P<0.01). The total effective rate was 93.3% (28/30) in the observation group, which was superior to 80.0% (24/30) in the control group (P<0.01). Acupuncture combined with wheat-grain moxibustion can effectively treat perimenopausal depression with kidney deficiency and liver depression, and have more stable and sustained therapeutic effect compared with oral fluoxetine hydrochloride capsule.

Differential effects of estradiol on neural and emotional stress response in postmenopausal women with remitted Major Depressive Disorder

<h3>Introduction</h3> Ovarian hormones can influence neural systems involved in mood regulation, suggesting a pathway explaining why women have a greater incidence of Major Depressive Disorder (MDD) than men primarily beginning at puberty. Estrogen fluctuations may contribute to MDD risk through effects on brain networks important in emotion processing, stress responding, and mood regulation. Although there is evidence to support the use of ovarian hormone treatment for peri-menopausal depression, postmenopausal use has not been as well examined. As the neural systems involved in emotional processing and stress response are altered in MDD, it is possible that the effect of estrogen treatment on these systems may differ between postmenopausal women with and without a history of MDD. The objective of this study was to investigate whether estrogen modulation of the neural and emotional cognitive responses to stress differs between postmenopausal women with and without MDD vulnerability. <h3>Methods</h3> 60 postmenopausal women completed this fMRI study including a psychosocial stress task, the Montreal Imaging Stress Task (MIST), after receiving no drug or 3 months of daily 2mg 17β estradiol (E2). Participants included women with no personal history of MDD by SCID interview and women with remitted MDD with at least one episode in the last ten years and no depressive episodes within the last year. There were 4 participant groups: 1) MDD+/E2+ (n=10), 2) MDD+/E2- (n=12), 3) MDD-/E2= (n=20), 4) MDD-/E2- (n=18). All groups were euthymic at the time of study with non-clinical scores on the Beck Depression and Anxiety Inventories. Subjective mood response to the MIST was assessed as change score on the Stress-Arousal Checklist (SACL stress) before and after the MIST. fMRI analyses examined activity differences between the "stress and "control" conditions of the MIST using SPM 12. Second level analyses included 2 × 2 interactions (MDD history X E2 administration), whole-brain (gray matter masked), and cluster threshold corrected for multiple comparisons (p<0.005, K >102, FDR<0.05) for differences in activity during the MIST between the 4 groups and the relationship between activity during the MIST and SACL stress score in each group. <h3>Results</h3> E2 administration was associated with different effects in post-menopausal women with or without a history of MDD. In accordance with our previous work, the MDD-/E2+ group had a more negative mood response (higher SACL stress score) to the stress task than the MDD-/E2- group. In contrast, this effect was reversed in women with a history of MDD, where the MDD+/E2+ group had a less negative mood response than the MDD+/E2- group. Additionally, both groups who exhibited more negative mood responses also showed greater activity in emotional perception areas (left inferior frontal and left angular gyri) during the stress condition of the task than the groups which showed less negative mood responses. Group differences were also observed on fMRI. Women who did not receive E2 showed a positive correlation between greater right inferior frontal activity and higher SACL stress score, while the MDD+/E2- group additionally showed a positive correlation between right insula activity and SACL score. The MDD+/E2+ group showed negative correlations between activity in each area and SACL stress score in both the "stress" and "control" conditions of the MIST, while the MDD-/E2+ did not show significant correlations between activity in any area and SACL stress Score. <h3>Conclusions</h3> These results support a differential effect of estrogen administration on emotional and neural responses to psychosocial stress in postmenopausal women with and without a history of MDD. We had previously show that in women without a history of MDD, E2 is associated with a more negative mood response to stress than placebo. The results of this study replicated those findings in women without a history of MDD and show that E2 is also associated with increased activity in brain areas involved in emotion perception and response. Additionally, the result of this study support that the effect of E2 is reversed in women with a history of MDD, such that E2 is associated with a less negative mood response to stress and a differential relationship between activity in brain areas involved in emotion response. This suggests that women with a history of MDD, even while currently euthymic, have both a different mood and neural response to psychosocial stress and may show a beneficial mood effect E2 that is not seen in women without a history of MDD. These results may provide a neurological basis for recurrence risk and the beneficial mood effects of post-menopausal hormone treatment in women with a history of MDD. <h3>Funding</h3> This work was supported by the National Institutes of Aging R01AG021476, the National Institutes of Mental Health H110598, and Vanderbilt CTSA grant UL1 TR002243 from National Center for Advancing Translational Sciences.

The short-term effects of estradiol, raloxifene, and a phytoestrogen in women with perimenopausal depression.

We examined the short-term efficacies of three estrogen-like compounds under placebo-controlled conditions in women with perimenopause-related depression (PMD). Women 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. Sixty-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. This 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).

Effect of Xiaoyao San on OVX combined with CUS anxiety and depression model rats based on hippocampal microglia M1 polarization

To investigate the anti-anxiety and anti-depression effect and mechanism of Xiaoyao San on rats with ovariectomy(OVX) combined with chronic unpredictable stress(CUS) model. The model of perimenopausal depression was established by OVX and CUS; the level of anxiety and depression was evaluated by open field test; the levels of interleukin-1β(IL-1β) and interleukin-6(IL-6) mRNA in rat hippocampus were detected by Real-time qPCR; double staining immunofluorescence was used to detect the expression of ionized calcium binding adaptor molecule-1(Iba-1) and inducible nitric oxide synthase(iNOS) in microglia of rat dentate gyrus(DG); Western blot was used to detect the protein expression of Iba-1 and iNOS of microglia in DG region of rat hippocampus. The results showed that in the model group, the number of horizontal movement, the number of vertical movement and central residence time were significantly reduced, and the grooming time was significantly prolonged(P&lt;0.05 or P&lt;0.01); the levels of IL-1β and IL-6 in hippocampus increased significantly(P&lt;0.05); the number of positive cells with co-expression of Iba-1/iNOS of microglia cells in DG region of hippocampus increased; the expression levels of Iba-1 and iNOS protein in hippocampus were significantly increased(P&lt;0.01), suggesting that microglia in DG region of hippocampus was activated and polarized toward M1 type in rats with stress. The high dose group of Xiaoyao San significantly increased the number of horizontal movement, vertical movement and central residence time of model rats(P&lt;0.05 or P&lt;0.01), and significantly down-regulated the levels of inflammatory factors IL-1β and IL-6(P&lt;0.05). Meanwhile, it reversed the activation and quantity change of microglia in hippocampus. Although the Xiaoyao San low dose group had no significant effect on the behavioral indicators in the open field test and the levels of IL-1β and IL-6, they all showed a trend of improvement. Low dose Xiaoyao San significantly decreased iNOS protein level(P&lt;0.05), and high dose Xiaoyao San significantly down-regulated the protein expression of Iba-1 and iNOS in hippocampus microglia(P&lt;0.05 or P&lt;0.01). In conclusion, Xiaoyao San can improve anxiety and depression-like behavior in OVX combined with CUS model rats, and its mechanism is related to its anti-inflammatory effect by inhibiting M1 polarization of hippocampal microglia.

Symptoms assessed in studies on perimenopausal depression: A narrative review

The menopausal transition constitutes a phase of major biopsychosocial changes associated with an elevated risk for the development of depression. Perimenopausal depression is highly prevalent and usually characterized by core symptoms of a major depressive disorder combined with menopausal complaints such as vasomotor symptoms or other physical complaints. However, a distinct definition of the condition is lacking. The aim of this review is to portray the symptoms assessed in studies on perimenopausal depression in order to provide relevant information on the current understanding of this condition.A literature search was conducted using the databases PubMed, Cochrane Library, and PsycINFO. A total of 37 studies were included.Various assessment tools have been used to measure symptoms related to perimenopausal depression. Fifteen symptoms were identified. Depressed mood was assessed across all studies. Low energy or sleep disturbances, as acknowledged symptoms of a major depressive disorder, were surveyed in most studies. However, the assessment of menopausal complaints was rather heterogeneous. While vasomotor symptoms were often measured, other menopausal symptoms such as mood swings or pain were investigated less frequently. Sexual problems were only rarely assessed.Studies on perimenopausal depression regularly include the assessment of core symptoms of a major depressive disorder, but the assessment of menopausal complaints is inconsistent. While certain symptoms are commonly measured, others are not assessed. Such inconsistencies underline an ambiguous understanding of perimenopausal depression, which in turn affects the evaluation and treatment of the condition. Thus, the use of the existing guidelines on perimenopausal depression is recommended.

In vitro model of perimenopausal depression implicates steroid metabolic and proinflammatory genes.

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 which 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.

Depression and the Perimenopause Transition: A Prospective Longitudinal Study

Community-based studies document the increased risk of depression in women during the perimenopause compared with both the premenopause and the later postmenopause. The timing of the onset of depressive episodes during the perimenopause and the clinical characteristics of women with perimenopausal depression (PMD) remain to be fully characterized. This longitudinal study prospectively defined the clinical characteristics throughout reproductive aging in women with and without PMD.

BDNF and Mood in Perimenopausal Depression

BDNF and Mood in Perimenopausal Depression

Electroacupuncture Promotes Neural Proliferation in Hippocampus of Perimenopausal Depression Rats via Wnt/β-Catenin Signaling Pathway

Background and ObjectivePerimenopausal depression is caused by the impaired function of the ovarium before menopause and with a series of symptoms. Electroacupuncture (EA) therapy has been demonstrated to improve clinically depression. However, the mechanism underlying its therapeutic activity remains unknown. This study aimed to investigat the effects of EA treatment on the hippocampal neural proliferation through Wnt signaling pathway. MethodsChronic unpredictable mild stress (CUMS) combined with bilateral ovariectomy (OVX) were used to establish a rat model of perimenopausal depression. The open field test (OFT) and sucrose preference test (SPT) were used to assess depression-like behaviors in rats. ELISAs were used to measure estrogen (E2), luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) levels in the serum. RT-PCR and Western blot assay were utilized for measuring the mRNA expressions and protein expressions of GSK-3β/β-catenin. ResultsFour-week EA treatment at three points including “Shenshu” (BL23), “Baihui” (GV20) and “Sanyinjiao” (SP6) simultaneously ameliorated depression-like behaviors in rats with CUMS and OVX, whereas rescued the decreased serum level of E2 and prevented the increased serum levels of GnRH and LH. EA treatment ameliorated CUMS and OVX-induced alterations of glycogen synthase kinase-3β (GSK-3β) and β-catenin mRNA levels, β-catenin and phosphorylated β-catenin (p-β-catenin) protein levels. ConclusionsThe results showed that EA treatment promoted hippocampal neural proliferation in perimenopausal depression rats via activating the Wnt/β-catenin signaling pathway, indicating that EA may represent an efficacious therapy for perimenopausal depression.

Towards improving recognition and management of perimenopausal depression.

Towards improving recognition and management of perimenopausal depression.

Therapeutic effect on mild perimenopausal depression treated with acupuncture at the "thirteen ghost points" and kaixin powder

To compare the clinical therapeutic effect on perimenopausal depression between the combined treatment with acupuncture at the "thirteen ghost points" and kaixin powder and the single application of kaixin powder. A total of 60 patients with mild perimenopausal depression were randomized into a Chinese medication group (30 cases, 2 cases dropped off) and a combined treatment group (acupuncture and Chinese medication, 30 cases). In the Chinese medication group, the modified kaixin powder was administered, one dose a day, taking in the morning and the evening separately. In the combined treatment group, on the base of the treatment as the Chinese medication group, acupuncture was applied to the "thirteen ghost points" invented by SUN Si-miao, e.g. Shuigou (GV 26), Shaoshang (LU 11), Yinbai (SP 1), Daling (PC 7), Shenmai (BL 62), Jiache (ST 6), Chengjiang (CV 24), Laogong (PC 8), Shangxing (GV 23), etc. The needles were withdrawed after the qi was acquired, and acupuncture was given once every two days, 3 times a week. In both of the groups, the consecutive treatment for 12 weeks was required. Separately, before treatment, after treatment and in 1-month follow-up visit, the score of the Hamilton depression scale (HAMD), the score of the self-rating depression scale (SDS) and the score of the perimenopausal Kupperman were observed in the two groups. In 12 weeks of treatment, the clinical therapeutic effect was compared between the two groups. After treatment and during the follow-up, HAMD, SDS and Kupperman scores were all reduced obviously as compared with those before treatment in the two groups (P<0.05). These scores in the combined treatment group were all lower than those in the Chinese medication group (P<0.05). The total effective rate was 90.0% (27/30) in the combined treatment group, better than 78.6% (22/28) in the Chinese medication group (P<0.05). Either the combined treatment with acupuncture at the "thirteen ghost points" and kaixin powder or the single application of kaixin powder is effective on perimenopausal depression. The therapeutic effect of the combined treatment of acupuncture and Chinese medication is superior to the simple application of kaixin powder.

Mood sensitivity to estradiol predicts depressive symptoms in the menopause transition.

The risk for depression markedly rises during the 5-6 years leading up to the cessation of menstruation, known as the menopause transition. Exposure to extreme estradiol levels may help explain this increase but few studies have examined individual sensitivity to estradiol in predicting perimenopausal depression. The current study recruited 101 perimenopausal women. During Phase 1, we quantified each woman's sensitivity to changes in estradiol using 12 weekly measures of estrone-3-glucuronide (E1G), a urinary metabolite of estradiol, and concurrent depressive symptoms. The weekly cortisol awakening response was measured to examine the hypothalamic-pituitary-adrenal (HPA) axis in mediating mood sensitivity to estradiol. In Phase 2, depressive symptoms and major depression diagnoses were assessed monthly for 9 months. The relationship between Phase 1 E1G sensitivity and Phase 2 depressive symptoms and major depressive episodes was examined. Several baseline characteristics were examined as potential moderators of this relationship. The within-person correlation between weekly E1G and mood varied greatly from woman to woman, both in strength and direction. Phase 1 E1G mood sensitivity predicted the occurrence of clinically significant depressive symptoms in Phase 2 among certain subsets of women: those without a prior history of depression, reporting a low number of baseline stressful life events, and reporting fewer months since their last menstrual period. HPA axis sensitivity to estradiol fluctuation did not predict Phase 2 outcomes. Mood sensitivity to estradiol predicts risk for perimenopausal depression, particularly among women who are otherwise at low risk and among those who are early in the transition.

Correlation between perimenopausal syndromes and depression in nurses at Sanglah General Hospital

Background: Perimenopause covers the period immediately before the menopause and the first year after the last menstrual period. In addition to the changes in the menstrual cycle, women in the perimenopause phase often report a number of perimenopausal complaints and depressive disorders. This study aims to determine the prevalence of perimenopausal complaints and depression experienced in nurses at Sanglah General Hospital. Methods: The study uses a cross-sectional analytical. The measurement of perimenopause complaints uses the Menopause Rating Scale (MRS) questionnaire and the depression measurement uses the Beck Depression Inventory-II questionnaire (BDI-II). The data are analyzed descriptively, it uses the Fisher test and linear regression test with significance level p &lt;0.05. Results: Nurses who have perimenopausal complaints are 62.7%. Besides, depression is experienced by 23.8% of nurses who have perimenopausal complaints. The complained somatic symptoms with a mild degree are 50% and moderate degree is 40%. While the urogenital sexual symptoms with a moderate degree are 60%, and mild and severe degrees are 20%. Conclusion: This study shows the relationship between perimenopausal complaints and the depression of the nurses in Sanglah General Hospital. Therefore, it is necessary to hold an early detection of depression prevention by screening perimenopausal complaints.

Effectiveness and Safety of Acupuncture for Perimenopausal Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective To determine the effectiveness and safety of acupuncture for perimenopausal depression. Methods We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CNKI, VIP Citation Databases, Wan Fang, and online trial registries such as ClinicalTrials.gov for randomized controlled trials (RCTs) assessing the efficacy and safety of acupuncture for perimenopausal depression. Literature screening, data extraction, and determination of the risk of bias were performed by two researchers independently. The extracted data were pooled and meta-analyzed using RevMan5.3 software. Results In total, 16 RCTs covering 1311 patients were enrolled. Overall, the results showed that acupuncture was more effective in the treatment of perimenopausal depression than antidepressants (OR = 2.68, 95% CI (1.84, 3.90), P < 0.00001). Furthermore, HAMD scores in the manual acupuncture group and electroacupuncture group were lower than those of antidepressants (manual acupuncture vs. antidepressants (MD = −2.35, 95% CI (−2.93, −1.77), P < 0.00001) and electroacupuncture vs. antidepressants (MD = −1.2, 95% CI (−1.92, −0.48), P=0.001)). Data analysis revealed that the treatment effect of acupuncture was more stable than that of antidepressants (MD = −2.4, 95% CI (−3.37, −1.43), P < 0.00001). Moreover, acupuncture was safer than antidepressants based on the incidence of adverse events (OR = 0.23, 95% CI (0.1, 0.52), P=0.0004). But acupuncture has no effect on estrogen levels (P ≥ 0.05). Conclusions Acupuncture for perimenopausal depression is safe and effective. Moreover, it has more stable long-term effects than antidepressants and hormone replacement therapy (HRT). We recommend acupuncture as a clinical treatment of perimenopausal depression.

Mood and sleep improvement with critically-timed wake and light interventions in premenstrual, peripartum vs. perimenopausal depression depend on specific underlying melatonin and sleep circadian phase disturbances

Mood and sleep improvement with critically-timed wake and light interventions in premenstrual, peripartum vs. perimenopausal depression depend on specific underlying melatonin and sleep circadian phase disturbances

Antidepressant-like effects of Xiaochaihutang in perimenopausal mice.

Xiaochaihutang (XCHT) is a traditional Chinese medicine prescription for thousand years in China. Our previous researches show that XCHT has antidepressant-like effects in several depression models, but effect and mechanism of XCHT in perimenopausal depression are still vague. To reveal the antidepressant-like effect and mechanism of XCHT in perimenopausal mice. Perimenopausal depression model is executed by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS). Tail suspension test (TST), forced swim test (FST), elevated plus-maze (EPM), novelty suppressed feeding (NSF) and locomotor activity are used to assess antidepressant-like effects of XCHT. The Level of estradiol (E2), follicle-stimulating hormone (FSH), gonadotrophin releasing hormone (GnRH), corticosterone (CORT), adrenocorticotrophic hormone (ACTH) and corticotropin releasing hormone (CRH) are evaluated by ELISA. Antidepressant mechanisms of XCHT in OVX-CUMS mice are analyzed by 5-hydroxytryptamine (5-HT), tryptophan hydroxylase 2 (TPH2) and estrogen receptor α and β (ERα/β). The results show that OVX-CUMS significantly increases the immobility time in TST and FST, increases latency to feed, decreases food consumption in NSF and both the time spend and number of entries in open arms in EPM. While, oral administration of XCHT can significantly normalize above depression-like behaviors in OVX-CUMS mice. Moreover, XCHT also remarkably normalized levels of 5-HT, 5-HIAA, E2, GnRH, CORT, ACTH and CRH in OVX-CUMS mice. Finally, the expression of ERβ and TPH2 are decreased by OVX-CUMS in prefrontal cortex and hypothalamus, and XCHT can restore these decrease. Current findings suggest XCHT can alleviate perimenopausal depression-like behaviors, restore 5-HT and hormones in OVX-CUMS mice, which may be related to normalizing the functions of HPA/HPO axis and enhancing expression of ERβ and TPH2 in prefrontal cortex and hypothalamus.

PI3K-AKT Signaling Activation and Icariin: The Potential Effects on the Perimenopausal Depression-Like Rat Model.

Icariin is a prenylated flavonol glycoside isolated from Epimedium herb, and has been shown to be its main bioactive component. Recently, the antidepressant-like mechanism of icariin has been increasingly evaluated and demonstrated. However, there are few studies that have focused on the involvement of the phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT) signaling in mediating the perimenopausal depression effects of icariin. Perimenopausal depression is a chronic recurrent disease that leads to an increased risk of suicide, and poses a significant risk to public health. The aim of the present study was to explore the effect of icariin on the expression of the PI3K–AKT pathway related to proteins in a rat model of perimenopausal depression. Eighty percent of the left ovary and the entire right ovary were removed from the model rats. A perimenopausal depression model was created through 18 days of chronic unpredictable stimulation, followed by the gavage administration of target drugs for 30 consecutive days. We found that icariin administered at various doses significantly improved the apparent symptoms in the model rats, increased the organ indices of the uterus, spleen, and thymus, and improved the pathological changes in the ovaries. Moreover, icariin administration elevated the serum levels of female hormone estradiol (E2), testosterone (T), and interleukin (IL)-2, decreased those of follicle stimulating hormone (FSH) and luteotropic hormone (LH), promoted the expression levels of estrogen receptor (ER) and ERα in the hypothalamus, and increased those of serotonin (5-HT), dopamine (DA), and noradrenaline (NA) in the brain homogenate. Furthermore, icariin elevated the expression levels of AKT, phosphorylation-akt (p-AKT), PI3K (110 kDa), PI3K (85 kDa), and B-cell lymphoma 2 (Bcl-2) in the ovaries, and inhibited those of Bax. These results show that icariin administration rebalanced the disordered sex hormones in perimenopausal depression rats, regulated the secretion of neurotransmitters in the brain, boosted immune function, and improved the perimenopausal syndrome. The mechanism of action may be related to the regulation of the expression of PI3K–AKT pathway-related proteins.

Gamma-Aminobutyric Acid Levels in the Anterior Cingulate Cortex of Perimenopausal Women With Depression: A Magnetic Resonance Spectroscopy Study.

ObjectiveThe anterior cingulate cortex (ACC) is associated with the processing of negative emotions. Gamma-aminobutyric acid (GABA) metabolism plays an important role in the pathogenesis of mental disorders. We aimed to determine the changes in GABA levels in the ACC of perimenopausal women with depression.MethodsWe recruited 120 perimenopausal women, who were followed up for 18–24 months. After reaching menopause, the participants were divided into a control group (n = 71), an anxiety group (n = 30), and a depression group (n = 19). The participants were examined using proton magnetic resonance spectroscopy (MRS). TARQUIN software was used to calculate the GABA concentrations in the ACC before and after menopause. The relationship of the GABA levels with the patients’ scores on the 14-item Hamilton Anxiety Scale and 17-item Hamilton Depression Scale was determined.ResultsGABA decreased with time. The postmenopausal GABA levels were significantly lower in the depression group than in the anxiety group and were significantly lower in both these groups than in the normal group. The postmenopausal GABA levels were significantly lower than the premenopausal levels in the normal, anxiety, and depression groups (P = 0.014, <0.001, and <0.001, respectively). The premenopausal GABA levels did not significantly differ between the normal vs. anxiety group (P = 0.907), normal vs. depression group (P = 0.495), and anxiety vs. depression group. The postmenopausal GABA levels were significantly lower in the depression group than in the anxiety group and were significantly lower in both these groups than in the normal group, normal vs. anxiety group (P = 0.022), normal vs. depression group (P < 0.001), and anxiety vs. depression group (P = 0.047).ConclusionChanges in GABA concentrations in the anterior cingulate cortex are related with the pathophysiological mechanism and symptoms of perimenopausal depression.

Effect of electroacupuncture on mice model of permenopausal depressive disorder

ObjectiveStudy the effect of electroacupuncture on permenopausal depressive disorder (PDD) model through the peri-menopausal depression model mice.MethodsKM female mice were selected. Except for the blank group (BG), the other groups of mice were removed by castration method. The mice of PDD was prepared by combining chronic unpredictable stimulation. Mice in the model group (MG) were not treated and fed normally. The western medicine group (WG) was given the corresponding drug for treatment. The electroacupuncture group (EAG) was given the electroacupuncture for treatment, and consecutive for 28 days. The levels of T, E2, FSH and LH in serum of mice were measured, and the brain tissue of 5-HT, DA and NE level were measured. Through the HE staining observed the morphological changes of mice hypothalamus.ResultsCompared with MG, EAG could increase the number of spontaneous activities of PDD model mice, the level of T, E2 in serum and the level of 5-HT, DA, NE in brain tissue was improved, and the level of FSH, LH in serum was reduced, and the hypothalamic lesions was improved.ConclusionElectroacupuncture could improve the activity and memory of PDD mice, adjust the disorder of sex hormone, and increased the levels of monoamine transmitters (5-HT, NE, DA), and it could effectively improve the behavior and related biochemical indexes of PDD, and thus play an important therapeutic role.