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Frontiers in Pharmacology 2024Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic...
Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic psychological symptoms and its pathogenesis is still unclear. Abnormalities in the basolateral amygdala (BLA) orexin system, which are important causes of the development of depressive mood, have not been reported in PMDD, so exploring its intrinsic mechanisms is meaningful for enriching the pathomechanisms of PMDD. High performance liquid chromatography was used for the determination of the active ingredients of Jingqianshu granules. Developing a rat model of premenstrual depression using the forced swimming test (FST). The experiment consisted of two parts. In Part 1, the rats were divided into the control group, the model group, the model + Jingqianshu group, and the model + fluoxetine group. The FST, open field test, and elevated plus maze test, were used to assess the behavior of the rats as well as to evaluate the effect of drug intervention. Immunofluorescence and RT-qPCR were used to detect the expression of orexin and its receptors OX1R and OX2R genes and proteins. The expression of Toll-like receptor 4, nuclear factor kappa-B, tumor necrosis factor-α, interleukin 6, and interleukin-1β in the BLA brain region was detected by Western-Blot. In part 2, the rats were injected intracerebrally with orexin-A. Observe the behavioral activities of rats in the control group, model group, and model+orexin-A group. Immunofluorescence was used to detect microglia in the BLA area of rats, and the expression levels of the above inflammatory factors were detected by Western-Blot. The five components of Jingqianshu granules are: paeoniflorin, erulic acid, liquiritin, hesperidin, and paeonol. During the estrous cycle, rats exhibited depressive-like behavior during the non-receptive phase of the behavioral test, which disappeared during the receptive phase. Immunofluorescence and RT-qPCR showed reduced gene and protein expression of orexin, OX1R, and OX2R in the BLA region of rats in the model group.WB showed elevated levels of inflammatory factors. All returned to control levels after drug treatment. In part 2, injection of orexin-A into the BLA brain region of model rats resulted in reduced immunoreactivity of microglia and decreased expression levels of inflammatory factors. Jianqianshu granules can achieve the purpose of treating premenstrual depression by regulating orexin-mediated inflammatory factors, which provides a new idea for further research on the pathogenesis of PMDD. However, the current study is still preliminary and the pathogenesis of PMDD is complex. Therefore, more in-depth exploration is needed.
PubMed: 38948463
DOI: 10.3389/fphar.2024.1294122 -
Nature. Mental Health 2024Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical...
Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( = 1,384) of medication-free individuals with first-episode and recurrent MDD ( = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals ( = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter ( = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter ( = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) ( = -18.3, 95% CI (-34.3 to -2.3), = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.
PubMed: 38948238
DOI: 10.1038/s44220-023-00187-w -
Theranostics 2024: Recent evidence highlights the pivotal role of mitochondrial dysfunction in mood disorders, but the mechanism involved remains unclear. We studied whether the...
: Recent evidence highlights the pivotal role of mitochondrial dysfunction in mood disorders, but the mechanism involved remains unclear. We studied whether the Hippo/YAP/14-3-3η signaling pathway mediates mitochondrial abnormalities that result in the onset of major depressive disorder (MDD) in a mouse model. : The ROC algorithm was used to identify a subpopulation of mice that were exposed to chronic unpredictable mild stress (CUMS) and exhibited the most prominent depressive phenotype (Dep). Electron microscopy, biochemical assays, quantitative PCR, and immunoblotting were used to evaluate synaptic and mitochondrial changes in the basolateral amygdala (BLA). RNA sequencing was used to explore changes in the Hippo pathway and downstream target genes. pharmacological inhibition and immunoprecipitation was used to confirm YAP/14-3-3η interaction and its role in neuronal mitochondrial dysfunction. We used virus-mediated gene overexpression and knockout in YAP transgenic mice to verify the regulatory effect of the Hippo/YAP/14-3-3η pathway on depressive-like behavior. : Transcriptomic data identified a large number of genes and signaling pathways that were specifically altered from the BLA of Dep mice. Dep mice showed notable synaptic impairment in BLA neurons, as well as mitochondrial damage characterized by abnormal mitochondrial morphology, compromised function, impaired biogenesis, and alterations in mitochondrial marker proteins. The Hippo signaling pathway was activated in Dep mice during CUMS, and the transcriptional regulatory activity of YAP was suppressed by phosphorylation of its Ser127 site. 14-3-3η was identified as an important co-regulatory factor of the Hippo/YAP pathway, as it can respond to chronic stress and regulate cytoplasmic retention of YAP. Importantly, the integrated Hippo/YAP/14-3-3η pathway mediated neuronal mitochondrial dysfunction and depressive behavior in Dep mice. : The integrated Hippo/YAP/14-3-3η pathway in the BLA neuron is critical in mediating depressive-like behaviors in mice, suggesting a causal role for this pathway in susceptibility to chronic stress-induced depression. This pathway therefore may present a therapeutic target against mitochondrial dysfunction and synaptic impairment in MDD.
Topics: Animals; Disease Models, Animal; Mice; Mitochondria; YAP-Signaling Proteins; Signal Transduction; Hippo Signaling Pathway; Basolateral Nuclear Complex; Protein Serine-Threonine Kinases; Male; Stress, Psychological; 14-3-3 Proteins; Adaptor Proteins, Signal Transducing; Depressive Disorder, Major; Depression; Mice, Inbred C57BL; Neurons; Mice, Transgenic
PubMed: 38948066
DOI: 10.7150/thno.92676 -
Cureus May 2024Streff syndrome is a non-malingering visual disturbance commonly affecting near and color vision, which is prevalent in the younger population. This case report presents...
Streff syndrome is a non-malingering visual disturbance commonly affecting near and color vision, which is prevalent in the younger population. This case report presents Streff-like syndrome in a middle-aged woman. A 47-year-old woman with underlying major depressive disorder presented with bilateral reduced vision and a constricted visual field for one week. These symptoms were accompanied by additional neurological complaints of headache, weakness, and numbness triggered after a stressful event that affected her work performance. Examinations revealed reduced vision more toward near, diminished red saturation, color vision deficiencies, and bilateral tubular visual fields. Notably, the relative afferent pupillary defect was negative, with both anterior and posterior segments normal. Neuroimaging and inflammatory workup results were within normal limits. An additional +1.00 lens improved her symptoms and visual acuities. Collaborative management involving psychiatry, neurology, and ophthalmology, including psychotherapy, led to significant symptom improvement. At the five-month follow-up, the patient experienced a complete resolution of her visual symptoms. Although Streff syndrome is a primary visual problem, additional psychogenic factors may add to variable cases. This case underscores the importance of recognizing stress-induced psychogenic manifestation, particularly in patients with underlying mental health conditions, and emphasizes an interdisciplinary management approach.
PubMed: 38947604
DOI: 10.7759/cureus.61289 -
Frontiers in Public Health 2024Postpartum fatigue (PPF) can impair the physical and mental well-being of women. The aims of this study were to assess the associations between fatigue and maternal...
BACKGROUND
Postpartum fatigue (PPF) can impair the physical and mental well-being of women. The aims of this study were to assess the associations between fatigue and maternal health-related variables, specifically, sleep quality, depression symptoms, and resilience, and to explore the moderating role of resilience in the relationships between sleep quality, depression symptoms, and fatigue.
METHODS
This cross-sectional study used data collected from mothers during the postpartum period via an online platform. PPF was assessed using the Fatigue Severity Scale, whereas sleep quality and depression symptoms were assessed using the Pittsburgh Sleep Quality Index and Edinburgh Postnatal Depression Scale, respectively. The Brief Resilience Scale was used to assess resilience. Simple and multiple binary logistic regression analyses were performed to examine the association of each independent variable with PPF and to determine the most significant predictors of PFF. The data were analyzed using SPSS, and structural equation modeling was performed using AMOS 23. A moderation analysis was performed to explore the moderating role of resilience using the Hayes PROCESS macro.
RESULTS
A total of 1,443 postpartum mothers were included in the analysis. The simple binary logistic regression analysis showed that having chronic disease (odds: 1.52; = 0.02), mother's age (odds: 0.97; = 0.03), mother's body mass index (BMI; odds: 1.03; = 0.01), depression symptoms (odds: 1.09; ≤ 0.0001), sleep quality (odds: 1.17; ≤ 0.0001), and resilience (odds: 0.42; p ≤ 0.0001) all contributed to fatigue during postpartum. Multivariate logistic regression showed that the mother's BMI, sleep quality, depression symptoms, and resilience were significant predictors of PPF. Moderation analyses showed that resilience was not a significant moderator between the main effects of sleep quality and fatigue (interaction effect: = 0.01, = 0.31, 95% CI: -0.01 to 0.04) or between the main effects of depression symptoms and fatigue during postpartum (interaction effect: = 0.01, = 0.82, 95% CI: -0.01 to 0.02).
CONCLUSION
Given the deleterious effects of PPF on maternal health outcomes, factors associated with PPF should be assessed regularly. In addition to mothers' BMI, sleep quality, and depression symptoms, resilience could also be a crucial factor in predicting fatigue severity during this critical time for mothers even though it was not a significant moderator among this sample.
Topics: Humans; Female; Cross-Sectional Studies; Adult; Fatigue; Resilience, Psychological; Postpartum Period; Mothers; Sleep Quality; Surveys and Questionnaires; Depression, Postpartum; Depression; Risk Factors; Logistic Models
PubMed: 38947349
DOI: 10.3389/fpubh.2024.1394380 -
MedRxiv : the Preprint Server For... Jun 2024Individuals with major depressive disorder (MDD) can experience reduced motivation and cognitive function, leading to challenges with goal-directed behavior. When...
Individuals with major depressive disorder (MDD) can experience reduced motivation and cognitive function, leading to challenges with goal-directed behavior. When selecting goals, people maximize 'expected value' by selecting actions that maximize potential reward while minimizing associated costs, including effort 'costs' and the opportunity cost of time. In MDD, differential weighing of costs and benefits are theorized mechanisms underlying changes in goal-directed cognition and may contribute to symptom heterogeneity. We used the Effort Foraging Task to quantify cognitive and physical effort costs, and patch leaving thresholds in low effort conditions (hypothesized to reflect perceived opportunity cost of time) and investigated their shared versus distinct relationships to clinical features in participants with MDD (N=52, 43 in-episode) and comparisons (N=27). Contrary to our predictions, none of the decision-making measures differed with MDD diagnosis. However, each of the measures were related to symptom severity, over and above effects of ability (i.e., performance). Greater anxiety symptoms were selectively associated with cognitive effort cost (i.e. greater willingness to exert effort). Anhedonia symptoms were associated with increased physical effort costs. Finally, greater physical anergia was related to decreased patch leaving thresholds. Markers of effort-based decision-making may inform understanding of MDD heterogeneity. Increased willingness to exert cognitive effort may contribute to anxiety symptoms such as rumination and worry. The association of decreased leaving thresholds with symptom severity is consistent with reward rate-based accounts of reduced vigor in MDD. Future research should address subtypes of depression with or without anxiety, which may relate differentially to cognitive effort decisions.
PubMed: 38947009
DOI: 10.1101/2024.02.18.24302985 -
The American Journal of Psychiatry Jul 2024
Topics: Humans; Depressive Disorder, Treatment-Resistant; Medical Records
PubMed: 38946279
DOI: 10.1176/appi.ajp.20240377 -
The American Journal of Psychiatry Jul 2024
Topics: Humans; Brain; Multimodal Imaging; Neuroimaging; Magnetic Resonance Imaging; Brain Mapping; Depressive Disorder, Major; Stress, Psychological
PubMed: 38946274
DOI: 10.1176/appi.ajp.20240400 -
Nihon Yakurigaku Zasshi. Folia... 2024Major depressive disorder (MDD) is a psychiatric disorder that affects more than 300 million people worldwide and has a serious impact on society. Conventional... (Review)
Review
Major depressive disorder (MDD) is a psychiatric disorder that affects more than 300 million people worldwide and has a serious impact on society. Conventional antidepressants targeting monoamines in the brain based on the monoamine hypothesis are known to take a prolonged time to be effective or less effective in 30% of MDD patients. Hence, there is a need to develop antidepressants that are effective against treatment-resistant depression and have a new mechanism different from the monoamine hypothesis. An increasing number of research groups including us have been establishing that pituitary adenylate cyclase-activating polypeptide (PACAP) and one of its receptors, PAC1 receptor, are closely related to the etiology of stress-related diseases such as MDD. Therefore, it is strongly suggested that the PAC1 receptor is a promising target in the treatment of psychiatric disorders. We developed a novel, non-peptidic, small-molecule, high-affinity PAC1 receptor antagonists and conducted behavioral pharmacology experiments in mice to characterize a novel PAC1 receptor antagonist as a new option for MDD therapy. The results show that our novel PAC1 receptor antagonist has the potential to be a new antidepressant with a high safety profile. In this review, we would like to present the background of developing our novel PAC1 receptor antagonist and its effects on mouse models of acute stress.
Topics: Antidepressive Agents; Animals; Humans; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Drug Development; Depressive Disorder, Major; Molecular Targeted Therapy
PubMed: 38945904
DOI: 10.1254/fpj.24008 -
Nihon Yakurigaku Zasshi. Folia... 2024Major Depressive Disorder (MDD) poses a significant global health burden, with 30-40% patients developing resistance to standard clinical antidepressants, such as... (Review)
Review
Major Depressive Disorder (MDD) poses a significant global health burden, with 30-40% patients developing resistance to standard clinical antidepressants, such as selective serotonin reuptake inhibitors and tricyclic antidepressants. In 2016, Carhart-Harris and colleagues reported that psilocybin, the hallucinogenic compound derived from magic mushrooms, exhibits rapid and enduring antidepressant effects in patients with treatment-resistant depression. Subsequent clinical studies have found the therapeutic potential of psilocybin in MDD, depressive episode in bipolar disorder, anorexia, and drug addiction. In 2018 and 2019, the U.S. Food and Drug Administration designated psilocybin as a "breakthrough medicine" for treatment-resistant depression and MDD, respectively. Notably, the side effects of psilocybin are limited to transient and mild issues, such as headache and fatigue, suggesting its safety. In 2023, we published a review on the role of serotonin 5-HT receptors in the antidepressant effects of serotonergic psychedelics (Nihon Yakurigaku Zasshi, Volume 158, Issue 3, Page 229-232). Here, we present our study alongside the latest clinical and preclinical research on the antidepressant effects of psilocybin and provide an overview of the potential and issues related to psilocybin therapy.
Topics: Psilocybin; Humans; Animals; Antidepressive Agents; Hallucinogens; Depressive Disorder, Major; Receptor, Serotonin, 5-HT2A
PubMed: 38945903
DOI: 10.1254/fpj.24007