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Su C, Huang T, Zhang M, Zhang Y, Zeng Y, Chen X. Glucocorticoid receptor signaling in the brain and its involvement in cognitive function. Neural Regen Res 2025; 20:2520-2537. [PMID: 39248182 PMCID: PMC11801288 DOI: 10.4103/nrr.nrr-d-24-00355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 06/07/2024] [Accepted: 07/06/2024] [Indexed: 09/10/2024] Open
Abstract
The hypothalamic-pituitary-adrenal axis regulates the secretion of glucocorticoids in response to environmental challenges. In the brain, a nuclear receptor transcription factor, the glucocorticoid receptor, is an important component of the hypothalamic-pituitary-adrenal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity. The glucocorticoid receptor influences cognitive processes, including glutamate neurotransmission, calcium signaling, and the activation of brain-derived neurotrophic factor-mediated pathways, through a combination of genomic and non-genomic mechanisms. Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor, thereby affecting the hypothalamic-pituitary-adrenal axis and stress-related cognitive functions. An appropriate level of glucocorticoid receptor expression can improve cognitive function, while excessive glucocorticoid receptors or long-term exposure to glucocorticoids may lead to cognitive impairment. Patients with cognitive impairment-associated diseases, such as Alzheimer's disease, aging, depression, Parkinson's disease, Huntington's disease, stroke, and addiction, often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression. This review provides a comprehensive overview of the functions of the glucocorticoid receptor in the hypothalamic-pituitary-adrenal axis and cognitive activities. It emphasizes that appropriate glucocorticoid receptor signaling facilitates learning and memory, while its dysregulation can lead to cognitive impairment. This provides clues about how glucocorticoid receptor signaling can be targeted to overcome cognitive disability-related disorders.
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Affiliation(s)
- Chonglin Su
- Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Taiqi Huang
- Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Meiyu Zhang
- Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Yanyu Zhang
- Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Yan Zeng
- Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Xingxing Chen
- Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
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Kang X, Wang T, Wan H, Fu W, Lin S. Xiao Yao San mitigates corticosterone stimulation-induced hippocampal neuronal damage by inhibiting GR phosphorylation and nuclear translocation via FKBP4 involvement. BMC Complement Med Ther 2025; 25:155. [PMID: 40269902 PMCID: PMC12020241 DOI: 10.1186/s12906-025-04892-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 04/10/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND Corticosterone stimulation has profound physiological and neurological effects on individuals, necessitating effective interventions to mitigate its impact. Current therapeutic approaches for corticosterone stimulation injury have limitations, including addiction and tolerance issues. In contrast, historical formulations such as Xiao Yao San, a traditional Chinese medicine formula, have shown promise in addressing changes in corticosterone stimulation-related neuroplasticity. This study aimed to explore the potential of Xiao Yao San in modulating the glucocorticoid receptor (GR) signaling pathway and its downstream effects on hippocampal neuroplasticity under corticosterone stimulation conditions. METHODS Primary hippocampal neurons were cultured and exposed to corticosterone to establish a corticosterone stimulation model. Cellular viability, apoptosis, and protein expression were assessed via CCK-8 assays, flow cytometry, and immunoblotting, respectively. Interactions between FK506 binding protein 51 (FKBP51), GR, and p-GR were analyzed via coimmunoprecipitation and GST pull-down assays. The influence of FKBP4 on the competitive binding of GR was explored via similar techniques. The functional consequences of gene knockdown and overexpression were evaluated through cellular assays. RESULTS Xiao Yao San attenuated corticosterone-induced reductions in cell viability and apoptosis, counteracting the detrimental effects of corticosterone stimulation. It downregulated FKBP51 expression and suppressed GR phosphorylation and nuclear translocation. Additionally, it hindered the interaction between FKBP51 and GR/p-GR. FKBP4 overexpression rescued hippocampal neuron viability and protected against the GR phosphorylation and nuclear translocation induced by corticosterone. CONCLUSION Xiao Yao San exhibited promising effects in ameliorating changes in corticosterone stimulation-induced neuroplasticity through the modulation of the GR signaling pathway. By inhibiting FKBP51-mediated GR phosphorylation and nuclear translocation, Xiao Yao San has potential as an alternative therapeutic strategy for corticosterone stimulation-related conditions. Further clinical investigations and mechanistic studies are warranted to validate its therapeutic efficacy and elucidate its mechanisms of action.
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Affiliation(s)
- Xuedi Kang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, No. 1, Fuhua Road, Futian District, Shenzhen, Guangdong, 518033, China
| | - Ting Wang
- School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China
| | - Haiping Wan
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, No. 1, Fuhua Road, Futian District, Shenzhen, Guangdong, 518033, China
| | - Wenjun Fu
- School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China
| | - Songjun Lin
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, No. 1, Fuhua Road, Futian District, Shenzhen, Guangdong, 518033, China.
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Han M, Zeng D, Tan W, Chen X, Bai S, Wu Q, Chen Y, Wei Z, Mei Y, Zeng Y. Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior. Neural Regen Res 2025; 20:159-173. [PMID: 38767484 PMCID: PMC11246125 DOI: 10.4103/nrr.nrr-d-23-01419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 12/23/2023] [Accepted: 01/19/2024] [Indexed: 05/22/2024] Open
Abstract
Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response. Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region-specific, particularly involving the corticolimbic system, including the ventral tegmental area, nucleus accumbens, prefrontal cortex, amygdala, and hippocampus. Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology. In this review, we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression. We focused on associated molecular pathways and neural circuits, with special attention to the brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling pathway and the ventral tegmental area-nucleus accumbens dopamine circuit. We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature, severity, and duration of stress, especially in the above-mentioned brain regions of the corticolimbic system. Therefore, BDNF might be a biological indicator regulating stress-related processes in various brain regions.
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Affiliation(s)
- Man Han
- Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Deyang Zeng
- Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Wei Tan
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Xingxing Chen
- Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Shuyuan Bai
- Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Qiong Wu
- Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Yushan Chen
- Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Zhen Wei
- Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Yufei Mei
- Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Yan Zeng
- Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China
- School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
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Bahi A, Dreyer JL. Myelin Transcription Factor 1 (MyT1) overexpression mitigates social isolation-induced behavioral deficits: Insights into cortical synaptotagmin 1 regulation and antidepressant-like effects. Pharmacol Biochem Behav 2025; 246:173912. [PMID: 39592028 DOI: 10.1016/j.pbb.2024.173912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 10/16/2024] [Accepted: 11/19/2024] [Indexed: 11/28/2024]
Abstract
Social isolation (SI) stress is increasingly recognized as a concern, associated with detrimental effects on mood and emotional well-being. Myelin Transcription Factor 1 (MyT1) is known for its pivotal role in nervous system development and mood regulation. This study delves into the potential of MyT1 to mitigate SI-induced behavioral abnormalities in mice. Utilizing a chronic SI model involving neonatal and post-weaning SI, male and female mice were subjected to lentiviral overexpression of MyT1 specifically in the medial prefrontal cortex (mPFC). A battery of behavioral assessments, including novelty-suppressed feeding, sucrose preference, sucrose splash, tape grooming, tail suspension, and forced swim tests, revealed notable antidepressant-like effects in both sexes upon MyT1 overexpression. Enhanced MyT1 expression corresponded with increased feeding initiation, sucrose preference, and self-grooming, alongside decreased immobility time. Importantly, the upregulation of MyT1 was accompanied by a significant reduction in cortical synaptotagmin 1 (Syt1) level. These findings underscore the involvement of MyT1 in mitigating SI-induced depression-like behavior. Moreover, the observed alterations in behavior are closely associated with changes in cortical Syt1 expression, suggesting its potential role as a target for unraveling the molecular mechanisms underlying mood disorders induced by SI. This study sheds light on the intricate interplay between MyT1 and cortical function in modulating responses to SI, paving the way for potential therapeutic interventions targeting these pathways.
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Affiliation(s)
- Amine Bahi
- Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman, United Arab Emirates; Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates; CMHS, UAE University, Al Ain, United Arab Emirates.
| | - Jean-Luc Dreyer
- Division of Biochemistry, University of Fribourg, Fribourg, Switzerland
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Picheta N, Piekarz J, Daniłowska K, Mazur K, Piecewicz - Szczęsna H, Smoleń A. Phytochemicals in the treatment of patients with depression: a systemic review. Front Psychiatry 2024; 15:1509109. [PMID: 39717381 PMCID: PMC11663887 DOI: 10.3389/fpsyt.2024.1509109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 11/19/2024] [Indexed: 12/25/2024] Open
Abstract
Background Depression is a complex mental disease whose incidence increases every year; 300 million people worldwide currently suffer from it. Women are more likely to suffer from depression, twice the rate as men. It is one of the few illnesses that can lead to suicide, which makes it very dangerous - currently, 700,000 people die from suicide and it is the 4th most common cause of death in people aged 15-29. The treatment strategies for depression is a big challenge for physicians, pharmacists, scientists and classic remedies cause many side effects. Therefore, natural phytotherapy with herbs can prove to be a good solution. Phytotherapy is a popular treatment method used for centuries in Chinese medicine or Ayurveda. Materials and methods The study conducted a comprehensive database search PubMed, ClinicalKey and MedNar covered the years 2015 - 2024 to provide the most up-to-date data. 13 randomized controlled trials and 1 meta - analysis were included in the systematic review. Results Many plants show anti-inflammatory, antioxidant and cognitive enhancing effects, which are particularly important in depression. In the treatment of depression, plants such as Crocus sativus L. stigma, Lavandula angustifolia, Hypericum perforatum L. and Curcuma longa L. have proven to be effective. They show good effectiveness in human studies and alleviate the symptoms of depression. Herbal products can support classical pharmacotherapy, but this requires further research. Non-commercial clinical trials in the future should provide answers to research questions: at what stage of treatment of patients with MDD will the use of phytochemicals be most appropriate in terms of therapy efficacy and safety for the patient. Conclusions Crocus sativus L. stigma, Lavandula angustifolia, Hypericum perforatum L. and Curcuma longa L. in modern medicine can help improve the well-being of patients with depression. The use of herbs as an intervention was associated with a decrease in the concentration of proinflammatory cytokines and an overall improvement in the mood of patients. Further research should be undertaken into combining both therapies in order to improve patients' quality of life and reduce treatment costs.
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Affiliation(s)
- Natalia Picheta
- Chair and Department of Epidemiology and Clinical Research Methodology, Medical
University of Lublin, Lublin, Poland
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Shaikh M, Doshi G. Epigenetic aging in major depressive disorder: Clocks, mechanisms and therapeutic perspectives. Eur J Pharmacol 2024; 978:176757. [PMID: 38897440 DOI: 10.1016/j.ejphar.2024.176757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 06/09/2024] [Accepted: 06/16/2024] [Indexed: 06/21/2024]
Abstract
Depression, a chronic mental disorder characterized by persistent sadness, loss of interest, and difficulty in daily tasks, impacts millions globally with varying treatment options. Antidepressants, despite their long half-life and minimal effectiveness, leave half of patients undertreated, highlighting the need for new therapies to enhance well-being. Epigenetics, which studies genetic changes in gene expression or cellular phenotype without altering the underlying Deoxyribonucleic Acid (DNA) sequence, is explored in this article. This article delves into the intricate relationship between epigenetic mechanisms and depression, shedding light on how environmental stressors, early-life adversity, and genetic predispositions shape gene expression patterns associated with depression. We have also discussed Histone Deacetylase (HDAC) inhibitors, which enhance cognitive function and mood regulation in depression. Non-coding RNAs, (ncRNAs) such as Long Non-Coding RNAs (lncRNAs) and micro RNA (miRNAs), are highlighted as potential biomarkers for detecting and monitoring major depressive disorder (MDD). This article also emphasizes the reversible nature of epigenetic modifications and their influence on neuronal growth processes, underscoring the dynamic interplay between genetics, environment, and epigenetics in depression development. It explores the therapeutic potential of targeting epigenetic pathways in treating clinical depression. Additionally, it examines clinical findings related to epigenetic clocks and their role in studying depression and biological aging.
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Affiliation(s)
- Muqtada Shaikh
- SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, 400 056, India
| | - Gaurav Doshi
- SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, 400 056, India.
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Li F, Zheng X, Wang H, Meng L, Chen M, Hui Y, Liu D, Li Y, Xie K, Zhang J, Guo G. Mediodorsal thalamus projection to medial prefrontal cortical mediates social defeat stress-induced depression-like behaviors. Neuropsychopharmacology 2024; 49:1318-1329. [PMID: 38438592 PMCID: PMC11224337 DOI: 10.1038/s41386-024-01829-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 02/07/2024] [Accepted: 02/07/2024] [Indexed: 03/06/2024]
Abstract
Clinical studies have shown that the mediodorsal thalamus (MD) may play an important role in the development of depression. However, the molecular and circuit mechanisms by which the mediodorsal thalamus (MD) participates in the pathological processes of depression remain unclear. Here, we show that in male chronic social defeat stress (CSDS) mice, the calcium signaling activity of glutamatergic neurons in MD is reduced. By combining conventional neurotracer and transneuronal virus tracing techniques, we identify a synaptic circuit connecting MD and medial prefrontal cortex (mPFC) in the mouse. Brain slice electrophysiology and fiber optic recordings reveal that the reduced activity of MD glutamatergic neurons leads to an excitatory-inhibitory imbalance of pyramidal neurons in mPFC. Furthermore, activation of MD glutamatergic neurons restores the electrophysiological properties abnormal in mPFC. Optogenetic activation of the MD-mPFC circuit ameliorates anxiety and depression-like behaviors in CSDS mice. Taken together, these data support the critical role of MD-mPFC circuit on CSDS-induced depression-like behavior and provide a potential mechanistic explanation for depression.
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Affiliation(s)
- Fang Li
- Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, 510630, China
- Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
| | - Xuefeng Zheng
- Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, 510630, China
| | - Hanjie Wang
- Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, 510630, China
| | - Lianghui Meng
- Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, 510630, China
| | - Meiying Chen
- Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, 510630, China
| | - Yuqing Hui
- Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, 510630, China
- Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
| | - Danlei Liu
- Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, 510630, China
- Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
| | - Yifei Li
- Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, 510630, China
| | - Keman Xie
- Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, 510630, China
| | - Jifeng Zhang
- Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, 510630, China.
| | - Guoqing Guo
- Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, 510630, China.
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Xia J, Wu L, Yan B, Pan J, Fang L, Zhu W, Chen L. Correlation between uncertainty stress and depression among healthcare professionals in China: a nationwide cross-sectional survey. BMJ Open 2024; 14:e078198. [PMID: 38830732 PMCID: PMC11149129 DOI: 10.1136/bmjopen-2023-078198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 04/04/2024] [Indexed: 06/05/2024] Open
Abstract
OBJECTIVE This study investigated the correlation between uncertainty stress (US) and depression among healthcare professionals (HCPs) in China. DESIGN, SETTINGS AND PARTICIPANTS A cross-sectional online survey was conducted by recruiting HCPs from three provinces in China (central, eastern and western) through purposive sampling between 29 September 2022 and 18 January 2023. US was measured using the Life Stress Questionnaire and depression was measured using the Patient Health Questionnaire-9. In total, 2976 questionnaires were deemed valid. PRIMARY AND SECONDARY OUTCOME This study examined the prevalence of US and depression among HCPs in China; the correlating sociodemographic traits; and the correlation between US and depression. RESULTS The prevalence of US and depression among HCPs in China was 26.54% (790 out of 2976) and 71.63% (2132 out of 2976). Binary logistic analysis revealed that individuals with graduate degrees (OR: 1.83; 95% CI 1.07 to 3.11; p<0.05), central China (OR: 1.75; 95% CI 1.36 to 2.24; p<0.01), primary medical institutes (OR: 1.33; 95% CI 1.03 to 1.72; p<0.05), secondary medical institutes (OR: 1.30; 95% CI 1.01 to 1.68; p<0.05), an annual income of less than ¥50 000 (OR: 1.85; 95% CI 1.26 to 2.73; p<0.01) and an income range of ¥50 000-¥99 999 (OR: 1.49; 95% CI 1.10 to 2.03; p<0.05) were associated with a higher likelihood of US. The adjusted logistic regression model demonstrated that HCPs with higher US had a greater likelihood of depression (adjusted OR: 5.02; 95% CI 3.88 to 6.50; p<0.01). The increase in the US score was paralleled by an increased depression score (beta (B): 1.32; 95% CI 1.25 to 1.39; p<0.01). CONCLUSION These findings reveal a significant correlation between US and depression among HCPs and suggest that improving the management of US may help reduce the prevalence of depression among HCPs.
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Affiliation(s)
- Jingjing Xia
- Deparment of General Practice, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China
| | - Lihong Wu
- Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China
| | - Bo Yan
- Zhejiang University, Hangzhou, China
| | - Jianjiang Pan
- Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China
| | - Lizheng Fang
- Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China
| | - Wenhua Zhu
- Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China
| | - Liying Chen
- Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China
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Shinkre R, Mukherji I, Bharadwaj A, Suresh NV, Banik AD, Pednekar SJ, K SB, Eshwar S, Rajagopal P. Depression, Anxiety, Stress, and Pain Severity in Patients With Recurrent Aphthous Stomatitis: A Cross-Sectional Study. Cureus 2024; 16:e62694. [PMID: 39036205 PMCID: PMC11259517 DOI: 10.7759/cureus.62694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 06/19/2024] [Indexed: 07/23/2024] Open
Abstract
Background Recurrent aphthous stomatitis (RAS) is a chronic oral ulcerative condition with an elusive etiology that is associated with excruciating pain. Psychological factors have been suspected as a possible risk factor in its onset and development. Depression, anxiety, and stress play pivotal roles in how people experience pain. Hence, we aimed to explore the relationship between depression, anxiety, stress, and the severity of pain perceived due to recurrent ulcers in RAS patients. Materials and methods A cross-sectional comparative study was conducted on 248 patients, comprising 124 diagnosed with RAS and 124 healthy subjects without this oral condition. Patients from both of these groups were matched with regard to age and sex and recruited over a period of one year from a dental hospital in Bengaluru, India. Patients with any other oral lesions, painful oral conditions, or systemic and psychological illnesses were excluded. Depression, anxiety, and stress were assessed in these patients using the Depression Anxiety Stress Scale 21 (DASS-21). Utilizing a Visual Analog Scale, ulcer-related pain was assessed in patients with RAS. The data were analyzed using the chi-square test and Pearson's correlation test in IBM SPSS Statistics for Windows, Version 26.0 (released 2019, IBM Corp., Armonk, NY). Results The chi-square analysis showed that participants with RAS showed a statistically significant higher prevalence of extreme stress (n = 39, 31.5%), extreme anxiety (n = 82, 66.1%), and depression (n = 38, 30.6%) as opposed to those without this oral condition. A moderately positive correlation was observed in the Pearson's test between the severity of pain experienced and stress and anxiety (r = 0.65 and 0.60, respectively, p < 0.05), while a mild positive correlation was observed between the severity of pain and depression (r = 0.35, p < 0.05). Conclusion Depression, anxiety, and stress influenced the severity of pain in these lesions, dictating the need for a holistic approach that integrates psychological interventions in the management of such chronic oral conditions with psychological links.
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Affiliation(s)
- Rohan Shinkre
- Central Research, KLE Society's Institute of Dental Sciences, Bengaluru, Bengaluru, IND
| | - Ishan Mukherji
- Public Health Dentistry, Guru Nanak Institute of Dental Sciences and Research, Kolkata, IND
| | - Aarya Bharadwaj
- Public Health Dentistry, KLE Society's Institute of Dental Sciences, Bengaluru, Bengaluru, IND
| | - Nikhil V Suresh
- Public Health Dentistry, KLE Society's Institute of Dental Sciences, Bengaluru, Bengaluru, IND
| | - Ankita Dutta Banik
- Dentistry/Oral Medicine and Radiology, Karkinos Healthcare Private Limited/Medella-Karkinos Oncology Institute, Kolkata, IND
| | | | - Srivastava B K
- Public Health Dentistry, KLE Society's Institute of Dental Sciences, Bengaluru, Bengaluru, IND
| | - Shruthi Eshwar
- Public Health Dentistry, KLE Society's Institute of Dental Sciences, Bengaluru, Bengaluru, IND
| | - Parimala Rajagopal
- Public Health Dentistry, KLE Society's Institute of Dental Sciences, Bengaluru, Bengaluru, IND
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Nakamura M, Yoshimi A, Tokura T, Kimura H, Kishi S, Miyauchi T, Iwamoto K, Ito M, Sato-Boku A, Mouri A, Nabeshima T, Ozaki N, Noda Y. Duloxetine improves chronic orofacial pain and comorbid depressive symptoms in association with reduction of serotonin transporter protein through upregulation of ubiquitinated serotonin transporter protein. Pain 2024; 165:1177-1186. [PMID: 38227563 DOI: 10.1097/j.pain.0000000000003124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 10/26/2023] [Indexed: 01/18/2024]
Abstract
ABSTRACT Chronic orofacial pain (COP) is relieved by duloxetine (DLX) and frequently causes depressive symptoms. The aim of this study was to confirm effects of DLX on pain and depressive symptoms, and to associate with their effectiveness in platelet serotonin transporter (SERT) expression, which is a target molecule of DLX and plasma serotonin concentration in COP patients with depressive symptoms. We assessed for the severity of pain and depressive symptoms using the Visual Analog Scale (VAS) and 17-item Hamilton Depression Rating Scale (HDRS), respectively. Chronic orofacial pain patients were classified into 2 groups based on their HDRS before DLX-treatment: COP patients with (COP-D) and without (COP-ND) depressive symptoms. We found that the VAS and HDRS scores of both groups were significantly decreased after DLX treatment compared with those before DLX treatment. Upregulation of total SERT and downregulation of ubiquitinated SERT were observed before DLX treatment in both groups compared with healthy controls. After DLX treatment, there were no differences in total SERT of both groups and in ubiquitinated SERT of COP-D patients compared with healthy controls; whereas, ubiquitinated SERT of COP-ND patients remained downregulated. There were positive correlations between changes of serotonin concentrations and of VAS or HDRS scores in only COP-D patients. Our findings indicate that DLX improves not only pain but also comorbid depressive symptoms of COP-D patients. Duloxetine also reduces platelet SERT through upregulation of ubiquitinated SERT. As the result, decrease of plasma serotonin concentrations may be related to the efficacy of DLX in relieving pain and depression in COP patients.
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Grants
- 21H04815 Ministry of Education, Culture, Sports, Science and Technology
- 17K10325 Ministry of Education, Culture, Sports, Science and Technology
- 21K06719 Ministry of Education, Culture, Sports, Science and Technology
- 19K17108 Ministry of Education, Culture, Sports, Science and Technology
- JP21dk0307103, Japan Agency for Medical Research and Development
- JP21dk0307087 Japan Agency for Medical Research and Development
- P21wm0425007 Japan Agency for Medical Research and Development
- JP21dm0207075 Japan Agency for Medical Research and Development
- JP21ek0109498 Japan Agency for Medical Research and Development
- AS251Z03018 Adaptable and Seamless Technology Transfer Program through Target-Driven R and D
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Affiliation(s)
- Mariko Nakamura
- Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, Nagoya, Japan
| | - Akira Yoshimi
- Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, Nagoya, Japan
- Clinical OMICs and Translation Research Center, Meijo University, Nagoya, Japan
- Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tatsuya Tokura
- Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroyuki Kimura
- Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shinichi Kishi
- Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomoya Miyauchi
- Department of Psychiatry, KACHI Memorial Hospital, Toyohashi, Japan
| | - Kunihiro Iwamoto
- Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mikiko Ito
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi Gakuin University, Nagoya, Japan
| | - Aiji Sato-Boku
- Department of Anesthesiology, School of Dentistry, Aichi Gakuin University, Nagoya Japan
| | - Akihiro Mouri
- Department of Regulatory Science for Evaluation & Development of Pharmaceuticals and Devices, Graduate School of Health Science, Fujita Health University, Aichi, Japan
- Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan
| | - Toshitaka Nabeshima
- Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan
- Laboratory of Health and Medical Science Innovation, Graduate School of Health Sciences, Fujita Health University, Aichi, Japan
| | - Norio Ozaki
- Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yukihiro Noda
- Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, Nagoya, Japan
- Clinical OMICs and Translation Research Center, Meijo University, Nagoya, Japan
- Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Laboratory of Health and Medical Science Innovation, Graduate School of Health Sciences, Fujita Health University, Aichi, Japan
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11
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Liang JY, Gao S, Jiang JM, Zhang P, Zou W, Tang XQ, Tang YY. Itaconate inhibits corticosterone-induced necroptosis and neuroinflammation via up-regulating menin in HT22 cells. J Physiol Biochem 2024; 80:393-405. [PMID: 38427168 DOI: 10.1007/s13105-024-01012-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 02/21/2024] [Indexed: 03/02/2024]
Abstract
Corticosterone (CORT) damages hippocampal neurons as well as induces neuroinflammation. The tricarboxylic acid cycle metabolite itaconate has an anti-inflammatory role. Necroptosis is a form of programmed cell death, also known as inflammatory cell death. Menin is a multifunctional scaffold protein, which deficiency aggravates neuroinflammation. In this study, we explored whether itaconate inhibits CORT-induced neuroinflammation as well as necroptosis and further investigated the mediatory role of Menin in this protective effect of itaconate by using an exposure of CORT to HT22 cells (a hippocampal neuronal cell line). The viability of HT22 cells was examined by the cell counting kit 8 (CCK-8). The morphology of HT22 cells was observed by transmission electron microscope (TEM). The expressions of necroptosis-related proteins (p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL) were evaluated by western blotting. The contents of inflammatory factors were detected by an enzyme-linked immunosorbent assay (ELISA) kit. Our results showed that CORT increases the contents of pro-inflammatory factors (IL-1β, TNF-α) as well as decreases the contents of anti-inflammatory factors (IL-4, IL-10) in HT22 cells. We also found that CORT increases the expressions of necroptosis-related proteins (p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL) and decreases the cell viability in HT22 cells, indicating that CORT induces necroptosis in HT22 cells. Itaconate improves CORT-induced neuroinflammation and necroptosis. Furthermore, itaconate upregulates the expression of Menin in CORT-exposed HT22 cells. Importantly, silencing Menin abolishes the antagonistic effect of itaconate on CORT-induced necroptosis and neuroinflammation. In brief, these results indicated that itaconate protects HT22 cells against CORT-induced neuroinflammation and necroptosis via upregulating Menin.
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Affiliation(s)
- Jin-Yu Liang
- Institute of Neuroscience, Hengyang Medical School, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China
| | - Shan Gao
- Institute of Neuroscience, Hengyang Medical School, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China
| | - Jia-Mei Jiang
- Institute of Neuroscience, Hengyang Medical School, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China
| | - Pin Zhang
- Department of Neurology, Affiliated Nanhua Hospital, University of South China, No. 336 S Dongfeng Road, Hengyang, 421002, Hunan Province, People's Republic of China
| | - Wei Zou
- Department of Neurology, Affiliated Nanhua Hospital, University of South China, No. 336 S Dongfeng Road, Hengyang, 421002, Hunan Province, People's Republic of China
| | - Xiao-Qing Tang
- Institute of Neuroscience, Hengyang Medical School, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.
- Department of Neurology, The Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, People's Republic of China.
| | - Yi-Yun Tang
- Institute of Neuroscience, Hengyang Medical School, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.
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12
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Deb P, Chini A, Guha P, Rishi A, Bhan A, Brady B, Perrotti LI, Mandal SS. Dynamic regulation of BDNF gene expression by estradiol and lncRNA HOTAIR. Gene 2024; 897:148055. [PMID: 38043834 DOI: 10.1016/j.gene.2023.148055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 11/22/2023] [Accepted: 11/29/2023] [Indexed: 12/05/2023]
Abstract
Brain derived neurotrophic factor (BDNF) is a major neurotransmitter that controls growth and maintenance of neurons and its misregulation is linked to neurodegeneration and human diseases. Estradiol (E2) is well-known to regulate the process of differentiation and plasticity of hippocampal neurons. Here we examined the mechanisms of BDNF gene regulation under basal conditions and under stimuli such as E2. Our results demonstrated that BDNF expression is induced by E2 in vitro in HT22 cells (hippocampal neuronal cells) and in vivo (in ovariectomized mouse brain under E2-treatment). Using chromatin immunoprecipitation assay, we demonstrated that estrogen receptors (ERα, ERβ) were enriched at the BDNF promoter in presence of E2. Additionally, ER-coregulators (e.g., CBP/p300, MLL3), histone acetylation, H3K4-trimethylation, and RNA polymerase II levels were also elevated at the BDNF promoter in an E2-dependent manner. Additionally, under the basal conditions (in the absence of E2), the long noncoding RNA HOTAIR and its interacting partners PRC2 and LSD1 complexes binds to the promoter of BDNF and represses its expression. HOTAIR knockdown -relieves the repression resulting in elevation of BDNF expression. Further, levels of HOTAIR-interacting partners, EZH2 and LSD1 were reduced at the BDNF promoter upon HOTAIR-knockdown revealing that HOTAIR plays a regulatory role in BDNF gene expression by modulating promoter histone modifications. Additionally, we showed that E2 induced-BDNF expression is mediated by the displacement of silencing factors, EZH2 and LSD1 at BDNF promoter and subsequent recruitment of active transcription machinery. These results reveal the mechanisms of BDNF gene regulation under the basal condition and in presence of a positive regulator such as E2 in neuronal cells.
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Affiliation(s)
- Paromita Deb
- Gene Regulation and Epigenetics Research Lab, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States
| | - Avisankar Chini
- Gene Regulation and Epigenetics Research Lab, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States
| | - Prarthana Guha
- Gene Regulation and Epigenetics Research Lab, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States
| | - Ashcharya Rishi
- Gene Regulation and Epigenetics Research Lab, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States
| | - Arunoday Bhan
- Gene Regulation and Epigenetics Research Lab, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States
| | - Blake Brady
- Department of Psychology, The University of Texas at Arlington, Arlington, TX 76019, United States
| | - Linda I Perrotti
- Department of Psychology, The University of Texas at Arlington, Arlington, TX 76019, United States
| | - Subhrangsu S Mandal
- Gene Regulation and Epigenetics Research Lab, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States.
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13
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He H, Zhao Z, Xiao C, Li L, Liu YE, Fu J, Liao H, Zhou T, Zhang J. Gut microbiome promotes mice recovery from stress-induced depression by rescuing hippocampal neurogenesis. Neurobiol Dis 2024; 191:106396. [PMID: 38176570 DOI: 10.1016/j.nbd.2023.106396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 12/19/2023] [Accepted: 12/29/2023] [Indexed: 01/06/2024] Open
Abstract
Studies from rodents to primates and humans indicate that individuals vary in how resilient they are to stress, and understanding the basis of these variations may help improve treatments for depression. Here we explored the potential contribution of the gut microbiome to such variation. Mice were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks then allowed to recover for 3 weeks, after which they were subjected to behavioral tests and categorized as showing low or high stress resilience. The two types of mouse were compared in terms of hippocampal gene expression using RNA sequencing, fecal microbiomes using 16S RNA sequencing, and extent of neurogenesis in the hippocampus using immunostaining of brain sections. Fecal microbiota were transplanted from either type of mouse into previously stress-exposed and stress-naïve animals, and the effects of the transplantation on stress-induced behaviors and neurogenesis in the hippocampus were examined. Finally, we blocked neurogenesis using temozolomide to explore the role of neurogenesis promoted by fecal microbiota transplantation in enhancing resilience to stress. Results showed that highly stress-resilient mice, but not those with low resilience, improved significantly on measures of anhedonia, behavioral despair, and anxiety after 3-week recovery from CUMS. Their feces showed greater abundance of Lactobacillus, Bifidobacterium and Romboutsia than feces from mice with low stress resilience, as well as lower abundance of Staphylococcus, Psychrobacter and Corynebacterium. Similarly, highly stress-resilient mice showed greater neurogenesis in hippocampus than animals with low stress resilience. Transplanting fecal microbiota from mice with high stress resilience into previously CUMS-exposed recipients rescued neurogenesis in hippocampus, facilitating recovery from stress-induced depression and cognitive decline. Blockade of neurogenesis with temozolomide abolished recovery of recipients from CUMS-induced depression and cognitive decline in mice transplanted with fecal microbiota from mice with high stress resilience. In conclusion, our results suggested that remodeling of the gut microbiome after stress may reverse stress-induced impairment of hippocampal neurogenesis and thereby promote recovery from stress-induced depression.
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Affiliation(s)
- Haili He
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Zhihuang Zhao
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Chenghong Xiao
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Liangyuan Li
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Yu-E Liu
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Juan Fu
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Hongyu Liao
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Tao Zhou
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
| | - Jinqiang Zhang
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
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14
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Guo H, Liu X, Chen T, Wang X, Zhang X. Akkermansia muciniphila Improves Depressive-Like Symptoms by Modulating the Level of 5-HT Neurotransmitters in the Gut and Brain of Mice. Mol Neurobiol 2024; 61:821-834. [PMID: 37668965 PMCID: PMC10861622 DOI: 10.1007/s12035-023-03602-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 08/21/2023] [Indexed: 09/06/2023]
Abstract
Accumulating evidence has suggested that the gut microbiome plays an important role in depression. Akkermansia muciniphila (AKK), a next-generation probiotic, shows a beneficial effect on immune and metabolic homeostasis. The relative abundance of AKK was found negatively correlated with depressive symptoms in both clinical and pre-clinical studies. To evaluate the potential antidepressant effect of AKK and explore the possible mechanism, we used chronic alcohol exposure and chronic unpredictable mild stress (CUMS) to induce depressive-like behaviors in mice. We found that oral AKK administration significantly reduced the immobility time in the force swimming test (FST) and tail suspension test (TST) in the mice with chronic alcohol exposure and the CUMS mice. The sucrose preference in the mice receiving AKK was significantly increased in the sucrose preference test (SPT). More importantly, AKK implantation significantly increased the level of 5-HT in the gut and PFC of both the alcohol exposure mice and the CUMS mice. Furthermore, AKK had inhibited the expression of SERT in the gut but not in the brain for both NIAAA and the CUMS model mice. Interestingly, the expression of cFos in enteric nerves in the gut significantly decreased after AKK administration. In conclusion, our study demonstrated the antidepressant effect of AKK in mice exposed to alcohol exposure and CUMS, with the potential mechanism that AKK implantation might lead to an increased level of 5-HT and inhibited SERT expression in the gut, and might alter the gut-to-brain signal through suppression of enteric nerves activation.
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Affiliation(s)
- Huijuan Guo
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, No. 139, Renmin Middle Road, Furong District, Changsha, 410011, Hunan Province, China
| | - Xinxu Liu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, No. 139, Renmin Middle Road, Furong District, Changsha, 410011, Hunan Province, China
| | - Ti Chen
- Clinical Laboratory, The Third Xiangya Hospital, Central South University, Changsha, 410000, Hunan, China
| | - Xiaoping Wang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, No. 139, Renmin Middle Road, Furong District, Changsha, 410011, Hunan Province, China
| | - Xiaojie Zhang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, No. 139, Renmin Middle Road, Furong District, Changsha, 410011, Hunan Province, China.
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15
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He H, He H, Mo L, You Z, Zhang J. Priming of microglia with dysfunctional gut microbiota impairs hippocampal neurogenesis and fosters stress vulnerability of mice. Brain Behav Immun 2024; 115:280-294. [PMID: 37914097 DOI: 10.1016/j.bbi.2023.10.031] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 10/26/2023] [Accepted: 10/29/2023] [Indexed: 11/03/2023] Open
Abstract
BACKGROUND Mental disorders may be involved in neuroinflammatory processes that are triggered by gut microbiota. How gut microbiota influence microglia-mediated sensitivity to stress remains unclear. Here we explored in an animal model of depression whether disruption of the gut microbiome primes hippocampal microglia, thereby impairing neurogenesis and sensitizing to stress. METHODS Male C57BL/6J mice were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, and effects on gut microbiota were assessed using 16S rRNA sequencing. Fecal microbiota was transplanted from control or CUMS mice into naïve animals. The depression-like behaviors of recipients were evaluated in a forced swimming test and sucrose preference test. The morphology and phenotype of microglia in the hippocampus of recipients were examined using immunohistochemistry, quantitative PCR, and enzyme-linked immunosorbent assays. The recipients were treated with lipopolysaccharide or chronic stress exposure, and effects were evaluated on behavior, microglial responses and hippocampal neurogenesis. Finally, we explored the ability of minocycline to reverse the effects of CUMS on hippocampal neurogenesis and stress sensitivity in recipients. RESULTS CUMS altered the gut microbiome, leading to higher relative abundance of some bacteria (Helicobacter, Bacteroides, and Desulfovibrio) and lower relative abundance of some bacteria (Lactobacillus, Bifidobacterium, and Akkermansia). Fecal microbiota transplantation from CUMS mice to naïve animals induced microglial priming in the dentate gyrus of recipients. This microglia showed hyper-ramified morphology, and became more sensitive to LPS challenge or chronic stress, which characterized by more significant morphological changes and inflammatory responses, as well as impaired hippocampal neurogenesis and increased depressive-like behaviors. Giving minocycline to recipients reversed these effects of fecal transplantation. CONCLUSIONS These findings suggest that gut microbiota from stressed animals can induce microglial priming in the dentate gyrus, which is associated with a hyper-immune response to stress and impaired hippocampal neurogenesis. Remodeling the gut microbiome or inhibiting microglial priming may be strategies to reduce sensitivity to stress.
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Affiliation(s)
- Hui He
- Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China
| | - Haili He
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Li Mo
- Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China
| | - Zili You
- Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
| | - Jinqiang Zhang
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
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16
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Ellis RJ, Marquine MJ, Kaul M, Fields JA, Schlachetzki JCM. Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management. Nat Rev Neurol 2023; 19:668-687. [PMID: 37816937 PMCID: PMC11052664 DOI: 10.1038/s41582-023-00879-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/07/2023] [Indexed: 10/12/2023]
Abstract
People living with HIV are affected by the chronic consequences of neurocognitive impairment (NCI) despite antiretroviral therapies that suppress viral replication, improve health and extend life. Furthermore, viral suppression does not eliminate the virus, and remaining infected cells may continue to produce viral proteins that trigger neurodegeneration. Comorbidities such as diabetes mellitus are likely to contribute substantially to CNS injury in people living with HIV, and some components of antiretroviral therapy exert undesirable side effects on the nervous system. No treatment for HIV-associated NCI has been approved by the European Medicines Agency or the US Food and Drug Administration. Historically, roadblocks to developing effective treatments have included a limited understanding of the pathophysiology of HIV-associated NCI and heterogeneity in its clinical manifestations. This heterogeneity might reflect multiple underlying causes that differ among individuals, rather than a single unifying neuropathogenesis. Despite these complexities, accelerating discoveries in HIV neuropathogenesis are yielding potentially druggable targets, including excessive immune activation, metabolic alterations culminating in mitochondrial dysfunction, dysregulation of metal ion homeostasis and lysosomal function, and microbiome alterations. In addition to drug treatments, we also highlight the importance of non-pharmacological interventions. By revisiting mechanisms implicated in NCI and potential interventions addressing these mechanisms, we hope to supply reasons for optimism in people living with HIV affected by NCI and their care providers.
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Affiliation(s)
- Ronald J Ellis
- Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
| | - María J Marquine
- Department of Medicine, Duke University, Durham, NC, USA
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
| | - Marcus Kaul
- School of Medicine, Division of Biomedical Sciences, University of California Riverside, Riverside, CA, USA
| | - Jerel Adam Fields
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
| | - Johannes C M Schlachetzki
- Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA
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17
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Shi TS, Li WY, Chen YM, Huang J, Guan W, Xu DW, Jiang B. The antidepressant-like effects of escitalopram in mice require salt-inducible kinase 1 and CREB-regulated transcription co-activator 1 in the paraventricular nucleus of the hypothalamus. J Affect Disord 2023; 338:228-238. [PMID: 37257779 DOI: 10.1016/j.jad.2023.05.085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 05/22/2023] [Accepted: 05/23/2023] [Indexed: 06/02/2023]
Abstract
BACKGROUND The salt-inducible kinase 1 (SIK1)-CREB-regulated transcription co-activator 1 (CRTC1) system in the paraventricular nucleus (PVN) of the hypothalamus has been demonstrated to participate in not only depression neurobiology but also the antidepressant mechanisms of fluoxetine, paroxetine, venlafaxine, and duloxetine. Like fluoxetine and paroxetine, escitalopram is also a well-known selective serotonin (5-HT) reuptake inhibitor (SSRI). However, recently it has been found that escitalopram can modulate a lot of targets other than the 5-HT system. Here, we speculate that escitalopram produces effects on the SIK1-CRTC1 system in the PVN. METHODS Two mice models of depression (chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS)), various behavioral tests, enzyme linked immunosorbent assay (ELISA), western blotting, co-immunoprecipitation (Co-IP), quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence, and adeno-associated virus (AAV)-mediated gene transfer were used together in the present study. RESULTS It was found that escitalopram administration not only significantly prevented the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis induced by CSDS and CUMS, but also notably reversed the effects of CSDS and CUMS on SIK1, CRTC1, and CRTC1-CREB binding in the PVN of mice. AAV-based genetic knock-down of SIK1 in PVN neurons evidently abolished the antidepressant-like effects of escitalopram in mice. LIMITATION A shortage of this study is that only rodent models of depression were used, while human samples were not included. CONCLUSIONS In summary, regulating the SIK1-CRTC1 system in the PVN participates in the antidepressant mechanism of escitalopram, which extends the knowledge of the pharmacological actions of escitalopram.
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Affiliation(s)
- Tian-Shun Shi
- Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, Jiangsu, China
| | - Wei-Yu Li
- Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, Jiangsu, China
| | - Yan-Mei Chen
- Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, Jiangsu, China
| | - Jie Huang
- Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, Jiangsu, China
| | - Wei Guan
- Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, Jiangsu, China
| | - Da-Wei Xu
- Department of Orthopedics, Affiliated Hospital 2 of Nantong University, Nantong 226006, Jiangsu, China.
| | - Bo Jiang
- Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, Jiangsu, China.
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18
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Hühne V, Chacur C, de Oliveira MVS, Fortes PP, Bezerra de Menezes GM, Fontenelle LF. Considerations for the treatment of obsessive-compulsive disorder in patients who have comorbid major depression. Expert Rev Neurother 2023; 23:955-967. [PMID: 37811649 DOI: 10.1080/14737175.2023.2265066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 09/26/2023] [Indexed: 10/10/2023]
Abstract
INTRODUCTION Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder that affects a significant number of individuals worldwide. Major depressive disorder (MDD) is among the most common comorbidities reported in people with OCD. The emergence of MDD in individuals with OCD can be attributed to the increased severity of OCD symptoms and their profound impact on daily functioning. Depressive symptoms can also modify the course of OCD. AREAS COVERED In this review, the authors explore potential shared neurobiological mechanisms that may underlie both OCD and MDD, such as disturbed sleep patterns, immunological dysregulations, and neuroendocrine changes. Furthermore, they address the challenges clinicians face when managing comorbid OCD and MDD. The authors also discuss a range of treatment options for OCD associated with MDD, including augmentation strategies for serotonin reuptake inhibitors (e.g. aripiprazole), psychotherapy (especially CBT/EPR), transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), and deep brain stimulation (DBS). EXPERT OPINION Although there is no 'rule of thumb' or universally acceptable strategy in the treatment of OCD comorbid with MDD, many clinicians, including the authors, tend to adopt a unique transdiagnostic approach to the treatment of OCD and related disorders, focusing on strategies known to be effective across diagnoses. Nevertheless, the existing 'cisdiagnostic approaches' still retain importance, i.e. specific therapeutic strategies tailored for more severe forms of individual disorders.
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Affiliation(s)
- Verônica Hühne
- Obsessive, Compulsive, and Anxiety Spectrum Research Program, Institute of Psychiatry of the Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Carina Chacur
- Obsessive, Compulsive, and Anxiety Spectrum Research Program, Institute of Psychiatry of the Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Marcos Vinícius Sousa de Oliveira
- Obsessive, Compulsive, and Anxiety Spectrum Research Program, Institute of Psychiatry of the Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Pedro Pereira Fortes
- Obsessive, Compulsive, and Anxiety Spectrum Research Program, Institute of Psychiatry of the Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Gabriela M Bezerra de Menezes
- Obsessive, Compulsive, and Anxiety Spectrum Research Program, Institute of Psychiatry of the Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
| | - Leonardo F Fontenelle
- Obsessive, Compulsive, and Anxiety Spectrum Research Program, Institute of Psychiatry of the Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
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19
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Portella MJ, González-González I, Jubero M, Trujols J, Pérez V. Depressive-Like Effects of Foreclosing: A Cross-Sectional Study of Hair Cortisol Concentration. Psychopathology 2023; 57:10-17. [PMID: 37331349 DOI: 10.1159/000530706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 04/12/2023] [Indexed: 06/20/2023]
Abstract
INTRODUCTION Foreclosing and home eviction have been associated with various negative health outcomes, probably due to exposure to such stressful circumstance, but there is no evidence about foreclosure and home eviction to elicit cortisol responses. METHODS Participants who recently had received a court eviction notice were compared to subjects suffering a depressive disorder and to healthy controls in terms of hair cortisol concentrations. RESULTS Subjects under the stressful circumstance of foreclosure and patients with depression showed comparable concentrations in most of the hair segments while healthy subjects displayed the lowest levels of cortisol. CONCLUSION The findings show that foreclosure and home eviction are associated with increased cumulative hair cortisol and with depressive-like symptoms. Foreclosing procedures yielded to maintain high levels of cortisol which may increase the risk to develop major depression.
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Affiliation(s)
- Maria J Portella
- Mental Health, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain
| | | | - Miriam Jubero
- Mental Health, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain
| | - Joan Trujols
- Mental Health, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain
| | - Víctor Pérez
- Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain
- INAD Parc de Salut Mar, Barcelona, Spain
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20
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Tseng YT, Zhao B, Ding H, Liang L, Schaefke B, Wang L. Systematic evaluation of a predator stress model of depression in mice using a hierarchical 3D-motion learning framework. Transl Psychiatry 2023; 13:178. [PMID: 37231005 DOI: 10.1038/s41398-023-02481-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 05/07/2023] [Accepted: 05/16/2023] [Indexed: 05/27/2023] Open
Abstract
Investigation of the neurobiology of depression in humans depends on animal models that attempt to mimic specific features of the human disorder. However, frequently-used paradigms based on social stress cannot be easily applied to female mice which has led to a large sex bias in preclinical studies of depression. Furthermore, most studies focus on one or only a few behavioral assessments, with time and practical considerations prohibiting a comprehensive evaluation. In this study, we demonstrate that predator stress effectively induced depression-like behaviors in both male and female mice. By comparing predator stress and social defeat models, we observed that the former elicited a higher level of behavioral despair and the latter elicited more robust social avoidance. Furthermore, the use of machine learning (ML)-based spontaneous behavioral classification can distinguish mice subjected to one type of stress from another, and from non-stressed mice. We show that related patterns of spontaneous behaviors correspond to depression status as measured by canonical depression-like behaviors, which illustrates that depression-like symptoms can be predicted by ML-classified behavior patterns. Overall, our study confirms that the predator stress induced phenotype in mice is a good reflection of several important aspects of depression in humans and illustrates that ML-supported analysis can simultaneously evaluate multiple behavioral alterations in different animal models of depression, providing a more unbiased and holistic approach for the study of neuropsychiatric disorders.
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Affiliation(s)
- Yu-Ting Tseng
- CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
- Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
| | - Binghao Zhao
- CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
- Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
| | - Hui Ding
- CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
- Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
| | - Lisha Liang
- CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
- Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
| | - Bernhard Schaefke
- CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
| | - Liping Wang
- CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
- Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
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21
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Xu DH, Du JK, Liu SY, Zhang H, Yang L, Zhu XY, Liu YJ. Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1. Cell Death Dis 2023; 14:278. [PMID: 37076499 PMCID: PMC10115824 DOI: 10.1038/s41419-023-05800-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 04/02/2023] [Accepted: 04/06/2023] [Indexed: 04/21/2023]
Abstract
Neuronal apoptosis has been well-recognized as a critical mediator in the pathogenesis of depressive disorders. Tissue kallikrein-related peptidase 8 (KLK8), a trypsin-like serine protease, has been implicated in the pathogenesis of several psychiatric disorders. The present study aimed to explore the potential function of KLK8 in hippocampal neuronal cell apoptosis associated with depressive disorders in rodent models of chronic unpredictable mild stress (CUMS)-induced depression. It was found that depression-like behavior in CUMS-induced mice was associated with hippocampal KLK8 upregulation. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency attenuated CUMS-induced depression-like behaviors and hippocampal neuronal apoptosis. In HT22 murine hippocampal neuronal cells and primary hippocampal neurons, adenovirus-mediated overexpression of KLK8 (Ad-KLK8) was sufficient to induce neuron apoptosis. Mechanistically, it was identified that the neural cell adhesion molecule 1 (NCAM1) may associate with KLK8 in hippocampal neurons as KLK8 proteolytically cleaved the NCAM1 extracellular domain. Immunofluorescent staining exhibited decreased NCAM1 in hippocampal sections obtained from mice or rats exposed to CUMS. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency largely prevented CUMS-induced loss of NCAM1 in the hippocampus. Both adenovirus-mediated overexpression of NCAM1 and NCAM1 mimetic peptide rescued KLK8-overexpressed neuron cells from apoptosis. Collectively, this study identified a new pro-apoptotic mechanism in the hippocampus during the pathogenesis of CUMS-induced depression via the upregulation of KLK8, and raised the possibility of KLK8 as a potential therapeutic target for depression.
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Affiliation(s)
- Dan-Hong Xu
- School of Kinesiology, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, The Key Laboratory of Exercise and Health Sciences of Ministry of Education Shanghai University of Sport, Shanghai, 200438, China
- Department of Physiology, Navy Medical University, Shanghai, 200433, China
| | - Jian-Kui Du
- National Clinical Research Center for Geriatric Disorders and National International Joint Research Center for Medical Metabolomics, Xiangya Hospital, Central South University, Changsha, Hunan, 41008, China
| | - Shi-Yu Liu
- School of Kinesiology, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, The Key Laboratory of Exercise and Health Sciences of Ministry of Education Shanghai University of Sport, Shanghai, 200438, China
| | - Hui Zhang
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Lu Yang
- School of Kinesiology, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, The Key Laboratory of Exercise and Health Sciences of Ministry of Education Shanghai University of Sport, Shanghai, 200438, China
| | - Xiao-Yan Zhu
- Department of Physiology, Navy Medical University, Shanghai, 200433, China.
| | - Yu-Jian Liu
- School of Kinesiology, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, The Key Laboratory of Exercise and Health Sciences of Ministry of Education Shanghai University of Sport, Shanghai, 200438, China.
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22
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Goldstein Ferber S, Shoval G, Rossi R, Trezza V, Di Lorenzo G, Zalsman G, Weller A, Mann JJ. Transdiagnostic considerations of mental health for the post-COVID era: Lessons from the first surge of the pandemic. World J Clin Cases 2023; 11:809-820. [PMID: 36818632 PMCID: PMC9928692 DOI: 10.12998/wjcc.v11.i4.809] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 11/28/2022] [Accepted: 01/16/2023] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND The Coronavirus disease 19 (COVID-19)-related psychiatric burden partly results from prolonged social stress world-wide. Studies have examined the psychiatric impact of COVID-19 on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) and International Classification of Diseases 11th Revision (ICD-11) categories, implicating multiple diagnoses, complicating clinical management. AIM To verify whether COVID-19-related psychopathology spans multiple DSM-5 and ICD-11 diagnoses, but not in a random pattern. Consequently, empirical analysis of the multiple associated symptoms will better describe COVID-19-related psychopathology. METHODS We conducted a bi-national study during the first surge of the pandemic: an Italian sample (n = 21217, studied March-April 2020); and three representative longitudinal samples from Israel (n = 1276, 1189, and 1432 respectively, studied May-July 2020). Data in Italy were collected by a national internet-based survey with an initially approached sample of about one million persons and in Israel by the Israeli Central Bureau of Statistics using probability-based national representative sampling. Data analysis focused on the frequency and patterns of reported multiple mental health symptoms. RESULTS Combinations with all symptoms were more prevalent than combinations with fewer symptoms, with no majorities-minorities differences in both countries, demonstrating the generalizability of the transdiagnostic pattern of mental health issues in both nations. A history of previous mental disorder (Italian study) and an increase in symptom prevalence over time (Israel study) were associated with an increased number of symptoms. Conclusions: Based on finding correlated symptom diversity spanning conventional diagnostic categories, we suggest that the pattern of mental health issues associated with the COVID-19 pandemic is transdiagnostic. CONCLUSION The findings have implications for improving prevention and treatment of COVID-19 related psychopathology and for post-pandemic times in conditions resulting from multiplicity of stressors with mixed symptomatology in the clinical picture.
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Affiliation(s)
| | - Gal Shoval
- Department of Neuroscience, Princeton University, Princeton NJ 08544, United States
- Geha Mental Health Center, Petah Tiqva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 77096, Israel
| | - Rodolfo Rossi
- Department of Systems Medicine, University of Rome Tor Vergata, Rome 00133, Italy
| | - Viviana Trezza
- Department of Science, Rome Tre University, Rome 00154, Italy
| | - Giorgio Di Lorenzo
- Department of Psychiatry, Rome University Tor Vergata, Rome 00179, Italy and IRCCS—Fondazione Santa Lucia, Rome 00179, Italy
| | - Gil Zalsman
- Geha Mental Health Center, Petah Tiqva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 77096, Israel
- Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University, NY, 10032, United States
| | - Aron Weller
- Department of Psychology, Bar Ilan University, Ramat Gan 5290002, Israel
| | - J John Mann
- Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University, NY, 10032, United States
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23
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Nowak M, Schindler S, Storch M, Geyer S, Schönknecht P. Mammillary body and hypothalamic volumes in mood disorders. J Psychiatr Res 2023; 158:216-225. [PMID: 36603316 DOI: 10.1016/j.jpsychires.2022.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 10/20/2022] [Accepted: 12/10/2022] [Indexed: 12/15/2022]
Abstract
We have previously reported an in vivo enlargement of the left hypothalamus in mood disorders using 7 T magnetic resonance imaging. The aim of this follow-up study was to find out whether the hypothalamic volume difference may be located in the mammillary bodies (MB) rather than being widespread across the hypothalamus. We developed and evaluated a detailed segmentation algorithm that allowed a reliable segmentation of the MBs, and applied it to 20 unmedicated (MDDu) and 20 medicated patients with major depressive disorder, 21 medicated patients with bipolar disorder, and 23 controls. 20 out of 23 healthy controls were matched to the MDDu. We tested for group differences in MB and hypothalamus without MB (HTh) volumes using analyses of covariance. Associations between both volumes of interest were analysed using bivariate and partial correlations. In contrast to postmortem findings, we found no statistically significant differences of the MB volumes between the study groups. Left HTh volumes differed significantly across the study groups after correction for intracranial volume (ICV) and for ICV and sex. Our result of an HTh enlargement in mood disorders was confirmed by a paired t-test between the matched pairs of MDDu and healthy controls using the native MB and HTh volumes. In the whole sample, MB volumes correlated significantly with the ipsilateral HTh volumes. Our results indicate a structural relationship between both volumes, and that our previous in vivo finding of a hypothalamus enlargement does not extend to the MB, but is limited to the HTh. The enlargement is more likely related to the dysregulation of the HPA axis than to cognitive dysfunctions accompanying mood disorders.
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Affiliation(s)
- Markus Nowak
- University Hospital Leipzig, Department of Psychiatry and Psychotherapy, Semmelweisstraße 10, 04103, Leipzig, Germany; Charité University of Medicine, Department of Psychiatry and Psychotherapy and St. Hedwig Hospital Berlin, Große Hamburger Straße 5-11, 10115, Berlin, Germany.
| | - Stephanie Schindler
- University Hospital Leipzig, Department of Psychiatry and Psychotherapy, Semmelweisstraße 10, 04103, Leipzig, Germany
| | - Melanie Storch
- University Hospital Leipzig, Department of Psychiatry and Psychotherapy, Semmelweisstraße 10, 04103, Leipzig, Germany
| | - Stefan Geyer
- Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurophysics, Stephanstraße 1a, 04103, Leipzig, Germany
| | - Peter Schönknecht
- University Hospital Leipzig, Department of Psychiatry and Psychotherapy, Semmelweisstraße 10, 04103, Leipzig, Germany; University Hospital Leipzig, Out-patient Department for Sexual-therapeutic Prevention and Forensic Psychiatry, Semmelweisstraße 10, 04103, Leipzig, Germany; Academic State Hospital Arnsdorf, Hufelandstraße 15, 01477, Arnsdorf, Germany
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24
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Liu D, Liu B, Lin T, Liu G, Yang G, Qi D, Qiu Y, Lu Y, Yuan Q, Shuai SC, Li X, Liu O, Tang X, Shuai J, Cao Y, Lin H. Measuring depression severity based on facial expression and body movement using deep convolutional neural network. Front Psychiatry 2022; 13:1017064. [PMID: 36620657 PMCID: PMC9810804 DOI: 10.3389/fpsyt.2022.1017064] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 12/02/2022] [Indexed: 12/24/2022] Open
Abstract
Introduction Real-time evaluations of the severity of depressive symptoms are of great significance for the diagnosis and treatment of patients with major depressive disorder (MDD). In clinical practice, the evaluation approaches are mainly based on psychological scales and doctor-patient interviews, which are time-consuming and labor-intensive. Also, the accuracy of results mainly depends on the subjective judgment of the clinician. With the development of artificial intelligence (AI) technology, more and more machine learning methods are used to diagnose depression by appearance characteristics. Most of the previous research focused on the study of single-modal data; however, in recent years, many studies have shown that multi-modal data has better prediction performance than single-modal data. This study aimed to develop a measurement of depression severity from expression and action features and to assess its validity among the patients with MDD. Methods We proposed a multi-modal deep convolutional neural network (CNN) to evaluate the severity of depressive symptoms in real-time, which was based on the detection of patients' facial expression and body movement from videos captured by ordinary cameras. We established behavioral depression degree (BDD) metrics, which combines expression entropy and action entropy to measure the depression severity of MDD patients. Results We found that the information extracted from different modes, when integrated in appropriate proportions, can significantly improve the accuracy of the evaluation, which has not been reported in previous studies. This method presented an over 74% Pearson similarity between BDD and self-rating depression scale (SDS), self-rating anxiety scale (SAS), and Hamilton depression scale (HAMD). In addition, we tracked and evaluated the changes of BDD in patients at different stages of a course of treatment and the results obtained were in agreement with the evaluation from the scales. Discussion The BDD can effectively measure the current state of patients' depression and its changing trend according to the patient's expression and action features. Our model may provide an automatic auxiliary tool for the diagnosis and treatment of MDD.
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Affiliation(s)
- Dongdong Liu
- Department of Physics, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
| | - Bowen Liu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
- Department of Psychiatry, Baoan Mental Health Center, Shenzhen Baoan Center for Chronic Disease Control, Shenzhen, China
| | - Tao Lin
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China
| | - Guangya Liu
- Integrated Chinese and Western Therapy of Depression Ward, Hunan Brain Hospital, Changsha, China
| | - Guoyu Yang
- Department of Physics, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
| | - Dezhen Qi
- Department of Physics, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
| | - Ye Qiu
- Department of Physics, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China
| | - Yuer Lu
- Department of Physics, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China
| | - Qinmei Yuan
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Stella C. Shuai
- Department of Biological Sciences, Northwestern University, Evanston, IL, United States
| | - Xiang Li
- Department of Physics, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
| | - Ou Liu
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China
| | - Xiangdong Tang
- Sleep Medicine Center, Mental Health Center, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Jianwei Shuai
- Department of Physics, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China
- State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, China
| | - Yuping Cao
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Hai Lin
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China
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25
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Yao H, Yang H, Wang Y, Xing Q, Yan L, Chai Y. Gut microbiome and fecal metabolic alteration in systemic lupus erythematosus patients with depression. Front Cell Infect Microbiol 2022; 12:1040211. [PMID: 36506019 PMCID: PMC9732533 DOI: 10.3389/fcimb.2022.1040211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 11/07/2022] [Indexed: 11/26/2022] Open
Abstract
Background Mental health disorders in systemic lupus erythematosus (SLE) are gradually getting recognized; however, less is known regarding the actual structure and compositional alterations in gut microbiome and metabolism and the mechanisms of how they affect depression development in SLE patients. Methods Twenty-one SLE patients with depression (SLE-d), 17 SLE patients without depression (SLE-nd), and 32 healthy controls (HC) were included in this study. Fecal samples were collected for 16S rRNA gene sequencing and ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) based metabolomics. Results The structure of gut microbiome in the SLE-d group changed compared with that in the other two groups. The microbiome composition of SLE-d group showed decreased species richness indices, characterized by low ACE and Chao1 indices, a decrease in the ratio of phylum Firmicutes to Bacteroidetes, genus Faecalibacterium and Roseburia. A downregulation of the metabolite fexofenadine involved in bile secretion was positively correlated with the genus Faecalibacterium, Subdoligranulum and Agathobacter. Compared with the SLE-nd group, the SLE-d group had elevated serum levels of IL-2 and IL-6 and decreased BDNF. Interestingly, abundance of the genus Faecalibacterium and Roseburia was negatively correlated with IL-6, abundance of the genus Roseburia was negatively correlated with IL-2, and abundance of the genus Bacteroides was positively correlated with IL-2. Conclusion This study identified specific fecal microbes and their metabolites that may participate in the development of SLE-d. Our findings provide a new perspective for improving depression in SLE patients by regulating the gut-brain axis.
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Affiliation(s)
- Han Yao
- Department of Immunology and Rheumatology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, Shandong, China
| | - Hao Yang
- School of Clinical Medicine, Weifang Medical University, Weifang, Shandong, China
| | - Yueying Wang
- Department of Immunology and Rheumatology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, Shandong, China
| | - Qian Xing
- Department of Immunology and Rheumatology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, Shandong, China,*Correspondence: Qian Xing,
| | - Lin Yan
- School of Clinical Medicine, Graduate School of Dalian Medical University, Dalian, Liaoning, China
| | - Yaru Chai
- School of Clinical Medicine, Weifang Medical University, Weifang, Shandong, China
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26
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Martinez-Fierro ML, Ayala-Haro AE, Pinedo-Hurtado ME, Solis-Galvan JA, Garza-Veloz I, Velazquez-Lopez ZY, Camacho-Martinez AG, Avila-Carrasco L, Vazquez-Reyes S, Velasco-Elizondo P, Mauricio-Gonzalez A, Ortiz-Castro Y. Usefulness of a Mobile Application (Mentali) for Anxiety and Depression Screening in Medical Students and Description of the Associated Triggering Factors. Brain Sci 2022; 12:1223. [PMID: 36138959 PMCID: PMC9496953 DOI: 10.3390/brainsci12091223] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 09/04/2022] [Accepted: 09/07/2022] [Indexed: 12/26/2022] Open
Abstract
The impact of the COVID-19 health crisis on the mental health of the population requires the implementation of new primary screening strategies of mental health disorders to intervene in a timelier manner, and technology may provide solutions. We aimed to evaluate the usefulness of the mobile app Mentali (version 1.1.2; creators: Jorge Alfonso Solís Galván Sodel Vázquez Reyes, Margarita de la Luz Martínez Fierro, Perla Velasco Elizondo, Idalia Garza Veloz, Alejandro Mauricio González and Claudia Caldera Villalobos, Zacatecas, México) as a primary screening tool for anxiety and depression disorders in medical students and to assess the triggering risk factors. This was a descriptive and longitudinal study and included 155 Mexican medical students. Participants interacted with Mentali for 6 months. The mobile app integrated the Beck anxiety and depression inventories together with a mood module. At the end of the interaction, the students received psychological and psychiatric interventions to confirm their primary diagnoses. Symptoms of moderate/severe anxiety and depression were present in 62.6% and 54.6% of the studied population. When corroborating the diagnoses, Mentali obtained a sensitivity of 100%, 95%, and 43% to classify a mental health disorder, anxiety, and depression, respectively. The most important triggers found were as follows: belonging to a dysfunctional family, being introverted, and having suffered from bullying. The proportion of users with excellent/good mood decreased from 78.7% to 34.4% at the end of the semester, and the proportion of users who claimed to have bad/very bad mood increased from 7.4% to 34.4% at the end of the semester (p < 0.05). Mentali was useful for identifying users with anxiety and/or depression, and as an auxiliary tool to coordinate the provision of specialized interventions, allowing us to increase the proportion of patients who needed psychological care and received it by 30%. The efficacy of Mentali in identifying activities through time with an impact on the mood and mental health of the users was confirmed. Our results support the use of Mentali for the primary screening of mental health disorders in young adults, including medical students.
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Affiliation(s)
- Margarita L. Martinez-Fierro
- Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico
| | - Anayantzin E. Ayala-Haro
- Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico
| | - Martha E. Pinedo-Hurtado
- Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico
| | - Jorge A. Solis-Galvan
- Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico
| | - Idalia Garza-Veloz
- Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico
| | - Zihomara Y. Velazquez-Lopez
- Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico
| | - Antonio G. Camacho-Martinez
- Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico
| | - Lorena Avila-Carrasco
- Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico
| | - Sodel Vazquez-Reyes
- Academic Unit of Electrical Engineering, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico
| | - Perla Velasco-Elizondo
- Academic Unit of Electrical Engineering, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico
| | - Alejandro Mauricio-Gonzalez
- Academic Unit of Electrical Engineering, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico
| | - Yolanda Ortiz-Castro
- Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Universidad Autónoma de Zacatecas, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico
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Mental health and the effects on methylation of stress-related genes in front-line versus other health care professionals during the second wave of COVID-19 pandemic: an Italian pilot study. Eur Arch Psychiatry Clin Neurosci 2022; 273:347-356. [PMID: 36001138 PMCID: PMC9399986 DOI: 10.1007/s00406-022-01472-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 08/02/2022] [Indexed: 11/12/2022]
Abstract
Healthcare workers experienced high degree of stress during COVID-19. Purpose of the present article is to compare mental health (depressive and Post-Traumatic-Stress-Disorders-PTSD-symptoms) and epigenetics aspects (degree of methylation of stress-related genes) in front-line healthcare professionals versus healthcare working in non-COVID-19 wards. Sixty-eight healthcare workers were included in the study: 39 were working in COVID-19 wards (cases) and 29 in non-COVID wards (controls). From all participants, demographic and clinical information were collected by an ad-hoc questionnaire. Depressive and PTSD symptoms were evaluated by the Patient Health Questionnaire-9 (PHQ-9) and the Impact of Event Scale-Revised (IES-R), respectively. Methylation analyses of 9 promoter/regulatory regions of genes known to be implicated in depression/PTSD (ADCYAP1, BDNF, CRHR1, DRD2, IGF2, LSD1/KDM1A, NR3C1, OXTR, SLC6A4) were performed on DNA from blood samples by the MassARRAY EpiTYPER platform, with MassCleave settings. Controls showed more frequent lifetime history of anxiety/depression with respect to cases (χ2 = 5.72, p = 0.03). On the contrary, cases versus controls presented higher PHQ-9 (t = 2.13, p = 0.04), PHQ-9 sleep item (t = 2.26, p = 0.03), IES-R total (t = 2.17, p = 0.03), IES-R intrusion (t = 2.46, p = 0.02), IES-R avoidance (t = 1.99, p = 0.05) mean total scores. Methylation levels at CRHR1, DRD2 and LSD1 genes was significantly higher in cases with respect to controls (p < 0.01, p = 0.03 and p = 0.03, respectively). Frontline health professionals experienced more negative effects on mental health during COVID-19 pandemic than non-frontline healthcare workers. Methylation levels were increased in genes regulating HPA axis (CRHR1) and dopamine neurotransmission (DRD2 and LSD1), thus supporting the involvement of these biological processes in depression/PTSD and indicating that methylation of these genes can be modulated by stress conditions, such as working as healthcare front-line during COVID-19 pandemic.
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Markova EV, Knyazheva MA, Tikhonova MA, Amstislavskaya TG. Structural and functional characteristics of the hippocampus in depressive-like recipients after transplantation of in vitro caffeine-modulated immune cells. Neurosci Lett 2022; 786:136790. [PMID: 35839995 DOI: 10.1016/j.neulet.2022.136790] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 07/05/2022] [Accepted: 07/08/2022] [Indexed: 10/17/2022]
Abstract
The hippocampus is a key anatomical brain region associated with depression. On the other hand, immune cells and their releasing cytokines play an essential role in stress and depression. Noteworthy that the most of psychoactive drugs produce unidirectional effects on the cells of both nervous and immune systems. This suggests the immunotherapy for behavioral disorders based on the treatment with autologous immune cells in which functional activity was modulated ex vivo by a psychoactive drug. Here, we treated the immune cells of depressive-like mice in vitro with caffeine (100 μg per 15 × 106 cells). The effects of caffeine-treated immune cells transplantation on neuronal density, production of brain-derived neurotrophic factor (BDNF) and a number of cytokines in the hippocampus of depressive-like syngeneic animals were studied. In depressive-like recipients, an increase in the density of pyramidal neurons in CA1 and CA3 hippocampal regions, accompanied with augmented level of BDNF, decreased levels of pro-inflammatory (IL-1β, IL-6, INF-γ, and TNF-α) and increased levels of anti-inflammatory (IL-10 and IL-4) cytokines was found. The mechanisms of the revealed structural and functional alterations in the hippocampus of depressive-like recipients after transplantation of caffeine-treated immune cells are discussed.
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Affiliation(s)
- Evgeniya V Markova
- Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology" (RIFCI), Yadrintsevskaya st., 14, 630099 Novosibirsk, Russia.
| | - Maria A Knyazheva
- Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology" (RIFCI), Yadrintsevskaya st., 14, 630099 Novosibirsk, Russia
| | - Maria A Tikhonova
- Scientific Research Institute of Neurosciences and Medicine (SRINM), Timakov str., 4, 630117 Novosibirsk, Russia.
| | - Tamara G Amstislavskaya
- Scientific Research Institute of Neurosciences and Medicine (SRINM), Timakov str., 4, 630117 Novosibirsk, Russia
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Zhang Y, Hou F, Cheng J, Chen G, Wang L, Jiang X, Chen R, Shen G. The association between leftover food consumption and depression among older adults: Findings from a cross-sectional study. J Affect Disord 2022; 307:157-162. [PMID: 35390351 DOI: 10.1016/j.jad.2022.03.074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 03/27/2022] [Accepted: 03/31/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Leftover food consumption is very prevalent among the Chinese older adults, however, the potential effects of leftover eating consumption on depression have not yet been investigated. OBJECTIVES The study aims to determine the association between leftover consumption on depression among older adults. METHODS Data of leftover consumption frequency was collected in a cross-sectional study with a provincial representative sample of 5992 older adults (aged 60 or older) in 2019. Depression symptoms were assessed by the 9-item screener Patient Health Questionnaire (PHQ-9). Multiple logistic regression models were applied to analyze the association of the frequency of leftover eating consumption and the presence and the severity of depression. RESULTS After controlling for all the covariates, the participants who consume leftover food everyday had higher risk of having depression symptom comparing to those who had the lowest frequency of leftover eating (OR: 1.675, 95% CI: 1.435-1.956, p < 0.001). The participants who consume leftover food every day was also associated with more severe depression symptoms (OR: 1.621, 95% CI: 1.397-1.881, p < 0.001), when comparing to the reference group. The associations seemed stronger in men than women. LIMITATIONS The causal relationship between leftover consumption behavior and depression could not be determined due to the cross-sectional design. Moreover, the variety or handling method of the leftover food was not specified. CONCLUSION Leftovers eating frequency was associated with the presence and severity of depression symptoms among older adults.
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Affiliation(s)
- Yan Zhang
- School of Health Service Management, Anhui Medical University, Hefei 230032, Anhui, PR China
| | - Fangfang Hou
- School of Health Service Management, Anhui Medical University, Hefei 230032, Anhui, PR China
| | - Jing Cheng
- School of Health Service Management, Anhui Medical University, Hefei 230032, Anhui, PR China
| | - Guimei Chen
- School of Health Service Management, Anhui Medical University, Hefei 230032, Anhui, PR China
| | - Li Wang
- School of Health Service Management, Anhui Medical University, Hefei 230032, Anhui, PR China
| | - Xiaodong Jiang
- Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, PR China.
| | - Ren Chen
- School of Health Service Management, Anhui Medical University, Hefei 230032, Anhui, PR China; The Affiliated Suzhou Hospital of Anhui Medical University, Suzhou 234000, Anhui, PR China.
| | - Guodong Shen
- Department of Geriatrics, The First Affiliated Hospital of University of Science and Technology of China, Gerontology Institute of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui, PR China; Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei 230001, Anhui, PR China.
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Associations between Autoimmunity and Depression: Serum IL-6 and IL-17 Have Directly Impact on the HAMD Scores in Patients with First-Episode Depressive Disorder. J Immunol Res 2022; 2022:6724881. [PMID: 35615531 PMCID: PMC9126704 DOI: 10.1155/2022/6724881] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 03/28/2022] [Accepted: 03/29/2022] [Indexed: 11/17/2022] Open
Abstract
Objective. The study is aimed at evaluating the immune-activation state before and after treatment in patients with first-episode depressive disorder (FDD) with evaluating the ILs and CRP levels and further clarifying the association between autoimmunity and the etiology and pathogenesis of FDD. Methods. We designed a case-control study. FDD patients and healthy subjects were enrolled in the FDD group and control group. Serum IL-6, IL-17, and CRP were measured before and after selective serotonin reuptake inhibitor (SSRI) therapy, as well as Hamilton rating scale for depression (HAMD) and life event scale (LES) scores. The correlations between IL-6 and IL-17 and HAMD and LES scores were analysed, and multiple linear regression analysis was performed for HAMD score. Results. 40 FDD patients and 40 healthy subjects were included in the FDD and control group from October 2009 to September 2012. Before treatment, the IL-6 (
,
) and IL-17 (
,
) in the FDD group were significantly higher than the control group (
and
, respectively). The C-reactive protein (CRP) level in two groups was comparable (
). After treatment, the IL-6 (
,
) and IL-17 (
,
) levels and HAMD scores (
) in the FDD group were significantly decreased than before treatment (
, respectively). CRP level was slightly increased after treatment without statistically significant (
). The HAMD score correlated with IL-6 (
,
) and IL-17 (
,
); the total LES and negative LES also correlated with IL-6 (
,
) (
, P <0.001) and IL-17 (
,
) (
,
). Multiple linear regression analysis showed that both of the IL-6 and IL-17 had direct impact on HAMD score. Conclusion. The autoimmunity status was overactivated in FDD patients, and serum IL-6 and IL-17 levels had direct impact on the HAMD score. Patients who experienced more negative life events had higher activation level of autoimmunity status and HAMD scores, and serum IL-6 and IL-17 levels can be decreased by SSRI treatment.
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Wu Z, Cai Z, Shi H, Huang X, Cai M, Yuan K, Huang P, Shi G, Yan T, Li Z. Effective biomarkers and therapeutic targets of nerve-immunity interaction in the treatment of depression: an integrated investigation of the miRNA-mRNA regulatory networks. Aging (Albany NY) 2022; 14:3569-3596. [PMID: 35468096 PMCID: PMC9085226 DOI: 10.18632/aging.204030] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 04/11/2022] [Indexed: 11/25/2022]
Abstract
Background: Major depressive disorder (MDD) is an emotional condition that interferes with sufferers’ work and daily life. Numerous studies have found that miRNAs play a significant role in the development of MDD and can be utilized as a biomarker for its diagnosis and therapy. However, there have been few studies on nerve-immunity interaction treatment for the brains of MMD patients. Methods: The work is performed on microarray data. We analyzed the differences of miRNAs (GSE58105, GSE81152, GSE152267, and GSE182194) and mRNA (GSE19738, GSE32280, GSE44593, GSE53987, and GSE98793) in MDD and healthy samples from GEO datasets. FunRich was used to predict the transcription factors and target genes of the miRNAs, and TF and GO enrichment analyses were performed. Then, by comparing the differential expression of the anticipated target genes and five mRNAs, intersecting mRNAs were discovered. The intersecting genes were submitted to GO and KEGG analyses to determine their functions. These intersecting potential genes and pathways that linked to MDD in neurological and immunological aspects have been identified for future investigation. Results: We discovered five hub genes: KCND2, MYT1L, GJA1, CHL1, and SNAP25, which were all up-regulated genes. However, in MMD, the equivalent miRNAs, hsa-miR-206 and hsa-miR-338-3p, were both down-regulated. These miRNAs can activate or inhibit the T cell receptor signal pathway, JAK-STAT and other signal pathways, govern immune-inflammatory response, neuronal remodeling, and mediate the onset and development of MMD Conclusions: The results of a thorough bioinformatics investigation of miRNAs and mRNAs in MDD showed that miR-338-3P and miR-206 might be effective biomarkers and possible therapeutic targets for the treatment of MDD via nerve-immunity interaction.
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Affiliation(s)
- Zixuan Wu
- Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Zhixiang Cai
- Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Hongshuo Shi
- Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
| | - Xuyan Huang
- Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Minjie Cai
- Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China.,Shantou Health School, Shantou 515061, Guangdong Province, China
| | - Kai Yuan
- Yunnan University of Chinese Medicine, Kunming 650500, Yunnan Province, China
| | - Peidong Huang
- Yunnan University of Chinese Medicine, Kunming 650500, Yunnan Province, China
| | - Guoqi Shi
- Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Tao Yan
- Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China.,Department of Cardiovascular Surgery, General Hospital of Southern Theater Command, PLA 510010, Guangdong Province, China
| | - Zhichao Li
- The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
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Meng P, Li C, Duan S, Ji S, Xu Y, Mao Y, Wang H, Tian J. Epigenetic Mechanism of 5-HT/NE/DA Triple Reuptake Inhibitor on Adult Depression Susceptibility in Early Stress Mice. Front Pharmacol 2022; 13:848251. [PMID: 35370730 PMCID: PMC8968447 DOI: 10.3389/fphar.2022.848251] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 02/07/2022] [Indexed: 11/16/2022] Open
Abstract
Major depressive disorder (MDD) is a chronic, remitting and debilitating disease and the etiology of MDD is highly complicated that involves genetic and environmental interactions. Despite many pharmacotherapeutic options, many patients remain poorly treated and the development of effective treatments remains a high priority in the field. LPM570065 is a potent 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA) triple reuptake inhibitor and both preclinical and clinical results demonstrate significant efficacy against MDD. This study extends previous findings to examine the effects and underlying mechanisms of LPM570065 on stress vulnerability using a "two-hit" stress mouse model. The "two-hit" stress model used adult mice that had experienced early life maternal separation (MS) stress for social defeat stress (SDS) and then they were evaluated in three behavioral assays: sucrose preference test, tail suspension test and forced swimming test. For the mechanistic studies, methylation-specific differentially expressed genes in mouse hippocampal tissue and ventral tegmental area (VTA) were analyzed by whole-genome transcriptome analysis along with next-generation bisulfite sequencing analysis, followed by RT-PCR and pyrophosphate sequencing to confirm gene expression and methylation. LPM570065 significantly reversed depressive-like behaviors in the mice in the sucrose preference test, the tail suspension test, and the forced swimming test. Morphologically, LPM570065 increased the density of dendritic spines in hippocampal CA1 neurons. Hypermethylation and downregulation of oxytocin receptor (Oxtr) in the hippocampal tissues along with increased protein expression of Dnmt1 and Dnmt3a in mice that experienced the "two-hit" stress compared to those that only experienced adulthood social defeat stress, and LPM570065 could reverse these changes. Combined, these results suggest that methylation specificity of the gene Oxtr in the hippocampus may play an important role in early life stress-induced susceptibility to depression and that the5-HT/NE/DA triple reuptake inhibitor LPM570065 may reduce depression susceptibility via the reversal of the methylation of the gene Oxtr.
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Affiliation(s)
| | - Chunmei Li
- *Correspondence: Chunmei Li, ; Jingwei Tian,
| | | | | | | | | | | | - Jingwei Tian
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, China
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Riveros ME, Ávila A, Schruers K, Ezquer F. Antioxidant Biomolecules and Their Potential for the Treatment of Difficult-to-Treat Depression and Conventional Treatment-Resistant Depression. Antioxidants (Basel) 2022; 11:540. [PMID: 35326190 PMCID: PMC8944633 DOI: 10.3390/antiox11030540] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 03/09/2022] [Accepted: 03/10/2022] [Indexed: 11/23/2022] Open
Abstract
Major depression is a devastating disease affecting an increasing number of people from a young age worldwide, a situation that is expected to be worsened by the COVID-19 pandemic. New approaches for the treatment of this disease are urgently needed since available treatments are not effective for all patients, take a long time to produce an effect, and are not well-tolerated in many cases; moreover, they are not safe for all patients. There is solid evidence showing that the antioxidant capacity is lower and the oxidative damage is higher in the brains of depressed patients as compared with healthy controls. Mitochondrial disfunction is associated with depression and other neuropsychiatric disorders, and this dysfunction can be an important source of oxidative damage. Additionally, neuroinflammation that is commonly present in the brain of depressive patients highly contributes to the generation of reactive oxygen species (ROS). There is evidence showing that pro-inflammatory diets can increase depression risk; on the contrary, an anti-inflammatory diet such as the Mediterranean diet can decrease it. Therefore, it is interesting to evaluate the possible role of plant-derived antioxidants in depression treatment and prevention as well as other biomolecules with high antioxidant and anti-inflammatory potential such as the molecules paracrinely secreted by mesenchymal stem cells. In this review, we evaluated the preclinical and clinical evidence showing the potential effects of different antioxidant and anti-inflammatory biomolecules as antidepressants, with a focus on difficult-to-treat depression and conventional treatment-resistant depression.
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Affiliation(s)
- María Eugenia Riveros
- Centro de Fisiología Celular e Integrativa, Facultad de Medicina Clínica Alemana-Universidad del Desarrollo, Santiago 7710162, Chile
| | - Alba Ávila
- Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana-Universidad del Desarrollo, Santiago 7710162, Chile;
| | - Koen Schruers
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, 6229 Maastricht, The Netherlands;
| | - Fernando Ezquer
- Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana-Universidad del Desarrollo, Santiago 7710162, Chile;
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Zheng K, Chu J, Zhang X, Ding Z, Song Q, Liu Z, Peng W, Cao W, Zou T, Yi J. Psychological resilience and daily stress mediate the effect of childhood trauma on depression. CHILD ABUSE & NEGLECT 2022; 125:105485. [PMID: 35026440 DOI: 10.1016/j.chiabu.2022.105485] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 12/28/2021] [Accepted: 01/04/2022] [Indexed: 06/14/2023]
Abstract
OBJECTIVE Childhood trauma (CT) is a well-recognized distal risk factor for depression. Previous studies suggested that the psychological mechanism of the impact of childhood trauma on depression may be attributed to some mediators such as daily stress and psychological resilience. This study aimed to assess how daily stress and resilience affect the relationship between childhood trauma and depression in adult clinical context. METHOD In this cross-section survey, a total of 569 clinical patients with psychological disorders completed a series of psychological scales such as the Childhood Trauma Questionnaire (CTQ), the Center for Epidemiologic Studies Depression Scale (CESD), the Perceived Stress Scale (PSS) and Connor-Davidson Resilience Scale (CD-RISC). To show the relationship among childhood trauma, psychological resilience, daily stress and depression, structural equation modeling (SEM) was performed. RESULTS The results indicated that psychological resilience and daily stress partially mediated the relationship between childhood trauma and depressive symptoms. Childhood trauma not only exerted direct effect on depressive symptoms, but also had indirect effect through the mediation pathway (resilience → daily stress) on depressive symptoms. The chain mediation pathway through resilience and daily stress was weighted 43.31%. CONCLUSIONS The study provides novel evidence on the underlying process between childhood trauma and depression. The distal factor childhood trauma can influence the latter depression by the chain effect of psychological resilience and daily stress. Therefore, some clinical interventions to improve psychological resilience to carry off daily stress are the way to reduce the impact of childhood trauma on depression.
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Affiliation(s)
- Kaili Zheng
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Medical Psychology Institution, Central South University, Changsha 410011, Hunan, China
| | - Jun Chu
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Medical Psychology Institution, Central South University, Changsha 410011, Hunan, China
| | - Xiaocui Zhang
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Medical Psychology Institution, Central South University, Changsha 410011, Hunan, China
| | - Zixia Ding
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Medical Psychology Institution, Central South University, Changsha 410011, Hunan, China
| | - Qian Song
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Medical Psychology Institution, Central South University, Changsha 410011, Hunan, China
| | - Zhaoxia Liu
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Medical Psychology Institution, Central South University, Changsha 410011, Hunan, China
| | - Wanrong Peng
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Medical Psychology Institution, Central South University, Changsha 410011, Hunan, China
| | - Wanyi Cao
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Medical Psychology Institution, Central South University, Changsha 410011, Hunan, China
| | - Tao Zou
- Department of psychiatry, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China.
| | - Jinyao Yi
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Medical Psychology Institution, Central South University, Changsha 410011, Hunan, China; National Clinical Research Center for Mental Disorders, Changsha, Hunan, China.
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Gao S, Zhang X, Xu H, Miao D, Qian J, Wu Z, Shi W. Promoting the hippocampal PPARα expression participates in the antidepressant mechanism of reboxetine, a selective norepinephrine reuptake inhibitor. Behav Brain Res 2022; 416:113535. [PMID: 34416301 DOI: 10.1016/j.bbr.2021.113535] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 07/11/2021] [Accepted: 08/13/2021] [Indexed: 12/18/2022]
Abstract
Reboxetine, the first selective norepinephrine (NA) reuptake inhibitor used in the treatment of depression, mainly acts by binding to the NA transporter and blocking reuptake of extracellular NA. Recently, some other pharmacological targets beyond the NA transporter are being demonstrated for reboxetine. Peroxisome proliferator activated receptor α (PPARα) is a member of the nuclear hormone receptor family of ligand-dependent transcription factors. Previous reports have demonstrated the role of hippocampal PPARα in the pathophysiology of depression. Here we assume that hippocampal PPARα may participate in the antidepressant mechanism of reboxetine. Therefore, the chronic social defeat stress (CSDS) model of depression, various behavioral tests, the western blotting and adenovirus associated virus (AAV)-mediated genetic knockdown methods were used together in the present study. Our results showed that repeated reboxetine treatment markedly restored the decreasing effects of CSDS on the expression of hippocampal PPARα, brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein (pCREB). Pharmacological blockade of PPARα notably prevented the antidepressant-like effects of reboxetine in the CSDS model. Furthermore, genetic knockdown of hippocampal PPARα also fully abolished the antidepressant-like effects of reboxetine in the CSDS model. Taken together, promoting the hippocampal PPARα expression participates in the antidepressant mechanism of reboxetine.
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Affiliation(s)
- Shangyan Gao
- Department of Neurology, The Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Nantong, 226011, Jiangsu, China
| | - Xueling Zhang
- Department of Neurology, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, 223800, Jiangsu, China
| | - Hui Xu
- Department of Neurosurgery, The Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Nantong, 226011, Jiangsu, China
| | - Dongjin Miao
- Department of Neurology, The Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Nantong, 226011, Jiangsu, China
| | - Jiaoni Qian
- Department of Neurology, The Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Nantong, 226011, Jiangsu, China
| | - Zhonghua Wu
- Department of Neurosurgery, The Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Nantong, 226011, Jiangsu, China.
| | - Weihua Shi
- Department of Traditional Chinese Medicine, The Affiliated Hospital of Nantong University, No. 20 Xisi Road, Nantong, 226001, Jiangsu, China.
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Wang S, Liu X, Shi W, Qi Q, Zhang G, Li Y, Cong B, Zuo M. Mechanism of Chronic Stress-Induced Glutamatergic Neuronal Damage in the Basolateral Amygdaloid Nucleus. Anal Cell Pathol (Amst) 2021; 2021:8388527. [PMID: 34858775 PMCID: PMC8632434 DOI: 10.1155/2021/8388527] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/23/2021] [Accepted: 10/21/2021] [Indexed: 11/17/2022] Open
Abstract
Stress is a ubiquitous part of our life, while appropriate stress levels can help improve the body's adaptability to the environment. However, sustained and excessive levels of stress can lead to the occurrence of multiple devastating diseases. As an emotional center, the amygdala plays a key role in the regulation of stress-induced psycho-behavioral disorders. The structural changes in the amygdala have been shown to affect its functional characteristics. The amygdala-related neurotransmitter imbalance is closely related to psychobehavioral abnormalities. However, the mechanism of structural and functional changes of glutamatergic neurons in the amygdala induced by stress has not been fully elucidated. Here, we identified that chronic stress could lead to the degeneration and death of glutamatergic neurons in the lateral amygdaloid nucleus, resulting in neuroendocrine and psychobehavioral disorders. Therefore, our studies further suggest that the Protein Kinase R-like ER Kinase (PERK) pathway may be therapeutically targeted as one of the key mechanisms of stress-induced glutamatergic neuronal degeneration and death in the amygdala.
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Affiliation(s)
- Songjun Wang
- Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang, China
| | - Xia Liu
- Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang, China
| | - Weibo Shi
- Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang, China
| | - Qian Qi
- Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang, China
| | - Guozhong Zhang
- Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang, China
| | - Yingmin Li
- Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang, China
| | - Bin Cong
- Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang, China
| | - Min Zuo
- Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang, China
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Ferber SG, Braun K, Weller A. The roots of paternal depression: Experienced and nonexperienced trauma or Folie a Deux? Dev Psychobiol 2021; 63:e22197. [PMID: 34674247 DOI: 10.1002/dev.22197] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 08/19/2021] [Accepted: 08/30/2021] [Indexed: 12/14/2022]
Abstract
The transition to fatherhood may be challenged with anxiety and trepidation. A high prevalence has been found for paternal depression and it is reactive to maternal depression. This review aims to address potential sources of paternal depression, which may have adverse consequences on child development. We describe through three hypotheses how fathers may be at risk of depression during the transition to fatherhood: (1) psychological (interacting with ecological systems); (2) brain functional∖structural changes; and (3) (epi)genomic. We propose that paternal stressful experiences during the transition to fatherhood may be the source for paternal depression through direct stressful paternal experiences or via (potential, currently debated) nonexperienced (by the father) epigenomic transgenerational transmission. On the other hand, we suggest that resilient fathers may undergo a transient dysphoric period affected by identifying with the newborn's vulnerability as well as with the mother's postpartum vulnerability resulting in "paternity blues." In accordance with recent views on paternal "heightened sensitivity" toward the infant, we propose that the identification of both parents with the vulnerability of the newborn creates a sensitive period of Folie a Deux (shared madness) which may be a healthy transient, albeit a quasi-pathological period, recruited by the orienting response of the newborn for survival.
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Affiliation(s)
- Sari Goldstein Ferber
- Department of Psychology and the Gonda Brain Research Center, Bar Ilan University, Ramat Gan, Israel
| | - Katharina Braun
- Department of Zoology and Developmental Neurobiology, Otto von Guericke University Magdeburg, Magdeburg, Germany
- Center for Behavioral and Brain Science, Otto von Guericke University Magdeburg, Magdeburg, Germany
| | - Aron Weller
- Department of Psychology and the Gonda Brain Research Center, Bar Ilan University, Ramat Gan, Israel
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Abstract
Epigenetic mechanisms such as DNA methylation (DNAm) have been associated with stress responses and increased vulnerability to depression. Abnormal DNAm is observed in stressed animals and depressed individuals. Antidepressant treatment modulates DNAm levels and regulates gene expression in diverse tissues, including the brain and the blood. Therefore, DNAm could be a potential therapeutic target in depression. Here, we reviewed the current knowledge about the involvement of DNAm in the behavioural and molecular changes associated with stress exposure and depression. We also evaluated the possible use of DNAm changes as biomarkers of depression. Finally, we discussed current knowledge limitations and future perspectives.
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Wang XL, Feng ST, Wang YT, Chen NH, Wang ZZ, Zhang Y. Paeoniflorin: A neuroprotective monoterpenoid glycoside with promising anti-depressive properties. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 90:153669. [PMID: 34334273 DOI: 10.1016/j.phymed.2021.153669] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 07/07/2021] [Accepted: 07/13/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Depression, as a prevalent and debilitating psychiatric disease, severely decreases the life quality of individuals and brings heavy burdens to the whole society. Currently, some antidepressants are applied in the treatment of severe depressive symptoms, while there are still some undesirable drawbacks. Paeoniflorin is a monoterpenoid glycoside that was firstly extracted from Paeonia lactiflora Pall, a traditional Chinese herb that is widely used in the Chinese herbal formulas for treating depression. PURPOSE This review summarized the previous pre-clinical studies of paeoniflorin in treating depression and further discussed the potential anti-depressive mechanisms for that paeoniflorin to be further explored and utilized in the treatment of depression clinically. METHODS Some electronic databases, e.g., PubMed and China National Knowledge Infrastructure, were searched from inception until April 2021. RESULTS This review summarized the effective anti-depressive properties of paeoniflorin, which is related to its functions in the upregulation of the levels of monoaminergic neurotransmitters, inhibition of the hypothalamic-pituitary-adrenal axis hyperfunction, promotion of neuroprotection, promotion of hippocampus neurogenesis, and upregulation of brain-derived neurotrophic factor level, inhibition of inflammatory reaction, downregulation of nitric oxide level, etc. CONCLUSION: This review focused on the pre-clinical studies of paeoniflorin in depression and summarized the recent development of the anti-depressive mechanisms of paeoniflorin, which approves the role of paeoniflorin plays in anti-depression. However, more high-quality pre-clinical and clinical studies are expected to be conducted in the future.
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Affiliation(s)
- Xiao-Le Wang
- Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Sunshine Southern Avenue, Fang-Shan District, Beijing 102488, China
| | - Si-Tong Feng
- Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Sunshine Southern Avenue, Fang-Shan District, Beijing 102488, China
| | - Ya-Ting Wang
- Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Sunshine Southern Avenue, Fang-Shan District, Beijing 102488, China
| | - Nai-Hong Chen
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian-Nong-Tan Street, Xi-Cheng District, Beijing 100050, China
| | - Zhen-Zhen Wang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian-Nong-Tan Street, Xi-Cheng District, Beijing 100050, China.
| | - Yi Zhang
- Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Sunshine Southern Avenue, Fang-Shan District, Beijing 102488, China.
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Shirvani-Farsani Z, Maloum Z, Bagheri-Hosseinabadi Z, Vilor-Tejedor N, Sadeghi I. DNA methylation signature as a biomarker of major neuropsychiatric disorders. J Psychiatr Res 2021; 141:34-49. [PMID: 34171761 DOI: 10.1016/j.jpsychires.2021.06.013] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 05/27/2021] [Accepted: 06/09/2021] [Indexed: 02/07/2023]
Abstract
DNA methylation is a broadly-investigated epigenetic modification that has been considered as a heritable and reversible change. Previous findings have indicated that DNA methylation regulates gene expression in the central nervous system (CNS). Also, disturbance of DNA methylation patterns has been associated with destructive consequences that lead to human brain diseases such as neuropsychiatric disorders (NPDs). In this review, we comprehensively discuss the mechanism and function of DNA methylation and its most recent associations with the pathology of NPDs-including major depressive disorder (MDD), schizophrenia (SZ), autism spectrum disorder (ASD), bipolar disorder (BD), and attention/deficit hyperactivity disorder (ADHD). We also discuss how heterogeneous findings demand further investigations. Finally, based on the recent studies we conclude that DNA methylation status may have implications in clinical diagnostics and therapeutics as a potential epigenetic biomarker of NPDs.
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Affiliation(s)
- Zeinab Shirvani-Farsani
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University G.C., Tehran, IR, Iran.
| | - Zahra Maloum
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University G.C., Tehran, IR, Iran.
| | - Zahra Bagheri-Hosseinabadi
- Department of Clinical Biochemistry, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
| | - Natalia Vilor-Tejedor
- BarcelonaBeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Carrer Wellington 30, 08005, Barcelona, Spain; Center for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain; Erasmus University Medical Center, Department of Clinical Genetics, Rotterdam, the Netherlands; Pompeu Fabra University, Barcelona, Spain.
| | - Iman Sadeghi
- BarcelonaBeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Carrer Wellington 30, 08005, Barcelona, Spain; Center for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain.
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Chen LM, Bao CH, Wu Y, Liang SH, Wang D, Wu LY, Huang Y, Liu HR, Wu HG. Tryptophan-kynurenine metabolism: a link between the gut and brain for depression in inflammatory bowel disease. J Neuroinflammation 2021; 18:135. [PMID: 34127024 PMCID: PMC8204445 DOI: 10.1186/s12974-021-02175-2] [Citation(s) in RCA: 103] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 05/13/2021] [Indexed: 02/08/2023] Open
Abstract
Inflammatory bowel disease (IBD), which mainly includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic bowel diseases that are characterized by abdominal pain, diarrhea, and bloody stools. IBD is strongly associated with depression, and its patients have a higher incidence of depression than the general population. Depression also adversely affects the quality of life and disease prognosis of patients with IBD. The tryptophan-kynurenine metabolic pathway degrades more than 90% of tryptophan (TRP) throughout the body, with indoleamine 2,3-dioxygenase (IDO), the key metabolic enzyme, being activated in the inflammatory environment. A series of metabolites of the pathway are neurologically active, among which kynerunic acid (KYNA) and quinolinic acid (QUIN) are molecules of great interest in recent studies on the mechanisms of inflammation-induced depression. In this review, the relationship between depression in IBD and the tryptophan-kynurenine metabolic pathway is overviewed in the light of recent publications.
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Affiliation(s)
- Li-Ming Chen
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No.110 Ganhe Road, Shanghai, 200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, No. 650 South Wanping Road, Shanghai, 200030, China
| | - Chun-Hui Bao
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No.110 Ganhe Road, Shanghai, 200437, China.
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, No. 650 South Wanping Road, Shanghai, 200030, China.
| | - Yu Wu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No.110 Ganhe Road, Shanghai, 200437, China
| | - Shi-Hua Liang
- Faculty of Economics and Business, University of Groningen, Nettelbosje 2, Groningen, 9747 AE, The Netherlands
| | - Di Wang
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No.110 Ganhe Road, Shanghai, 200437, China
| | - Lu-Yi Wu
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, No. 650 South Wanping Road, Shanghai, 200030, China
| | - Yan Huang
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, No. 650 South Wanping Road, Shanghai, 200030, China
| | - Hui-Rong Liu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No.110 Ganhe Road, Shanghai, 200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, No. 650 South Wanping Road, Shanghai, 200030, China
| | - Huan-Gan Wu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No.110 Ganhe Road, Shanghai, 200437, China.
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, No. 650 South Wanping Road, Shanghai, 200030, China.
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Mohamed AE, Yousef AM. Depressive, anxiety, and post-traumatic stress symptoms affecting hospitalized and home-isolated COVID-19 patients: a comparative cross-sectional study. MIDDLE EAST CURRENT PSYCHIATRY 2021. [PMCID: PMC8093000 DOI: 10.1186/s43045-021-00105-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background Coronavirus has affected more than 100 million people. Most of these patients are hospitalized in isolation wards or self-quarantined at home. A significant percentage of COVID-19 patients may experience psychiatric symptoms. This study attempts to assess depressive, anxiety, and post-traumatic stress symptoms in home-isolated and hospitalized COVID-19 patients, besides whether the isolation setting affected these symptoms’ presentation. Results The study involved 89 patients with confirmed COVID-19 virus, and the patients were divided into 2 groups: 43 patients in the home-isolated group (group A) and 46 patients in the hospital-isolated group (group B). The majority of subjects were male and married; also, they were highly educated. 30.2% from group A and 47.8% from group B had a medical occupation. There was a statistically significant difference (p= 0.03) between both groups in the presence of chronic disease. There was a statistically significant increase in suicidal thoughts in the home-isolated group (37.2%) (p = 0.008**). We found a statistically significant increase in the abnormal scores of Hospital Anxiety Depression Scale–Depression (HADS–Depression) in the home-isolated group (69.7%) compared to the hospital-isolated group (32.6%) (p <0.001**) which denotes considerable symptoms of depression. Moreover, we found that (32.6%) from the home-isolated group and (39.1%) from the hospital-isolated group had abnormal scores of Hospital Anxiety Depression Scale–Anxiety (HADS–Anxiety) which denotes considerable symptoms of anxiety. Also, we found 66.7% and 87.2% scored positive by the Davidson Trauma Scale (DTS) in the home-isolated group and hospital-isolated group, respectively. Which was statistically significant (p = 0.02**). On doing a binary logistic regression analysis of HADS and DTS with significantly related independent factors, we revealed that lower education levels and family history of psychiatric disorder were risk factors for abnormal HADS–Anxiety scores in COVID-19 patients. The medical occupation was a protective factor against having abnormal HADS–Depression scores in COVID-19 patients, while home isolation was a risk factor. On the contrary, the medical occupation was a risk factor for scoring positive in DTS in COVID-19 patients. Simultaneously, low levels of education and home isolation were protective factors. Conclusion A significant number of patients diagnosed with the COVID-19 virus develop depressive, anxiety, and post-traumatic stress symptoms, whether they were isolated in the hospital or at home; besides, the isolation setting may affect the presenting symptoms.
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Stadtler H, Shaw G, Neigh GN. Mini-review: Elucidating the psychological, physical, and sex-based interactions between HIV infection and stress. Neurosci Lett 2021; 747:135698. [PMID: 33540057 PMCID: PMC9258904 DOI: 10.1016/j.neulet.2021.135698] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/26/2021] [Accepted: 01/28/2021] [Indexed: 12/21/2022]
Abstract
Stress is generally classified as any mental or emotional strain resulting from difficult circumstances, and can manifest in the form of depression, anxiety, post-traumatic stress disorder (PTSD), or other neurocognitive disorders. Neurocognitive disorders such as depression, anxiety, and PTSD are large contributors to disability worldwide, and continue to affect individuals and communities. Although these disorders affect men and women, women are disproportionately represented among those diagnosed with affective disorders, a result of both societal gender roles and physical differences. Furthermore, the incidence of these neurocognitive disorders is augmented among People Living with HIV (PLWH); the physical ramifications of stress increase the likelihood of HIV acquisition, pathogenesis, and treatment, as both stress and HIV infection are characterized by chronic inflammation, which creates a more opportunistic environment for HIV. Although the stress response is facilitated by the autonomic nervous system (ANS) and the hypothalamic pituitary adrenal (HPA) axis, when the response involves a psychological component, additional brain regions are engaged. The impact of chronic stress exposure and the origin of individual variation in stress responses and resilience are at least in part attributable to regions outside the primary stress circuity, including the amygdala, prefrontal cortex, and hippocampus. This review aims to elucidate the relationship between stress and HIV, how these interact with sex, and to understand the physical ramifications of these interactions.
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Affiliation(s)
- Hannah Stadtler
- Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Gladys Shaw
- Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA
| | - Gretchen N Neigh
- Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA.
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Becker M, Pinhasov A, Ornoy A. Animal Models of Depression: What Can They Teach Us about the Human Disease? Diagnostics (Basel) 2021; 11:123. [PMID: 33466814 PMCID: PMC7830961 DOI: 10.3390/diagnostics11010123] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/28/2020] [Accepted: 01/08/2021] [Indexed: 12/14/2022] Open
Abstract
Depression is apparently the most common psychiatric disease among the mood disorders affecting about 10% of the adult population. The etiology and pathogenesis of depression are still poorly understood. Hence, as for most human diseases, animal models can help us understand the pathogenesis of depression and, more importantly, may facilitate the search for therapy. In this review we first describe the more common tests used for the evaluation of depressive-like symptoms in rodents. Then we describe different models of depression and discuss their strengths and weaknesses. These models can be divided into several categories: genetic models, models induced by mental acute and chronic stressful situations caused by environmental manipulations (i.e., learned helplessness in rats/mice), models induced by changes in brain neuro-transmitters or by specific brain injuries and models induced by pharmacological tools. In spite of the fact that none of the models completely resembles human depression, most animal models are relevant since they mimic many of the features observed in the human situation and may serve as a powerful tool for the study of the etiology, pathogenesis and treatment of depression, especially since only few patients respond to acute treatment. Relevance increases by the fact that human depression also has different facets and many possible etiologies and therapies.
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Affiliation(s)
- Maria Becker
- Adelson School of Medicine, Ariel University, Ariel 40700, Israel;
| | - Albert Pinhasov
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel 40700, Israel;
| | - Asher Ornoy
- Adelson School of Medicine, Ariel University, Ariel 40700, Israel;
- Hebrew University Hadassah Medical School, Jerusalem 9112102, Israel
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Changes in Hippocampal Plasticity in Depression and Therapeutic Approaches Influencing These Changes. Neural Plast 2020; 2020:8861903. [PMID: 33293948 PMCID: PMC7718046 DOI: 10.1155/2020/8861903] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 09/30/2020] [Accepted: 11/11/2020] [Indexed: 02/06/2023] Open
Abstract
Depression is a common neurological disease that seriously affects human health. There are many hypotheses about the pathogenesis of depression, and the most widely recognized and applied is the monoamine hypothesis. However, no hypothesis can fully explain the pathogenesis of depression. At present, the brain-derived neurotrophic factor (BDNF) and neurogenesis hypotheses have highlighted the important role of plasticity in depression. The plasticity of neurons and glial cells plays a vital role in the transmission and integration of signals in the central nervous system. Plasticity is the adaptive change in the nervous system in response to changes in external signals. The hippocampus is an important anatomical area associated with depression. Studies have shown that some antidepressants can treat depression by changing the plasticity of the hippocampus. Furthermore, caloric restriction has also been shown to affect antidepressant and hippocampal plasticity changes. In this review, we summarize the latest research, focusing on changes in the plasticity of hippocampal neurons and glial cells in depression and the role of BDNF in the changes in hippocampal plasticity in depression, as well as caloric restriction and mitochondrial plasticity. This review may contribute to the development of antidepressant drugs and elucidating the mechanism of depression.
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Xu Q, Jiang M, Gu S, Wang F, Yuan B. Early Life Stress Induced DNA Methylation of Monoamine Oxidases Leads to Depressive-Like Behavior. Front Cell Dev Biol 2020; 8:582247. [PMID: 33015076 PMCID: PMC7505948 DOI: 10.3389/fcell.2020.582247] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Accepted: 08/18/2020] [Indexed: 12/13/2022] Open
Abstract
Major depressive disorder (MDD) is coming to be the regarded as one of the leading causes for human disabilities. Due to its complicated pathological process, the etiology is still unclear and the treatment is still targeting at the monoamine neurotransmitters. Early life stress has been known as a major cause for MDD, but how early life stress affects adult monoaminergic activity is not clear either. Recently, DNA methylation is considered to be the key mechanism of epigenetics and might play a role in early life stress induced mental illness. DNA methylation is an enzymatic covalent modification of DNA, has been one of the main epigenetic mechanisms investigated. The metabolic enzyme for the monoamine neurotransmitters, monoamine oxidases A/B (MAO A/MAO B) are the prime candidates for the investigation into the role of DNA methylation in mental disorders. In this review, we will review recent advances about the structure and physiological function of monoamine oxidases (MAO), brief narrative other factors include stress induced changes, early life stress, perinatal depression (PD) relationship with other epigenetic changes, such as DNA methylation, microRNA (miRNA). This review will shed light on the epigenetic changes involved in MDD, which may provide potential targets for future therapeutics in depression pathogenesis.
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Affiliation(s)
- Qiuyue Xu
- School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mingchen Jiang
- School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Simeng Gu
- Department of Psychology, Jiangsu University Medical School, Zhenjiang, China
| | - Fushun Wang
- Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, China
| | - Bin Yuan
- School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China.,Jiangsu Key Laboratory of Pediatric Respiratory Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Association Between the Location of Secondhand Smoke Exposure and Depressive Symptoms among South Korean Adolescents. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17145116. [PMID: 32679863 PMCID: PMC7400535 DOI: 10.3390/ijerph17145116] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/09/2020] [Accepted: 07/11/2020] [Indexed: 12/27/2022]
Abstract
The incidence of depression among adolescents has gradually increased, leading to adult psychological outcomes and suicide. Although the rate of secondhand smoke exposure (SHSE) has recently decreased, SHSE remains high in children. We aimed to determine the association between depressive symptoms in adolescents and the locations of SHSE using an extensive population survey. Using data from the 14th Korea Youth Risk Behavior Web-based Survey, we assessed self-reported data of depressive symptoms and SHSE among non-smokers. SHSE locations were classified into four groups: only at school, only at home, at both school and home, and other places. Multiple logistic regression analysis was performed to identify the associations between SHSE locations and depressive symptoms. The relationship between SHSE and depressive symptoms was the highest in the “SHSE at home and school” group (boys: odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.44–1.80; girls: OR = 1.72, 95% CI = 1.54–1.91), followed by the “school” (boys: OR = 1.53, 95% CI = 1.39–1.67; girls: OR = 1.36, 95% CI = 1.25–1.48) and “home” groups (boys: OR = 1.23, 95% CI = 1.12–1.35; girls: OR = 1.30, 95% CI = 1.20–1.40). These results emphasize the importance of stricter smoking regulations not only in public places, but also in households. Adolescents and their families should be educated on the dangers of smoking and the effects of SHSE on mental health.
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Ma FQ, Sun CJ, Wei JJ, Wang YD, Shen JC, Chang JJ. Electro-acupuncture regulates glucose metabolism in chronic stress model rats. Sci Rep 2020; 10:11281. [PMID: 32647204 PMCID: PMC7347532 DOI: 10.1038/s41598-020-68132-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 06/17/2020] [Indexed: 11/09/2022] Open
Abstract
Studies have shown that acupuncture is very effective in treating chronic stress depression. However, little is known about the therapeutic mechanism of electro-acupuncture. Metabolomics, on the other hand, is a technology that determines the metabolic changes of organisms caused by various interventions as a whole and is related to the overall effect of electro-acupuncture (EA). 1HNMR, serum sample analysis, and histopathology and molecular biology analysis were used to evaluate the effects of EA. The results show that electro-acupuncture points can regulate the heat pain threshold of chronic stress model rats and change the morphology of adrenal cortex cells Structure, and regulate the contents of corticotropin-releasing hormone, Corticosterone (CORT), glucose, alanine and valine in the samples. These findings help to clarify the therapeutic mechanism of electro-acupuncture on heterologous chronic stress model rats. The effect of electro-acupuncture on improving chronic stress is likely to be achieved by regulating glucose metabolism, which can provide a reference for clinical acupuncture treatment of chronic stress depression.
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Affiliation(s)
- Fu-Qiang Ma
- Luoyang Traditional Chinese Medicine Hospital, Luoyang, 471000, People's Republic of China. .,Department of Traditional Chinese Medicine, Xiamen University, Xiamen, 361005, People's Republic of China.
| | - Chan-Juan Sun
- Luoyang Traditional Chinese Medicine Hospital, Luoyang, 471000, People's Republic of China
| | - Jun-Jie Wei
- Luoyang Traditional Chinese Medicine Hospital, Luoyang, 471000, People's Republic of China
| | - Ya-Dong Wang
- Department of Traditional Chinese Medicine, Xiamen University, Xiamen, 361005, People's Republic of China
| | - Jia-Cheng Shen
- Shanghai Research Institute of Acupuncture and Meridian, Shanghai, 200030, People's Republic of China
| | - Jin-Jian Chang
- Luoyang Traditional Chinese Medicine Hospital, Luoyang, 471000, People's Republic of China
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Li H, Xue Q, Xu X. Involvement of the Nervous System in SARS-CoV-2 Infection. Neurotox Res 2020; 38:1-7. [PMID: 32399719 PMCID: PMC7220627 DOI: 10.1007/s12640-020-00219-8] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 04/22/2020] [Accepted: 04/24/2020] [Indexed: 02/07/2023]
Abstract
As a severe and highly contagious infectious disease, coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several case reports have demonstrated that the respiratory system is the main target in patients with COVID-19, but the disease is not limited to the respiratory system. Case analysis indicated that the nervous system can be invaded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that 36.4% of COVID-19 patients had neurological symptoms. Importantly, the involvement of the CNS may be associated with poor prognosis and disease worsening. Here, we discussed the symptoms and evidence of nervous system involvement (directly and indirectly) caused by SARS-CoV-2 infection and possible mechanisms. CNS symptoms could be a potential indicator of poor prognosis; therefore, the prevention and treatment of CNS symptoms are also crucial for the recovery of COVID-19 patients.
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Affiliation(s)
- Hao Li
- Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China
| | - Qun Xue
- Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China.
| | - Xingshun Xu
- Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China.
- Institute of Neuroscience, Soochow University, Suzhou, 215123, Jiangsu, China.
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, China.
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