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Baj J, Forma A, Karakuła K, Flieger W, Flieger M, Kowalska B, Kamińska I, Majerek D, Teresiński G, Maciejewski R, Radzikowska-Büchner E, Flieger J. Changes in the distribution of elements in the liver and various brain regions in suicides from southeastern Poland. Sci Rep 2025; 15:18946. [PMID: 40442250 PMCID: PMC12123043 DOI: 10.1038/s41598-025-03283-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 05/20/2025] [Indexed: 06/02/2025] Open
Abstract
The anthropogenic environment and diet are sources of chemical elements, both essential and toxic. Many of them play a key role in the proper functioning of the brain by controlling oxidative metabolism, neurotransmission and the production of neurotransmitters. Disturbances in element homeostasis are associated with the development of depression and many neurodegenerative diseases. The study examined the content of several elements in liver and brain samples taken from autopsies of residents of south-eastern Poland (n = 40). In order to determine the differences in the elemental composition of tissues collected from suicide victims compared to the control group who died from another cause, the Mann-Whitney U test was performed. There was a significant difference in the correlation patterns between the two groups for both brain (χ² = 1490.19, df = 1378, p < 7e-122, z = 3.72) and liver χ² = 2998.7, df = 1378, p < 0.018, z = 126.71). Two-way non-parametric Spearman rank correlation matrices showed different numbers and strengths of correlations for most brain regions in the compared groups, especially for the head of the caudate nucleus (Latin: caput nuclei caudati), superior longitudinal fasciculus (Latin: fasciculus longitudinalis superior cerebri), and hippocampus (Latin: hippocampus). Differences between groups reached statistical significance in the case of higher lanthanide content in the liver of suicides and lower Ca content in the basal ganglia (head of the caudate nucleus, nucleus accumbens septum), dorsal thalamus and insula. Brain samples from different regions of suicide victims were characterized by higher levels of, among others: Ag, P, Fe and Cu. Our findings suggest clear differences in trace metal content and inter-correlations in the brain and liver tissues of suicide victims compared to controls.
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Affiliation(s)
- Jacek Baj
- Department of Correct, Clinical and Imaging Anatomy, Medical University of Lublin, ul. Jaczewskiego 4, Lublin, 20-090, Poland
| | - Alicja Forma
- Department of Forensic Medicine, Medical University of Lublin, ul. Jaczewskiego 8b, Lublin, 20-090, Poland
| | - Kaja Karakuła
- Department of Correct, Clinical and Imaging Anatomy, Medical University of Lublin, ul. Jaczewskiego 4, Lublin, 20-090, Poland
| | - Wojciech Flieger
- Department of Correct, Clinical and Imaging Anatomy, Medical University of Lublin, ul. Jaczewskiego 4, Lublin, 20-090, Poland
- Institute of Health Sciences, John Paul II Catholic University of Lublin, Konstantynów 1 H, Lublin, 20-708, Poland
| | - Michał Flieger
- Department of Forensic Medicine, Medical University of Lublin, ul. Jaczewskiego 8b, Lublin, 20-090, Poland
| | - Beata Kowalska
- Department of Water Supply and Wastewater Disposal, Lublin University of Technology, Nadbystrzycka 40B, Lublin, 20-618, Poland
| | - Iwona Kamińska
- Environmental Analysis Laboratory, Lublin University of Technology, Nadbystrzycka 40B, Lublin, 20-618, Poland
| | - Dariusz Majerek
- Department of Applied Mathematics, Lublin University of Technology, Nadbystrzycka 38D, Lublin, 20-618, Poland
| | - Grzegorz Teresiński
- Department of Forensic Medicine, Medical University of Lublin, ul. Jaczewskiego 8b, Lublin, 20-090, Poland
| | - Ryszard Maciejewski
- Institute of Health Sciences, John Paul II Catholic University of Lublin, Konstantynów 1 H, Lublin, 20-708, Poland
| | - Elżbieta Radzikowska-Büchner
- Institute of Health Sciences, John Paul II Catholic University of Lublin, Konstantynów 1 H, Lublin, 20-708, Poland
- Department of Plastic, Reconstructive and Hand Surgery, National Medical Institute of the Ministry of the Interior and Administration, Wołoska 137, Warsaw, 02-507, Poland
| | - Jolanta Flieger
- Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4a (Collegium Pharmaceuticum), Lublin, 20-093, Poland.
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Nakagawa Y, Yamada S. Novel hypothesis and therapeutic interventions for irritable bowel syndrome: interplay between metal dyshomeostasis, gastrointestinal dysfunction, and neuropsychiatric symptoms. Mol Cell Biochem 2025; 480:2661-2676. [PMID: 39503802 DOI: 10.1007/s11010-024-05153-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 10/26/2024] [Indexed: 05/03/2025]
Abstract
Irritable bowel syndrome is a gastrointestinal disorder due to multiple pathologies. While patients with this condition experience anxiety and depressed mood more frequently than healthy individuals, it is unclear how gastrointestinal dysfunction interacts with such neuropsychiatric symptoms. Data suggest that irritable bowel syndrome patients predominantly display a lower zinc intake, which presumably impairs enterochromaffin cells producing 5-hydroxytryptamine, gut bacteria fermenting short-chain fatty acids, and barrier system in the intestine, with the accompanying constipation, diarrhea, low-grade mucosal inflammation, and visceral pain. Dyshomeostasis of copper and zinc concentrations as well as elevated pro-inflammatory cytokine levels in the blood can disrupt blood-cerebrospinal fluid barrier function, leading to locus coeruleus neuroinflammation and hyperactivation with resultant amygdalar overactivation and dorsolateral prefrontal cortex hypoactivation as found in neuropsychiatric disorders. The dysregulation between the dorsolateral prefrontal cortex and amygdala is likely responsible for visceral pain-related anxiety, depressed mood caused by anticipatory anxiety, and visceral pain catastrophizing due to catastrophic thinking or cognitive distortion. Collectively, these events can result in a spiral of gastrointestinal symptoms and neuropsychiatric signs, prompting the progression of irritable bowel syndrome. Given that the negative feedback mechanism in regulation of the hypothalamic-pituitary-adrenal axis is preserved in a subset of neuropsychiatric cases, dorsolateral prefrontal cortex abnormality accompanied by neuropsychiatric symptoms may be a more significant contributing factor in brain-gut axis malfunction than activation of the hypothalamic corticotropin-releasing hormone system. The proposed mechanistic model could predict novel therapeutic interventions for comorbid irritable bowel syndrome and neuropsychiatric disorders.
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Affiliation(s)
- Yutaka Nakagawa
- Center for Pharma-Food Research (CPFR), Division of Pharmaceutical Sciences, Graduate School of Integrative Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-Ku, Shizuoka, 422-8526, Japan.
| | - Shizuo Yamada
- Center for Pharma-Food Research (CPFR), Division of Pharmaceutical Sciences, Graduate School of Integrative Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-Ku, Shizuoka, 422-8526, Japan
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Kim JS, Kim JH, Eo H, Ju IG, Son SR, Kim JW, Jang DS, Oh MS. Inulae Flos has Anti-Depressive Effects by Suppressing Neuroinflammation and Recovering Dysfunction of HPA-axis. Mol Neurobiol 2024; 61:8038-8050. [PMID: 38457106 DOI: 10.1007/s12035-024-04094-8] [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: 11/28/2023] [Accepted: 03/05/2024] [Indexed: 03/09/2024]
Abstract
Depression is a debilitating mood disorder that causes persistent feelings of sadness, emptiness, and a loss of joy. However, the clinical efficacy of representative drugs for depression, such as selective serotonin reuptake inhibitors, remains controversial. Therefore, there is an urgent need for more effective therapies to treat depression. Neuroinflammation and the hypothalamic-pituitary-adrenal (HPA) axis are pivotal factors in depression. Inulae Flos (IF), the flower of Inula japonica Thunb, is known for its antioxidant and anti-inflammatory effects. This study explored whether IF alleviates depression in both in vitro and in vivo models. For in vitro studies, we treated BV2 and PC12 cells damaged by lipopolysaccharides or corticosterone (CORT) with IF to investigate the mechanisms of depression. For in vivo studies, C57BL/6 mice were exposed to chronic restraint stress and were administered IF at doses of 0, 100, and 300 mg/kg for 2 weeks. IF inhibited pro-inflammatory mediators, such as nitric oxide, inducible nitric oxide synthase, and interleukins in BV2 cells. Moreover, IF increased the viability of CORT-damaged PC12 cells by modulating protein kinase B, a mammalian target of the rapamycin pathway. Behavioral assessments demonstrated that IF reduced depression-like behaviors in mice. We found that IF reduced the activation of microglia and astrocytes, and regulated synapse plasticity in the mice brains. Furthermore, IF lowered elevated CORT levels in the plasma and restored glucocorticoid receptor expression in the hypothalamus. Collectively, these findings suggest that IF can alleviate depression by mitigating neuroinflammation and recovering dysfunction of the HPA-axis.
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Affiliation(s)
- Jin Se Kim
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, Republic of Korea
| | - Jin Hee Kim
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, Republic of Korea
| | - Hyeyoon Eo
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, Republic of Korea
| | - In Gyoung Ju
- Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - So-Ri Son
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, Republic of Korea
| | - Ji-Woon Kim
- College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea
| | - Dae Sik Jang
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, Republic of Korea
| | - Myung Sook Oh
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
- Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea.
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Liu M, Yan R, Lu S, Zhang P, Xu S. Pathogenesis and therapeutic strategies for cancer-related depression. Am J Cancer Res 2024; 14:4197-4217. [PMID: 39417166 PMCID: PMC11477823 DOI: 10.62347/wvvg5364] [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: 07/11/2024] [Accepted: 08/29/2024] [Indexed: 10/19/2024] Open
Abstract
Depression is a common co-morbidity among cancer cases, which has a detrimental influence on cancer treatment and prognosis. Recent advancements in the neurobiology of depression and cancer pathophysiology have revealed several shared biobehavioral mechanisms and introduced new therapeutic strategies. In this review, we summarize the biological mechanisms driving cancer-related depression, including psychosocial factors, immuno-inflammatory processes, chronic stress, dysbiosis of gut microbiota, and medically-induced factors. Interventions used for cancer-related depression may include psychosocial therapies, pharmacological therapies, immunotherapies, psychobiological medications, and dietary strategies. This review could inspire the elucidation of possible co-occurring mechanisms and complex interactions between cancer and depression, provide an opportunity to propose faster and more effective therapies for cancer-related depression, and well as new strategies for cancer in the future.
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Affiliation(s)
- Meishan Liu
- National Key Laboratory of Immunity and Inflammation and Institute of Immunology, Navy Medical University/Second Military Medical UniversityShanghai 200433, China
| | - Ran Yan
- National Key Laboratory of Immunity and Inflammation and Institute of Immunology, Navy Medical University/Second Military Medical UniversityShanghai 200433, China
| | - Shaoteng Lu
- National Key Laboratory of Immunity and Inflammation and Institute of Immunology, Navy Medical University/Second Military Medical UniversityShanghai 200433, China
| | - Ping Zhang
- Department of Neurology, Naval Medical Center of PLA, Naval Medical UniversityShanghai 200052, China
| | - Sheng Xu
- National Key Laboratory of Immunity and Inflammation and Institute of Immunology, Navy Medical University/Second Military Medical UniversityShanghai 200433, China
- Shanghai Institute of Stem Cell Research and Clinical TranslationShanghai 200120, China
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Banerjee P, Chau K, Kotla S, Davis EL, Turcios EB, Li S, Pengzhi Z, Wang G, Kolluru GK, Jain A, Cooke JP, Abe J, Le NT. A Potential Role for MAGI-1 in the Bi-Directional Relationship Between Major Depressive Disorder and Cardiovascular Disease. Curr Atheroscler Rep 2024; 26:463-483. [PMID: 38958925 PMCID: PMC12124319 DOI: 10.1007/s11883-024-01223-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2024] [Indexed: 07/04/2024]
Abstract
PURPOSE OF REVIEW Major Depressive Disorder (MDD) is characterized by persistent symptoms such as fatigue, loss of interest in activities, feelings of sadness and worthlessness. MDD often coexist with cardiovascular disease (CVD), yet the precise link between these conditions remains unclear. This review explores factors underlying the development of MDD and CVD, including genetic, epigenetic, platelet activation, inflammation, hypothalamic-pituitary-adrenal (HPA) axis activation, endothelial cell (EC) dysfunction, and blood-brain barrier (BBB) disruption. RECENT FINDINGS Single nucleotide polymorphisms (SNPs) in the membrane-associated guanylate kinase WW and PDZ domain-containing protein 1 (MAGI-1) are associated with neuroticism and psychiatric disorders including MDD. SNPs in MAGI-1 are also linked to chronic inflammatory disorders such as spontaneous glomerulosclerosis, celiac disease, ulcerative colitis, and Crohn's disease. Increased MAGI-1 expression has been observed in colonic epithelial samples from Crohn's disease and ulcerative colitis patients. MAGI-1 also plays a role in regulating EC activation and atherogenesis in mice and is essential for Influenza A virus (IAV) infection, endoplasmic reticulum stress-induced EC apoptosis, and thrombin-induced EC permeability. Despite being understudied in human disease; evidence suggests that MAGI-1 may play a role in linking CVD and MDD. Therefore, further investigation of MAG-1 could be warranted to elucidate its potential involvement in these conditions.
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Affiliation(s)
- Priyanka Banerjee
- Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA
- Medical Physiology, College of Medicine, Texas A&M Health Science Center, Bryan, TX, USA
| | - Khanh Chau
- Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA
| | - Sivareddy Kotla
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Eleanor L Davis
- Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA
| | - Estefani Berrios Turcios
- Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA
| | - Shengyu Li
- Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA
| | - Zhang Pengzhi
- Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA
| | - Guangyu Wang
- Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA
| | | | - Abhishek Jain
- Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA
- Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX, USA
- Department of Medical Physiology, School of Medicine, Texas A&M Health Science Center, Bryan, USA
| | - John P Cooke
- Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA
| | - Junichi Abe
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Nhat-Tu Le
- Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA.
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Rani R, Astha. Association between household air pollution due to unclean fuel use and depression among older adults in India: A cross-sectional study. Indian J Psychiatry 2024; 66:814-822. [PMID: 39502595 PMCID: PMC11534128 DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_317_24] [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: 04/10/2024] [Revised: 08/30/2024] [Accepted: 09/08/2024] [Indexed: 11/08/2024] Open
Abstract
Background Depression is a major public concern among older adults. However, limited studies have examined the association of depression and household air pollution (HAP). Therefore, this study examines the association between HAP due to unclean fuel use and depression among older adults in India. Methods Data from Longitudinal Aging Study of India (LASI), wave-1 (2017-18) were used (N = 50,206, ≥50 years). Depression measured by CIDI-SF (Composite International Diagnostic Interview-Short Form) was the outcome variable. Household unclean fuel use was considered as proxy of HAP. Bivariate analyses and multivariate logistic regression were used to fulfil the study objectives. Results The prevalence of depression was greater among unclean fuel users than clean fuel users (9.6% vs 6.6%). Results showed that household unclean fuel use was associated with higher odds of depression. The interaction analyses showed that females and rural residents were at higher risk of depression due to HAP exposure. Furthermore, household cooking conditions also played an important role in the association between HAP exposure and depression. Unclean fuel use indoors without ventilation and with traditional chullah/stove was associated with higher odds of depression among older adults. Conclusion The study concludes that exposure to HAP due to unclean fuel use should be considered as a potential risk factor of depression among older adults. Therefore, the study suggests an urgent need to create awareness about negative effects of unclean fuel use on mental health and promote clean fuel usage in households to ensure healthy aging.
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Affiliation(s)
- Ritu Rani
- Centre on Aging Studies, International Institute for Population Science (IIPS), Mumbai, Maharashtra, India
- French National Institute of Medical Health and Research (INSERM), Paris, France
| | - Astha
- Departement of Psychiatry, University College of Medical Sciences, Delhi, India
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Kołodziej-Sobczak D, Sobczak Ł, Łączkowski KZ. Protein Tyrosine Phosphatase 1B (PTP1B): A Comprehensive Review of Its Role in Pathogenesis of Human Diseases. Int J Mol Sci 2024; 25:7033. [PMID: 39000142 PMCID: PMC11241624 DOI: 10.3390/ijms25137033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 06/23/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024] Open
Abstract
Overexpression of protein tyrosine phosphatase 1B (PTP1B) disrupts signaling pathways and results in numerous human diseases. In particular, its involvement has been well documented in the pathogenesis of metabolic disorders (diabetes mellitus type I and type II, fatty liver disease, and obesity); neurodegenerative diseases (Alzheimer's disease, Parkinson's disease); major depressive disorder; calcific aortic valve disease; as well as several cancer types. Given this multitude of therapeutic applications, shortly after identification of PTP1B and its role, the pursuit to introduce safe and selective enzyme inhibitors began. Regrettably, efforts undertaken so far have proved unsuccessful, since all proposed PTP1B inhibitors failed, or are yet to complete, clinical trials. Intending to aid introduction of the new generation of PTP1B inhibitors, this work collects and organizes the current state of the art. In particular, this review intends to elucidate intricate relations between numerous diseases associated with the overexpression of PTP1B, as we believe that it is of the utmost significance to establish and follow a brand-new holistic approach in the treatment of interconnected conditions. With this in mind, this comprehensive review aims to validate the PTP1B enzyme as a promising molecular target, and to reinforce future research in this direction.
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Affiliation(s)
- Dominika Kołodziej-Sobczak
- Department of Chemical Technology and Pharmaceuticals, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Jurasza 2, 85-089 Bydgoszcz, Poland;
| | - Łukasz Sobczak
- Hospital Pharmacy, Multidisciplinary Municipal Hospital in Bydgoszcz, Szpitalna 19, 85-826 Bydgoszcz, Poland
| | - Krzysztof Z. Łączkowski
- Department of Chemical Technology and Pharmaceuticals, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Jurasza 2, 85-089 Bydgoszcz, Poland;
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James Vibin A, Niharika N, Valliappan V, Lamo P, Parajuli N, Jat M, Lama S, Agarwal A, Sagar R, Sharma G. Effect of Integrated Yoga as an add-on therapy in adults with clinical depression - A randomized controlled trial. Int J Soc Psychiatry 2024; 70:709-719. [PMID: 38279599 DOI: 10.1177/00207640231223431] [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] [Indexed: 01/28/2024]
Abstract
BACKGROUND Depression is a leading cause of disability and the conventional management has several limitations. Recent studies demonstrated the benefits of yoga in psychological disorders. AIMS To evaluate the efficacy of the Integrated Yoga Module (IYM) to standard care with added yogic education on lifestyle modification (YELM) in patients with clinical depression. METHODS A PROBE trial was conducted at a single tertiary care hospital in India. Adults aged 18 to 64 with clinical depression were randomized to either an IYM or an active control group using a computer-generated mixed block randomization sequence. Both groups received YELM in addition to standard care and the intervention group practiced IYM, for 8 weeks. The primary outcome was the reduction in depression symptoms assessed using the Beck Depression Inventory (BDI-II), and secondary outcomes involved self-compassion, brief resilience, positive and negative experiences, and quality of life, evaluated at 8 weeks. RESULTS The mean ± SD age of participants was 32.2 ± 10.0 and 54.3% were females. The IYM group showed statistically significant improvements in BDI-II scores β = -6.7 (95% CI [-10.8, -2.5]; p = .001), resilience β = 0.4 (95% CI [0.02, 0.80]; p = .037), physical health domain of WHOQOL - BREF β = 10.1 (95% CI [0.7, 19.5]; p = .035) and negative emotions (SPANE-N) β = 2.8 (95% CI [0.1, 5.4]; p = .037). However, no significant differences were found in SCS-SF β = -0.3 (95% CI [-0.7, 0.0]; p = .053). CONCLUSIONS IYM as an adjunct is superior to conventional medical management in reducing symptoms and improving positive psychological resources in clinical depression.
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Affiliation(s)
- Anu James Vibin
- Centre for Integrative Medicine and Research, All India Institute of Medical Sciences, New Delhi, India
| | - Niharika Niharika
- Centre for Integrative Medicine and Research, All India Institute of Medical Sciences, New Delhi, India
| | - Varun Valliappan
- Centre for Integrative Medicine and Research, All India Institute of Medical Sciences, New Delhi, India
| | - Pasang Lamo
- Centre for Integrative Medicine and Research, All India Institute of Medical Sciences, New Delhi, India
| | - Niranjan Parajuli
- Centre for Integrative Medicine and Research, All India Institute of Medical Sciences, New Delhi, India
| | - Mansingh Jat
- Centre for Integrative Medicine and Research, All India Institute of Medical Sciences, New Delhi, India
| | - Sudha Lama
- Centre for Integrative Medicine and Research, All India Institute of Medical Sciences, New Delhi, India
| | - Aman Agarwal
- Centre for Integrative Medicine and Research, All India Institute of Medical Sciences, New Delhi, India
| | - Rajesh Sagar
- Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
| | - Gautam Sharma
- Centre for Integrative Medicine and Research, All India Institute of Medical Sciences, New Delhi, India
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
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Kaddoura R, Faraji H, Othman M, Abu Hijleh A, Loney T, Goswami N, Benamer HTS. Exploring Factors Associated with Falls in Multiple Sclerosis: Insights from a Scoping Review. Clin Interv Aging 2024; 19:923-938. [PMID: 38803468 PMCID: PMC11129740 DOI: 10.2147/cia.s460475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 04/17/2024] [Indexed: 05/29/2024] Open
Abstract
Multiple sclerosis (MS) is a chronic inflammatory condition that causes demyelination of the central nervous system accompanied by a wide range of symptoms. The high prevalence of falls among patients diagnosed with MS within the initial six months highlights the importance of this issue. The objective of this study is to identify factors associated with falls in MS patients in order to increase awareness and reduce the risk of falls. This scoping review used specific Mesh terms to formulate the literature search around falls and MS using Medline, Google Scholar, Scopus, and Embase search engines. English papers published between 2012 and 2022, studies with a clear definition of falls, McDonald's diagnostic criteria for MS, and those with Expanded Disability Status Scale (EDSS) or Patient Determined Disease Steps (PDDS) scores were included. Critical data from the selected articles were extracted and classified according to the different factors associated with falls in MS patients. Eighteen articles were included in this review. The most important factors associated with falls in MS patients identified were the severity and progression of the disease, mobility and balance problems, bladder dysfunction, fear of falling, fatigue, and cognitive dysfunction. In conclusion, this scoping review yielded the most common factors associated with falls in patients with MS. Study findings can be used to develop future interventions focusing on improving mobility, proprioception, and balance to decrease fall risk and injury amongst MS patients.
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Affiliation(s)
- Rachid Kaddoura
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Hanan Faraji
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Malek Othman
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Amin Abu Hijleh
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Tom Loney
- Department of Basic Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Nandu Goswami
- Division of Physiology and Pathophysiology, Medical University of Graz, Graz, Austria
- Center for Space and Aviation Health, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Hani T S Benamer
- Department of Clinical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
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Potter K, Gayle EJ, Deb S. Effect of gut microbiome on serotonin metabolism: a personalized treatment approach. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:2589-2602. [PMID: 37922012 DOI: 10.1007/s00210-023-02762-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 09/29/2023] [Indexed: 11/05/2023]
Abstract
Several factors including diet, exercise, and medications influence the makeup of the resilient but adaptable gut microbiome. Bacteria in the gut have a significant role in the homeostasis of the neurotransmitter serotonin, also known as 5-hydroxytryptamine, involved in mood and behavior. The goal of the current work is to review the effect of the gut microbiome on serotonin metabolism, and how it can potentially contribute to the development of a personalized treatment approach for depression and anxiety. Bacterial strains provide innovative therapeutic targets that can be used for disorders, such as depression, that involve dysregulation of serotonin. Advances in bacterial genomic sequencing have increased the accessibility and affordability of microbiome testing, which unlocks a new targeted pathway to modulate serotonin metabolism by targeting the gut-brain axis. Microbiome testing can facilitate the recommendation of strain-specific probiotic supplements based on patient-specific microbial profiles. Several studies have shown that supplementation with probiotics containing specific species of bacteria, such as Bifidobacterium and Lactobacillus, can improve symptoms of depression. Further research is needed to improve the process and interpretation of microbiome testing and how to successfully incorporate testing results into guiding clinical decision-making. This targeted approach centered around the gut-brain axis can provide a novel way to personalize therapy for mental health disorders.
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Affiliation(s)
- Kristal Potter
- College of Pharmacy, Larkin University, 18301 N. Miami Avenue, Miami, FL, 33169, USA
| | - Erysa J Gayle
- College of Biomedical Sciences, Larkin University, 18301 N. Miami Avenue, Miami, FL, 33169, USA
| | - Subrata Deb
- College of Pharmacy, Larkin University, 18301 N. Miami Avenue, Miami, FL, 33169, USA.
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Chang HC, Lu HY, Guo YC, Lin CY, Chen SJ, Gau SY. Depression risk in chronic tonsillitis patients underwent tonsillectomy: a global federated health network analysis. Int J Med Sci 2024; 21:949-957. [PMID: 38616998 PMCID: PMC11008477 DOI: 10.7150/ijms.93977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 03/21/2024] [Indexed: 04/16/2024] Open
Abstract
Background: Tonsillectomy is a common surgery in the US, with possible postoperative complications. While small studies indicate postoperative depressive symptoms may occur, large-scale evidence is lacking on the tonsillectomy-depression link. Methods: We conducted a retrospective cohort study using the TriNetX US collaborative network, offering de-identified electronic health data from 59 collaborative healthcare organizations (HCOs) in the United States. In this study, people being diagnosed of chronic tonsillitis between January 2005 and December 2017 were enrolled. Patients deceased, with previous record of cancers or psychiatric events before index date were excluded. 14,874 chronic tonsillitis patients undergoing tonsillectomy were propensity score matched 1:1 to controls for age, sex, and race. New-onset depression risks were evaluated over 5 years post-tonsillectomy and stratified by age and sex. Confounders were adjusted for including demographics, medications, comorbidities and socioeconomic statuses. Results: After matching, the difference of key baseline characteristics including age, sex, comedications status and obesity status was insignificant between tonsillectomy and non-tonsillectomy groups. Tonsillectomy had a 1.29 times higher 5-year depression risk versus matched controls (95% CI, 1.19-1.40), with elevated risks seen at 1 year (HR=1.51; 95% CI, 1.28-1.79) and 3 years (HR=1.30; 95% CI, 1.18-1.43). By stratifications, risks were increased for both males (HR=1.30; 95% CI, 1.08-1.57) and females (HR=1.30; 95% CI, 1.18-1.42), and significantly higher in ages 18-64 years (HR=1.37; 1.26-1.49), but no significance observed for those 65 years and older. After performing sensitivity analyses and applying washout periods of 6, 12, and 36 months, the outcome remained consistent with unadjusted results. Conclusion: This real-world analysis found tonsillectomy was associated with a 30% higher 5-year depression risk versus matched non-tonsillectomy patients with chronic tonsillitis. Further mechanistic research is needed to clarify the pathophysiologic association between depression and tonsillectomy. Depression is not commonly mentioned in the current post-tonsillectomy care realm; however, the outcome of our study emphasized the possibility of these suffering condition after operation. Attention to psychological impacts following tonsillectomy is warranted to support patient well-being, leading to better management of post-tonsillectomy individuals.
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Affiliation(s)
- Hui-Chin Chang
- Evidence-based Medicine Center, Chung Shan Medical University Hospital, Taichung, Taiwan
- Library, Chung Shan Medical University Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Hsin-Yo Lu
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Yu-Chen Guo
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Chen-Yu Lin
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Shiu-Jau Chen
- Department of Neurosurgery, Mackay Memorial Hospital, Taipei, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Shuo-Yan Gau
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Medical Education, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Orthopedics Department, Chi-Mei Medical Center, Tainan, Taiwan
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Diksha, Singh L, Bhatia D. Mechanistic interplay of different mediators involved in mediating the anti-depressant effect of isoflavones. Metab Brain Dis 2024; 39:199-215. [PMID: 37855935 DOI: 10.1007/s11011-023-01302-7] [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: 04/18/2023] [Accepted: 09/24/2023] [Indexed: 10/20/2023]
Abstract
Depression is one of the most prevalent severe CNS disorders, which negatively affects social lives, the ability to work, and the health of people. As per the World Health Organisation (WHO), it is a psychological disorder that is estimated to be a leading disease by 2030. Clinically, various medicines have been formulated to treat depression but they are having a setback due to their side effects, slow action, or poor bioavailability. Nowadays, flavonoids are regarded as an essential component in a variety of nutraceutical, pharmaceutical and medicinal. Isoflavones are a distinctive and important subclass of flavonoids that are generally obtained from soybean, chickpeas, and red clover. The molecules of this class have been extensively explored in various CNS disorders including depression and anxiety. Isoflavones such as genistein, daidzein, biochanin-A, formononetin, and glycitein have been reported to exert an anti-depressant effect through the modulation of different mediators. Fatty acid amide hydrolase (FAAH) mediated depletion of anandamide and hypothalamic-pituitary-adrenal (HPA) axis-mediated modulation of brain-derived neurotrophic factor (BDNF), monoamine oxidase (MAO) mediated depletion of biogenic amines and inflammatory signaling are the important underlying pathways leading to depression. Upregulation in the levels of BDNF, anandamide, antioxidants and monoamines, along with inhibition of MAO, FAAH, HPA axis, and inflammatory stress are the major modulations produced by different isoflavones in the observed anti-depressant effect. Therefore, the present review has been designed to explore the mechanistic interplay of various mediators involved in mediating the anti-depressant action of different isoflavones.
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Affiliation(s)
- Diksha
- University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India
| | - Lovedeep Singh
- University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India.
| | - Deepika Bhatia
- University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India
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Irmak-Yazicioglu MB, Arslan A. Navigating the Intersection of Technology and Depression Precision Medicine. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1456:401-426. [PMID: 39261440 DOI: 10.1007/978-981-97-4402-2_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/13/2024]
Abstract
This chapter primarily focuses on the progress in depression precision medicine with specific emphasis on the integrative approaches that include artificial intelligence and other data, tools, and technologies. After the description of the concept of precision medicine and a comparative introduction to depression precision medicine with cancer and epilepsy, new avenues of depression precision medicine derived from integrated artificial intelligence and other sources will be presented. Additionally, less advanced areas, such as comorbidity between depression and cancer, will be examined.
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Affiliation(s)
| | - Ayla Arslan
- Department of Molecular Biology and Genetics, Üsküdar University, İstanbul, Türkiye.
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14
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Chahuan S, Grover S, Singh S. Amelioration of modified chronic unpredictable stress using Celastrus paniculatus seed oil alone and in combination with fluoxetine. Drug Chem Toxicol 2023; 46:879-894. [PMID: 35943180 DOI: 10.1080/01480545.2022.2105862] [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: 01/04/2022] [Revised: 06/09/2022] [Accepted: 07/18/2022] [Indexed: 11/03/2022]
Abstract
The various stressors in chronic unpredictable stress (CUS) triggers depressive behavior, impairs learning, and decision-making abilities. The present study investigated the effects of Celastrus paniculatus seed oil (CPSO) alone and in combination with fluoxetine (FLU) in modified CUS (mCUS) induced depression in mice. In this study, adult albino mice were subjected to a modified version of CUS protocol having six different stressors and were applied daily consistently for 15 days. The post-treatment with CPSO (50 and 100 mg/kg) and FLU (10 mg/kg) alone and in combination from day 16th to 36th. Group I: normal control; group II: diseased control (mCUS subjected group); group III: CPSO (50 mg/kg); group IV: CPSO (100 mg/kg); group V: CPSO (50 mg/kg)+FLU (10 mg/kg); group VI: CPSO (100 mg/kg)+FLU (10 mg/kg); group VII: FLU (10 mg/kg); group VIII: FLU (20 mg/kg). During experimentation, various behavioral, biochemical, oxidative stress, inflammatory, and neurotransmitters level were checked. The CUS treated mice exhibited increased escaped latency, decreased number of open arm entries, increased immobility time, decreased percentage of sucrose consumption, and number of the boxes crossed as compared to the normal group. The post-treatment with the CPSO 50 + FLU 10, CPSO 100 + FLU 10, FLU 10 significantly (p < 0.05) attenuated behavioral, biochemical, inflammation, corticosteroid, and neurotransmitters level as compared to CPSO 50, CPSO 100, and FLU 20 alone. CPSO along with FLU appreciably achieved anti-depressant effect via lowering stress, inflammation, corticosteroid level, and restoration of neurotransmitters level in mCUS induced depression mice model.
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Affiliation(s)
- Sanjana Chahuan
- Department of Pharmacology, ISF College of Pharmacy, Moga, India
| | - Sania Grover
- Department of Pharmacology, ISF College of Pharmacy, Moga, India
| | - Shamsher Singh
- Department of Pharmacology, ISF College of Pharmacy, Moga, India
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15
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Cai W, Ma W, Mueller C, Stewart R, Ji J, Shen WD. Association between late-life depression or depressive symptoms and stroke morbidity in elders: A systematic review and meta-analysis of cohort studies. Acta Psychiatr Scand 2023; 148:405-415. [PMID: 37728003 DOI: 10.1111/acps.13613] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 08/17/2023] [Accepted: 08/24/2023] [Indexed: 09/21/2023]
Abstract
OBJECTIVE Whether late-life depression or depressive symptoms are a risk factor of future stroke in elders is important for prevention measures. A systematic review and meta-analysis were used to investigate the association between depression or depressive symptoms and risk of stroke in elders. METHODS Embase, MEDLINE, PsychINFO, and Web of Science were searched for studies published from inception to January 6, 2023. Prospective cohort studies reporting quantitative estimates of the association between depression or depressive symptoms and stroke morbidity in participants aged over 60 years were included. Reviews, meta-analyses, case reports, retrospective, cross-sectional, and theoretical studies were excluded. Study screening and data extraction were conducted by two researchers independently. Random-effects meta-analysis was used to estimate pooled adjusted hazard ratios (HRs). Publication bias was evaluated via the symmetry of funnel plots and Egger tests. The Newcastle Ottawa Scale was used to assess the risk of bias. The quality of evidence of synthesis was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). The primary outcome was any stroke, including non-fatal, fatal, ischemic and hemorrhagic sub-types. RESULTS Seventeen studies of 57,761 patients in total were included in the meta-analysis. A positive association was found between depressive disorder or symptoms and stroke risk (HR: 1.39; 95% CI: 1.22-1.58; p < 0.001). CONCLUSIONS Late-life depression or depressive symptoms are a significant risk factor for stroke in older people. Regular assessment and more effective management of associated comorbidities are recommended to reduce stroke risk.
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Affiliation(s)
- Wa Cai
- Department of Acupuncture, Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wen Ma
- Department of Acupuncture, Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Christoph Mueller
- King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK
- Department of Psychological Medicine and Older Adults, South London and Maudsley NHS Foundation Trust, London, UK
| | - Robert Stewart
- King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK
- Department of Psychological Medicine and Older Adults, South London and Maudsley NHS Foundation Trust, London, UK
| | - Jun Ji
- Department of Acupuncture Literature, Shanghai Research Institute of Acupuncture and Meridian, Shanghai, China
| | - Wei-Dong Shen
- Department of Acupuncture, Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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16
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Vu T, Smith JA. The pathophysiology and management of depression in cardiac surgery patients. Front Psychiatry 2023; 14:1195028. [PMID: 37928924 PMCID: PMC10623009 DOI: 10.3389/fpsyt.2023.1195028] [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: 03/27/2023] [Accepted: 10/06/2023] [Indexed: 11/07/2023] Open
Abstract
Background Depression is common in the cardiac surgery population. This contemporary narrative review aims to explore the main pathophysiological disturbances underpinning depression specifically within the cardiac surgery population. The common non-pharmacological and pharmacological management strategies used to manage depression within the cardiac surgery patient population are also explored. Methods A total of 1291 articles were identified through Ovid Medline and Embase. The findings from 39 studies were included for qualitative analysis in this narrative review. Results Depression is associated with several pathophysiological and behavioral factors which increase the likelihood of developing coronary heart disease which may ultimately require surgical intervention. The main pathophysiological factors contributing to depression are well characterized and include autonomic nervous system dysregulation, excessive inflammation and disruption of the hypothalamic-pituitary-adrenal axis. There are also several behavioral factors in depressed patients associated with the development of coronary heart disease including poor diet, insufficient exercise, poor compliance with medications and reduced adherence to cardiac rehabilitation. The common preventative and management modalities used for depression following cardiac surgery include preoperative and peri-operative education, cardiac rehabilitation, cognitive behavioral therapy, religion/prayer/spirituality, biobehavioral feedback, anti-depressant medications, and statins. Conclusion This contemporary review explores the pathophysiological mechanisms leading to depression following cardiac surgery and the current management modalities. Further studies on the preventative and management strategies for postoperative depression in the cardiac surgery patient population are warranted.
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Affiliation(s)
- Tony Vu
- Department of Cardiothoracic Surgery, The Alfred Hospital, Melbourne, VIC, Australia
- Department of Surgery, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia
| | - Julian A. Smith
- Department of Surgery, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia
- Department of Cardiothoracic Surgery, Monash Health, Melbourne, VIC, Australia
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17
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Pan KY, Almroth M, Nevriana A, Hemmingsson T, Kjellberg K, Falkstedt D. Trajectories of psychosocial working conditions and all-cause and cause-specific mortality: a Swedish register-based cohort study. Scand J Work Environ Health 2023; 49:496-505. [PMID: 37522817 PMCID: PMC10830330 DOI: 10.5271/sjweh.4111] [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: 05/01/2023] [Indexed: 08/01/2023] Open
Abstract
OBJECTIVES While psychosocial working conditions have been associated with morbidity, their associations with mortality, especially cause-specific mortality, have been less studied. Additionally, few studies considered the time-varying aspect of exposures. We aimed to examine trajectories of job demand-control status in relation to all-cause and cause-specific mortality, including cardiovascular diseases (CVD), suicide, and alcohol-related mortality. METHODS The study population consisted of around 4.5 million individuals aged 16-60 years in Sweden in 2005. Job control and demands were respectively measured using job exposure matrices (JEM). Trajectories of job control and demands throughout 2005-2009 were identified using group-based trajectory modelling, and job demand-control categories were subsequently classified. Deaths in 2010-2019 were recorded in the national cause of death register. Cox regression models were used. RESULTS A total of 116 242 individuals died in 2010-2019. For both job control and demands, we identified four trajectories, which were parallel to each other and represented four levels of exposures. Low control and passive jobs were associated with higher all-cause, CVD, and suicide mortality among both men and women. High strain jobs were associated with higher all-cause and CVD mortality among men, while low control, passive jobs, and high strain jobs were associated with higher alcohol-related mortality among women. CONCLUSIONS The trajectories identified may suggest stable levels of job control and demands over time. Poor psychosocial working conditions are related to all-cause and cause-specific mortality, and these patterns vary to some extent between men and women.
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Affiliation(s)
- Kuan-Yu Pan
- Unit of Occupational Medicine, Institute of Environmental Medicine, Karolinska Institutet, Solnavägen 4, 113 65 Stockholm, Sweden.
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18
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GÖKDAĞ C, KIZILTEPE R. Risk Factors in Depression and Anxiety Disorders from the Framework of Developmental Psychopathology. PSIKIYATRIDE GUNCEL YAKLASIMLAR - CURRENT APPROACHES IN PSYCHIATRY 2023. [DOI: 10.18863/pgy.1118163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/27/2023]
Abstract
Depression and anxiety disorders are among the most prevalent psychiatric disorders that negatively affect individuals’ life in many ways. Understanding how these highly comorbid emotional disorders develop and persist might guide prevention, intervention, and treatment studies. Some common vulnerability factors underlie depression and anxiety disorders. Developmental psychopathology deals with these vulnerabilities and risk factors from a lifetime perspective. The aim of this review is to present the risk factors associated with depression and anxiety from the perspective of developmental psychopathology. For this purpose, we discussed genetic and biological factors, temperament, negative childhood experiences, family and peer relationships, and some cognitive and emotional factors as risk factors. Also, we discussed how these risk factors lead to depression and anxiety disorders. This review emphasizes that some common transdiagnostic risk factors underlie emotional disorders and highlights the importance of a developmental psychopathology perspective to understand the developmental pathways of depression and anxiety disorders.
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19
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Fu X, Wang Y, Zhao F, Cui R, Xie W, Liu Q, Yang W. Shared biological mechanisms of depression and obesity: focus on adipokines and lipokines. Aging (Albany NY) 2023; 15:5917-5950. [PMID: 37387537 PMCID: PMC10333059 DOI: 10.18632/aging.204847] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 06/01/2023] [Indexed: 07/01/2023]
Abstract
Depression and obesity are both common disorders currently affecting public health, frequently occurring simultaneously within individuals, and the relationship between these disorders is bidirectional. The association between obesity and depression is highly co-morbid and tends to significantly exacerbate metabolic and related depressive symptoms. However, the neural mechanism under the mutual control of obesity and depression is largely inscrutable. This review focuses particularly on alterations in systems that may mechanistically explain the in vivo homeostatic regulation of the obesity and depression link, such as immune-inflammatory activation, gut microbiota, neuroplasticity, HPA axis dysregulation as well as neuroendocrine regulators of energy metabolism including adipocytokines and lipokines. In addition, the review summarizes potential and future treatments for obesity and depression and raises several questions that need to be answered in future research. This review will provide a comprehensive description and localization of the biological connection between obesity and depression to better understand the co-morbidity of obesity and depression.
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Affiliation(s)
- Xiying Fu
- Department of Endocrinology, The Second Hospital of Jilin University, Changchun 130041, P.R. China
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
| | - Yicun Wang
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
| | - Fangyi Zhao
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
| | - Ranji Cui
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
| | - Wei Xie
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
| | - Qianqian Liu
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
| | - Wei Yang
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
- Department of Neurology, The Second Hospital of Jilin University, Changchun 130041, P.R. China
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20
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Malekpour M, Shekouh D, Safavinia ME, Shiralipour S, Jalouli M, Mortezanejad S, Azarpira N, Ebrahimi ND. Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery. Front Psychiatry 2023; 14:1182345. [PMID: 37398599 PMCID: PMC10313426 DOI: 10.3389/fpsyt.2023.1182345] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 05/24/2023] [Indexed: 07/04/2023] Open
Abstract
Stress-induced mental health disorders are affecting many people around the world. However, effective drug therapy for curing psychiatric diseases does not occur sufficiently. Many neurotransmitters, hormones, and mechanisms are essential in regulating the body's stress response. One of the most critical components of the stress response system is the hypothalamus-pituitary-adrenal (HPA) axis. The FKBP prolyl isomerase 51 (FKBP51) protein is one of the main negative regulators of the HPA axis. FKBP51 negatively regulates the cortisol effects (the end product of the HPA axis) by inhibiting the interaction between glucocorticoid receptors (GRs) and cortisol, causing reduced transcription of downstream cortisol molecules. By regulating cortisol effects, the FKBP51 protein can indirectly regulate the sensitivity of the HPA axis to stressors. Previous studies have indicated the influence of FKBP5 gene mutations and epigenetic changes in different psychiatric diseases and drug responses and recommended the FKBP51 protein as a drug target and a biomarker for psychological disorders. In this review, we attempted to discuss the effects of the FKBP5 gene, its mutations on different psychiatric diseases, and drugs affecting the FKBP5 gene.
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Affiliation(s)
- Mahdi Malekpour
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Dorsa Shekouh
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Shadi Shiralipour
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Jalouli
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sahar Mortezanejad
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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21
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Rokoff LB, Cardenas A, Lin PID, Rifas-Shiman SL, Wright RO, Bosquet Enlow M, Coull BA, Oken E, Korrick SA. Early pregnancy essential and non-essential metal mixtures and maternal antepartum and postpartum depressive symptoms. Neurotoxicology 2023; 94:206-216. [PMID: 36526156 PMCID: PMC9839522 DOI: 10.1016/j.neuro.2022.12.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 11/20/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND Mood disorders are common during and after pregnancy, and environmental metals may contribute to increased risk. Antepartum metal exposures have not been well characterized in relation to maternal depression. We evaluated the extent to which early pregnancy erythrocyte concentrations of essential and non-essential metals were prospectively associated with antepartum and postpartum depressive symptoms. METHODS Participants were 1226 women in Project Viva, a longitudinal cohort recruited during pregnancy (1999-2002). We measured concentrations of 11 metals in maternal first trimester erythrocytes (arsenic, barium, cadmium, cesium, copper, mercury, magnesium, manganese, lead, selenium, zinc). Using the Edinburgh Postnatal Depression Scale (EPDS), we assessed elevated depressive symptoms (≥13; 0-30 scale) at mid-pregnancy and at 6 and 12 months postpartum. We applied latent class mixed modeling to identify symptom trajectories. Adjusting for maternal sociodemographics and co-exposures, we examined associations between the metal mixture and depressive symptoms using logistic (for EPDS≥13)/multinomial (for symptom trajectories) regression and quantile g-computation. RESULTS In this cohort of moderately high socioeconomic status participants (e.g., 72 % college graduate), low-level metal concentrations were weakly to moderately correlated (Spearman: -0.24 to 0.59); the prevalence of depressive symptoms ranged from 9 % (mid-pregnancy) to 6 % (12 months postpartum); and three trajectories (stable low; elevated mid-pregnancy, then decreasing; moderate mid-pregnancy, then increasing) best fit the EPDS data. The early pregnancy erythrocyte metal mixture was not associated with maternal depressive symptoms in logistic, multinomial, or mixture models. For individual metals, most confidence intervals (CI) included the null. There was weak evidence that arsenic, lead, and selenium were moderately associated with elevated odds of depressive symptoms and/or trajectories. However, the odds ratios (95 % CI) per doubling of these three metals were imprecise [e.g., arsenic: 1.13 (0.94, 1.40) for EPDS≥13 at six months postpartum; lead: 1.19 (0.80, 1.77) for EPDS≥13 at mid-pregnancy; selenium: 2.35 (0.84, 6.57) for elevated mid-pregnancy, then decreasing versus stable low trajectory]. DISCUSSION We did not observe strong, consistent evidence of associations between early pregnancy erythrocyte metal concentrations and subsequent maternal antepartum and postpartum depressive symptoms.
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Affiliation(s)
- Lisa B Rokoff
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Population Health Sciences Program, Harvard University, Cambridge, MA, USA.
| | - Andres Cardenas
- Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA
| | - Pi-I D Lin
- Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
| | - Sheryl L Rifas-Shiman
- Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
| | - Robert O Wright
- Department of Environmental Medicine and Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Michelle Bosquet Enlow
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Brent A Coull
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Emily Oken
- Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Susan A Korrick
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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22
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Is depression the missing link between inflammatory mediators and cancer? Pharmacol Ther 2022; 240:108293. [PMID: 36216210 DOI: 10.1016/j.pharmthera.2022.108293] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 09/14/2022] [Accepted: 09/26/2022] [Indexed: 11/05/2022]
Abstract
Patients with cancer are at greater risk of developing depression in comparison to the general population and this is associated with serious adverse effects, such as poorer quality of life, worse prognosis and higher mortality. Although the relationship between depression and cancer is now well established, a common underlying pathophysiological mechanism between the two conditions is yet to be elucidated. Existing theories of depression, based on monoamine neurotransmitter system dysfunction, are insufficient as explanations of the disorder. Recent advances have implicated neuroinflammatory mechanisms in the etiology of depression and it has been demonstrated that inflammation at a peripheral level may be mirrored centrally in astrocytes and microglia serving to promote chronic levels of inflammation in the brain. Three major routes to depression in cancer in which proinflammatory mediators are implicated, seem likely. Activation of the kynurenine pathway involving cytokines, increases tryptophan catabolism, resulting in diminished levels of serotonin which is widely acknowledged as being the hallmark of depression. It also results in neurotoxic effects on brain regions thought to be involved in the evolution of major depression. Proinflammatory mediators also play a crucial role in impairing regulatory glucocorticoid mediated feedback of the hypothalamic-pituitary-adrenal axis, which is activated by stress and considered to be involved in both depression and cancer. The third route is via the glutamatergic pathway, whereby glutamate excitotoxicity may lead to depression associated with cancer. A better understanding of the mechanisms underlying these dysregulated and other newly emerging pathways may provide a rationale for therapeutic targeting, serving to improve the care of cancer patients.
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Richardson B, MacPherson A, Bambico F. Neuroinflammation and neuroprogression in depression: Effects of alternative drug treatments. Brain Behav Immun Health 2022; 26:100554. [DOI: 10.1016/j.bbih.2022.100554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 10/29/2022] [Accepted: 11/06/2022] [Indexed: 11/09/2022] Open
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Neyer S, Witthöft M, Cropley M, Pawelzik M, Sütterlin S, Lugo RG. The cortisol awakening response at admission to hospital predicts depression severity after discharge in major depressive disorder patients—A replication study. Front Neurosci 2022; 16:952903. [DOI: 10.3389/fnins.2022.952903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 09/21/2022] [Indexed: 11/13/2022] Open
Abstract
The cortisol awakening response (CAR) is a non-invasive biomarker for hypothalamic-pituitary-adrenal axis (HPA) dysregulation, reflecting accumulated stress over time. In a previous study we reported that a blunted CAR before an inpatient treatment predicted self-reported depressive symptoms six weeks and six months after discharge [Eikeseth, F. F., Denninghaus, S., Cropley, M., Witthöft, M., Pawelzik, M., & Sütterlin, S. (2019). The cortisol awakening response at admission to hospital predicts depression severity after discharge in major depressive disorder (MDD) patients. Journal of Psychiatric Research, 111, 44-50)]. This replication study adopted an improved overall methodology with more stringent assessment protocols and monitoring. The longitudinal design included 122 inpatients from a psychosomatic hospital with a diagnosis of MDD displaying symptoms of moderate to severe major depression (n = 80 females). The CAR was measured at intake. Depression severity was assessed as Beck Depression Inventory II scores at intake, discharge, 6 weeks and 6 months following discharge. Results from the original study were replicated in terms of effect size but did not reach statistical significance (correlation between BDI-II 6 months after discharge and AUCg: r = −0.213; p = 0.054). The replication study yielded nearly identical correlation coefficients as in the original study (BDI-II 6 months and CAR, r = −0.223, p < 0.05). The replication of previously reported effect sizes with a concurrent lack of statistical significance in the more restrictive, larger and better controlled replication study may well inform research on psycho-endocrinological predictors for treatment success, but suggests a rather limited practical relevance for cortisol awakening response measures in this clinical context.
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Smith L, Veronese N, López Sánchez GF, Butler L, Barnett Y, Shin JI, Lee S, Oh JW, Soysal P, Pizzol D, Oh H, Kostev K, Jacob L, Koyanagi A. The association of cooking fuels with depression and anxiety symptoms among adults aged ≥65 years from low- and middle-income countries. J Affect Disord 2022; 311:494-499. [PMID: 35609766 DOI: 10.1016/j.jad.2022.05.103] [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: 04/07/2022] [Revised: 05/15/2022] [Accepted: 05/18/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND We aimed to investigate associations of unclean cooking fuels with depression and anxiety symptoms in a large sample of adults aged ≥65 years from six low- and middle-income countries (LMICs). METHODS Cross-sectional, community-based, nationally representative data from the WHO Study on global AGEing and adult health (SAGE) were analyzed. Unclean cooking fuel referred to kerosene/paraffin, coal/charcoal, wood, agriculture/crop, animal dung, and shrubs/grass. Depression referred to DSM-IV depression based on past 12-month symptoms or receiving depression treatment in the last 12 months. Anxiety symptoms referred to severe/extreme problems with worry or anxiety in the past 30 days. Multivariable logistic regression analysis and meta-analysis were conducted. RESULTS Data on 14,585 people aged ≥65 years were analyzed [mean (SD) age 72.6 (11.5) years; maximum age 114 years; 55.0% females]. After adjustment for potential confounders, unclean cooking fuel was associated with a significant 2.52 (95%CI = 1.66-3.82) times higher odds for depression with a low level of between-country heterogeneity (I2 = 0.0%). For anxiety symptoms, unclean fuel use was not significantly associated with anxiety symptoms (OR = 1.13; 95%CI = 0.77-1.68; I2 = 0.0%). LIMITATIONS 1. Cross-sectional design. 2. Self-reported measures. 3. No information about outdoor pollution exposure, personal exposure, and smoke composition of different cooking fuels. CONCLUSIONS Unclean cooking fuel was significantly associated with higher odds for depression, but not anxiety, with little observed variability between settings. Findings from the present study provide further support and call for action in appropriate implementation of the United Nations Sustainable Goal 7, which advocates affordable, reliable, sustainable, and modern energy for all.
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Affiliation(s)
- Lee Smith
- Centre for Health, Performance, and Wellbeing, Anglia Ruskin University, Cambridge, UK
| | - Nicola Veronese
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science King Saud University, Riyadh 11451, Saudi Arabia; University of Palermo, Department of Internal Medicine, Geriatrics Section, Palermo, Italy
| | - Guillermo F López Sánchez
- Division of Preventive Medicine and Public Health, Department of Public Health Sciences, School of Medicine, University of Murcia, Murcia, Spain.
| | - Laurie Butler
- Centre for Health, Performance, and Wellbeing, Anglia Ruskin University, Cambridge, UK
| | - Yvonne Barnett
- Centre for Health, Performance, and Wellbeing, Anglia Ruskin University, Cambridge, UK
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Yonsei-ro 50, Seodaemun-gu, 8044, 120-752 Seoul, Republic of Korea
| | - San Lee
- Department of Psychiatry and Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea
| | - Jae Won Oh
- Department of Psychiatry, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea
| | - Pinar Soysal
- Department of Geriatric Medicine, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Damiano Pizzol
- Italian Agency for Development Cooperation, Khartoum, Sudan
| | - Hans Oh
- Suzanne Dworak Peck School of Social Work, University of Southern California, Los Angeles, CA 90007, USA
| | | | - Louis Jacob
- Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, 08830 Barcelona, Spain; Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, 78000 Versailles, France
| | - Ai Koyanagi
- Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, 08830 Barcelona, Spain; ICREA, Pg. Lluis Companys 23, 08010 Barcelona, Spain
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Upadhyaya K, Sharma PK, Akhtar A, Pilkhwal Sah S. Protective Effects of Zingerone Against Depression-Like Behavior and Biochemical Changes in Chronic Stressed Rats: Antioxidant Effects. J Med Food 2022; 25:576-587. [PMID: 35639359 DOI: 10.1089/jmf.2021.k.0141] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Ginger contains zingerone, an active constituent possessing antioxidant and neuroprotective properties. The present study was designed to explore the efficacy of the bioactive compound, zingerone, for treating behavioral and biochemical alterations in rats exposed to chronic restraint stress (CRS). Female Wistar rats were administered zingerone (25, 50, and 100 mg/kg p.o.) once daily for a period of 28 days while being exposed to CRS (6 h/day). Our results indicated that the stressed animals depicted depression-like behavior (reduced sucrose preference and increased immobility time) associated with increased lipid peroxidation (LPO) (cortex), decreased catalase (CAT) (hippocampus and cortex), and increased superoxide dismutase (SOD) (hippocampus and cortex). In addition, metabolic alterations were characterized by hyperglycemia and increased glycosylated hemoglobin in the CRS rats. However, no alterations were observed for learning and memory and in the levels of reduced glutathione. Repeated zingerone administration significantly reversed depression-like behavior elicited by CRS in rats. Furthermore, a significant antioxidant effect was exhibited by zingerone, as shown by decreased LPO and enhanced activity of SOD and CAT in chronically stressed rats. The findings of our study demonstrated that zingerone possesses protective actions against chronic stress-induced depressive-like behavioral, biochemical, and metabolic alterations and that its underlying mechanism may be attributed to its antioxidant properties. The results also signify its pharmacological and possible nutritional importance.
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Affiliation(s)
- Kumud Upadhyaya
- Department of Pharmaceutical Sciences, Kumaun University, Nainital, India
| | | | - Ansab Akhtar
- Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC-CAS, Panjab University, Chandigarh, India
| | - Sangeeta Pilkhwal Sah
- Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC-CAS, Panjab University, Chandigarh, India
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Hou K, Wu ZX, Chen XY, Wang JQ, Zhang D, Xiao C, Zhu D, Koya JB, Wei L, Li J, Chen ZS. Microbiota in health and diseases. Signal Transduct Target Ther 2022; 7:135. [PMID: 35461318 PMCID: PMC9034083 DOI: 10.1038/s41392-022-00974-4] [Citation(s) in RCA: 1222] [Impact Index Per Article: 407.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 03/11/2022] [Accepted: 03/15/2022] [Indexed: 02/07/2023] Open
Abstract
The role of microbiota in health and diseases is being highlighted by numerous studies since its discovery. Depending on the localized regions, microbiota can be classified into gut, oral, respiratory, and skin microbiota. The microbial communities are in symbiosis with the host, contributing to homeostasis and regulating immune function. However, microbiota dysbiosis can lead to dysregulation of bodily functions and diseases including cardiovascular diseases (CVDs), cancers, respiratory diseases, etc. In this review, we discuss the current knowledge of how microbiota links to host health or pathogenesis. We first summarize the research of microbiota in healthy conditions, including the gut-brain axis, colonization resistance and immune modulation. Then, we highlight the pathogenesis of microbiota dysbiosis in disease development and progression, primarily associated with dysregulation of community composition, modulation of host immune response, and induction of chronic inflammation. Finally, we introduce the clinical approaches that utilize microbiota for disease treatment, such as microbiota modulation and fecal microbial transplantation.
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Affiliation(s)
- Kaijian Hou
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, 515000, China
| | - Zhuo-Xun Wu
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Xuan-Yu Chen
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Jing-Quan Wang
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Dongya Zhang
- Microbiome Research Center, Moon (Guangzhou) Biotech Ltd, Guangzhou, 510535, China
| | - Chuanxing Xiao
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, 515000, China
| | - Dan Zhu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, 515000, China
| | - Jagadish B Koya
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Liuya Wei
- School of Pharmacy, Weifang Medical University, Weifang, Shandong, 261053, China
| | - Jilin Li
- Department of Cardiovascular, The Second Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, 515000, China
| | - Zhe-Sheng Chen
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
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Kamran M, Bibi F, ur. Rehman A, Morris DW. Major Depressive Disorder: Existing Hypotheses about Pathophysiological Mechanisms and New Genetic Findings. Genes (Basel) 2022; 13:646. [PMID: 35456452 PMCID: PMC9025468 DOI: 10.3390/genes13040646] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 03/16/2022] [Accepted: 03/23/2022] [Indexed: 01/08/2023] Open
Abstract
Major depressive disorder (MDD) is a common mental disorder generally characterized by symptoms associated with mood, pleasure and effectiveness in daily life activities. MDD is ranked as a major contributor to worldwide disability. The complex pathogenesis of MDD is not yet understood, and this is a major cause of failure to develop new therapies and MDD recurrence. Here we summarize the literature on existing hypotheses about the pathophysiological mechanisms of MDD. We describe the different approaches undertaken to understand the molecular mechanism of MDD using genetic data. Hundreds of loci have now been identified by large genome-wide association studies (GWAS). We describe these studies and how they have provided information on the biological processes, cell types, tissues and druggable targets that are enriched for MDD risk genes. We detail our understanding of the genetic correlations and causal relationships between MDD and many psychiatric and non-psychiatric disorders and traits. We highlight the challenges associated with genetic studies, including the complexity of MDD genetics in diverse populations and the need for a study of rare variants and new studies of gene-environment interactions.
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Affiliation(s)
- Muhammad Kamran
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan; (M.K.); (A.u.R.)
- Centre for Neuroimaging, Cognition and Genomics (NICOG), Discipline of Biochemistry, National University of Ireland Galway, H91 CF50 Galway, Ireland
| | - Farhana Bibi
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan;
| | - Asim. ur. Rehman
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan; (M.K.); (A.u.R.)
| | - Derek W. Morris
- Centre for Neuroimaging, Cognition and Genomics (NICOG), Discipline of Biochemistry, National University of Ireland Galway, H91 CF50 Galway, Ireland
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Meinert S, Leehr EJ, Grotegerd D, Repple J, Förster K, Winter NR, Enneking V, Fingas SM, Lemke H, Waltemate L, Stein F, Brosch K, Schmitt S, Meller T, Linge A, Krug A, Nenadić I, Jansen A, Hahn T, Redlich R, Opel N, Schubotz RI, Baune BT, Kircher T, Dannlowski U. White matter fiber microstructure is associated with prior hospitalizations rather than acute symptomatology in major depressive disorder. Psychol Med 2022; 52:1166-1174. [PMID: 32921338 DOI: 10.1017/s0033291720002950] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness. METHODS A total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects. RESULTS Disease state (pFWE < 0.042) and number of hospitalizations (pFWE< 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF. CONCLUSIONS Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.
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Affiliation(s)
- Susanne Meinert
- Department of Psychiatry, University of Münster, Münster, Germany
| | | | | | - Jonathan Repple
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Katharina Förster
- Department of Psychiatry, University of Münster, Münster, Germany
- Clinical Psychology and Behavioral Neuroscience, Faculty of Psychology, Technische Universität Dresden, Dresden, Germany
| | - Nils R Winter
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Verena Enneking
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Stella M Fingas
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Hannah Lemke
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Lena Waltemate
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Frederike Stein
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
| | - Katharina Brosch
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
| | - Simon Schmitt
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
| | - Tina Meller
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
| | - Anna Linge
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Axel Krug
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany
| | - Igor Nenadić
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
| | - Andreas Jansen
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
- Core-Unit Brainimaging, Faculty of Medicine, University of Marburg, Marburg, Germany
| | - Tim Hahn
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Ronny Redlich
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Nils Opel
- Department of Psychiatry, University of Münster, Münster, Germany
- Interdisciplinary Centre for Clinical Research (IZKF) Münster, University of Münster, Münster, Germany
| | | | - Bernhard T Baune
- Department of Psychiatry, University of Münster, Münster, Germany
- Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia
- The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
| | - Tilo Kircher
- Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
| | - Udo Dannlowski
- Department of Psychiatry, University of Münster, Münster, Germany
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Kirsch DE, Lippard ET. Early life stress and substance use disorders: The critical role of adolescent substance use. Pharmacol Biochem Behav 2022; 215:173360. [PMID: 35219756 PMCID: PMC8983562 DOI: 10.1016/j.pbb.2022.173360] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 12/06/2021] [Accepted: 02/20/2022] [Indexed: 12/12/2022]
Abstract
Early life stress (ELS) is a well-established risk factor for many psychiatric and medical disorders, including substance use disorders (SUDs). The relationship between ELS and SUDs is complex and there are likely multiple pathways from ELS to adverse substance use outcomes. The association between ELS and substance use emerges in adolescence. Adolescence is a critical period in development during which substance exposure markedly increases risk for SUDs. Therefore, this review focuses on the literature supporting the hypothesis that ELS increases risk for the development of SUDs through its influence on adolescent substance use. We discuss studies substantiating the role of ELS in adolescent substance use and explore how internalizing and externalizing psychopathology may be antecedents of substance use in adolescence. We examine clinical work suggesting ELS sculpts the Hypothalamic-Pituitary-Adrenal (HPA) Axis and developing brain-particularly subcortical brain regions that underlie stress response, mesocorticolimbic brain systems associated with reward sensitivity, and prefrontal regions that underlie executive control-in a way that increases risk for adolescent substance use and SUDs. We further explore how substance use during adolescence alters structure and function of these same systems, and how brain changes following ELS and adolescent substance use may independently, additively, or interactively contribute to risk for addiction. We conclude by discussing how the current literature can inform interventions aimed at reducing risk for SUDs in individuals with a history of ELS.
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Zajkowska Z, Gullett N, Walsh A, Zonca V, Pedersen GA, Souza L, Kieling C, Fisher HL, Kohrt BA, Mondelli V. Cortisol and development of depression in adolescence and young adulthood - a systematic review and meta-analysis. Psychoneuroendocrinology 2022; 136:105625. [PMID: 34920399 PMCID: PMC8783058 DOI: 10.1016/j.psyneuen.2021.105625] [Citation(s) in RCA: 88] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 11/03/2021] [Accepted: 12/06/2021] [Indexed: 01/30/2023]
Abstract
INTRODUCTION Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of major depressive disorder (MDD) in adulthood. Less work has focused on the role of the HPA axis in depression in adolescence and young adulthood globally. The aim of this study was to conduct a systematic review and meta-analysis of worldwide research investigating the relationship between cortisol, a measure of HPA axis activity, and MDD in adolescence and young adulthood. METHOD We searched MEDLINE, PsycINFO, Cochrane Database of Systematic Reviews, Web of Science, Lilacs, African Journals Online, and Global Health for studies which examined the relationship between cortisol and MDD in global youth (10-24 years old). RESULTS Twenty-six studies were included in the systematic review and 14 were eligible for the meta-analysis, but only one study included young adults in their sample. Results from the meta-analysis demonstrated that elevated morning, but not evening, cortisol levels was prospectively associated with later MDD development in adolescence and young adulthood. However, morning cortisol levels did not significantly differ between healthy controls and individuals with MDD in cross-sectional studies. Afternoon cortisol and cortisol stress response also did not differ between adolescents with MDD and healthy controls. Qualitative synthesis of the three studies examining nocturnal cortisol showed higher nocturnal cortisol was both longitudinally and cross-sectionally associated with MDD in adolescence. CONCLUSION Our findings suggest elevated morning cortisol precedes depression in adolescence. Despite this, we did not find any differences in other cortisol measures in association with MDD in cross-sectional studies. Taken together, these findings suggest that elevated morning and nocturnal cortisol are risk factors for depression in adolescence rather than a biomarker of existing MDD. This supports a role for the hyperactivity of the HPA axis in the development of MDD in adolescence. Most of the studies were from high-income-countries (HICs) and thus further work would need to be conducted in low- and middle-income countries (LMICs) to understand if our findings are generalisable also to these populations.
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Affiliation(s)
- Zuzanna Zajkowska
- King’s College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK
| | - Nancy Gullett
- King’s College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK
| | - Annabel Walsh
- King’s College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK
| | - Valentina Zonca
- King’s College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK,Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Gloria A. Pedersen
- Division of Global Mental Health, Department of Psychiatry, School of Medicine and Health Sciences, The George Washington University, 2120L St NW, Ste 600, Washington, DC 20037, USA
| | - Laila Souza
- Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Child & Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350 – 400N, Porto Alegre, RS 90035–903, Brazil
| | - Christian Kieling
- Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Child & Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350 – 400N, Porto Alegre, RS 90035–903, Brazil
| | - Helen L. Fisher
- King’s College London, Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, London, UK,ESRC Centre for Society and Mental Health, King’s College London, London, UK
| | - Brandon A. Kohrt
- Division of Global Mental Health, Department of Psychiatry, School of Medicine and Health Sciences, The George Washington University, 2120L St NW, Ste 600, Washington, DC 20037, USA
| | - Valeria Mondelli
- King's College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK; National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, King's College London, London, UK.
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Association between physical hazardous agent exposure and mental health in the Korean working population: the 5th Korean Working Conditions Survey. Ann Occup Environ Med 2022; 33:e33. [PMID: 35024150 PMCID: PMC8668812 DOI: 10.35371/aoem.2021.33.e33] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 10/21/2021] [Indexed: 01/22/2023] Open
Abstract
Background Mental health problems are emerging issues in occupational safety and health, whereas the findings on the relationship between physical hazards and mental health are not consistent. The aim of our study was to investigate the association between physical hazard exposure and mental health outcomes including depression and anxiety. Methods We included 48,476 participants from the fifth Korean Working Conditions Survey (KWCS) in this study. The χ2 test and logistic regression analyses were conducted to assess the association between physical hazard exposures and mental health. All statistical analyses were performed sex-specifically. Results In logistic regression analysis, the odds ratios (ORs) of depression were significantly increased in male workers who were exposed to vibration (severe OR: 1.54, 95% confidence interval [CI]: 1.21–1.95) and noise (severe OR: 1.93, 95% CI: 1.49–2.48) whereas the ORs of depression were not significant in female workers from vibration (severe OR: 0.86, 95% CI: 0.50–1.38) or noise exposure (severe OR: 1.39, 95% CI: 0.84–2.17). The ORs of anxiety were significantly increased in male workers with vibration (severe OR: 1.76, 95% CI: 1.43–2.15) and noise exposure (severe OR: 2.12, 95% CI: 1.69–2.63) whereas the OR between vibration and anxiety (severe OR: 1.45, 95% CI: 0.91–2.21) was not significant in female workers. High or low temperature exposure had significant associations with depression and anxiety in both male and female subjects. Conclusions Results of our study suggest that physical hazard exposures may be associated with increased risk of mental health problems including depression and anxiety. These associations are more prominent in male workers in comparison with female workers.
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Löffler-Stastka H, Dietrich D, Sauter T, Fittner M, Steinmair D. Simulating the mind and applications – a theory-based chance for understanding psychic transformations in somatic symptom disorders. World J Meta-Anal 2021; 9:474-487. [DOI: 10.13105/wjma.v9.i6.474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 11/15/2021] [Accepted: 12/24/2021] [Indexed: 02/06/2023] Open
Abstract
With the new category of somatic symptom disorder/bodily distress disorder in ICD-11, research into pathogenetic and therapeutic pathways is stimulated. By turning away from the definition of somatoform disorders as “the lack of something physical explaining everything”, this new classification might offer a way to put the focus on the individual patient’s psychodynamic balance and conflicts and their condensation in the symptom. Modelling and simulation have a long history in science to gain insight also into complex phenomena. Considering the evolution of precision medicine many different parameters are meanwhile operationalised and ready for consequent process research. Calculation models have to fit to the complexity of this disorder category. In an interdisciplinary discourse between computer and medical/psychoanalytic scientists a multilayer, fine grained calculation model is elaborated. Starting from a clinical case history, within iterative discussion, by acknowledging the demand for interdisciplinary synergy and cooperation in science, psychoanalytic theory served as the basis for computer-scientific information technique. A parallelisation with the Mealy model helped to establish a meaningful calculation possibility for further process research. How psychic transformations can be understood properly in order to provide meaningful treatments, the respective training, and to conduct appropriate process- and outcome-research is established in simulating the mind and applications.
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Affiliation(s)
| | | | - Thilo Sauter
- Institute of Computer Technology, TU Wien, Vienna 1040, Austria
- Center for Integrated Sensor Systems, Danube University Krems, Wiener Neustadt 2700, Austria
| | - Martin Fittner
- Institute of Computer Technology, TU Wien, Vienna 1040, Austria
| | - Dagmar Steinmair
- Department of Psychoanalysis and Psychotherapy, Medical University Vienna, Vienna 1090, Austria
- University Hospital St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten 3100, Austria
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Misztak P, Sowa-Kućma M, Pańczyszyn-Trzewik P, Szewczyk B, Nowak G. Antidepressant-like Effects of Combined Fluoxetine and Zinc Treatment in Mice Exposed to Chronic Restraint Stress Are Related to Modulation of Histone Deacetylase. Molecules 2021; 27:22. [PMID: 35011254 PMCID: PMC8746513 DOI: 10.3390/molecules27010022] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 12/13/2021] [Accepted: 12/16/2021] [Indexed: 11/17/2022] Open
Abstract
Chronic stress is the key factor contributing to the development of depressive symptoms. Chronic restraint stress (CRS) is well validated and is one of the most commonly used models to induce depressive-like behavior in rodents. The present study aimed to evaluate whether fluoxetine (FLU 5 mg/kg) and zinc (Zn 10mg/kg) given simultaneously induce a more pronounced antidepressant-like effect in the CRS model than both those compounds given alone. Behavioral assessment was performed using the tail suspension and splash tests (TST and ST, respectively). Furthermore, the effects of CRS, FLU and Zn given alone and combined treatment with FLU + Zn on the expression of proteins involved in the apoptotic, inflammatory, and epigenetic processes were evaluated in selected brain structures (prefrontal cortex, PFC; and hippocampus, Hp) using Western blot analysis or enzyme-linked immunosorbent assays (ELISA). The results obtained indicated that three hours (per day) of immobilization for 4 weeks induced prominent depressive symptoms that manifested as increased immobility time in the TST, as well as decreased number and grooming time in the ST. Behavioral changes induced by CRS were reversed by both FLU (5 and 10 mg/kg) or Zn (10 mg/kg). Zinc supplementation (10 mg/kg) slightly increases the effectiveness of FLU (5 mg/kg) in the TST. However, it significantly increased the activity of FLU in the ST compared to the effect induced by FLU and Zn alone. Biochemical studies revealed that neither CRS nor FLU and Zn given alone or in combined treatment alter the expression of proteins involved in apoptotic or inflammatory processes. CRS induced major alterations in histone deacetylase (HDAC) levels by increasing the level of HADC1 and decreasing the level of HADC4 in the PFC and Hp, decreasing the level of HADC6 in the PFC but increasing it in Hp. Interestingly, FLU + Zn treatment reversed CRS-induced changes in HDAC levels in the Hp, indicating that HDAC modulation is linked to FLU + Zn treatment and this effect is structure-specific.
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Affiliation(s)
- Paulina Misztak
- Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, 30-668 Krakow, Poland; (G.N.)
- Department of Neurobiology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland
| | - Magdalena Sowa-Kućma
- Department of Human Physiology, Institute of Medical Sciences, Medical College of Rzeszow University, Kopisto 2a, 35-959 Rzeszow, Poland; (M.S.-K.); (P.P.-T.)
| | - Patrycja Pańczyszyn-Trzewik
- Department of Human Physiology, Institute of Medical Sciences, Medical College of Rzeszow University, Kopisto 2a, 35-959 Rzeszow, Poland; (M.S.-K.); (P.P.-T.)
| | - Bernadeta Szewczyk
- Department of Neurobiology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland
| | - Gabriel Nowak
- Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, 30-668 Krakow, Poland; (G.N.)
- Department of Neurobiology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland
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Kim HJ, Min JY, Seo YS, Min KB. Relationship between chronic exposure to ambient air pollution and mental health in Korean adult cancer survivors and the general population. BMC Cancer 2021; 21:1298. [PMID: 34863123 PMCID: PMC8645076 DOI: 10.1186/s12885-021-09013-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 11/16/2021] [Indexed: 11/10/2022] Open
Abstract
Background Although a significant association between air pollution and mental health has been identified, few studies have addressed this relationship based on cancer diagnosis. This study investigated whether associations between long-term air pollution and mental health conditions differ based on whether the individual has been diagnosed with cancer. Methods Nationally representative data were used and a total of 38,101 adults were included in the analyses. We assessed mental health factors such as perceived stress, depressive symptoms, and suicidal ideation, and analyzed the associations between these factors and individuals’ annual average exposure to air pollutants, including particulate matter with an aerodynamic diameter ≤ 10 μm (PM10), nitrogen dioxide, sulfur dioxide, and carbon monoxide. Results Compared with the general population, PM10 exposure in cancer survivors predicted a higher risk of depressive symptoms (odds ratio [OR] =1.34; 95% confidence interval [CI] = 1.06–1.69) and suicidal ideation (OR = 1.29; 95% CI = 1.01–1.64). Notably, the statistically significant relationship between PM10 exposure and suicidal ideation in cancer survivors disappeared after further adjustment for depressive symptoms (p = 0.3103). This pattern was also observed in the result of propensity score-matched analysis for comparison between cancer survivors and the general population. Conclusions This study provides the first evidence that cancer survivors with depressive symptoms may be more susceptible to suicidal ideation in the context of persistent PM10 exposure.
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Affiliation(s)
- Hyun-Jin Kim
- National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea
| | - Jin-Young Min
- Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Republic of Korea
| | - Yong-Seok Seo
- Young Jin Ind., Ltd., Icheon-si, Gyeonggi-do, Republic of Korea
| | - Kyoung-Bok Min
- Department of Preventive Medicine, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Republic of Korea.
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Bhadra S, Chen S, Liu C. Analysis of Differentially Expressed Genes That Aggravate Metabolic Diseases in Depression. Life (Basel) 2021; 11:life11111203. [PMID: 34833079 PMCID: PMC8620538 DOI: 10.3390/life11111203] [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: 08/19/2021] [Revised: 10/22/2021] [Accepted: 10/25/2021] [Indexed: 12/14/2022] Open
Abstract
Depression is considered the second leading cause of the global health burden after cancer. It is recognized as the most common physiological disorder. It affects about 350 million people worldwide to a serious degree. The onset of depression, inadequate food intake, abnormal glycemic control and cognitive impairment have strong associations with various metabolic disorders which are mediated through alterations in diet and physical activities. The regulatory key factors among metabolic diseases and depression are poorly understood. To understand the molecular mechanisms of the dysregulation of genes affected in depressive disorder, we employed an analytical, quantitative framework for depression and related metabolic diseases. In this study, we examined datasets containing patients with depression, obesity, diabetes and NASH. After normalizing batch effects to minimize the heterogeneity of all the datasets, we found differentially expressed genes (DEGs) common to all the datasets. We identified significantly associated enrichment pathways, ontology pathways, protein–protein cluster networks and gene–disease associations among the co-expressed genes co-expressed in depression and the metabolic disorders. Our study suggested potentially active signaling pathways and co-expressed gene sets which may play key roles in crosstalk between metabolic diseases and depression.
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Wong WLE, Dawe GS, Young AH. The putative role of the relaxin-3/RXFP3 system in clinical depression and anxiety: A systematic literature review. Neurosci Biobehav Rev 2021; 131:429-450. [PMID: 34537263 DOI: 10.1016/j.neubiorev.2021.09.028] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 09/13/2021] [Accepted: 09/13/2021] [Indexed: 12/14/2022]
Abstract
The relaxin-3/RXFP3 system is one of several neuropeptidergic systems putatively implicated in regulating the behavioural alterations that characterise clinical depression and anxiety, making it a potential target for clinical translation. Accordingly, this systematic review identified published reports on the role of relaxin-3/RXFP3 signalling in these neuropsychiatric disorders and their behavioural endophenotypes, evaluating evidence from animal and human studies to ascertain any relationship. We searched PubMed, EMBASE, PsycINFO and Google Scholar databases up to February 2021, finding 609 relevant records. After stringent screening, 51 of these studies were included in the final synthesis. There was considerable heterogeneity in study designs and some inconsistency across study outcomes. However, experimental evidence is consistent with an ability of relaxin-3/RXFP3 signalling to promote arousal and suppress depressive- and anxiety-like behaviour. Moreover, meta-analyses of six to eight articles investigating food intake revealed that acute RXFP3 activation had strong orexigenic effects in rats. This appraisal also identified the lack of high-quality clinical studies pertinent to the relaxin-3/RXFP3 system, a gap that future research should attempt to bridge.
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Affiliation(s)
- Win Lee Edwin Wong
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
| | - Gavin Stewart Dawe
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore
| | - Allan H Young
- Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; South London & Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Monks Orchard Road, London, United Kingdom
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Zhang Y, Cong P, Tong C, Jin H, Liu Y, Hou M. Melatonin pretreatment alleviates blast-induced oxidative stress in the hypothalamic-pituitary-gonadal axis by activating the Nrf2/HO-1 signaling pathway. Life Sci 2021; 280:119722. [PMID: 34153300 DOI: 10.1016/j.lfs.2021.119722] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 06/02/2021] [Accepted: 06/09/2021] [Indexed: 01/14/2023]
Abstract
Although melatonin has been demonstrated to exert a potent antioxidant effect, the ability of melatonin to alleviate blast-induced oxidative stress in the hypothalamic-pituitary-gonadal (HPG) axis remains unclear. This study aimed to elucidate the effects and underlying mechanism of melatonin pretreatment on the HPG axis disrupted by blast injury. Sixty C57BL/6 mice were randomly divided into control, blast, and blast + melatonin groups for behavioral experiments. The elevated maze experiment, open field experiment, and Morris Water Maze experiment were carried out on the 7th, 14th and 28th day after the blast injury. Fifty Sprague Dawley rats were randomly divided into control, blast, blast + melatonin, and blast + melatonin + luzindole groups for hormone assays and molecular and pathological experiments. Blood samples were used for HPG axis hormone detection and ELISA assays, and tissue samples were used to detect oxidative stress, inflammation, apoptosis, and stress-related protein levels. The results showed that melatonin pretreatment alleviated blast-induced behavioral abnormalities in mice and maintained the HPG axis hormone homeostasis in rats. Additionally, melatonin significantly reduced MDA5 expression and increased the expression of Nrf2/HO-1. Moreover, melatonin significantly inhibited NF-κB expression and upregulated IL-10 expression, and it reversed the blast-induced high expression of caspase-3 and Bax and the low expression of Bcl-2. Furthermore, luzindole counteracted melatonin inhibition of NF-κB and upregulated Nrf2/HO-1. Melatonin significantly alleviated blast-induced HPG axis hormone dyshomeostasis, behavioral abnormalities, oxidative stress, inflammation, and apoptosis, which may be achieved by upregulating the Nrf2/HO-1 signaling pathway. Our study suggested that melatonin pretreatment is a potential treatment for blast-induced HPG axis hormonal and behavioral abnormalities.
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Affiliation(s)
- Yin Zhang
- Graduate School, Dalian Medical University, Dalian, Liaoning Province 116044, China
| | - Peifang Cong
- Department of Emergency Medicine, The General Hospital of Northern Theater Command, Laboratory of Rescue Center of Severe Trauma PLA, Shenyang, Liaoning Province 116044, China
| | - Changci Tong
- Department of Emergency Medicine, The General Hospital of Northern Theater Command, Laboratory of Rescue Center of Severe Trauma PLA, Shenyang, Liaoning Province 116044, China
| | - Hongxu Jin
- Department of Emergency Medicine, The General Hospital of Northern Theater Command, Laboratory of Rescue Center of Severe Trauma PLA, Shenyang, Liaoning Province 116044, China
| | - Yunen Liu
- The Second Affiliated Hospital of Shenyang Medical College, The Veterans General Hospital of Liaoning Province, No. 20 Beijiu Road, Heping District, Shenyang 110001, China; Shenyang Medical College, No. 146, Huanghe North Street, Shenyang 110034, China.
| | - Mingxiao Hou
- Graduate School, Dalian Medical University, Dalian, Liaoning Province 116044, China; Department of Emergency Medicine, The General Hospital of Northern Theater Command, Laboratory of Rescue Center of Severe Trauma PLA, Shenyang, Liaoning Province 116044, China.
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Padda J, Khalid K, Hitawala G, Batra N, Pokhriyal S, Mohan A, Zubair U, Cooper AC, Jean-Charles G. Depression and Its Effect on the Menstrual Cycle. Cureus 2021; 13:e16532. [PMID: 34430141 PMCID: PMC8378322 DOI: 10.7759/cureus.16532] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/20/2021] [Indexed: 01/30/2023] Open
Abstract
A strong association is noted between depression and early perimenopause as well as menopause. The association was found to be the greatest in women with natural menopause at the age less than 40 years. Excessive corticotropin-releasing hormone (CRH) levels in depression lead to inhibition of the hypothalamic-pituitary-gonadal (HPG) axis and increased cortisol levels which further inhibits the action of gonadotropin-releasing hormone (GnRH) neurons, gonadotrophs, and gonads. The resulting changes in luteinizing hormone (LH) amplitude, follicle-stimulating hormone (FSH) levels, and LH pulse frequency were noted in patients with depression. Besides depression, earlier surgical menopause is associated with cognitive decline. In addition, it is seen that menopausal changes predisposed females to an increased risk of depression. The association between dysmenorrhea and depression was found to be bidirectional and congruent in most studies. Patients with dysmenorrhea and coexisting depression had enhanced pain perception along with a poor response to pain relief measures. Even the treatment of underlying depression has been shown to cause menorrhagia. On the other hand, amenorrhea has also been reported as a side effect of sertraline and electroconvulsive therapy. Menstrual disorders contribute to a significant number of outpatient gynecological visits per year in the United States. Co-existing or history of depression can either be the cause of or interfere in the treatment of these disorders. Furthermore, the treatment of depression can be the etiology of various menstrual abnormalities, while menstrual disorders themselves could be the cause of depression. The increasing prevalence of depression, women’s health, multiple female-specific subtypes, and the preexisting burden of menstrual disorders necessitates more detailed studies on the effects of depression on the menstrual cycle.
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Affiliation(s)
- Jaskamal Padda
- Internal Medicine, JC Medical Center, Orlando, USA.,Internal Medicine, Avalon University School of Medicine, Willemstad, CUW
| | | | | | - Nitya Batra
- Internal Medicine, JC Medical Center, Orlando, USA
| | | | - Ayushi Mohan
- Internal Medicine, JC Medical Center, Orlando, USA
| | - Ujala Zubair
- Family Medicine, Dow University of Health Sciences, Karachi, PAK
| | | | - Gutteridge Jean-Charles
- Internal Medicine, JC Medical Center, Orlando, USA.,Internal Medicine, Advent Health and Orlando Health Hospital, Orlando, USA
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Lee HJ, Hong JK, Kim JK, Kim DH, Jang SW, Han SW, Yoon IY. Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients 2021; 13:2660. [PMID: 34444820 PMCID: PMC8398773 DOI: 10.3390/nu13082660] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 07/28/2021] [Accepted: 07/29/2021] [Indexed: 12/19/2022] Open
Abstract
The human gut microbiome is closely linked to mental health and sleep. We aimed to verify the efficacy and safety of probiotic NVP-1704, a mixture of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98, in improving stress, depression, anxiety, and sleep disturbances, along with the measurement of some blood biomarkers. A total of 156 healthy adults with subclinical symptoms of depression, anxiety, and insomnia were retrospectively registered and randomly assigned to receive either NVP-1704 (n = 78) or a placebo (n = 78) for eight weeks. Participants completed the Stress Response Inventory, Beck's Depression and Anxiety Inventory, Pittsburg Sleep Quality Index, and Insomnia Severity Index at baseline, at four and eight weeks of treatment. Pre- and post-treatment blood tests for biomarkers were conducted. After intervention, gut microbiota composition was quantified by pyrosequencing the bacterial 16S rRNA gene. The NVP-1704 group had a more significant reduction in depressive symptoms at four and eight weeks of treatment, and anxiety symptoms at four weeks compared to the placebo group. Those receiving NVP-1704 also experienced an improvement in sleep quality. NVP-1704 treatment led to a decrease in serum interleukin-6 levels. Furthermore, NVP-1704 increased Bifidobacteriaceae and Lactobacillacea, whereas it decreased Enterobacteriaceae in the gut microbiota composition. Our findings suggest that probiotic NVP-1704 could be beneficial for mental health and sleep.
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Affiliation(s)
- Hyuk Joo Lee
- Department of Psychiatry, Uijeongbu Eulji Medical Center, Eulji University, Gyeonggi 11759, Korea;
- Department of Neuropsychiatry, School of Medicine, Eulji University, Daejeon 34824, Korea
| | - Jung Kyung Hong
- Department of Psychiatry, Bundang Hospital, Seoul National University, Seongnam 13620, Korea;
| | - Jeon-Kyung Kim
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea; (J.-K.K.); (D.-H.K.)
| | - Dong-Hyun Kim
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea; (J.-K.K.); (D.-H.K.)
| | - Seok Won Jang
- PB Department, Navipharm Inc., Suwon 16209, Korea; (S.W.J.); (S.-W.H.)
| | - Seung-Won Han
- PB Department, Navipharm Inc., Suwon 16209, Korea; (S.W.J.); (S.-W.H.)
| | - In-Young Yoon
- Department of Psychiatry, Bundang Hospital, Seoul National University, Seongnam 13620, Korea;
- Department of Psychiatry, School of Medicine, Seoul National University, Seoul 03080, Korea
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Atanasova D, Lazarov N, Stoyanov DS, Spassov RH, Tonchev AB, Tchekalarova J. Reduced neuroinflammation and enhanced neurogenesis following chronic agomelatine treatment in rats undergoing chronic constant light. Neuropharmacology 2021; 197:108706. [PMID: 34274352 DOI: 10.1016/j.neuropharm.2021.108706] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 07/03/2021] [Accepted: 07/05/2021] [Indexed: 10/20/2022]
Abstract
Experimental studies have revealed the involvement of neuroinflammation mediated by activated microglia in the pathophysiology of depression, suggesting a novel target for treatment. The atypical antidepressant Agomelatine (Ago) has an advantage compared to the classical antidepressants due to its chronobiotic activity and unique pharmacological profile as a selective agonist at the melatonin receptors and an antagonist at the 5HT2C receptors. We have recently revealed that Ago can exert a potent antidepressant effect in rats exposed to a chronic constant light (CCL). In the present study, we hypothesized that the anti-inflammatory activity of this melatonin analog on activated neuroglia in specific brain structures might contribute to its antidepressant effect in this model. Chronic Ago treatment (40 mg/kg, i.p. for 21 days) was executed during the last 3 weeks of a 6-week period of CCL exposure in rats. The CCL-vehicle-treated rats showed a profound neuroinflammation characterized by microgliosis and astrogliosis in the hippocampus, basolateral amygdala (BL) and partly in the piriform cortex (Pir) confirmed by immunohistochemistry. With the exception of the Pir, the CCL regime was accompanied by neuronal damage, identified by Nissl staining, in the hippocampus and basolateral amygdala and impaired neurogenesis with reduced dendritic complexity of hippocampal neuroprogenitor cells detected by doublecortin-positive cells in the dentate gyrus (DG) subgranular zone compared to the control group. Ago reversed the gliosis in a region-specific manner and partially restored the suppressed DG neurogenesis. Ago failed to produce neuroprotection in CCL exposed rats. The present results suggest that the beneficial effects of Ago represent an important mechanism underlying its antidepressant effect in models characterized by impaired circadian rhythms.
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Affiliation(s)
- Dimitrinka Atanasova
- Institute of Neurobiology, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria; Department of Anatomy, Faculty of Medicine, Trakia University, 6003, Stara Zagora, Bulgaria
| | - Nikolai Lazarov
- Institute of Neurobiology, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria; Department of Anatomy and Histology, Medical University of Sofia, 1431, Sofia, Bulgaria
| | - Dimo S Stoyanov
- Department of Anatomy and Cell Biology, Faculty of Medicine, Medical University - Varna "Prof. Dr. Paraskev Stoyanov", 9002, Varna, Bulgaria
| | - Radoslav H Spassov
- Department of Anatomy and Cell Biology, Faculty of Medicine, Medical University - Varna "Prof. Dr. Paraskev Stoyanov", 9002, Varna, Bulgaria
| | - Anton B Tonchev
- Department of Anatomy and Cell Biology, Faculty of Medicine, Medical University - Varna "Prof. Dr. Paraskev Stoyanov", 9002, Varna, Bulgaria
| | - Jana Tchekalarova
- Institute of Neurobiology, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria.
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Choi K, Lee J, Kang HJ. Myelination defects in the medial prefrontal cortex of Fkbp5 knockout mice. FASEB J 2021; 35:e21297. [PMID: 33410216 DOI: 10.1096/fj.202001883r] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 11/14/2020] [Accepted: 12/07/2020] [Indexed: 12/13/2022]
Abstract
The hypothalamic-pituitary-adrenal (HPA) axis plays a principal role in stress response regulation and has been implicated in the etiology of stress-related disorders. The HPA axis regulates the normal synthesis and release of glucocorticoids; dysregulation of the HPA axis causes abnormal responses to stress. FK506-binding protein 5 (FKBP5), a co-chaperone of heat shock protein 90 in the glucocorticoid receptor (GR) molecular complex, is a key GR sensitivity regulator. FKBP5 single nucleotide polymorphisms are associated with dysregulated HPA axis and increased risk of stress-related disorders, including posttraumatic stress disorder (PTSD) and depression. In this study, we profiled the microRNAs (miRNAs) in the medial prefrontal cortex of Fkbp5 knockout (Fkbp5-/- ) mice and identified the target genes of differentially expressed miRNAs using sequence-based miRNA target prediction. Gene ontology analysis revealed that the differentially expressed miRNAs were involved in nervous system development, regulation of cell migration, and intracellular signal transduction. The validation of the expression of predicted target genes using quantitative polymerase chain reaction revealed that the expression of axon development-related genes, specifically actin-binding LIM protein 1 (Ablim1), lemur tyrosine kinase 2 (Lmtk2), kinesin family member 5c (Kif5c), neurofascin (Nfasc), and ephrin type-A receptor 4 (Epha4), was significantly decreased, while that of brain-derived neurotrophic factor (Bdnf) was significantly increased in the brain of Fkbp5-/- mice. These results suggest that axonal development-related genes can serve as potential targets in future studies focused on understanding the pathophysiology of PTSD.
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Affiliation(s)
- Koeul Choi
- Department of Life Science, Chung-Ang University, Seoul, Korea
| | - Joonhee Lee
- Department of Life Science, Chung-Ang University, Seoul, Korea
| | - Hyo Jung Kang
- Department of Life Science, Chung-Ang University, Seoul, Korea
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Merging the Multi-Target Effects of Kleeb Bua Daeng, a Thai Traditional Herbal Formula in Unpredictable Chronic Mild Stress-Induced Depression. Pharmaceuticals (Basel) 2021; 14:ph14070659. [PMID: 34358084 PMCID: PMC8308724 DOI: 10.3390/ph14070659] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/05/2021] [Accepted: 07/07/2021] [Indexed: 01/19/2023] Open
Abstract
Major depressive disorder (MDD) is a common and debilitating psychiatric disease characterized by persistent low mood, lack of energy, hypoactivity, anhedonia, decreased libido, and impaired cognitive and social functions. However, the multifactorial etiology of MDD remains largely unknown due the complex interaction between genetics and environment involved. Kleeb Bua Daeng (KBD) is a Thai traditional herbal formula that has been used to promote brain health. It consists of a 1:1:1 ratio of the aerial part of Centella asiatica, Piper nigrum fruit, and the petals of Nelumbo nucifera. According to the pharmacological activities of the individual medicinal plants, KBD has good potential as a treatment for MDD. The present study investigated the antidepressant activity of KBD in an unpredictable chronic mild stress (UCMS) mouse model. Daily administration of KBD to UCMS mice ameliorated both anhedonia, by increasing 2% sucrose intake, and hopeless behavior, by reducing immobility times in the forced swimming test (FST) and tail suspension test (TST) without any effect on locomotor activity. The mechanism of KBD activity was multi-modal. KBD promoted neurogenesis by upregulation of brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding (CREB) mRNA expression in the frontal cortex and hippocampus. Daily treatment with KBD significantly reversed UCMS-induced HPA axis dysregulation by upregulating the glucocorticoid receptor (GR) while downregulating serum- and glucocorticoid-inducible kinase 1 (SGK1) and FK506 binding protein 5 (FKBP5) mRNA expression. KBD treatment also normalized proinflammatory cytokine expression including tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1β and IL-6. KBD and its component extracts also exhibited an inhibitory effect in vitro on monoamine oxidase (MAO) A and B. The multiple antidepressant actions of KBD emphasize its potential as an effective, novel treatment for MDD.
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Kumar A, Salinas J. The Long-Term Public Health Impact of Social Distancing on Brain Health: Topical Review. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:7307. [PMID: 34299756 PMCID: PMC8305633 DOI: 10.3390/ijerph18147307] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 07/03/2021] [Accepted: 07/07/2021] [Indexed: 12/26/2022]
Abstract
Social distancing has been a critical public health measure for the COVID-19 pandemic, yet a long history of research strongly suggests that loneliness and social isolation play a major role in several cognitive health issues. What is the true severity and extent of risks involved and what are potential approaches to balance these competing risks? This review aimed to summarize the neurological context of social isolation and loneliness in population health and the long-term effects of social distancing as it relates to neurocognitive aging, health, and Alzheimer's disease and related dementias. The full scope of the underlying causal mechanisms of social isolation and loneliness in humans remains unclear partly because its study is not amenable to randomized controlled trials; however, there are many detailed experimental and observational studies that may provide a hypothesis-generating theoretical framework to better understand the pathophysiology and underlying neurobiology. To address these challenges and inform future studies, we conducted a topical review of extant literature investigating associations of social isolation and loneliness with relevant biological, cognitive, and psychosocial outcomes, and provide recommendations on how to approach the need to fill key knowledge gaps in this important area of research.
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Affiliation(s)
- Anagha Kumar
- Harvard College, Harvard University, Cambridge, MA 02138, USA;
- Center for Cognitive Neurology, Department of Neurology, New York University Grossman School of Medicine, New York University, New York, NY 10017, USA
| | - Joel Salinas
- Center for Cognitive Neurology, Department of Neurology, New York University Grossman School of Medicine, New York University, New York, NY 10017, USA
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Methiwala HN, Vaidya B, Addanki VK, Bishnoi M, Sharma SS, Kondepudi KK. Gut microbiota in mental health and depression: role of pre/pro/synbiotics in their modulation. Food Funct 2021; 12:4284-4314. [PMID: 33955443 DOI: 10.1039/d0fo02855j] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The microbiome residing in the human gut performs a wide range of biological functions. Recently, it has been elucidated that a change in dietary habits is associated with alteration in the gut microflora which results in increased health risks and vulnerability towards various diseases. Falling in line with the same concept, depression has also been shown to increase its prevalence around the globe, especially in the western world. Various research studies have suggested that changes in the gut microbiome profile further result in decreased tolerance of stress. Although currently available medications help in relieving the symptoms of depressive disorders briefly, these drugs are not able to completely reverse the multifactorial pathology of depression. The discovery of the communication pathway between gut microbes and the brain, i.e. the Gut-Brain Axis, has led to new areas of research to find more effective and safer alternatives to current antidepressants. The use of probiotics and prebiotics has been suggested as being effective in various preclinical studies and clinical trials for depression. Therefore, in the present review, we address the new antidepressant mechanisms via gut microbe alterations and provide insight into how these can provide an alternative to antidepressant therapy without the side effects and risk of adverse drug reactions.
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Affiliation(s)
- Hasnain N Methiwala
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab, India.
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Bourbeau KC, Moriarty TA, Bellovary BN, Bellissimo GF, Ducharme JB, Haeny TJ, Zuhl MN. Cardiovascular, Cellular, and Neural Adaptations to Hot Yoga versus Normal-Temperature Yoga. Int J Yoga 2021; 14:115-126. [PMID: 34188383 PMCID: PMC8191229 DOI: 10.4103/ijoy.ijoy_134_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 02/28/2021] [Accepted: 03/25/2021] [Indexed: 11/25/2022] Open
Abstract
CONTEXT Chronic heat exposure promotes cardiovascular and cellular adaptations, improving an organism's ability to tolerate subsequent stressors. Heat exposure may also promote neural adaptations and alter the neural-hormonal stress response. Hot-temperature yoga (HY) combines mind-body exercise with heat exposure. The added heat component in HY may induce cardiovascular and cellular changes, along with neural benefits and modulation of stress hormones. AIMS The purpose of the present study is to compare the cardiovascular, cellular heat shock protein 70 (HSP70), neural, and hormonal adaptations of HY versus normal-temperature yoga (NY). SETTINGS AND DESIGN Twenty-two subjects (males = 11 and females = 11, 26 ± 6 years) completed 4 weeks of NY (n = 11) or HY (n = 11, 41°C, 40% humidity). Yoga sessions were performed 3 times/week following a modified Bikram protocol. SUBJECTS AND METHODS Pre- and posttesting included (1) hemodynamic measures during a heat tolerance test and maximal aerobic fitness test; (2) neural and hormonal adaptations using serum brain-derived neurotrophic factor (BDNF) and adrenocorticotropic hormone (ACTH), along with a mental stress questionnaire; and (3) cellular adaptations (HSP70) in peripheral blood mononuclear cells (PBMCs). STATISTICAL ANALYSIS Within- and between-group Student's t-test analyses were conducted to compare pre- and post-VO2 max, perceived stress, BDNF, HSP70, and ACTH in HY and NY groups. RESULTS Maximal aerobic fitness increased in the HY group only. No evidence of heat acclimation or change in mental stress was observed. Serum BDNF significantly increased in yoga groups combined. Analysis of HSP70 suggested higher expression of HSP70 in the HY group only. CONCLUSIONS Twelve sessions of HY promoted cardiovascular fitness and cellular thermotolerance adaptations. Serum BDNF increased in response to yoga (NY + HY) and appeared to not be temperature dependent.
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Affiliation(s)
- Kelsey Christian Bourbeau
- Department of Kinesiology, University of Northern Iowa, Cedar Falls, Iowa, USA
- Department of Health, Exercise and Sports Science, University of New Mexico, Albuquerque, NM, USA
| | - Terence A Moriarty
- Department of Kinesiology, University of Northern Iowa, Cedar Falls, Iowa, USA
| | | | - Gabriella F Bellissimo
- Department of Kinesiology, State University of New York College at Cortland, Cortland, NY, USA
| | - Jeremy B Ducharme
- Department of Health, Exercise and Sports Science, University of New Mexico, Albuquerque, NM, USA
| | - Truman J Haeny
- Department of Health, Exercise and Sports Science, University of New Mexico, Albuquerque, NM, USA
| | - Micah N Zuhl
- School of Health Sciences, Central Michigan University, Mount Pleasant, Michigan, USA
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Foubert L, Noël Y, Spahr CM, Slavich GM. Beyond WEIRD: Associations between socioeconomic status, gender, lifetime stress exposure, and depression in Madagascar. J Clin Psychol 2021; 77:1644-1665. [PMID: 33825203 DOI: 10.1002/jclp.23131] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 02/05/2021] [Accepted: 03/03/2021] [Indexed: 11/10/2022]
Abstract
OBJECTIVE Although research has examined associations between socioeconomic status (SES), gender, and acute and chronic life stressors in depression, most studies have been conducted in Western, educated, industrialized, rich, democratic (WEIRD) populations. METHOD We addressed this issue by interviewing 65 adults (55 women, M age = 37) living in Madagascar, a typical low- and middle-income country. RESULTS As hypothesized, women experienced more life stressors and depressive symptoms, on average, than men, as did those from lower (vs. higher) SES backgrounds. Additionally, lifetime stress exposure was associated with greater symptoms of depression, accounting for 19% of the variability in depressive symptom levels. These effects differed for acute versus chronic and distal versus recent stressors. Finally, stress exposure significantly mediated the relation between SES and gender on depressive symptoms, accounting for 24.0%-70.8% of the SES/gender-depression association depending on stressor type. CONCLUSION These data extend prior research by describing how social stratification and gender relate to lifetime stress exposure and depressive symptoms in a non-WEIRD population.
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Affiliation(s)
- Laurent Foubert
- Department of Psychology, Rennes 2 University, Rennes, France
| | - Yvonnick Noël
- Department of Psychology, Rennes 2 University, Rennes, France
| | - Chandler M Spahr
- Department of Psychology, University of California, Riverside, California, USA
| | - George M Slavich
- Cousins Center for Psychoneuroimmunology and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California, USA
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Abstract
UNLABELLED Abstract. AIMS The longitudinal relationship between depression and the risk of non-alcoholic fatty liver disease is uncertain. We examined: (a) the association between depressive symptoms and incident hepatic steatosis (HS), both with and without liver fibrosis; and (b) the influence of obesity on this association. METHODS A cohort of 142 005 Korean adults with neither HS nor excessive alcohol consumption at baseline were followed for up to 8.9 years. The validated Center for Epidemiologic Studies-Depression score (CES-D) was assessed at baseline, and subjects were categorised as non-depressed (a CES-D < 8, reference) or depression (CES-D ⩾ 16). HS was diagnosed by ultrasonography. Liver fibrosis was assessed by the fibrosis-4 index (FIB-4). Parametric proportional hazards models were used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS During a median follow-up of 4.0 years, 27 810 people with incident HS and 134 with incident HS plus high FIB-4 were identified. Compared with the non-depressed category, the aHR (95% CIs) for incident HS was 1.24 (1.15-1.34) for CES-D ⩾ 16 among obese individuals, and 1.00 (0.95-1.05) for CES-D ⩾ 16 among non-obese individuals (p for interaction with obesity <0.001). The aHR (95% CIs) for developing HS plus high FIB-4 was 3.41 (1.33-8.74) for CES-D ⩾ 16 among obese individuals, and 1.22 (0.60-2.47) for CES-D ⩾ 16 among non-obese individuals (p for interaction = 0.201). CONCLUSIONS Depression was associated with an increased risk of incident HS and HS plus high probability of advanced fibrosis, especially among obese individuals.
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Impact of Surgical Status, Loneliness, and Disability on Interleukin 6, C-Reactive Protein, Cortisol, and Estrogen in Females with Symptomatic Type I Chiari Malformation. THE CEREBELLUM 2021; 20:872-886. [PMID: 33677786 DOI: 10.1007/s12311-021-01251-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/24/2021] [Indexed: 10/22/2022]
Abstract
Chiari malformation type I (CMI) provides an opportunity for examining possible moderators of allostatic load. CMI patients who had (n = 43) and had not (n = 19) undergone decompression surgery completed questionnaires regarding pain, disability, and loneliness, and provided serum samples for IL-6, CRP, estrogen, and free estradiol assays, and saliva samples to assess diurnal cortisol curves. ANOVAs examining surgical status (decompressed versus non-decompressed), loneliness (high vs. low), and disability (high vs. low) as independent variables and biomarker variables as dependent factors found that loneliness was associated with higher levels of cortisol, F(1, 37) = 4.91, p = .04, η2P = .11, and lower levels of estrogen, F(1, 36) = 7.29, p = .01, η2P = .17, but only in decompressed patients. Results highlight the possible impact of loneliness on biological stress responses and the need to intervene to reduce loneliness in patients with symptomatic CMI.
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Kunz N, Kemper C. Complement Has Brains-Do Intracellular Complement and Immunometabolism Cooperate in Tissue Homeostasis and Behavior? Front Immunol 2021; 12:629986. [PMID: 33717157 PMCID: PMC7946832 DOI: 10.3389/fimmu.2021.629986] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 01/13/2021] [Indexed: 12/20/2022] Open
Abstract
The classical liver-derived and serum-effective complement system is well appreciated as a key mediator of host protection via instruction of innate and adaptive immunity. However, recent studies have discovered an intracellularly active complement system, the complosome, which has emerged as a central regulator of the core metabolic pathways fueling human immune cell activity. Induction of expression of components of the complosome, particularly complement component C3, during transmigration from the circulation into peripheral tissues is a defining characteristic of monocytes and T cells in tissues. Intracellular complement activity is required to induce metabolic reprogramming of immune cells, including increased glycolytic flux and OXPHOS, which drive the production of the pro-inflammatory cytokine IFN-γ. Consequently, reduced complosome activity translates into defects in normal monocyte activation, faulty Th1 and cytotoxic T lymphocyte responses and loss of protective tissue immunity. Intriguingly, neurological research has identified an unexpected connection between the physiological presence of innate and adaptive immune cells and certain cytokines, including IFN-γ, in and around the brain and normal brain function. In this opinion piece, we will first review the current state of research regarding complement driven metabolic reprogramming in the context of immune cell tissue entry and residency. We will then discuss how published work on the role of IFN-γ and T cells in the brain support a hypothesis that an evolutionarily conserved cooperation between the complosome, cell metabolism and IFN-γ regulates organismal behavior, as well as immunity.
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Affiliation(s)
- Natalia Kunz
- Complement and Inflammation Research Section (CIRS), National Heart, Lung and Blood Institute, Bethesda, MD, United States
| | - Claudia Kemper
- Complement and Inflammation Research Section (CIRS), National Heart, Lung and Blood Institute, Bethesda, MD, United States.,Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany
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