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1
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Zhang Q, Zhao Y, Cheng GY. Effect of negative mood, serum inflammatory factors, miR-155, and brain-derived neurotrophic factor. World J Psychiatry 2025; 15:99573. [PMID: 39974477 PMCID: PMC11758059 DOI: 10.5498/wjp.v15.i2.99573] [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: 10/31/2024] [Revised: 11/29/2024] [Accepted: 12/19/2024] [Indexed: 01/14/2025] Open
Abstract
BACKGROUND Abdominal postoperative patients are susceptible to postoperative depression resulting from pain and stress, which can hinder their rehabilitation. Acupuncture has shown potential to relieve this condition. AIM To analyze the mechanism by which acupuncture relieves postoperative depression in patients post-abdominal surgery. METHODS Abdominal postoperative patients with depression between January 2015 and December 2023 at the First Affiliated Hospital of Heilongjiang University of Chinese Medicine were enrolled. Patients were divided into two groups using the random throwing method: Observation (250 cases, fluoxetine hydrochloride + acupuncture treatment) and control (250 cases, fluoxetine hydrochloride treatment). Changes in negative emotions Hamilton Depression Scale 24, serum inflammatory factors [tumor necrosis factor α, interleukin (IL)-1β, IL-6], miR-155 expression levels, and BDNF levels were assessed. RESULTS Significant improvements were observed in the observation group compared to the control group in all assessed parameters after six weeks (P < 0.05). This suggests that the combination of fluoxetine hydrochloride and acupuncture may be more effective in managing postoperative depression than medication alone. CONCLUSION Acupuncture complies with the principle of traditional Chinese medicine syndrome differentiation and ensures the pertinence and effectiveness of treatment. In addition, it not only actively improves depressive symptoms but also effectively regulates the serum level of inflammatory factors.
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Affiliation(s)
- Qi Zhang
- Prevention and Treatment Center, First Affiliated Hospital Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Yue Zhao
- Department of Medical, First Affiliated Hospital Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Guang-Yu Cheng
- Traditional Chinese Medicine Translational Medicine Research Center, First Affiliated Hospital Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
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Eslami M, Monemi M, Nazari MA, Azami MH, Shariat Rad P, Oksenych V, Naderian R. The Anti-Inflammatory Potential of Tricyclic Antidepressants (TCAs): A Novel Therapeutic Approach to Atherosclerosis Pathophysiology. Pharmaceuticals (Basel) 2025; 18:197. [PMID: 40006011 PMCID: PMC11858810 DOI: 10.3390/ph18020197] [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: 01/01/2025] [Revised: 01/24/2025] [Accepted: 01/28/2025] [Indexed: 02/27/2025] Open
Abstract
Atherosclerosis, a chronic inflammatory disease, is driven by complex molecular mechanisms involving inflammatory cytokines and immune pathways. According to recent research, tricyclic antidepressants (TCAs), which are typically prescribed to treat depressive disorders, have strong anti-inflammatory effects. TCAs, including imipramine and amitriptyline, alter inflammatory signaling cascades, which include lowering the levels pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6 and inhibiting NF-κB activation. By inhibiting the NLRP3 inflammasome and suppressing pathways including JAK/STAT, MAPK, and PI3K, these effects are produced, improving endothelial function and reducing oxidative stress. The intricacy of TCAs' anti-inflammatory actions has demonstrated by the existence of contradictory findings about how they alter IL-6 levels. The dependence of the heterogeneity of the reaction on the use of particular TCAs and experimental settings is shown by the fact that some studies show reduced IL-6 production, while others indicate increases or no changes. This review explores the multifaceted mechanisms through which TCAs modulate inflammatory pathways. TCAs inhibit NF-κB activation, reduce oxidative stress, and suppress the production of key inflammatory mediators, including IL-6 and TNF-α. They also regulate Toll-like receptor (TLR) signaling and NOD-, LRR-, and NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome activation, reducing the release of IL-1β and IL-18, critical drivers of endothelial dysfunction and plaque instability. Given their capacity to target critical inflammatory molecules and pathways, TCAs provide great potential in the therapy of atherosclerosis, particularly for individuals with associated depression and cardiovascular risk factors. Nevertheless, further research is essential to clarify the precise molecular mechanisms, resolve inconsistencies in current findings, and establish the clinical applicability of TCAs as anti-inflammatory agents in atherosclerosis management.
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Affiliation(s)
- Majid Eslami
- Cancer Research Center, Semnan University of Medical Sciences, Semnan 35147-99442, Iran;
| | - Marzieh Monemi
- Department of Basic Science, Faculty of Pharmacy and Pharmaceutical Science, Tehran Medical Science, Islamic Azad University, Tehran 19395-1495, Iran
| | - Mohammad Ali Nazari
- Student Research Committee, Faculty of Medicine, Iran University of Medical Sciences, Tehran 14496-1453, Iran
| | - Mohammad Hossein Azami
- Student Research Committee, Faculty of Medicine, Iran University of Medical Sciences, Tehran 14496-1453, Iran
| | - Parand Shariat Rad
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah 67158-47141, Iran
| | | | - Ramtin Naderian
- Clinical Research Development Unit, Kowsar Educational, Research and Therapeutic Hospital, Semnan University of Medical Sciences, Semnan 35147-99442, Iran
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Onisor D, Avram C, Ruta F, Brusnic O, Boeriu A, Stoian M, Boicean A, Sasaran M. Burden of Common Mental Disorders in Ulcerative Colitis and Irritable Bowel Syndrome Patients: An Analysis of Risk Factors. J Clin Med 2025; 14:499. [PMID: 39860505 PMCID: PMC11766210 DOI: 10.3390/jcm14020499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 12/31/2024] [Accepted: 01/10/2025] [Indexed: 01/27/2025] Open
Abstract
Background: Common mental disorders are an underdiagnosed comorbidity, which can significantly worsen the prognosis of the main disease and decrease the quality of life. We aimed to investigate the prevalence of depression and anxiety in a cohort of irritable bowel syndrome with diarrhea (IBS-D) and ulcerative colitis (UC) patients and to evaluate the risk factors for their occurrence. Materials and Methods: A total of 112 patients were evaluated. Multivariable analysis was used to determine associations between patient factors and common mental disorders, evaluated with PHQ-9 and GAD-7 questionnaires. Results: We found a significantly higher prevalence of moderate and severe anxiety among patients with IBS-D, when compared with the UC group (p < 0.01). Linear regression analysis revealed an inverse association between anti-TNF-alpha monoclonal antibodies treatment and a higher PHQ-9 score (p = 0.02). Multivariate analysis revealed that, in patients with UC, the presence of children has been associated with a higher GAD-7 score (p = 0.01), both individually and in combination with a higher duration of the disease. (p < 0.01). For IBS-D, a combination of active employment status and religious belief, active employment status and higher educational level, as well as religious belief and the presence of children correlated with higher GAD-7 scores (p = 0.03, p = 0.03 and p = 0.02, respectively). Conclusions: Infliximab used in the treatment for UC improved the parameters of depression. Patients with UC who have university education and a longer duration of the disease are at increased risk of developing depression and anxiety, especially if they have children in care. Regarding IBS-D patients who have an active work status, religious beliefs and caregivers are at increased risk of developing anxiety.
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Affiliation(s)
- Danusia Onisor
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania; (D.O.); (O.B.); (A.B.)
| | - Calin Avram
- Department of Medical Informatics and Biostatistics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania
| | - Florina Ruta
- Department Community Nutrition and Food Safety, Faculty of General Medicine, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Olga Brusnic
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania; (D.O.); (O.B.); (A.B.)
| | - Alina Boeriu
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania; (D.O.); (O.B.); (A.B.)
| | - Mircea Stoian
- Department of Anesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540139 Targu Mures, Romania;
| | - Adrian Boicean
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania;
| | - Maria Sasaran
- Department of Pediatrics III, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania;
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Schmitz CN, Sammer G, Neumann E, Blecker C, Gründer G, Adolphi H, Lamadé EK, Pedraz-Petrozzi B. Functional resting state connectivity is differentially associated with IL-6 and TNF-α in depression and in healthy controls. Sci Rep 2025; 15:1769. [PMID: 39800770 PMCID: PMC11725594 DOI: 10.1038/s41598-025-85514-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 01/03/2025] [Indexed: 01/16/2025] Open
Abstract
Inflammatory processes have been implicated in the pathophysiology of depression. In human studies, inflammation has been shown to act as a critical disease modifier, promoting susceptibility to depression and modulating specific endophenotypes of depression. However, there is scant documentation of how inflammatory processes are associated with neural activity in patients with depression. We therefore tested the hypothesis that the peripheral inflammation markers IL-6 and TNF-α correlate with neural resting state network functional connectivity in depression using functional magnetic resonance imaging (fMRI) and compared it with healthy controls. We used fMRI to investigate the functional connectivity (FC) of the resting state Default Mode Network (DMN) and Salience/Ventral Attention Network (SAL) and their association with the peripheral inflammation markers IL-6 and TNF-α in 25 patients with depression and compared it to 24 healthy subjects. Results of this imaging study revealed that both DMN and SAL resting state networks are differentially associated with distinct immunological pathways depending on whether a person has a depressive phenotype or is healthy. While the DMN FC correlated with the concentration of the cytokine IL-6 in healthy subjects, SAL FC's connectivity correlated with the cytokine TNF-α's concentration. This study highlights the importance of peripheral inflammatory processes in depression and suggests a modulatory effect on neural resting state networks depending on the state of depression.
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Affiliation(s)
- Christian N Schmitz
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany
- German Center for Mental Health (DZPG), Partner Site Mannheim, Mannheim, Germany
- Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Gebhard Sammer
- Faculty of Psychology and Sports Science, Justus-Liebig University, Giessen, Hessen, Germany
- Cognitive Neurosciences at the Centre for Psychiatry, Justus-Liebig University, Giessen, Hessen, Germany
- Bender Institute of Neuroimaging (BION), Faculty of Psychology and Sports Science, Justus-Liebig University, Giessen, Hessen, Germany
| | - Elena Neumann
- Internal Medicine and Rheumatology, Justus-Liebig University, Campus Kerckhoff, Bad Nauheim, Hessen, Germany
| | - Carlo Blecker
- Bender Institute of Neuroimaging (BION), Faculty of Psychology and Sports Science, Justus-Liebig University, Giessen, Hessen, Germany
| | - Gerhard Gründer
- German Center for Mental Health (DZPG), Partner Site Mannheim, Mannheim, Germany
- Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Hana Adolphi
- German Center for Mental Health (DZPG), Partner Site Mannheim, Mannheim, Germany
- Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Eva Kathrin Lamadé
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany
- German Center for Mental Health (DZPG), Partner Site Mannheim, Mannheim, Germany
- Research Group of Stress-Related Disorders, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Clinical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Bruno Pedraz-Petrozzi
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany.
- German Center for Mental Health (DZPG), Partner Site Mannheim, Mannheim, Germany.
- Research Group of Stress-Related Disorders, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Clinical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
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Suzuki E, Sueki A, Takahashi H, Ishigooka J, Nishimura K. Association between TNF-α & IL-6 level changes and remission from depression with duloxetine treatment. Int J Neurosci 2024:1-6. [PMID: 39392051 DOI: 10.1080/00207454.2024.2414279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 09/24/2024] [Accepted: 10/04/2024] [Indexed: 10/12/2024]
Abstract
PURPOSE/AIM OF THE STUDY The pathophysiology of major depressive disorder (MDD) involves multiple factors, including inflammatory processes. This study investigated the relationship between changes in the levels of cytokines and remission in patients with MDD following duloxetine treatment. MATERIALS AND METHODS MDD patients were administered duloxetine for 16 weeks. Clinical evaluation and immunological monitoring were performed every 4 weeks. RESULTS Our results indicated that changes in serum levels of TNF-α and IL-6 were associated with remission following duloxetine treatment in MDD patients. There was a slight increase in TNF-α levels in the first four weeks following duloxetine treatment, which correlated significantly with patients who were in remission. Furthermore, patients in remission exhibited an initial increase in IL-6 levels in the first four weeks, followed by a decrease at 16 weeks. CONCLUSIONS These results suggest an important relationship between changes in cytokine levels and remission in patients with major depression after duloxetine treatment.
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Affiliation(s)
- Eriko Suzuki
- Department of Neuropsychiatry, Tokyo Women's Medical University Hospital, Tokyo, Japan
| | - Akitsugu Sueki
- Department of Neuropsychiatry, Tokyo Women's Medical University Hospital, Tokyo, Japan
| | - Hitoshi Takahashi
- Department of Neuropsychiatry, Tokyo Women's Medical University Hospital, Tokyo, Japan
| | - Jun Ishigooka
- Department of Neuropsychiatry, Tokyo Women's Medical University Hospital, Tokyo, Japan
| | - Katsuji Nishimura
- Department of Neuropsychiatry, Tokyo Women's Medical University Hospital, Tokyo, Japan
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Goel N, Wallace EB, Lindsay C. Hot Topics: Depression in Individuals With Psoriasis and Psoriatic Arthritis. J Rheumatol 2024; 51:43-50. [PMID: 39009389 DOI: 10.3899/jrheum.2024-0362] [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] [Accepted: 04/07/2024] [Indexed: 07/17/2024]
Abstract
Psoriasis and psoriatic arthritis are associated with an increased risk of mental health conditions such as depression and anxiety. People with psoriatic disease (PsD) are also more likely to die by suicide than those without. Mood disorders affect people with PsD in a multitude of ways, such as in effectiveness of care, response to treatment, remission rates, and quality of life. Although the links between PsD and mental health conditions have not been fully elucidated, this review will highlight recent studies investigating shared biologic mechanisms between depression and PsD. Since mental health disorders can be assessed and treated effectively, dermatologists and rheumatologists should be aware of the mental health burden in individuals with PsD to accomplish the following: (1) educate their patients with PsD about this association, (2) screen for mental health conditions on an ongoing basis in their clinical practice, (3) refer their patients with PsD to a mental health professional when needed, and (4) ensure selection of a safe PsD treatment in the setting of comorbid mental health disease. Finally, important treatment considerations for individuals with PsD and depression are reviewed. This topic was presented at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting.
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Affiliation(s)
- Niti Goel
- N. Goel, MD, Caduceus Biomedical Consulting, LLC, and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina;
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Krsek A, Ostojic L, Zivalj D, Baticic L. Navigating the Neuroimmunomodulation Frontier: Pioneering Approaches and Promising Horizons-A Comprehensive Review. Int J Mol Sci 2024; 25:9695. [PMID: 39273641 PMCID: PMC11396210 DOI: 10.3390/ijms25179695] [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: 07/31/2024] [Revised: 08/30/2024] [Accepted: 09/03/2024] [Indexed: 09/15/2024] Open
Abstract
The research in neuroimmunomodulation aims to shed light on the complex relationships that exist between the immune and neurological systems and how they affect the human body. This multidisciplinary field focuses on the way immune responses are influenced by brain activity and how neural function is impacted by immunological signaling. This provides important insights into a range of medical disorders. Targeting both brain and immunological pathways, neuroimmunomodulatory approaches are used in clinical pain management to address chronic pain. Pharmacological therapies aim to modulate neuroimmune interactions and reduce inflammation. Furthermore, bioelectronic techniques like vagus nerve stimulation offer non-invasive control of these systems, while neuromodulation techniques like transcranial magnetic stimulation modify immunological and neuronal responses to reduce pain. Within the context of aging, neuroimmunomodulation analyzes the ways in which immunological and neurological alterations brought on by aging contribute to cognitive decline and neurodegenerative illnesses. Restoring neuroimmune homeostasis through strategies shows promise in reducing age-related cognitive decline. Research into mood disorders focuses on how immunological dysregulation relates to illnesses including anxiety and depression. Immune system fluctuations are increasingly recognized for their impact on brain function, leading to novel treatments that target these interactions. This review emphasizes how interdisciplinary cooperation and continuous research are necessary to better understand the complex relationship between the neurological and immune systems.
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Affiliation(s)
- Antea Krsek
- Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
| | - Leona Ostojic
- Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
| | - Dorotea Zivalj
- Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
| | - Lara Baticic
- Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
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Charoensaensuk V, Yeh WL, Huang BR, Hsu TC, Xie SY, Chen CW, Wang YW, Yang LY, Tsai CF, Lu DY. Repetitive Administration of Low-Dose Lipopolysaccharide Improves Repeated Social Defeat Stress-Induced Behavioral Abnormalities and Aberrant Immune Response. J Neuroimmune Pharmacol 2024; 19:38. [PMID: 39066908 DOI: 10.1007/s11481-024-10141-x] [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: 01/30/2024] [Accepted: 07/14/2024] [Indexed: 07/30/2024]
Abstract
Repetitive exposure of innate immune cells to a subthreshold dosage of endotoxin components may modulate inflammatory responses. However, the regulatory mechanisms in the interactions between the central nervous system (CNS) and the immune system remain unclear. This study aimed to investigate the effects of lipopolysaccharide (LPS) preconditioning in repeated social defeat stress (RSDS)-induced abnormal immune responses and behavioral impairments. This study aimed to elucidate the mechanisms that underlie the protective effects of repeated administration of a subthreshold dose LPS on behavioral impairments using the RSDS paradigm. LPS preconditioning improved abnormal behaviors in RSDS-defeated mice, accompanied by decreased monoamine oxidases and increased glucocorticoid receptor expression in the hippocampus. In addition, pre-treated with LPS significantly decreased the recruited peripheral myeloid cells (CD11b+CD45hi), mainly circulating inflammatory monocytes (CD11b+CD45hiLy6ChiCCR2+) into the brain in response to RSDS challenge. Importantly, we found that LPS preconditioning exerts its protective properties by regulating lipocalin-2 (LCN2) expression in microglia, which subsequently induces expressions of chemokine CCL2 and pro-inflammatory cytokine. Subsequently, LPS-preconditioning lessened the resident microglia population (CD11b+CD45intCCL2+) in the brains of the RSDS-defeated mice. Moreover, RSDS-associated expressions of leukocytes (CD11b+CD45+CCR2+) and neutrophils (CD11b+CD45+Ly6G+) in the bone marrow, spleen, and blood were also attenuated by LPS-preconditioning. In particular, LPS preconditioning also promoted the expression of endogenous antioxidants and anti-inflammatory proteins in the hippocampus. Our results demonstrate that LPS preconditioning ameliorates lipocalin 2-associated microglial activation and aberrant immune response and promotes the expression of endogenous antioxidants and anti-inflammatory protein, thereby maintaining the homeostasis of pro-inflammation/anti-inflammation in both the brain and immune system, ultimately protecting the mice from RSDS-induced aberrant immune response and behavioral changes.
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Affiliation(s)
- Vichuda Charoensaensuk
- Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
| | - Wei-Lan Yeh
- Department of Biochemistry, School of Medicine, China Medical University, Taichung, 40402, Taiwan
- Institute of New Drug Development, China Medical University, Taichung, Taiwan
| | - Bor-Ren Huang
- Department of Neurosurgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Tsung-Che Hsu
- School of Medicine, China Medical University, Taichung, 40402, Taiwan
| | - Sheng-Yun Xie
- Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
| | - Chao-Wei Chen
- Institute of New Drug Development, China Medical University, Taichung, Taiwan
| | - Yu-Wen Wang
- Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan
| | - Liang-Yo Yang
- Department of Physiology, School of Medicine, China Medical University, Taichung, 404328, Taiwan
- Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
- Laboratory for Neural Repair, China Medical University Hospital, Taichung, 404327, Taiwan
| | - Cheng-Fang Tsai
- Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan
| | - Dah-Yuu Lu
- Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
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Groer ME, Baumgartel K, Springer C, Mutka T, Postolache TT. Depression in pregnant Hispanic women: Risk factors, pregnancy outcomes and plasma cytokines. Brain Behav Immun Health 2024; 38:100765. [PMID: 38590760 PMCID: PMC11000106 DOI: 10.1016/j.bbih.2024.100765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 03/24/2024] [Accepted: 03/28/2024] [Indexed: 04/10/2024] Open
Abstract
Background Maternal depression is considered a major contributor to morbidity and mortality in pregnancy. A population at risk are U.S. born or immigrant Hispanic women, and few prenatal depression or immune studies have focused on this population. Objective The research questions for the study were 1) What are the occurrences, risk factors and outcomes associated with depression in Hispanic pregnant women in the United States and 2) What are the associations of plasma immune cytokines and prenatal depression in this population. Study design Women of self-reported Hispanic ethnicity were born in the continental United States or foreign-born. Screening of potential participants (n = 690) at a first prenatal clinic visit consisted of antibody testing for Toxoplasma gondii antibodies in a larger grant, and only the women with antibody levels below the cutoff for T. gondii positivity (N = 536) were included in the present study. All participants completed a health and demographic questionnaire, the Edinburgh Postpartum Depression (EPDS) scale, the Perceived Stress Scale (PSS), and the Medical Outcomes Study Social Support (MOS) scale. We surveyed electronic health records (EHR) for risk factors and adverse pregnancy outcomes in the sample. We further measured physical and mental health and seven plasma immune cytokines at four study visits during pregnancy in a longitudinal subsample (N = 128). Results The frequency of EPDS scores of 10 (depression risk) or above was 18.6 % at the time of enrollment. Socioeconomic factors such as less education, greater unemployment, and U.S. born nativity were associated with greater depression risk, but these relationships became insignificant when we corrected for false discovery rate. Depression scores were not associated with adverse birth and pregnancy outcomes. The inflammatory cytokine TNF-α was significantly higher across pregnancy in women with depression risk (p < 0.03). Other inflammatory cytokines were higher in depressed women, but only at one time point in mid-pregnancy. Conclusions Prenatal depression occurs in early pregnancy and then declines in Hispanic women. The frequency of depression and stress were higher in U.S. born compared to immigrant Hispanic women. There was an elevation in plasma levels of TNF-α through the pregnancy in depressed women, and elevations in other cytokines, at midpregnancy. The adverse pregnancy outcomes, including preterm delivery, known to be associated with prenatal depression were not present in this cohort.
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Affiliation(s)
| | | | | | | | - Teodor T. Postolache
- Department of Psychiatry, University of Maryland School of Medicine, Rocky Mountain MIRECC for Suicide Prevention, Aurora, CO, USA
- VISN 5 MIRECC, Baltimore, MD, USA
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Gao W, Gao Y, Xu Y, Liang J, Sun Y, Zhang Y, Shan F, Ge J, Xia Q. Effect of duloxetine on changes in serum proinflammatory cytokine levels in patients with major depressive disorder. BMC Psychiatry 2024; 24:449. [PMID: 38877455 PMCID: PMC11179362 DOI: 10.1186/s12888-024-05910-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 06/13/2024] [Indexed: 06/16/2024] Open
Abstract
OBJECTIVE Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a serotonin-norepinephrine reuptake inhibitor, exhibits anti-inflammatory effects both in vitro and in vivo. In this study, we investigated the impact of duloxetine on changes in serum proinflammatory cytokine levels among individuals diagnosed with MDD. METHODS A cohort of 23 drug-naïve individuals diagnosed with MDD and 23 healthy controls were included in this study. The severity of depressive symptoms was evaluated using the 24-item Hamilton Depression Scale (HAMD-24). A panel of 7 proinflammatory cytokines, including interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), were quantified using multiplex Luminex assays. The levels of serum cytokines in healthy controls and patients with MDD were compared at baseline. All patients received duloxetine at a dosage range of 40-60 mg/day for a duration of 4 weeks. The HAMD-24 scores and serum cytokine levels were compared before and after duloxetine treatment. RESULTS Compared with healthy controls, patients with MDD had significantly greater levels of IL-2, IL-6, IL-8, IL-12, TNF-α, and IFN-γ (P < 0.05). Moreover, there was a significant decrease in HAMD-24 scores observed pre- and post-treatment (t = 13.161, P < 0.001). Furthermore, after 4 weeks of treatment, the serum levels of IL-8 (t = 3.605, P = 0.002), IL-12 (t = 2.559, P = 0.018), and IFN-γ (t = 3.567, P = 0.002) decreased significantly. However, there were no significant differences in other cytokines, including IL-1β, IL-2, IL-6, and TNF-α, before and after treatment (P > 0.05). CONCLUSIONS These findings present compelling evidence, potentially for the first time, indicating that duloxetine treatment may effectively reduce the serum concentrations of IL-8, IL-12, and IFN-γ in individuals diagnosed with MDD. However, the precise mechanisms underlying this effect remain unclear and warrant further investigation.
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Affiliation(s)
- Wenfan Gao
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- Department of Pharmacy, Hefei Fourth People's Hospital, Hefei, China
- Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China
- Anhui Clinical Research Center for Mental Disorders, Hefei, China
| | - Yejun Gao
- School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230000, PR China
- Department of Science and Education, Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
| | - Yayun Xu
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- Department of Pharmacy, Hefei Fourth People's Hospital, Hefei, China
- Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China
- Anhui Clinical Research Center for Mental Disorders, Hefei, China
| | - Jun Liang
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- Department of Pharmacy, Hefei Fourth People's Hospital, Hefei, China
- Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China
- Anhui Clinical Research Center for Mental Disorders, Hefei, China
| | - Yanhong Sun
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- Department of Pharmacy, Hefei Fourth People's Hospital, Hefei, China
- Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China
- Anhui Clinical Research Center for Mental Disorders, Hefei, China
| | - Yuanyuan Zhang
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- Department of Pharmacy, Hefei Fourth People's Hospital, Hefei, China
- Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China
- Anhui Clinical Research Center for Mental Disorders, Hefei, China
| | - Feng Shan
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- Department of Pharmacy, Hefei Fourth People's Hospital, Hefei, China
- Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China
- Anhui Clinical Research Center for Mental Disorders, Hefei, China
| | - Jinfang Ge
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei, China.
- The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China.
- School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230000, PR China.
| | - Qingrong Xia
- School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230000, PR China.
- Department of Science and Education, Affiliated Psychological Hospital of Anhui Medical University, Hefei, China.
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11
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Varghese TP, Chand S, Varghese NM, Singh R, Yadav SK. Interplay of inflammatory biomarkers in heart disease patients with depressive symptoms: An update. Curr Probl Cardiol 2024; 49:102352. [PMID: 38128639 DOI: 10.1016/j.cpcardiol.2023.102352] [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: 12/13/2023] [Accepted: 12/18/2023] [Indexed: 12/23/2023]
Abstract
The pathophysiological mechanisms that connect heart disease and depressive disorders have been identified as abnormal endothelial function, dysregulation of the Hypothalamic Pituitary Adrenal (HPA) axis and abnormal platelet activities. Among these mechanisms, both endothelial dysfunction and HPA axis dysregulation are influenced by low grade inflammation and play significant roles in both conditions. Consequently, it is hypothesized that inflammation is an integral part of the formation of atherosclerotic plaques, linking the occurrence of heart diseases to the activation and shedding of intercellular adhesion molecules (ICAMs), especially soluble ICAM-1. This process is accompanied by the local and systemic secretion of various inflammatory markers like interleukin-6, Tumour Necrosis Factor, and C-reactive protein. Therefore, this review primarily focuses on defining the potential role of different inflammatory biomarkers in depression and heart disease and assessing whether mediators could serve as predictive biomarkers for detecting depressive symptoms in patients with heart disease.
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Affiliation(s)
- Treesa P Varghese
- Associate Professor, Department of Pharmacy Practice, Yenepoya Pharmacy College & Research Centre (Yenepoya deemed to be University), Naringana, Mangalore, Karnataka, India.
| | - Sharad Chand
- Assistant Professor, Department of Pharmaceutical Sciences, School of Health Sciences and Technology, Dr. Vishwanath Karad MIT World Peace University, Pune, Maharashtra - 411038, India.
| | - Nila Mary Varghese
- Professor, Department of Pharmaceutics, ELIMS College of Pharmacy, Thrissur, Kerala, India.
| | - Rohit Singh
- Assistant Professor, Department of Pharmaceutical Sciences, School of Health Sciences and Technology, Dr. Vishwanath Karad MIT World Peace University, Pune, Maharashtra - 411038, India.
| | - Shiv Kumar Yadav
- Assistant Professor, Department of Pharmacy Practice, RC Patel Institute of Pharmaceutical Education and Research, Shirpur, India.
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12
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Arockiaraj N, Gupta R, Ahmad R, Halder S, Bhatia MS. Sertraline with desvenlafaxine and sertraline with mirtazapine as treatment initiation in MDD patients with moderate to severe depression and effect on inflammatory markers. Int J Psychiatry Clin Pract 2024; 28:9-16. [PMID: 38019131 DOI: 10.1080/13651501.2023.2287754] [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: 04/17/2023] [Accepted: 09/11/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND This study evaluated the effect of sertraline with desvenlafaxine and sertraline with mirtazapine on HAM-D score and inflammatory markers (IL-6 and TNF-α levels) in major depressive disorder. METHODS Patients (18-60 years) with MDD diagnosed by DSM-V criteria and HAM-D score 18 or more were included (n = 60). Group A patients (n = 30) received sertraline 50 mg/day and desvenlafaxine 50 mg/day. Group B patients (n = 30) received sertraline 50 mg/day and mirtazapine 30 mg/day. All patients were followed up for 8 weeks for the evaluation of clinical efficacy, safety, serum IL-6, and TNF-α levels. RESULTS Our study showed a comparatively similar and statistically significant (p < 0.05) reduction in HAM-D score in both groups in the 4th and 8th week of the treatment. Both drug combinations significantly (p < 0.05) decreased serum IL-6 and TNF-α after 8 weeks of treatment. CONCLUSION The present study suggests that the combination therapy (as treatment initiation) with sertraline and desvenlafaxine, and sertraline with mirtazapine is effective and well tolerated in MDD patients with moderate to severe depression, and their therapeutic efficacy is accompanied by decreased inflammatory markers (serum IL-6 and TNF-α).
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Affiliation(s)
- Norman Arockiaraj
- Department of Pharmacology, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, New Delhi, India
| | - Rachna Gupta
- Department of Pharmacology, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, New Delhi, India
| | - Rafat Ahmad
- Department of Biochemistry, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, New Delhi, India
| | - Sumita Halder
- Department of Pharmacology, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, New Delhi, India
| | - M S Bhatia
- Department of Psychiatry, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, New Delhi, India
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13
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Dvorak NM, Domingo ND, Tapia CM, Wadsworth PA, Marosi M, Avchalumov Y, Fongsaran C, Koff L, Di Re J, Sampson CM, Baumgartner TJ, Wang P, Villarreal PP, Solomon OD, Stutz SJ, Aditi, Porter J, Gbedande K, Prideaux B, Green TA, Seeley EH, Samir P, Dineley KT, Vargas G, Zhou J, Cisneros I, Stephens R, Laezza F. TNFR1 signaling converging on FGF14 controls neuronal hyperactivity and sickness behavior in experimental cerebral malaria. J Neuroinflammation 2023; 20:306. [PMID: 38115011 PMCID: PMC10729485 DOI: 10.1186/s12974-023-02992-7] [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: 08/25/2023] [Accepted: 12/11/2023] [Indexed: 12/21/2023] Open
Abstract
BACKGROUND Excess tumor necrosis factor (TNF) is implicated in the pathogenesis of hyperinflammatory experimental cerebral malaria (eCM), including gliosis, increased levels of fibrin(ogen) in the brain, behavioral changes, and mortality. However, the role of TNF in eCM within the brain parenchyma, particularly directly on neurons, remains underdefined. Here, we investigate electrophysiological consequences of eCM on neuronal excitability and cell signaling mechanisms that contribute to observed phenotypes. METHODS The split-luciferase complementation assay (LCA) was used to investigate cell signaling mechanisms downstream of tumor necrosis factor receptor 1 (TNFR1) that could contribute to changes in neuronal excitability in eCM. Whole-cell patch-clamp electrophysiology was performed in brain slices from eCM mice to elucidate consequences of infection on CA1 pyramidal neuron excitability and cell signaling mechanisms that contribute to observed phenotypes. Involvement of identified signaling molecules in mediating behavioral changes and sickness behavior observed in eCM were investigated in vivo using genetic silencing. RESULTS Exploring signaling mechanisms that underlie TNF-induced effects on neuronal excitability, we found that the complex assembly of fibroblast growth factor 14 (FGF14) and the voltage-gated Na+ (Nav) channel 1.6 (Nav1.6) is increased upon tumor necrosis factor receptor 1 (TNFR1) stimulation via Janus Kinase 2 (JAK2). On account of the dependency of hyperinflammatory experimental cerebral malaria (eCM) on TNF, we performed patch-clamp studies in slices from eCM mice and showed that Plasmodium chabaudi infection augments Nav1.6 channel conductance of CA1 pyramidal neurons through the TNFR1-JAK2-FGF14-Nav1.6 signaling network, which leads to hyperexcitability. Hyperexcitability of CA1 pyramidal neurons caused by infection was mitigated via an anti-TNF antibody and genetic silencing of FGF14 in CA1. Furthermore, knockdown of FGF14 in CA1 reduced sickness behavior caused by infection. CONCLUSIONS FGF14 may represent a therapeutic target for mitigating consequences of TNF-mediated neuroinflammation.
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Affiliation(s)
- Nolan M Dvorak
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Nadia D Domingo
- Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX, 77555, USA
- Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Cynthia M Tapia
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Paul A Wadsworth
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Mate Marosi
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Yosef Avchalumov
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Chanida Fongsaran
- Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Leandra Koff
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Jessica Di Re
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Catherine M Sampson
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Timothy J Baumgartner
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Pingyuan Wang
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Paula P Villarreal
- Department of Neurobiology, University of Texas Medical Branch, Galveston, TX, 77555, USA
- Clinical Sciences Program, The Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Olivia D Solomon
- Department of Neurobiology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Sonja J Stutz
- Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Aditi
- Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Jacob Porter
- Department of Chemistry, University of Texas, Austin, TX, 78712, USA
| | - Komi Gbedande
- Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX, 77555, USA
- Center for Immunity and Inflammation and Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ, 07301, USA
| | - Brendan Prideaux
- Department of Neurobiology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Thomas A Green
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Erin H Seeley
- Department of Chemistry, University of Texas, Austin, TX, 78712, USA
| | - Parimal Samir
- Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Kelley T Dineley
- Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Gracie Vargas
- Department of Neurobiology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Jia Zhou
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Irma Cisneros
- Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Robin Stephens
- Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX, 77555, USA.
- Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
- Center for Immunity and Inflammation and Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ, 07301, USA.
| | - Fernanda Laezza
- Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
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14
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Nayem J, Sarker R, Roknuzzaman ASM, Qusar MMAS, Raihan SZ, Islam MR, Mahmud ZA. Altered serum TNF-α and MCP-4 levels are associated with the pathophysiology of major depressive disorder: A case-control study results. PLoS One 2023; 18:e0294288. [PMID: 37967104 PMCID: PMC10651034 DOI: 10.1371/journal.pone.0294288] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 10/28/2023] [Indexed: 11/17/2023] Open
Abstract
BACKGROUND Major Depressive Disorder (MDD) is a debilitating mental health condition with complex etiology, and recent research has focused on pro-inflammatory cytokines and chemokines as potential contributors to its pathogenesis. However, studies investigating the roles of TNF-α and MCP-4 in MDD within the Bangladeshi population are scarce. This study aimed to assess the association between serum TNF-α and MCP-4 levels and the severity of MDD, exploring their potential as risk indicators for MDD development. METHODS This case-control study enrolled 58 MDD patients from Bangabandhu Sheikh Mujib Medical University (BSMMU) Hospital, Dhaka, Bangladesh, alongside 30 age, sex, and BMI-matched healthy controls. MDD diagnosis followed DSM-5 criteria and disease severity using the 17-item Hamilton Depression Rating Scale (Ham-D). We measured serum TNF-α and MCP-4 levels using ELISA assays according to the supplied protocols. RESULTS The study revealed significantly elevated serum TNF-α levels in MDD patients (47±6.6 pg/ml, mean±SEM) compared to controls (28.06±1.07 pg/ml). These increased TNF-α levels positively correlated with Ham-D scores (Pearson's r = 0.300, p = 0.038), suggesting a potential association between peripheral TNF-α levels and MDD pathology. Additionally, MDD patients exhibited significantly higher serum MCP-4 levels (70.49±6.45 pg/ml) than controls (40.21±4.08 pg/ml). However, serum MCP-4 levels showed a significant negative correlation (r = -0.270, P = 0.048) with Ham-D scores in MDD patients, indicating a more complex role for MCP-4 in MDD pathogenesis. CONCLUSION This study highlights that Bangladeshi MDD patients exhibit heightened inflammatory and immune responses compared to controls, supporting the cytokine hypothesis in MDD pathogenesis. Serum TNF-α, but not MCP-4, shows promise as a potential biomarker for assessing the risk of MDD development, which could aid in early detection. Future investigations involving larger populations and longitudinal studies are essential to confirm the utility of these cytokines as biomarkers for MDD.
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Affiliation(s)
- Jannatul Nayem
- Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Rapty Sarker
- Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
| | | | | | - Sheikh Zahir Raihan
- Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | | | - Zobaer Al Mahmud
- Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
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15
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Mandal S, Spoorthy MS, Godi SM, Nanda R, Mukherjee B, Mishra NR. Inflammatory Markers in Patients With Major Depressive Disorder: A Prospective, Clinic-Based, Cohort Study From India. Cureus 2023; 15:e43059. [PMID: 37680396 PMCID: PMC10481369 DOI: 10.7759/cureus.43059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/06/2023] [Indexed: 09/09/2023] Open
Abstract
Background Patients with major depressive disorder have varying response rates to treatment. Multiple factors such as non-adherence, comorbidity, chronic stressors, and biological factors may be responsible for this variation. Inflammatory (pro and anti) markers have been well studied as a cause for depression, predisposing factors, and a consequence of depression. Among these, interleukins (ILs), interferons, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) have been studied repeatedly. We conducted a pilot study to assess the levels of these inflammatory markers in patients with major depressive disorder. The specific objectives of this study were to compare and correlate changes in pro- and anti-inflammatory markers throughout different phases of depression, including pretreatment and posttreatment periods, and to evaluate the pattern of pro- and anti-inflammatory markers in patients who experienced remission or showed a positive response to treatment. Methodology This was a prospective, clinic-based, cohort study done for a period of one and a half years. Patients aged 18-65 years with depressive disorder per the International Classification of Diseases Tenth Edition and who scored more than 7 on the Hamilton Depression Rating Scale were included in this study. A total of 81 patients were recruited who were followed up till eight weeks after inclusion. A total of 31 patients completed the eight weeks of follow-up. Levels of IL-10 and TNF-α were assessed at baseline, two weeks, four weeks, and eight weeks of follow-up. Results This study tried to compare the levels of pro- and anti-inflammatory markers across pretreatment and various posttreatment phases of depression. Results showed that the levels of pro-inflammatory cytokine TNF-α increased from baseline till eight weeks of follow-up, and levels of IL-10 decreased from baseline till eight weeks of follow-up. However, these changes were not statistically significant. Conclusions This study supports the hypothesis that inflammatory markers can be trait markers of depression rather than the consequence or result.
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Affiliation(s)
- Sucharita Mandal
- Psychiatry, All India Institute of Medical Sciences, Kalyani, Kalyani, IND
| | | | - Sangha Mitra Godi
- Psychiatry, All India Institute of Medical Sciences, Mangalagiri, Mangalagiri, IND
| | - Rachita Nanda
- Biochemistry, All India Institute of Medical Sciences, Raipur, Raipur, IND
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Sibilia F, Sheikh-Bahaei N, Mack WJ, Choupan J. Perivascular spaces in Alzheimer's disease are associated with inflammatory, stress-related, and hypertension biomarkers. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.06.02.543504. [PMID: 37333097 PMCID: PMC10274635 DOI: 10.1101/2023.06.02.543504] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/20/2023]
Abstract
Perivascular spaces (PVS) are fluid-filled spaces surrounding the brain vasculature. Literature suggests that PVS may play a significant role in aging and neurological disorders, including Alzheimer's disease (AD). Cortisol, a stress hormone, has been implicated in the development and progression of AD. Hypertension, a common condition in older adults, has been found to be a risk factor for AD. Hypertension may contribute to PVS enlargement, impairing the clearance of waste products from the brain and promoting neuroinflammation. This study aims to understand the potential interactions between PVS, cortisol, hypertension, and inflammation in the context of cognitive impairment. Using MRI scans acquired at 1.5T, PVS were quantified in a cohort of 465 individuals with cognitive impairment. PVS was calculated in the basal ganglia and centrum semiovale using an automated segmentation approach. Levels of cortisol and angiotensin-converting enzyme (ACE) (an indicator of hypertension) were measured from plasma. Inflammatory biomarkers, such as cytokines and matrix metalloproteinases, were analyzed using advanced laboratory techniques. Main effect and interaction analyses were performed to examine the associations between PVS severity, cortisol levels, hypertension, and inflammatory biomarkers. In the centrum semiovale, higher levels of inflammation reduced cortisol associations with PVS volume fraction. For ACE, an inverse association with PVS was seen only when interacting with TNFr2 (a transmembrane receptor of TNF). There was also a significant inverse main effect of TNFr2. In the PVS basal ganglia, a significant positive association was found with TRAIL (a TNF receptor inducing apoptosis). These findings show for the first time the intricate relationships between PVS structure and the levels of stress-related, hypertension, and inflammatory biomarkers. This research could potentially guide future studies regarding the underlying mechanisms of AD pathogenesis and the potential development of novel therapeutic strategies targeting these inflammation factors.
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Affiliation(s)
- Francesca Sibilia
- Laboratory of Neuro Imaging, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Nasim Sheikh-Bahaei
- Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA
- Department of Radiology, Keck School of Medicine, University of Southern California, 1520 San Pablo Street, Los Angeles, CA, 90033, USA
| | - Wendy J Mack
- Department of Population and Public Health Sciences, Keck School of Medicine, University of University of Southern California, Los Angeles, CA, USA
| | - Jeiran Choupan
- Laboratory of Neuro Imaging, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- NeuroScope Inc. Scarsdale, New York
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17
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Gladkova MG, Leidmaa E, Anderzhanova EA. Epidrugs in the Therapy of Central Nervous System Disorders: A Way to Drive on? Cells 2023; 12:1464. [PMID: 37296584 PMCID: PMC10253154 DOI: 10.3390/cells12111464] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 05/01/2023] [Accepted: 05/16/2023] [Indexed: 06/12/2023] Open
Abstract
The polygenic nature of neurological and psychiatric syndromes and the significant impact of environmental factors on the underlying developmental, homeostatic, and neuroplastic mechanisms suggest that an efficient therapy for these disorders should be a complex one. Pharmacological interventions with drugs selectively influencing the epigenetic landscape (epidrugs) allow one to hit multiple targets, therefore, assumably addressing a wide spectrum of genetic and environmental mechanisms of central nervous system (CNS) disorders. The aim of this review is to understand what fundamental pathological mechanisms would be optimal to target with epidrugs in the treatment of neurological or psychiatric complications. To date, the use of histone deacetylases and DNA methyltransferase inhibitors (HDACis and DNMTis) in the clinic is focused on the treatment of neoplasms (mainly of a glial origin) and is based on the cytostatic and cytotoxic actions of these compounds. Preclinical data show that besides this activity, inhibitors of histone deacetylases, DNA methyltransferases, bromodomains, and ten-eleven translocation (TET) proteins impact the expression of neuroimmune inflammation mediators (cytokines and pro-apoptotic factors), neurotrophins (brain-derived neurotropic factor (BDNF) and nerve growth factor (NGF)), ion channels, ionotropic receptors, as well as pathoproteins (β-amyloid, tau protein, and α-synuclein). Based on this profile of activities, epidrugs may be favorable as a treatment for neurodegenerative diseases. For the treatment of neurodevelopmental disorders, drug addiction, as well as anxiety disorders, depression, schizophrenia, and epilepsy, contemporary epidrugs still require further development concerning a tuning of pharmacological effects, reduction in toxicity, and development of efficient treatment protocols. A promising strategy to further clarify the potential targets of epidrugs as therapeutic means to cure neurological and psychiatric syndromes is the profiling of the epigenetic mechanisms, which have evolved upon actions of complex physiological lifestyle factors, such as diet and physical exercise, and which are effective in the management of neurodegenerative diseases and dementia.
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Affiliation(s)
- Marina G. Gladkova
- Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia
| | - Este Leidmaa
- Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, 53127 Bonn, Germany
- Institute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 50411 Tartu, Estonia
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18
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Islam MR, Sohan M, Daria S, Masud AA, Ahmed MU, Roy A, Shahriar M. Evaluation of inflammatory cytokines in drug-naïve major depressive disorder: A systematic review and meta-analysis. Int J Immunopathol Pharmacol 2023; 37:3946320231198828. [PMID: 37625799 PMCID: PMC10467201 DOI: 10.1177/03946320231198828] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 08/07/2023] [Indexed: 08/27/2023] Open
Abstract
Objective: Altered levels of peripheral inflammatory and proinflammatory cytokine markers affect the different clinical stages of major depressive disorder (MDD). A concrete understanding of the causal mechanism of MDD is a prerequisite in developing treatment strategies and preventive plans. Here we aimed to conduct an updated systematic review and meta-analysis of studies assessing the association of C-reactive protein (CRP), INF-γ, MCP-1, and TNF-α in the peripheral fluid of drug-naïve MDD patients and healthy controls (HCs). Methods: We extracted articles from PubMed, ProQuest, PsycINFO, Web of Science, and Scopus databases from inception until 14 February 2021, to find relevant studies. In this meta-analysis, we included a total of 23 eligible studies (1,366 MDD patients and 1,342 controls) in the final meta-analysis. The Cochran's chi-square Q-test and I2-index were applied to measure the heterogeneity and inconsistency of all combined results. We selected a random-effect model during the analysis and measured publication biases using the funnel plot. We performed Bonferroni adjustment for multiple testing. Results: We found a high level of TNF-α in MDD patients than in control subjects Standardized Mean Difference (SMD) with a random-effects model: 1.04, 95% CI: 0.69-1.39, z = 5.84, p < 0.001). The levels of CRP (SMD with a random-effects model: 0.18, 95% CI: -0.85-1.23, z = 0.35, p = 0.73), INF-ɤ (SMD with a random-effects model: -0.05, 95% CI: -2.72-2.62, z = 0.03, p = 0.97), and MCP-1 (SMD with a random-effects model: 0.70, 95% CI: -0.09-1.49, z = 1.73, p = 0.08) were not significantly varies between MDD patients and HCs. Conclusion: The present study findings suggest the upregulated level of peripheral TNF-α but not CRP, INF-γ, and MCP-1 involve in depression. The elevated inflammatory cytokines confirmed the inflammatory state of depression. Therefore, inflammatory cytokines might serve as potential risk assessment markers in MDD.
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Affiliation(s)
- Md Rabiul Islam
- Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
- School of Pharmacy, BRAC University, Dhaka, Bangladesh
| | - Md Sohan
- Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
| | - Sohel Daria
- Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
| | | | | | - Arpita Roy
- Department of Biotechnology, School of Engineering & Technology, Sharda University, Greater Noida, India
| | - Mohammad Shahriar
- Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
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19
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Vaseghi S, Mostafavijabbari A, Alizadeh MS, Ghaffarzadegan R, Kholghi G, Zarrindast MR. Intricate role of sleep deprivation in modulating depression: focusing on BDNF, VEGF, serotonin, cortisol, and TNF-α. Metab Brain Dis 2023; 38:195-219. [PMID: 36399239 DOI: 10.1007/s11011-022-01124-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 11/06/2022] [Indexed: 11/19/2022]
Abstract
In this review article, we aimed to discuss intricate roles of SD in modulating depression in preclinical and clinical studies. Decades of research have shown the inconsistent effects of SD on depression, focusing on SD duration. However, inconsistent role of SD seems to be more complicated, and SD duration cannot be the only one factor. Regarding this issue, we chose some important factors involved in the effects of SD on cognitive functions and mood including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), serotonin, cortisol, and tumor necrosis factor-alpha (TNF-α). It was concluded that SD has a wide-range of inconsistent effects on BDNF, VEGF, serotonin, and cortisol levels. It was noted that BDNF diurnal rhythm is significantly involved in the modulatory role of SD in depression. Furthermore, the important role of VEGF in blood-brain barrier permeability which is involved in modulating depression was discussed. It was also noted that there is a negative correlation between cortisol and BDNF that modulates depression. Eventually, it was concluded that TNF-α regulates sleep/wake cycle and is involved in the vulnerability to cognitive and behavioral impairments following SD. TNF-α also increases the permeability of the blood-brain barrier which is accompanied by depressive behavior. In sum, it was suggested that future studies should focus on these mechanisms/factors to better investigate the reasons behind intricate roles of SD in modulating depression.
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Affiliation(s)
- Salar Vaseghi
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran.
| | | | - Mohammad-Sadegh Alizadeh
- Department of Cognitive Neuroscience, Institute for Cognitive Science Studies (ICSS), Tehran, Iran
- Department of Cellular and Molecular Sciences, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Reza Ghaffarzadegan
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran
| | - Gita Kholghi
- Department of Psychology, Faculty of Human Sciences, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
| | - Mohammad-Reza Zarrindast
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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20
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Lu J, Huang C, Lu Q, Lu X. Therapeutic and Prophylactic Effects of Amphotericin B Liposomes on Chronic Social Defeat Stress-Induced Behavioral Abnormalities in Mice. Front Pharmacol 2022; 13:918177. [PMID: 35910388 PMCID: PMC9335357 DOI: 10.3389/fphar.2022.918177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 05/30/2022] [Indexed: 11/13/2022] Open
Abstract
Recently, innate immune system stimulants, such as lipopolysaccharide (LPS) and macrophage-colony stimulating factor (M-CSF), were reported to prevent and reverse chronic stress-induced behavioral abnormalities, suggesting that innate immune stimulation could be a potential strategy for the treatment and prevention of mental disorders. Amphotericin B liposome is a clinically available antifungal medication that can stimulate macrophages and microglia. We hypothesize that amphotericin B liposome may be used to prevent and reverse behavioral abnormalities triggered by chronic stress. As expected, our results showed that a single injection of amphotericin B liposome (1 mg/kg) immediately after stress cessation reversed the decrease in time spent in the interaction zone in the social interaction test (SIT) and the increase in immobility time in the tail suspension test (TST) and forced swimming test (FST) in mice caused by chronic social defeat stress (CSDS). In addition, a single injection of amphotericin B liposomes (1 mg/kg) 1 day before stress exposure was found to prevent the CSDS-induced decrease in time spent in the interaction zone in the SIT and the increase in immobility time in the TST and FST in mice. Pretreatment with minocycline to inhibit the innate immune response was able to abolish the reversal effect of post-stress injection of amphotericin B liposomes on CSDS-induced behavioral abnormalities and the prophylactic effect of pre-stress injection of amphotericin B liposomes on CSDS-induced behavioral abnormalities. These results demonstrate that amphotericin B liposomes have both therapeutic and prophylactic effects on chronic stress-induced behavioral abnormalities in mice by mobilizing the innate immune response.
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Affiliation(s)
- Jiashu Lu
- Department of Pharmacy, The People’s Hospital of Taizhou, The Fifth Affiliated Hospital of Nantong University, Taizhou, China
- *Correspondence: Jiashu Lu,
| | - Chao Huang
- Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China
| | - Qun Lu
- Department of Pharmacy, Nantong Third Hospital Affiliated to Nantong University, Nantong, China
| | - Xu Lu
- Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China
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21
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Zaazaa AM, Daoud NN, El-Gendy OA, Al-Shafei AI. Neuroprotective role of Bacopa monnieri extract in modulating depression in an experimental rat model. J Affect Disord 2022; 308:229-235. [PMID: 35413358 DOI: 10.1016/j.jad.2022.04.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 03/03/2022] [Accepted: 04/06/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Depression is a common illness with no definite treatment. METHODS The study involved 2 experimental periods; 45-day (P1) followed by 30-day (P2). 40 adult albino rats were randomly divided into 4 groups. Grp 1 received saline orally while Grp 2 reserpine inraperitoneally (ip) during P1 and P2. Grps 3 and 4 received reserpine during P1, followed by reserpine plus B. monnieri, and reserpine plus citalopram ip during P2, respectively. Forced swimming test (FST) was performed at beginning and end of P1 and P2. Animals were sacrificed by end of P2 and brain taken for histopathological examination and ELISA estimation of serotonin, dopamine, norepinephrine, BDNF, MCP-1, FAS, and Bcl-2. RESULTS During P1, reserpine prolonged immobility time (IT) in FST in Grps 2, 3, and 4. IT was subsequently lowered in Grps 3 and 4 but remained elevated in Grp 2 by end of P2. Serotonin, dopamine and norepinephrine were lowered in Grps 2, 3, and 4, but in Grps 3 and 4, levels were comparable to Grp1. BDNF and Bc1-2 were reduced in Grps 2, 3, and 4, with higher levels in Grps 3 and 4 than Grp 2. MCP-1 and FAS were elevated in Grps 2, 3, and 4, but levels were lower in Grps 3 and 4 than in Grp 2. Histopathology showed congested cerebral cortex in Grp 2 and normal cortex in other groups. LIMITATIONS Only adult male rats were involved and effects of co-administration of B. monnieri and citalopram were not characterized. CONCLUSION B. monnieri improves depression comparable to citalopram in reserpine-induced depression.
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Affiliation(s)
- Asmaa M Zaazaa
- Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt
| | - Nadia N Daoud
- Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt
| | - Ola A El-Gendy
- Basic Medical Sciences Department, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah, Kingdom of Saudi Arabia
| | - Ahmad I Al-Shafei
- Basic Medical Sciences Department, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah, Kingdom of Saudi Arabia.
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22
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Lino A, Erickson TA, Nolan MS, Murray KO, Ronca SE. A Preliminary Study of Proinflammatory Cytokines and Depression Following West Nile Virus Infection. Pathogens 2022; 11:pathogens11060650. [PMID: 35745504 PMCID: PMC9230011 DOI: 10.3390/pathogens11060650] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/23/2022] [Accepted: 05/25/2022] [Indexed: 01/25/2023] Open
Abstract
West Nile virus (WNV) is a neurotropic flavivirus that can cause acute febrile illness leading to neuroinvasive disease. Depression is a well-described outcome following infection, but the underlying pathogenic mechanisms are unknown. Proinflammatory cytokines play important roles in WNV infection, but their role in depression post-WNV remains unstudied. This research aimed to retrospectively evaluate associations between proinflammatory cytokines and new onset depression in a WNV cohort. Participants with asymptomatic WNV infection were significantly less likely to report new onset depression when compared to those with symptomatic disease. Participants with encephalitis and obesity were significantly more likely to report new onset depression post-infection. Based on univariate analysis of 15 antiviral or proinflammatory cytokines, depression was associated with elevated MCP-1 and decreased TNFα, whereas G-CSF was significantly elevated in those with a history of neuroinvasive WNV. However, no cytokines were statistically significant after adjusting for multiple comparisons using the Bonferroni method. While symptomatic WNV infection, encephalitis, and obesity were associated with new onset depression following infection, the role of proinflammatory cytokines requires additional studies. Further research involving paired acute-convalescent samples, larger sample sizes, and additional data points would provide additional insight into the impact of the inflammatory response on WNV-mediated depression.
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Affiliation(s)
- Allison Lino
- Department of Pediatrics, Section Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA; (A.L.); (T.A.E.)
| | - Timothy A. Erickson
- Department of Pediatrics, Section Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA; (A.L.); (T.A.E.)
| | - Melissa S. Nolan
- Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA;
| | - Kristy O. Murray
- Department of Pediatrics, Section Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA; (A.L.); (T.A.E.)
- Correspondence: (K.O.M.); (S.E.R.)
| | - Shannon E. Ronca
- Department of Pediatrics, Section Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA; (A.L.); (T.A.E.)
- Correspondence: (K.O.M.); (S.E.R.)
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Gawlik-Kotelnicka O, Margulska A, Gabryelska A, Sochal M, Białasiewicz P, Strzelecki D. “Leaky Gut” as a Keystone of the Connection between Depression and Obstructive Sleep Apnea Syndrome? A Rationale and Study Design. Metabolites 2022; 12:metabo12020152. [PMID: 35208226 PMCID: PMC8878827 DOI: 10.3390/metabo12020152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/29/2022] [Accepted: 02/01/2022] [Indexed: 11/16/2022] Open
Abstract
Obstructive sleep apnea (OSA) and depression are highly comorbid. Immune alterations, oxidative stress or microbiota dysfunction have been proposed as some mechanisms underlying this association. The aim of the proposed study is to assess the severity and profile of OSA and depressive symptoms in the context of serum microbiota metabolites, biomarkers of intestinal permeability, inflammation and oxidative stress in adult patients diagnosed with OSA syndrome. The study population consists of 200 subjects. An apnoea-hypopnoea index ≥ 5/hour is used for the diagnosis. Depressive symptoms are assessed with Beck Depression Inventory. Measured serum markers are: tumour necrosis factor–alpha and interleukin-6 for inflammation, total antioxidant capacity and malondialdehyde concentration for oxidative stress, zonulin, calprotectin, lipopolisaccharide-binding protein and intestinal fatty acids-binding protein for intestinal permeability. All of the above will be measured by enzyme-linked immunosorbent assay (ELISA). Associations between clinical symptoms profile and severity and the above markers levels will be tested. It would be valuable to seek for overlap indicators of depression and OSA to create this endophenotype possible biomarkers and form new prophylactic or therapeutic methods. The results may be useful to establish a subpopulation of patients sensitive to microbiota therapeutic interventions (probiotics, prebiotics, and microbiota transplantation).
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Affiliation(s)
- Oliwia Gawlik-Kotelnicka
- Department of Affective and Psychotic Disorders, Medical University of Lodz, 90-419 Lodz, Poland;
- Correspondence: ; Tel.: +48-603819776
| | | | - Agata Gabryelska
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 90-419 Lodz, Poland; (A.G.); (M.S.); (P.B.)
| | - Marcin Sochal
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 90-419 Lodz, Poland; (A.G.); (M.S.); (P.B.)
| | - Piotr Białasiewicz
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 90-419 Lodz, Poland; (A.G.); (M.S.); (P.B.)
| | - Dominik Strzelecki
- Department of Affective and Psychotic Disorders, Medical University of Lodz, 90-419 Lodz, Poland;
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Malik S, Alnaji O, Malik M, Gambale T, Rathbone MP. Correlation between Mild Traumatic Brain Injury-Induced Inflammatory Cytokines and Emotional Symptom Traits: A Systematic Review. Brain Sci 2022; 12:brainsci12010102. [PMID: 35053845 PMCID: PMC8773760 DOI: 10.3390/brainsci12010102] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 01/04/2022] [Accepted: 01/05/2022] [Indexed: 01/09/2023] Open
Abstract
Both mild traumatic brain injuries (mTBI) and systemic injuries trigger a transient neuroinflammatory response that result in similar clinical outcome. The ensuing physical, cognitive, and emotional symptoms fail to subside in approximately 15–20% of the concussed population. Emotional impairments, particularly depression, anxiety, and post-traumatic stress disorder (PTSD), are commonly associated with poor recovery following mTBI. These emotional impairments also have a significant neuroinflammatory component. We hypothesized that the inflammatory cytokines seen in mTBI patients with emotional symptoms would coincide with those commonly seen in patients with emotional symptoms without mTBI. A systematic review was conducted to identify the most common neuroinflammatory cytokines in the mTBI population with psychological symptoms (depression, anxiety, PTSD). The electronic databases EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and PSYCINFO were searched from data inception to 31 August 2021. A systematic screening approach was employed from screening to data analysis. A total of 994 articles were screened, 108 were selected for full article review, and 8 were selected for data analysis. The included studies consisted of 875 patients of which 81.3% were male. The mean sample size of patients with at least one mTBI was 73.8 ± 70.3 (range, 9–213), with a mean age of 33.9 ± 4.8 years. The most common cytokines associated with poor psychological outcomes involving PTSD and/or depression in the chronic mTBI population were IL-6, TNFα, IL-10, and CRP.
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Affiliation(s)
- Shazia Malik
- Neurosciences Graduate Program, McMaster University, Hamilton, ON L8S 4L8, Canada
- Correspondence:
| | - Omar Alnaji
- Faculty of Life Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada;
| | - Mahnoor Malik
- Bachelor of Health Sciences Program, McMaster University, Hamilton, ON L8S 4L8, Canada;
| | - Teresa Gambale
- Division of Neurology, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada; (T.G.); (M.P.R.)
| | - Michel Piers Rathbone
- Division of Neurology, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada; (T.G.); (M.P.R.)
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25
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Wang Q, Zeng L, Hong W, Luo M, Zhao N, Hu X, Shi M, Qiu J, Shen Y, Teng X, Min H, Liu W. Inflammatory Cytokines Changed in Patients With Depression Before and After Repetitive Transcranial Magnetic Stimulation Treatment. Front Psychiatry 2022; 13:925007. [PMID: 35722555 PMCID: PMC9201075 DOI: 10.3389/fpsyt.2022.925007] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 05/16/2022] [Indexed: 12/28/2022] Open
Abstract
Studies have found that repetitive transcranial magnetic stimulation rTMS can produce antidepressant effects by affecting inflammatory cytokines in patients with depression, which plays a key role in the therapeutic mechanism of antidepressants. This study aimed to explore the changes in inflammatory cytokine levels in patients with depression after 4 weeks of rTMS treatment to determine the possible antidepressant mechanism of rTMS. This prospective, double-blind, pseudo-stimulus-controlled study was conducted, and a total of 57 patients with depression and 30 healthy controls were recruited. Patients were randomly divided into the active rTMS (n = 29) and sham rTMS groups (n = 28). The Hamilton Depression Scale was used to evaluate depressive symptoms and their severity. The serum levels of seven inflammatory cytokines were measured using enzyme-linked immunosorbent assay. Inflammatory cytokines include high-sensitivity C-reactive protein (CRP-hc); tumor necrosis factor (TNF-α); interferon (IFN-γ); interleukin-2 (IL-2); interleukin-4 (IL-4); interleukin-6 (IL-6); and interleukin-8 (IL-8). At baseline, TNF-α (F = 36.699, p < 0.001), IFN-γ (F = 8.907, p < 0.001), IL-4 (F = 66.256, p < 0.001), and IL-2 (F = 9.162, p < 0.001) levels in the depression group were significantly different from those of healthy controls. In the self-control analysis of the active rTMS group, the levels of IL-2 and CRP-hc increased significantly after 2 and 12 weeks of treatment. In the sham-rTMS group, IFN-γ increased after 2 and 12 weeks of treatment. Our results revealed that the changes in inflammatory cytokines after rTMS treatment showed different patterns compared to the sham group, suggesting that the antidepressant effect of rTMS may be related to changes in inflammatory cytokines.
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Affiliation(s)
- Qiang Wang
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China
| | - Lingyun Zeng
- Department of Psychiatric Rehabilitation, Shenzhen Kangning Hospital, Shenzhen, China
| | - Wenjuan Hong
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China
| | - Mingying Luo
- Department of Anatomy, Histology and Embryology, Kunming Medical University, Kunming, China
| | - Nan Zhao
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China
| | - Xiaofen Hu
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China
| | - Meili Shi
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China
| | - Jing Qiu
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China
| | - Yanmin Shen
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China
| | - Xiuju Teng
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China
| | - Haiying Min
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China
| | - Weiqing Liu
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China
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26
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Gao W, Xu Y, Liang J, Sun Y, Zhang Y, Shan F, Ge J, Xia Q. Comparison of serum cytokines levels in normal-weight and overweight patients with first-episode drug-naïve major depressive disorder. Front Endocrinol (Lausanne) 2022; 13:1048337. [PMID: 36387880 PMCID: PMC9647627 DOI: 10.3389/fendo.2022.1048337] [Citation(s) in RCA: 3] [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: 09/19/2022] [Accepted: 10/18/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE Abnormal levels of blood cytokines have been demonstrated to be associated with both excess weight and major depressive disorder (MDD). However, few studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode drug-naïve MDD. METHODS A total of 49 patients with first-episode drug-naïve MDD were categorized into normal weight (18.5 ≤ BMI < 25 kg/m2) and overweight (25 ≤ BMI < 30 kg/m2) groups according to WHO-criteria. The severity of depressive symptoms was assessed using the 24-items Hamilton Depression Scale (HAMD-24). A total of 37 cytokines were measured using Multiplex Luminex Assays. The scores of HAMD-24 and the levels of serum cytokines between normal weight group and overweight group were compared. Multiple linear regression analysis was performed to evaluate the association between abnormal serum cytokines levels and group after adjusting for HAMD-24 scores. The correlation between BMI and the scores of HAMD-24 and the levels of serum cytokines was evaluated using Pearson correlation analysis. RESULTS The scores of HAMD-24 in overweight group were significantly higher than normal weight group (t = -2.930, P = 0.005). Moreover, the levels of IL-1α, IL-1RA, IL-3, CXCL10, TNF-α, and ICAM-1 in overweight patients with MDD were significantly higher than those in normal-weight patients with MDD (all P < 0.05). Furthermore, after adjustment for HAMD-24 scores, there was a significant correlation between abnormal serum cytokines levels (IL-1α, IL-1RA, IL-3, CXCL10, TNF-α, and ICAM-1) and group (all P < 0.05). Additionally, BMI was positively correlated to the serum levels of IL-1α (r = 0.428, P = 0.002), IL-3 (r = 0.529, P < 0.001), IL-6 (r = 0.285, P = 0.050), IL-10 (r = 0.423, P = 0.003), IL-12 (r = 0.367, P = 0.010), IL-15 (r = 0.300, P = 0.036), CXCL10 (r = 0.316, P = 0.030), TNF-α (r = 0.338, P = 0.021), and ICAM-1 (r = 0.440, P = 0.002) in MDD patients. CONCLUSIONS These results provide direct evidence, probably for the first time, that overweight may be associated with several serum cytokines in patients with first-episode drug-naïve MDD. The underlying mechanisms are unclear and require further investigation.
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Affiliation(s)
- Wenfan Gao
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, China
- Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China
- Department of Science and Education, Anhui Clinical Research Center for Mental Disorders, Hefei, China
| | - Yayun Xu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei, China
- The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China
| | - Jun Liang
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, China
- Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China
- Department of Science and Education, Anhui Clinical Research Center for Mental Disorders, Hefei, China
| | - Yanhong Sun
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, China
- Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China
- Department of Science and Education, Anhui Clinical Research Center for Mental Disorders, Hefei, China
| | - Yuanyuan Zhang
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, China
- Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China
- Department of Science and Education, Anhui Clinical Research Center for Mental Disorders, Hefei, China
| | - Feng Shan
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, China
- Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China
- Department of Science and Education, Anhui Clinical Research Center for Mental Disorders, Hefei, China
| | - Jinfang Ge
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei, China
- The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China
- School of Pharmacy, Anhui Medical University, Hefei, China
- *Correspondence: Jinfang Ge, ; Qingrong Xia,
| | - Qingrong Xia
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, China
- Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China
- Department of Science and Education, Anhui Clinical Research Center for Mental Disorders, Hefei, China
- *Correspondence: Jinfang Ge, ; Qingrong Xia,
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