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de Oliveira ICV, Alencar-Júnior HDS, Campos HRSS, Rodrigues VP, Branco-de-Almeida LS. Influence of antidepressant use on periodontal status: a systematic review and meta-analysis. Clin Oral Investig 2025; 29:229. [PMID: 40198453 DOI: 10.1007/s00784-025-06317-1] [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: 08/09/2024] [Accepted: 03/31/2025] [Indexed: 04/10/2025]
Abstract
OBJECTIVE The aim of this review was to evaluate the influence of antidepressant use on inflammatory and clinical data related to periodontal status in animal and human studies. MATERIALS AND METHODS A systematic review was conducted according to the PRISMA guidelines. The potential risk of bias was assessed using the SYRCLE RoB or the Joanna Briggs Institute tools. For human studies, a meta-analysis was performed to compare periodontal parameters between users and non-users of antidepressants, and to estimate the mean difference using random effects models. RESULTS Twelve studies met the inclusion criteria: eight were conducted on animal models, and four were human studies. Tianeptine, desipramine, imipramine, and fluoxetine effectively reduced alveolar bone loss in experimental periodontitis. Furthermore, desipramine, imipramine, and fluoxetine were observed to reduce the expressions of inflammatory markers in gingival tissue. The meta-analysis found no differences in the influence of antidepressant use on periodontal pocket depth, clinical attachment level, and gingival index between users and non-users. There was no standardization of the duration of use, type, and dosage of medication between studies. CONCLUSIONS Animal studies suggest antidepressants modulate the immunoinflammatory response and prevent alveolar bone loss in experimental periodontitis, but their impact on human periodontal status remains controversial. Standardized methods are needed to clarify antidepressant effects on the periodontium. CLINICAL RELEVANCE This study informs health professionals that certain antidepressants may positively impact the periodontium, while also highlighting the need for further research evaluating their possible influence on the human periodontal condition and their potentially associated local/systemic adverse effects.
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Affiliation(s)
- Izabel C V de Oliveira
- Post Graduate Program in Dentistry, Federal University of Maranhão, Av. dos Portugueses, 1966 - Vila Bacanga, São Luís, Maranhão, 65085-580, Brazil
| | - Heracílio de S Alencar-Júnior
- School of Dentistry, Federal University of Maranhão, Av. dos Portugueses, 1966 - Vila Bacanga, São Luís, Maranhão, 65085-580, Brazil
| | - Handreza R S S Campos
- Post Graduate Program in Dentistry, Federal University of Maranhão, Av. dos Portugueses, 1966 - Vila Bacanga, São Luís, Maranhão, 65085-580, Brazil
| | - Vandilson P Rodrigues
- Post Graduate Program in Dentistry, Federal University of Maranhão, Av. dos Portugueses, 1966 - Vila Bacanga, São Luís, Maranhão, 65085-580, Brazil
| | - Luciana S Branco-de-Almeida
- Post Graduate Program in Dentistry, Federal University of Maranhão, Av. dos Portugueses, 1966 - Vila Bacanga, São Luís, Maranhão, 65085-580, Brazil.
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Lion M, Ibrahim EC, Caccomo-Garcia E, Bourret J, Cinquanta G, Khalfallah O, Glaichenhaus N, Davidovic L, Courtet P, Turecki G, Tzavara E, Belzeaux R. A specific GPR56/ADGRG1 splicing isoform is associated with antidepressant response in major depressive disorder. Eur Neuropsychopharmacol 2025; 93:5-14. [PMID: 39874727 DOI: 10.1016/j.euroneuro.2025.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 12/20/2024] [Accepted: 01/07/2025] [Indexed: 01/30/2025]
Abstract
Major Depressive Episode (MDE) is one of the most common psychiatric disorders. Often difficult to treat, this disease is one of the leading causes of suicide. A recent study showed an association between GPR56/ADGRG1 mRNA, MDE and response to antidepressant treatment in blood and in brain. Among GPR56 splicing variant, the S4 isoform has recently been associated with microglial synaptic pruning, while microglia are already known as a central player in MDE. Therefore, we hypothesized that S4 is the specific isoform associated to MDE and antidepressant response. To test our hypothesis, an in silico analysis was first performed to identify the different proteins and transcript isoforms of GPR56. This analysis allowed to design PCR and qPCR primers. GPR56 total, S4 and S3 were assessed by RT-qPCR in leukocytes from a cohort of 46 MDE patients including non-responders (NR, n = 31) and responders-remitters (R, n = 17) to antidepressant treatment. We replicated the result of one of our previous studies, which described an increase in total GPR56 mRNA in Rs. Additionally, we observed that this variation differs among mRNA splicing variants, with S4 exhibiting a similar pattern of variation while S3 shows no significant change. The differences observed withstood statistical correction for covariates of interest such as smoking, gender and suicidal ideation, demonstrating the robustness of the model. These findings confirm our hypothesis that certain mRNA splicing variants of GPR56 may play a more significant role in depression. This study highlighted a link between the GPR56-S4 and response to antidepressant treatment.
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Affiliation(s)
- Montaine Lion
- Aix-Marseille Univ, CNRS, INT, Inst Neurosci Timone, Marseille, France.
| | - El Chérif Ibrahim
- Aix-Marseille Univ, CNRS, INT, Inst Neurosci Timone, Marseille, France; Fondation FondaMental, Créteil, France.
| | | | - Julie Bourret
- IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France.
| | - Guillaume Cinquanta
- Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR7275, Université Côte d'Azur, INSERM U1318, Valbonne, France.
| | - Olfa Khalfallah
- Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR7275, Université Côte d'Azur, INSERM U1318, Valbonne, France.
| | - Nicolas Glaichenhaus
- Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR7275, Université Côte d'Azur, INSERM U1318, Valbonne, France.
| | - Laetitia Davidovic
- Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR7275, Université Côte d'Azur, INSERM U1318, Valbonne, France.
| | - Philippe Courtet
- IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France; Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France
| | - Gustavo Turecki
- Department of Psychiatry, McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
| | - Eleni Tzavara
- Fondation FondaMental, Créteil, France; Hôpital Sainte Marguerite, Pôle de psychiatrie, AP-HM, Marseille, France; CNRS (Integrative Neuroscience and Cognition Center, UMR 8002, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
| | - Raoul Belzeaux
- IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France; Departement of psychiatry, CHU Montpellier, Montpellier, France.
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Ávila Hernández FP, Sevilla Fuentes S, Serrano CJ. Tuberculous meningitis as an underlying cause of rapid neurological deterioration in a patient with a history of psychiatric disorder: Clinical case report. Diagn Microbiol Infect Dis 2025; 111:116625. [PMID: 39616687 DOI: 10.1016/j.diagmicrobio.2024.116625] [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: 06/25/2024] [Revised: 11/15/2024] [Accepted: 11/21/2024] [Indexed: 03/03/2025]
Abstract
Tuberculous meningitis (TBM), the least common of extrapulmonary tuberculosis presentations, one of the most severe. Highly prevalent in immunosuppressed individuals it is associated with high mortality and significant neurological sequelae. TBM main complications are hydrocephalus, increased intracranial pressure, and compromised blood flow with poor prognosis. The diagnostic approach is complex, as the manifestations of TBM are nonspecific. In the case reported here, the first symptoms of TBM were masked by clinical manifestations of depressive syndrome (previously diagnosed) and its management with antidepressants. The confirmatory diagnosis was based on GenXpert on cerebrospinal fluid and neuroimaging, as in our case, tools frequently delayed. The patient presented sudden neurological deterioration, probably due to dysregulation of the immune system associated with depression and smoking habits. In areas with a high incidence of TB, neurological manifestations, even in patients with psychiatric disorders, should be considered as a differential diagnosis or infectious comorbidity such as TBM.
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Affiliation(s)
- Fátima Paola Ávila Hernández
- Universidad Autónoma de Zacatecas, Unidad Académica de Medicina Humana y Ciencias de la Salud, Carretera Zacatecas-Villanueva 98160, Zacatecas, Mexico
| | - Samuel Sevilla Fuentes
- Infectious disease service. Hospital General de Zona 1, Instituto Mexicano del Seguro Social, Interior Alameda No. 45 Zac., Zacatecas 98000, Mexico
| | - Carmen Judith Serrano
- Unidad de Investigación Biomédica Zacatecas, Instituto Mexicano del Seguro Social, Interior Alameda No. 45 Zac., Zacatecas 98000, Mexico.
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Gallant RM, Sanchez KK, Joulia E, Snyder JM, Metallo CM, Ayres JS. Fluoxetine promotes IL-10-dependent metabolic defenses to protect from sepsis-induced lethality. SCIENCE ADVANCES 2025; 11:eadu4034. [PMID: 39951524 PMCID: PMC11827869 DOI: 10.1126/sciadv.adu4034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 01/15/2025] [Indexed: 02/16/2025]
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are some of the most prescribed drugs in the world. While they are used for their ability to increase serotonergic signaling in the brain, SSRIs are also known to have a broad range of effects beyond the brain, including immune and metabolic effects. Recent studies have demonstrated that SSRIs are protective in animal models and humans against several infections, including sepsis and COVID-19; however, the mechanisms underlying this protection are largely unknown. Here, we mechanistically link two previously described effects of the SSRI fluoxetine in mediating protection against sepsis. We show that fluoxetine-mediated protection is independent of peripheral serotonin and instead increases levels of circulating interleukin-10 (IL-10). IL-10 is necessary for protection from sepsis-induced hypertriglyceridemia, preventing cardiac effects including impairment of glucose oxidation, ectopic lipid accumulation, ventricular stretch and possibly cardiac failure. Our work reveals a beneficial "off-target" effect of fluoxetine, and reveals a protective immunometabolic defense mechanism with therapeutic potential.
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Affiliation(s)
- Robert M. Gallant
- Molecular and Systems Physiology Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
- Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
| | - Karina K. Sanchez
- Molecular and Systems Physiology Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
- NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
- Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
| | - Emeline Joulia
- Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
| | - Jessica M. Snyder
- Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Christian M. Metallo
- Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Department of Bioengineering, University of California San Diego, La Jolla, CA 92037, USA
| | - Janelle S. Ayres
- Molecular and Systems Physiology Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
- NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
- Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
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Cavaillon JM, Chaudry IH. Facing stress and inflammation: From the cell to the planet. World J Exp Med 2024; 14:96422. [PMID: 39713080 PMCID: PMC11551703 DOI: 10.5493/wjem.v14.i4.96422] [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: 05/06/2024] [Revised: 08/27/2024] [Accepted: 09/19/2024] [Indexed: 10/31/2024] Open
Abstract
As identified in 1936 by Hans Selye, stress is shaping diseases through the induction of inflammation. But inflammation display some yin yang properties. On one hand inflammation is merging with the innate immune response aimed to fight infectious or sterile insults, on the other hand inflammation favors chronic physical or psychological disorders. Nature has equipped the cells, the organs, and the individuals with mediators and mechanisms that allow them to deal with stress, and even a good stress (eustress) has been associated with homeostasis. Likewise, societies and the planet are exposed to stressful settings, but wars and global warming suggest that the regulatory mechanisms are poorly efficient. In this review we list some inducers of the physiological stress, psychologic stress, societal stress, and planetary stress, and mention some of the great number of parameters which affect and modulate the response to stress and render it different from an individual to another, from the cellular level to the societal one. The cell, the organ, the individual, the society, and the planet share many stressors of which the consequences are extremely interconnected ending in the domino effect and the butterfly effect.
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Affiliation(s)
| | - Irshad H Chaudry
- Department of Surgery, University of Alabama Birmingham, Birmingham, AL 35294, United States
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Li J, Mei B, Feng L, Wang X, Wang D, Huang J, Zhang G. Amitriptyline revitalizes ICB response via dually inhibiting Kyn/Indole and 5-HT pathways of tryptophan metabolism in ovarian cancer. iScience 2024; 27:111488. [PMID: 39759009 PMCID: PMC11697709 DOI: 10.1016/j.isci.2024.111488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 07/26/2024] [Accepted: 11/25/2024] [Indexed: 01/07/2025] Open
Abstract
Reprogramming tryptophan metabolism (TRP) may be able to overcome immunosuppression and restore the immune checkpoint blockade (ICB) response in patients with epithelial ovarian cancer (EOC) resistant to ICB therapy because TRP metabolism is involved in the kynurenine/indole and serotonin pathways of tryptophan metabolism. Herein, employing amitriptyline (AMI), an antagonist of TLR4 and serotonin transporter (SERT), we revealed that AMI remodels the immunological landscape of EOC. In particular, AMI lowered the expression of IDO1, IL-4I1, and PD-L1, the quantity of KYN and indoles, and the level of immunosuppressive immune cells MDSC, Tregs, and CD8+CD39+/PD-1+ T cell. AMI boosted the killing potential of anti-PD-1-directed CD8+T cells and worked in concert with PD-1 inhibitors to suppress tumor growth and to prolong the survival of EOC-bearing mice. This work highlights AMI as an effective regulator of ICB response by manipulating EOC cell TRP metabolism, indicating it could be a potential strategy for improving EOC ICB therapy.
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Affiliation(s)
- Junyang Li
- Department Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Bingjie Mei
- Department Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Lu Feng
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Xiaoxin Wang
- Department Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Dengfeng Wang
- Department Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Jianming Huang
- Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Guonan Zhang
- Department Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
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7
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Sidky H, Hansen KA, Girvin AT, Hotaling N, Michael SG, Gersing K, Sahner DK. Assessing the effect of selective serotonin reuptake inhibitors in the prevention of post-acute sequelae of COVID-19. Comput Struct Biotechnol J 2024; 24:115-125. [PMID: 38318198 PMCID: PMC10839808 DOI: 10.1016/j.csbj.2023.12.045] [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: 11/03/2023] [Revised: 12/27/2023] [Accepted: 12/28/2023] [Indexed: 02/07/2024] Open
Abstract
Background Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties although clinical trial data are lacking. Materials and Methods This retrospective study was conducted leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C) to evaluate whether SSRIs with agonist activity at the sigma-1 receptor (S1R) lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. Additionally, determine whether the potential benefit could be traced to S1R agonism. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code. Results Of the 17,908 patients identified, 1521 were exposed at baseline to a S1R agonist SSRI, 1803 to a non-S1R agonist SSRI, and 14,584 to neither. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed.A 29% reduction in the RR of PASC (0.704 [95% CI, 0.58-0.85]; P = 4 ×10-4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 21% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.79 [95% CI, 0.67 - 0.93]; P = 0.005).Thus, SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC.
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Affiliation(s)
- Hythem Sidky
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA
| | - Kristen A. Hansen
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA
- Axle Research and Technologies, Rockville, MD, USA
| | | | - Nathan Hotaling
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA
- Axle Research and Technologies, Rockville, MD, USA
| | - Sam G. Michael
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA
- Palantir Technologies, Denver, CO, USA
- Axle Research and Technologies, Rockville, MD, USA
| | - Ken Gersing
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA
| | - David K. Sahner
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA
- Axle Research and Technologies, Rockville, MD, USA
| | - on behalf of the N3C consortium
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA
- Palantir Technologies, Denver, CO, USA
- Axle Research and Technologies, Rockville, MD, USA
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Hall S, Parr BA, Hussey S, Anoopkumar-Dukie S, Arora D, Grant GD. The neurodegenerative hypothesis of depression and the influence of antidepressant medications. Eur J Pharmacol 2024; 983:176967. [PMID: 39222740 DOI: 10.1016/j.ejphar.2024.176967] [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: 07/04/2024] [Revised: 08/27/2024] [Accepted: 08/28/2024] [Indexed: 09/04/2024]
Abstract
Depression is a complex neurological disease that holds many theories on its aetiology and pathophysiology. The monoamine strategy of treating depression with medications to increase levels of monoamines in the (extra)synapse, primarily through the inhibition of monoamine transporters, does not always work, as seen in patients that lack a response to multiple anti-depressant exposures, as well as a lack of depressive symptoms in healthy volunteers exposed to monoamine reduction. Depression is increasingly being understood not as a single condition, but as a complex interplay of adaptations in various systems, including inflammatory responses and neurotransmission pathways in the brain. This understanding has led to the development of the neurodegenerative hypothesis of depression. This hypothesis, which is gaining widespread acceptance posits that both oxidative stress and inflammation play significant roles in the pathophysiology of depression. This article is a review of the literature focused on neuroinflammation in depression, as well as summarised studies of anti-inflammatory and antioxidant effects of antidepressants.
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Affiliation(s)
- Susan Hall
- School of Pharmacy and Medical Sciences, Griffith University Gold Coast Campus, Southport, 4222, Australia.
| | - Brie-Anne Parr
- School of Pharmacy and Medical Sciences, Griffith University Gold Coast Campus, Southport, 4222, Australia
| | - Sarah Hussey
- School of Pharmacy and Medical Sciences, Griffith University Gold Coast Campus, Southport, 4222, Australia
| | | | - Devinder Arora
- School of Pharmacy and Medical Sciences, Griffith University Gold Coast Campus, Southport, 4222, Australia
| | - Gary D Grant
- School of Pharmacy and Medical Sciences, Griffith University Gold Coast Campus, Southport, 4222, Australia
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Breivik TJ, Gjermo P, Gundersen Y, Opstad PK, Murison R, Hugoson A, von Hörsten S, Fristad I. Microbiota-immune-brain interactions: A new vision in the understanding of periodontal health and disease. Periodontol 2000 2024; 96:20-41. [PMID: 39233381 PMCID: PMC11579829 DOI: 10.1111/prd.12610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 08/01/2024] [Accepted: 08/19/2024] [Indexed: 09/06/2024]
Abstract
This review highlights the significance of interactions between the microbiota, immune system, nervous and hormonal systems, and the brain on periodontal health and disease. Microorganisms in the microbiota, immune cells, and neurons communicate via homeostatic nervous and hormonal systems, regulating vital body functions. By modulating pro-inflammatory and anti-inflammatory adaptive immune responses, these systems control the composition and number of microorganisms in the microbiota. The strength of these brain-controlled responses is genetically determined but is sensitive to early childhood stressors, which can permanently alter their responsiveness via epigenetic mechanisms, and to adult stressors, causing temporary changes. Clinical evidence and research with humans and animal models indicate that factors linked to severe periodontitis enhance the responsiveness of these homeostatic systems, leading to persistent hyperactivation. This weakens the immune defense against invasive symbiotic microorganisms (pathobionts) while strengthening the defense against non-invasive symbionts at the gingival margin. The result is an increased gingival tissue load of pathobionts, including Gram-negative bacteria, followed by an excessive innate immune response, which prevents infection but simultaneously destroys gingival and periodontal tissues. Thus, the balance between pro-inflammatory and anti-inflammatory adaptive immunity is crucial in controlling the microbiota, and the responsiveness of brain-controlled homeostatic systems determines periodontal health.
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Affiliation(s)
- Torbjørn Jarle Breivik
- Department of Periodontology, Faculty of Dentistry, Institute of Clinical OdontologyUniversity of OsloOsloNorway
- Division for ProtectionNorwegian Defence Research EstablishmentKjellerNorway
| | - Per Gjermo
- Department of Periodontology, Faculty of Dentistry, Institute of Clinical OdontologyUniversity of OsloOsloNorway
| | - Yngvar Gundersen
- Division for ProtectionNorwegian Defence Research EstablishmentKjellerNorway
| | - Per Kristian Opstad
- Division for ProtectionNorwegian Defence Research EstablishmentKjellerNorway
| | - Robert Murison
- Department of Biological and Medical Psychology, Faculty of PsychologyUniversity of BergenBergenNorway
| | - Anders Hugoson
- Department of Periodontology, Institute of OdontologyThe Sahlgrenska Academy at University of Gothenburg and School of Health and WelfareGothenburgSweden
| | - Stephan von Hörsten
- Department for Experimental Therapy, University Hospital Erlangen, Preclinical Experimental CenterFriedrich‐Alexander‐Universität Erlangen‐Nürnberg (FAU)ErlangenGermany
| | - Inge Fristad
- Department of Clinical Dentistry, Faculty of MedicineUniversity of BergenBergenNorway
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10
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Wang Y, Cao M, Zhang Y, Chen Q, Chen Z, Jia J. The CB2-PKC pathway is involved in esketamine-induced anti-inflammation in BV-2 microglial cells exposed to lipopolysaccharides. Am J Transl Res 2024; 16:4466-4478. [PMID: 39398580 PMCID: PMC11470345 DOI: 10.62347/rrzf5229] [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: 01/20/2024] [Accepted: 08/12/2024] [Indexed: 10/15/2024]
Abstract
OBJECTIVE Esketamine (ESK), an intravenous anesthetic, exerts antidepressant effects; however, the antidepression mechanism is not clear. The aim of this study was to explore whether microglial cannabinoid type 2 (CB2) receptor and protein kinase C (PKC) are involved in the antidepressant effects of ESK. METHODS In this investigation, lipopolysaccharide (LPS) was used to stimulate BV-2 microglia to mimic neuroinflammation. An enzyme-linked immunosorbent assay (ELISA) and Griess reagent kits were used to determine cytokine and nitrite concentrations in the medium. CB2, inducible nitric oxide synthase (iNOS) and nuclear factor (NF)-κB (p65) protein expression were evaluated by immunocytochemistry and western blot analysis. RESULTS Compared with the control, LPS enhanced proinflammatory factor and nitrite concentration in the medium, upregulated iNOS and NF-κB (p65) expressions, and coadministration of ESK decreased proinflammatory cytokine and nitrite levels, and downregulated iNOS and NF-κB (p65) expression. Moreover, ESK exposure enhanced CB2 receptor expression; coadministration of the CB2 receptor antagonist AM630 or the PKC inhibitor chelerythrine (Che), however, markedly blocked the anti-inflammatory effect of ESK in reducing cytokine and nitrite concentration, and downregulating iNOS and NF-κB (p65) expression. CONCLUSIONS These observations demonstrated that the microglial CB2-PKC pathway mediates ESK-induced anti-inflammation in LPS-stimulated microglial cells.
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Affiliation(s)
- Yuqing Wang
- The Fourth Resident Outpatient Department, General Hospital of Southern Theatre Command of PLAGuangzhou 510501, Guangdong, China
| | - Ming Cao
- Department of Anesthesiology, General Hospital of Southern Theatre Command of PLAGuangzhou 510501, Guangdong, China
| | - Yuanyuan Zhang
- Department of Geriatrics, General Hospital of Southern Theatre Command of PLAGuangzhou 510501, Guangdong, China
| | - Qian Chen
- Department of Anesthesiology, General Hospital of Southern Theatre Command of PLAGuangzhou 510501, Guangdong, China
| | - Zhaojie Chen
- Department of Anesthesiology, General Hospital of Southern Theatre Command of PLAGuangzhou 510501, Guangdong, China
| | - Ji Jia
- Department of Anesthesiology, General Hospital of Southern Theatre Command of PLAGuangzhou 510501, Guangdong, China
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Lin H, Zhang X, Zheng Y, Tang C, Wang J. Research on the soothing Liver - Qi stagnation method in the treatment of postoperative papillary thyroid carcinoma patients' concomitant depression: A randomized controlled clinical trial. Medicine (Baltimore) 2024; 103:e39325. [PMID: 39287310 PMCID: PMC11404975 DOI: 10.1097/md.0000000000039325] [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: 12/14/2023] [Revised: 04/25/2024] [Accepted: 07/25/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND Postoperative papillary thyroid carcinoma (P-PTC) patients often grapple with depression fueled by the looming threat of recurrence. While the Liver-Qi stagnation method is frequently employed for depression management, a notable scarcity of clinical trials exists regarding its application in patients with P-PTC and concurrent depression. This study presents a randomized controlled clinical trial, aiming to establish the efficacy of the Liver-Qi stagnation method in alleviating depression in patients with P-PTC. METHODS In this randomized controlled clinical trial, P-PTC patients diagnosed with concomitant depression were systematically enrolled. Subjects were randomly assigned to either the control or test group, both receiving standard treatment comprising Levothyroxine sodium tablets and decoction of benefiting Qi and nourishing Yin. Additionally, the test group received supplementation with bupleuri radix-paeoniae alba radix (CH-BS) alongside the baseline therapy. The intervention spanned 12 weeks. Pre- and post-treatment evaluations were conducted using the Hamilton Depression Scale (HAMD), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Traditional Chinese Medicine (TCM) syndrome score scale. Concurrently, blood inflammatory factors and serum 5-hydroxytryptamine (5-HT) levels were measured to comprehensively assess treatment outcomes. RESULTS During the 12-week intervention, the test group demonstrated a significant reduction in HAMD scores compared to the control group (P < .05). Moreover, post-treatment serum 5-HT levels were significantly elevated in the test group compared to the control group (P < .05). Findings gleaned from the EORTC QLQ - C30 revealed a noteworthy improvement in social function and overall quality of life scores within both groups post-treatment in comparison to baseline (P < .05). Concurrently, post-treatment scores for fatigue and insomnia symptoms witnessed a significant decrease compared to baseline (P < .05). Notably, the test group exhibited superior scores in the emotional domain in contrast to the control group (P < .05). Both groups exhibited a substantial decrease in TCM syndrome scores from baseline (P < .05). Noteworthy increases were found in IFN-γ < 2.44 rate (62.86%) and IL-6 < 2.44 rate (74.29%) in the test group compared to pretreatment levels (P < .05). CONCLUSION The soothing Liver-Qi stagnation method induces a rise in serum 5-HT levels, reducing depression-related inflammatory factors, culminating in the alleviation of depression for P-PTC.
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Affiliation(s)
- Huiyue Lin
- Oncology Department, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, Zhejiang Province, China
| | - Xueting Zhang
- Oncology Department, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yuqian Zheng
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chenchen Tang
- Department of Experimental Management, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Juyong Wang
- Oncology Department, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
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12
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Xie Y, Zhu H, Yuan Y, Guan X, Xie Q, Dong Z. Baseline gut microbiota profiles affect treatment response in patients with depression. Front Microbiol 2024; 15:1429116. [PMID: 39021622 PMCID: PMC11251908 DOI: 10.3389/fmicb.2024.1429116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 06/20/2024] [Indexed: 07/20/2024] Open
Abstract
The role of the gut microbiota in the pathophysiology of depression has been explored in numerous studies, which have confirmed that the baseline gut microbial profiles of patients with depression differ from those of healthy individuals. The gut microbiome affects metabolic activity in the immune and central nervous systems and regulates intestinal ecology through the neuroendocrine system. Additionally, baseline changes in the gut microbiota differed among patients with depression who demonstrated varying treatment response. Currently, probiotics are an emerging treatment for depression; however, the efficacy of modulating the gut microbiota in the treatment of depression remains uncertain. Additionally, the mechanisms by which changes in the gut microbiota affect treatment response in patients with depression remain unclear. In this review, we aimed to summarize the differences in the baseline gut microbiota between the remission and non-remission groups after antidepressant therapy. Additionally, we summarized the possible mechanisms that may contribute to antidepressant resistance through the effects of the gut microbiome on the immune and nervous systems, various enzymes, bioaccumulation, and blood-brain barrier, and provide a basis for treating depression by targeting the gut microbiota.
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Affiliation(s)
- Yingjing Xie
- West China Hospital, Sichuan University, Chengdu, China
| | - Hanwen Zhu
- West China Hospital, Sichuan University, Chengdu, China
| | - Yanling Yuan
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, China
| | - Xuan Guan
- Chengdu Medical College, Chengdu, China
| | - Qinglian Xie
- Department of Outpatient, West China Hospital, Sichuan University, Chengdu, China
| | - Zaiquan Dong
- Department of Psychiatry and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
- Mental Health Center, West China Hospital, Sichuan University, Chengdu, China
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13
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Wang S, Dong Y, Zhai L, Bai Y, Yang Y, Jia L. Decreased Treg cells induced by bisphenol A is associated with up-regulation of PI3K/Akt/mTOR signaling pathway and Foxp3 DNA methylation in spleen of adolescent mice. CHEMOSPHERE 2024; 357:141957. [PMID: 38641296 DOI: 10.1016/j.chemosphere.2024.141957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 03/29/2024] [Accepted: 04/08/2024] [Indexed: 04/21/2024]
Abstract
The current study aimed to explore whether bisphenol A (BPA) exposure aggravated the decrease in Tregs induced by ovalbumin (OVA) in adolescent female mouse models of asthma, and whether the process was associated with mTOR-mediated signaling pathways and DNA methylation levels. A total of 40 female C57BL/6 mice at the age of four weeks were used and divided into five groups after 1 week of domestication. Each group consisted of eight mice: the control group, OVA group, OVA + BPA (0.1 μg mL-1) group, OVA + BPA (0.2 μg mL-1) group, and OVA + BPA (0.4 μg mL-1) group. Results revealed that Foxp3 protein levels decreased in the spleens of mice exposed to BPA compared to those in the OVA group. After an elevation in BPA dose, the mRNAs of methyltransferases (Dnmt1, Dnmt3a, and Dnmt3b) were gradually upregulated. The mechanism was related to the activity of TLR4/NF-κB and PI3K/Akt/mTOR signaling pathways and the enhancement of Foxp3 DNA methylation. Our results, collectively, provided a new view for studying the mechanisms underlying BPA exposure-induced immune dysfunction. Investigation of the regulatory mechanisms of DNA methylation in the abnormal Th immune response caused by BPA exposure could help reveal the causes and molecular mechanisms underlying the high incidence of allergic diseases in children in recent years.
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Affiliation(s)
- Simeng Wang
- Institute for International Health Professions Education and Research, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.
| | - Youdan Dong
- Department of Rheumatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110022, PR China.
| | - Lingling Zhai
- Department of Child and Adolescent Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.
| | - Yinglong Bai
- Department of Child and Adolescent Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.
| | - Yilong Yang
- Department of Health Policy and Management, School of Public Health, Hangzhou Normal University, NO. 2318 Yuhangtang Road, Yuhang District, Hangzhou, Zhejiang, 311121, PR China.
| | - Lihong Jia
- Department of Child and Adolescent Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.
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Aebi N, Meier CR, Jick SS, Lang U, Spoendlin J. The risk of acute infections in new users of antidepressants: An observational cohort study. J Affect Disord 2024; 354:152-159. [PMID: 38479501 DOI: 10.1016/j.jad.2024.03.002] [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: 04/11/2023] [Revised: 01/13/2024] [Accepted: 03/03/2024] [Indexed: 03/19/2024]
Abstract
BACKGROUND Preclinical studies suggested that drugs that functionally inhibit acid sphingomyelinase (FIASMA)may enhance immune cell longevity and potentially offer protection against infections. Many antidepressants have shown FIASMA activity. METHODS We conducted a cohort study using primary-care data from the UK-based Clinical Practice Research Datalink (2000-2021). We assessed the association of composite diagnosed acute infections in new users of fluoxetine, sertraline, paroxetine, or venlafaxine aged 18-80 years compared to citalopram. We compared SARS-CoV-2 infections between groups in a secondary analysis. We estimated incidence rates (IR) and IR ratios (IRR) of acute infections in four pairwise comparisons using negative binomial regression. We applied propensity score (PS) fine stratification to control for confounding. RESULTS In the PS-weighted cohorts, we included 353,138 fluoxetine, 222,463 sertraline, 69,963 paroxetine, 32,608 venlafaxine, and between 515,996 and 516,583 new citalopram users. PS-weighted IRs ranged between 76.8 acute infections /1000 person-years (py) (sertraline) and 98.9 infections/1000 py (citalopram). We observed PS-weighted IRRs around unity for paroxetine (0.97, 95 % CI, 0.95-1.00), fluoxetine (0.94, 95 % CI, 0.92-0.95), and venlafaxine (0.90, 95 % CI, 0.87-0.94) vs citalopram. Reduced IRR for sertraline vs citalopram (0.84, 95 % CI, 0.82-0.85), became null within subgroups by cohort entry date. In the analysis of SARS-CoV-2 infection, no statistically relevant risk reduction was seen. LIMITATIONS Analysis not limited to patients with diagnosed depression, possible underestimation of infection incidence, and unclear FIASMA activity of citalopram. CONCLUSIONS Fluoxetine, sertraline, paroxetine, and venlafaxine were not associated with a reduced risk of acute infection when compared with the presumably weak FIASMA citalopram.
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Affiliation(s)
- N Aebi
- Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; Hospital Pharmacy, University Hospital Basel, Basel, Switzerland; University Psychiatric Clinics Basel, University Hospital Basel, Basel, Switzerland.
| | - C R Meier
- Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; Hospital Pharmacy, University Hospital Basel, Basel, Switzerland; Boston Collaborative Drug Surveillance Program, Lexington, MA, USA.
| | - S S Jick
- Boston Collaborative Drug Surveillance Program, Lexington, MA, USA; Boston University School of Public Health, Boston, MA, USA
| | - U Lang
- University Psychiatric Clinics Basel, University Hospital Basel, Basel, Switzerland
| | - J Spoendlin
- Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; Hospital Pharmacy, University Hospital Basel, Basel, Switzerland
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Geng M, Shao Q, Fu J, Gu J, Feng L, Zhao L, Liu C, Mu J, Zhang X, Zhao M, Guo X, Song C, Li Y, Wang H, Wang C. Down-regulation of MKP-1 in hippocampus protects against stress-induced depression-like behaviors and neuroinflammation. Transl Psychiatry 2024; 14:130. [PMID: 38424085 PMCID: PMC10904742 DOI: 10.1038/s41398-024-02846-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 02/15/2024] [Accepted: 02/21/2024] [Indexed: 03/02/2024] Open
Abstract
Chronic stress is the primary environmental risk factor for major depressive disorder (MDD), and there is compelling evidence that neuroinflammation is the major pathomechanism linking chronic stress to MDD. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a negative regulator of MAPK signaling pathways involved in cellular stress responses, survival, and neuroinflammation. We examined the possible contributions of MKP-1 to stress-induced MDD by comparing depression-like behaviors (anhedonia, motor retardation, behavioral despair), neuroinflammatory marker expression, and MAPK signaling pathways among rats exposed to chronic unpredictable mild stress (CUMS), overexpressing MKP-1 in the hippocampus, and CUMS-exposed rats underexpressing MKP-1 in the hippocampus. Rats exposed to CUMS exhibited MKP-1 overexpression, greater numbers of activated microglia, and enhanced expressions of neuroinflammatory markers (interleukin [IL]-6, [IL]-1β, tumor necrosis factor [TNF]-ɑ, and decreased phosphorylation levels of ERK and p38 in the hippocampus as well as anhedonia in the sucrose preference test, motor retardation in the open field, and greater immobility (despair) in the forced swimming tests. These signs of neuroinflammation and depression-like behaviors and phosphorylation levels of ERK and p38 were also observed in rats overexpressing MKP-1 without CUMS exposure, while CUMS-induced neuroinflammation, microglial activation, phosphorylation levels of ERK and p38, and depression-like behaviors were significantly reversed by MKP-1 knockdown. Moreover, MKP-1 knockdown promoted the activation of the MAPK isoform ERK, implying that the antidepressant-like effects of MKP-1 knockdown may be mediated by the ERK pathway disinhibition. These findings suggested that hippocampal MKP-1 is an essential regulator of stress-induced neuroinflammation and a promising target for antidepressant development.
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Affiliation(s)
- Mengjun Geng
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China
- Henan Key Laboratory of Biological Psychiatry, Xinxiang Medical University, 453002, Xinxiang, Henan, China
| | - Qiujing Shao
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China
- Henan Key Laboratory of Biological Psychiatry, Xinxiang Medical University, 453002, Xinxiang, Henan, China
| | - Jiacheng Fu
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China
- Henan Key Laboratory of Biological Psychiatry, Xinxiang Medical University, 453002, Xinxiang, Henan, China
| | - Jingyang Gu
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China
| | - Laipeng Feng
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China
- Henan Key Laboratory of Biological Psychiatry, Xinxiang Medical University, 453002, Xinxiang, Henan, China
| | - Liqin Zhao
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China
| | - Cong Liu
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China
| | - Junlin Mu
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China
| | - Xiaoli Zhang
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China
| | - Mingjun Zhao
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China
| | - Xinsheng Guo
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China
- Henan Key Laboratory of Biological Psychiatry, Xinxiang Medical University, 453002, Xinxiang, Henan, China
| | - Cai Song
- Guangdong Ocean University College of Food Science and Technoligy, Zhanjiang, China
| | - Yan Li
- The Second Affiliated Hospital of Zhengzhou University, 450014, Zhengzhou, Henan, China.
| | - Huiying Wang
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China.
- Henan Key Laboratory of Biological Psychiatry, Xinxiang Medical University, 453002, Xinxiang, Henan, China.
| | - Changhong Wang
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, 453002, Xinxiang, Henan, China.
- Henan Key Laboratory of Biological Psychiatry, Xinxiang Medical University, 453002, Xinxiang, Henan, China.
- Henan Provincial Key Laboratory of Sleep Medicine, 453002, Xinxiang, Henan, China.
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Li S, Lv D, Qian C, Jiang J, Zhang P, Xi C, Wu L, Gao X, Fu Y, Zhang D, Chen Y, Huang H, Zhu Y, Wang X, Lai J, Hu S. Circulating T-cell subsets discrepancy between bipolar disorder and major depressive disorder during mood episodes: A naturalistic, retrospective study of 1015 cases. CNS Neurosci Ther 2024; 30:e14361. [PMID: 37491837 PMCID: PMC10848094 DOI: 10.1111/cns.14361] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 06/06/2023] [Accepted: 07/03/2023] [Indexed: 07/27/2023] Open
Abstract
AIMS We aimed to investigate whether peripheral T-cell subsets could be a biomarker to distinguish major depressive disorder (MDD) and bipolar disorder (BD). METHODS Medical records of hospitalized patients in the Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2015 to September 2020 with a discharge diagnosis of MDD or BD were reviewed. Patients who underwent peripheral blood examination of T-cell subtype proportions, including CD3+, CD4+, CD8+ T-cell, and natural killer (NK) cells, were enrolled. The Chi-square test, t-test, or one-way analysis of variance were used to analyze group differences. Demographic profiles and T-cell data were used to construct a random forest classifier-based diagnostic model. RESULTS Totally, 98 cases of BD mania, 459 cases of BD depression (BD-D), and 458 cases of MDD were included. There were significant differences in the proportions of CD3+, CD4+, CD8+ T-cell, and NK cells among the three groups. Compared with MDD, the BD-D group showed higher CD8+ but lower CD4+ T-cell and a significantly lower ratio of CD4+ and CD8+ proportions. The random forest model achieved an area under the curve of 0.77 (95% confidence interval: 0.71-0.83) to distinguish BD-D from MDD patients. CONCLUSION These findings imply that BD and MDD patients may harbor different T-cell inflammatory patterns, which could be a potential diagnostic biomarker for mood disorders.
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Affiliation(s)
- Shaoli Li
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
- The Key Laboratory of Mental Disorder's Management in Zhejiang ProvinceHangzhouChina
- Department of Medical Oncology, The Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina
- Zhejiang Engineering Center for Mathematical Mental HealthHangzhouChina
| | - Duo Lv
- Department of Clinical Pharmacy, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Chao Qian
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
- Shaoxing 7th People's HospitalShaoxingChina
| | - Jiajun Jiang
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Peifen Zhang
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Caixi Xi
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Lingling Wu
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Xingle Gao
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Yaoyang Fu
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Danhua Zhang
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Yiqing Chen
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | | | - Yiyi Zhu
- Wenzhou Medical UniversityWenzhouChina
| | - Xiaorong Wang
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Jianbo Lai
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
- The Key Laboratory of Mental Disorder's Management in Zhejiang ProvinceHangzhouChina
- Zhejiang Engineering Center for Mathematical Mental HealthHangzhouChina
- Department of Neurobiology, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brian Medicine, MOE Frontier Science Center for Brain Science and Brain‐Machine IntegrationZhejiang University School of MedicineHangzhouChina
| | - Shaohua Hu
- Department of Psychiatry, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
- The Key Laboratory of Mental Disorder's Management in Zhejiang ProvinceHangzhouChina
- Zhejiang Engineering Center for Mathematical Mental HealthHangzhouChina
- Department of Neurobiology, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brian Medicine, MOE Frontier Science Center for Brain Science and Brain‐Machine IntegrationZhejiang University School of MedicineHangzhouChina
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Amerio A, Magnani L, Arduino G, Fesce F, de Filippis R, Parise A, Costanza A, Nguyen KD, Saverino D, De Berardis D, Aguglia A, Escelsior A, Serafini G, De Fazio P, Amore M. Immunomodulatory Effects of Clozapine: More Than Just a Side Effect in Schizophrenia. Curr Neuropharmacol 2024; 22:1233-1247. [PMID: 38031778 PMCID: PMC10964093 DOI: 10.2174/1570159x22666231128101725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 04/11/2023] [Accepted: 04/14/2023] [Indexed: 12/01/2023] Open
Abstract
Recent evidence suggests a possible relationship between the immune system and schizophrenia spectrum disorders (SSDs), as neuroinflammation appears to play a role in major psychiatric conditions. Neuroinflammation is as a broad concept representing a physiological protective response to infection or injury, but in some cases, especially if chronic, it may represent an expression of maladaptive processes, potentially driving to clinical dysfunction and neurodegeneration. Several studies are concurrently highlighting the importance of microglia, the resident immune cells of the central nervous system, in a huge number of neurodegenerative diseases, including multiple sclerosis, Alzheimer's and Parkinson's diseases, as well as SSDs. A more fundamental phenomenon of maladaptive coupling of microglia may contribute to the genesis of dysfunctional brain inflammation involved in SSDs, from the onset of their neurophenomenological evolution. Clozapine and other antipsychotic drugs seem to express a provable immunomodulant effect and a more specific action on microglia, while neuroactive steroids and nonsteroidal anti-inflammatory drugs may reduce some SSDs symptoms in add-on therapy. Given these theoretical premises, this article aims to summarize and interpret the available scientific evidence about psychotropic and anti-inflammatory drugs that could express an immunomodulant activity on microglia.
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Affiliation(s)
- Andrea Amerio
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Luca Magnani
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy
| | - Gabriele Arduino
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy
| | - Fabio Fesce
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy
| | - Renato de Filippis
- Psychiatry Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Alberto Parise
- Department of Geriatric-Rehabilitation,, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Alessandra Costanza
- Department of Psychiatry, Faculty of Medicine, University of Geneva (UNIGE), Geneva, Switzerland
- Department of Psychiatry, Faculty of Biomedical Sciences, University of Italian Switzerland (USI) Lugano, Switzerland
| | - Khoa D. Nguyen
- Department of Microbiology and Immunology, Stanford University, Palo Alto, CA, USA
- Tranquis Therapeutics, Palo Alto, CA, USA
| | - Daniele Saverino
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Department of Experimental Medicine (DiMeS), Section of Human Anatomy, University of Genoa, Genoa, Italy
| | - Domenico De Berardis
- NHS, Department of Mental Health, Psychiatric Service for Diagnosis and Treatment, Hospital “G. Mazzini”, Teramo, Italy
| | - Andrea Aguglia
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Andrea Escelsior
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Gianluca Serafini
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Pasquale De Fazio
- Psychiatry Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Mario Amore
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
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18
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Sokołowska P, Seweryn Karbownik M, Jóźwiak-Bębenista M, Dobielska M, Kowalczyk E, Wiktorowska-Owczarek A. Antidepressant mechanisms of ketamine's action: NF-κB in the spotlight. Biochem Pharmacol 2023; 218:115918. [PMID: 37952898 DOI: 10.1016/j.bcp.2023.115918] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 10/03/2023] [Accepted: 11/09/2023] [Indexed: 11/14/2023]
Abstract
Ketamine recently approved for therapy of treatment-resistant depression shows a complex and not fully understood mechanism of action. Apart from its classical glutamatergic N-methyl-D-aspartate receptor antagonistic action, it is thought that anti-inflammatory properties of the drug are of clinical relevance due to the contribution of activated inflammatory mediators to the pathophysiology of depression and non-responsiveness of a group of patients to current antidepressant therapies. In a search of the mechanism underlying anti-inflammatory effects of ketamine, the nuclear factor kappa B transcription factor (NF-κB) has been proposed as a target for ketamine. The NF-κB forms precisely regulated protein signaling cascades enabling a rapid response to cellular stimuli. In the central nervous systems, NF-κB signaling appears to have pleiotropic but double-edged functions: on the one hand it participates in the regulation of processes that are crucial in the treatment of depression, such as neuroplasticity, neurogenesis or neuronal survival, on the other - in the activation of neuroinflammation and cell death. Ketamine has been found to reduce inflammation mediated by NF-κB, leading to decreased level of pro-inflammatory cytokines and other inflammatory or stress mediators. Therefore, this review presents recent data on the significance of the NF-κB cascade in the mechanism of ketamine's action and its future perspectives in designing new strategies for the treatment of depression.
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Affiliation(s)
- Paulina Sokołowska
- Department of Pharmacology and Toxicology, Medical University of Lodz, 90-752 Lodz, Zeligowskiego 7/9, Poland.
| | - Michał Seweryn Karbownik
- Department of Pharmacology and Toxicology, Medical University of Lodz, 90-752 Lodz, Zeligowskiego 7/9, Poland
| | - Marta Jóźwiak-Bębenista
- Department of Pharmacology and Toxicology, Medical University of Lodz, 90-752 Lodz, Zeligowskiego 7/9, Poland
| | - Maria Dobielska
- Department of Pharmacology and Toxicology, Medical University of Lodz, 90-752 Lodz, Zeligowskiego 7/9, Poland
| | - Edward Kowalczyk
- Department of Pharmacology and Toxicology, Medical University of Lodz, 90-752 Lodz, Zeligowskiego 7/9, Poland
| | - Anna Wiktorowska-Owczarek
- Department of Pharmacology and Toxicology, Medical University of Lodz, 90-752 Lodz, Zeligowskiego 7/9, Poland
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Gallant RM, Snyder JM, Ayres JS. Fluoxetine promotes immunometabolic defenses to mediate host-pathogen cooperation during sepsis. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.11.18.567681. [PMID: 38013994 PMCID: PMC10680848 DOI: 10.1101/2023.11.18.567681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2023]
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are some of the most prescribed drugs in the world. While they are used for their ability to increase serotonergic signaling in the brain, SSRIs are also known to have a broad range of effects beyond the brain, including immune and metabolic effects. Recent studies have demonstrated that SSRIs are protective in animal models and humans against several infections, including sepsis and COVID-19, however the mechanisms underlying this protection are largely unknown. Here we mechanistically link two previously described effects of the SSRI fluoxetine in mediating protection against sepsis. We show that fluoxetine-mediated protection is independent of peripheral serotonin, and instead increases levels of circulating IL-10. IL-10 is necessary for protection from sepsis-induced hypertriglyceridemia and cardiac triglyceride accumulation, allowing for metabolic reprogramming of the heart. Our work reveals a beneficial "off-target" effect of fluoxetine, and reveals a protective immunometabolic defense mechanism with therapeutic potential.
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Affiliation(s)
- Robert M Gallant
- Molecular and Systems Physiology Lab, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
- Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA
- Gene Expression Lab, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
| | - Jessica M Snyder
- Department of Comparative Medicine, School of Medicine, University of Washington, Seattle WA
| | - Janelle S Ayres
- Molecular and Systems Physiology Lab, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
- NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA
- Gene Expression Lab, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
- Lead contact
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Hathaway CA, Townsend MK, Conejo-Garcia JR, Fridley BL, Moran Segura C, Nguyen JV, Armaiz-Pena GN, Sasamoto N, Saeed-Vafa D, Terry KL, Kubzansky LD, Tworoger SS. The relationship of lifetime history of depression on the ovarian tumor immune microenvironment. Brain Behav Immun 2023; 114:52-60. [PMID: 37557966 PMCID: PMC10592154 DOI: 10.1016/j.bbi.2023.08.006] [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: 04/02/2023] [Revised: 08/04/2023] [Accepted: 08/06/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND Depression is associated with a higher ovarian cancer risk. Prior work suggests that depression can lead to systemic immune suppression, which could potentially alter the anti-tumor immune response. METHODS We evaluated the association of pre-diagnosis depression with features of the anti-tumor immune response, including T and B cells and immunoglobulins, among women with ovarian tumor tissue collected in three studies, the Nurses' Health Study (NHS; n = 237), NHSII (n = 137) and New England Case-Control Study (NECC; n = 215). Women reporting depressive symptoms above a clinically relevant cut-point, antidepressant use, or physician diagnosis of depression at any time prior to diagnosis of ovarian cancer were considered to have pre-diagnosis depression. Multiplex immunofluorescence was performed on tumor tissue microarrays to measure immune cell infiltration. In pooled analyses, we estimated odds ratios (OR) and 95% confidence intervals (CI) for the positivity of tumor immune cells using a beta-binomial model comparing those with and without depression. We used Bonferroni corrections to adjust for multiple comparisons. RESULTS We observed no statistically significant association between depression status and any immune markers at the Bonferroni corrected p-value of 0.0045; however, several immune markers were significant at a nominal p-value of 0.05. Specifically, there were increased odds of having recently activated cytotoxic (CD3+CD8+CD69+) and exhausted-like T cells (CD3+Lag3+) in tumors of women with vs. without depression (OR = 1.36, 95 %CI = 1.09-1.69 and OR = 1.24, 95 %CI = 1.01-1.53, respectively). Associations were comparable when considering high grade serous tumors only (comparable ORs = 1.33, 95 %CI = 1.05-1.69 and OR = 1.25, 95 %CI = 0.99-1.58, respectively). There were decreased odds of having tumor infiltrating plasma cells (CD138+) in women with vs. without depression (OR = 0.54, 95 %CI = 0.33-0.90), which was similar among high grade serous carcinomas, although not statistically significant. Depression was also related to decreased odds of having naïve and memory B cells (CD20+: OR = 0.54, 95 %CI = 0.30-0.98) and increased odds of IgG (OR = 1.22, 95 %CI = 0.97-1.53) in high grade serous carcinomas. CONCLUSION Our results provide suggestive evidence that depression may influence ovarian cancer outcomes through changes in the tumor immune microenvironment, including increasing T cell activation and exhaustion and reducing antibody-producing B cells. Further studies with clinical measures of depression and larger samples are needed to confirm these results.
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Affiliation(s)
| | - Mary K Townsend
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA
| | | | - Brooke L Fridley
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA
| | - Carlos Moran Segura
- Advanced Analytical and Digital Laboratory, Moffitt Cancer Center, Tampa, FL, USA
| | - Jonathan V Nguyen
- Advanced Analytical and Digital Laboratory, Moffitt Cancer Center, Tampa, FL, USA
| | - Guillermo N Armaiz-Pena
- Department of Basic Sciences, Division of Pharmacology, School of Medicine, Ponce Health Sciences University, Ponce, PR, USA
| | - Naoko Sasamoto
- Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Daryoush Saeed-Vafa
- Advanced Analytical and Digital Laboratory, Moffitt Cancer Center, Tampa, FL, USA; Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, USA
| | - Kathryn L Terry
- Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Laura D Kubzansky
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Shelley S Tworoger
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
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21
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Wong C, Patel S, LaPorta A, Towne F, Gubler KD, Bartone P, Ryznar R. Correlation analysis of salivary cytokines and hormones with resiliency. J Trauma Acute Care Surg 2023; 95:664-671. [PMID: 37332103 PMCID: PMC10637304 DOI: 10.1097/ta.0000000000004026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 03/31/2023] [Accepted: 04/11/2023] [Indexed: 06/20/2023]
Abstract
BACKGROUND Frequent exposure to acute stress increases risk of suicide, posttraumatic stress disorder, and other stress-related disorders. Neuroendocrine and immunologic dysregulation associated with stress may underlie predispositions to psychological disorders and inflammatory disease processes in individuals, such as first-responders and other healthcare professionals, who function in high stress situations. The Hardiness Resilience Gauge (HRG) can be used to psychometrically measure resilience, a psychological modifier of the stress response. Using the HRG alongside salivary biomarker profiling, may help to identify low resilience phenotypes and allow mitigation and early therapeutic interventions. There is a paucity of knowledge regarding biomarkers of resilience. This study aims to evaluate the relationship between factors of resilience with salivary biomarker levels and fluctuations during and following acute stress. METHODS Sixty-three first responders underwent a standardized stress-inducing training exercise, providing salivary samples before (prestress), immediately after (post-stress), and 1 hour after the event (recovery). The HRG was administered before (initial) and after (final) the event. Multiplex ELISA panels quantified 42 cytokines and 6 hormones from the samples, which were analyzed for relationships to psychometric factors of resilience measured by the HRG. RESULTS Several biomarkers correlated with psychological resilience following the acute stress event. The HRG scores correlated ( p < 0.05) with a select set of biomarkers with moderate-to-strong correlations (|r| > 0.3). These included EGF, GROα, PDGFAA, TGFα, VEGFA, interleukin (IL)1Ra, TNFα, IL18, cortisol, FGF2, IL13, IL15, and IL6. Interestingly, fluctuations of EGF, GROα, and PDGFAA in post-stress compared with recovery were positively correlated with factors of resilience, which were negatively correlated from the pre-stress to post-stress period. CONCLUSION This exploratory analysis discovered a small subset of salivary biomarkers that are significantly correlated with acute stress and resilience. Further investigation of their specific roles in acute stress and associations with resiliency phenotypes is warranted.
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Karl T, Schuster A, Stangassinger LM, Stiboller T, Cadamuro J, Oostingh GJ. Factors Affecting SARS-CoV-2 IgG Production after Vaccination and/or Disease: A Large-Scale Seroprevalence Study. Vaccines (Basel) 2023; 11:1615. [PMID: 37897017 PMCID: PMC10611123 DOI: 10.3390/vaccines11101615] [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: 09/19/2023] [Revised: 10/13/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
This study aimed at identifying factors influencing SARS-CoV-2-specific IgG antibody levels after vaccination and/or infection. Between January 2022 and March 2023, 2000 adults (≥18 years, Salzburg, Austria) participated in this population-based seroprevalence study by providing 3 mL of blood to detect SARS-CoV-2-specific IgG antibodies using an anti-SARS-CoV-2 IgG quantitative assay and by completing a self-designed questionnaire including anthropometric factors, vaccination information, and medical history. For 77 of the participants, a time-course study up to 24 weeks post vaccination or quarantine end was performed. Convalescent-only subjects had the lowest median antibody titer (65.6 BAU/mL) compared to vaccinated and hybrid immunized subjects (p-value < 0.0001) The type of vaccine as well as vaccine combinations significantly influenced the levels of SARS-CoV-2 spike-protein-specific IgG, ranging from a median antibody level of 770.5 BAU/mL in subjects who were vaccinated only to 3020.0 BAU/mL in hybrid immunized subjects (p-value < 0.0001). Over time, a significant decline in the levels of neutralizing antibodies was found. Depending on the subpopulation analyzed, further significant influencing factors included sex assigned at birth, disease severity, chronic diseases, and medication. A hybrid immunization resulted in more robust immune responses. Nevertheless, there were multiple other factors impacting these responses. This knowledge should be included in future vaccination strategies and serve as a guide in the development of personalized medicine.
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Affiliation(s)
- Tanja Karl
- Department of Health Sciences, Biomedical Sciences, Salzburg University of Applied Sciences, 5412 Puch/Salzburg, Austria; (A.S.); (L.M.S.); (T.S.); (G.J.O.)
- Research Program of Medical Sciences, Paracelsus Medical University, 5020 Salzburg, Austria
| | - Anja Schuster
- Department of Health Sciences, Biomedical Sciences, Salzburg University of Applied Sciences, 5412 Puch/Salzburg, Austria; (A.S.); (L.M.S.); (T.S.); (G.J.O.)
| | - Lea Maria Stangassinger
- Department of Health Sciences, Biomedical Sciences, Salzburg University of Applied Sciences, 5412 Puch/Salzburg, Austria; (A.S.); (L.M.S.); (T.S.); (G.J.O.)
| | - Tanja Stiboller
- Department of Health Sciences, Biomedical Sciences, Salzburg University of Applied Sciences, 5412 Puch/Salzburg, Austria; (A.S.); (L.M.S.); (T.S.); (G.J.O.)
| | - Janne Cadamuro
- Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, Austria;
| | - Gertie Janneke Oostingh
- Department of Health Sciences, Biomedical Sciences, Salzburg University of Applied Sciences, 5412 Puch/Salzburg, Austria; (A.S.); (L.M.S.); (T.S.); (G.J.O.)
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23
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Speakman S, White K, LaPorta AJ, Payton ME, Gubler KD, Ryznar RJ. Cytokine fluctuation during acute stress is correlated to life trauma. J Trauma Acute Care Surg 2023; 95:535-541. [PMID: 37165473 PMCID: PMC10545070 DOI: 10.1097/ta.0000000000004006] [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: 02/09/2023] [Revised: 03/30/2023] [Accepted: 03/31/2023] [Indexed: 05/12/2023]
Abstract
BACKGROUND Multiple studies have demonstrated that human neurobiology and behavior are inextricably linked to the activity of our immune systems. Trauma is associated with a multitude of immune system changes; reflecting this, posttraumatic stress disorder (PTSD) is often comorbid with immune-related conditions such as autoimmune disorders. To further investigate this phenomenon, we tested our hypothesis that cytokine fluctuations during and after an acute stress response correlates with experienced life trauma. METHODS Using a prospective observational approach, this cohort study measured biomarker profiles in firefighter participants (n = 63), with 9 participants having prior PTSD diagnoses and 54 without prior PTSD diagnoses. In addition, life trauma scores were determined from all participants using the Life Events Checklist 5 (LEC-5) survey. Baseline salivary biomarker concentrations were determined, along with levels immediately before, immediately after, and 1 hour following a standardized stressful training event. Biomarkers measured using these salivary samples included 42 cytokines and 6 steroid and thyroid hormones. The concentrations of these markers were then correlated, using Pearson correlation coefficients, with the participants' LEC-5 scores. t Tests were also performed to compare cytokine values between the populations with and without prior PTSD diagnosis. RESULTS Included in the cytokine panel were interleukin (IL)-8, IL-10, IL-1B, GCSF, IL1-Ra, Groα, IFNa2, PDGFAA, and VEGF, all of which demonstrated positive correlation at various time points in individuals with increased severity of LEC-5 scores (and thus increased experienced life trauma). Concentrations of Groα, PDGFAA, IL1-Ra, IL-1a, Mip1a, IL-1a, IL-6, Mip1b, TNFα, and TGFα were also found to be significantly altered at various time points in participants with prior PTSD diagnoses, demonstrating some overlap with the LEC-5 Pearson correlations. CONCLUSION The results support our hypothesis and demonstrate that LEC-5 scores are indeed significantly correlated to cytokine concentrations and fluctuations surrounding a stress test. LEVEL OF EVIDENCE Diagnostic Tests or Criteria; Level IV.
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Gîlcă-Blanariu GE, Șchiopu CG, Ștefănescu G, Mihai C, Diaconescu S, Afrăsânie VA, Lupu VV, Lupu A, Boloș A, Ștefănescu C. The Intertwining Roads between Psychological Distress and Gut Microbiota in Inflammatory Bowel Disease. Microorganisms 2023; 11:2268. [PMID: 37764111 PMCID: PMC10538137 DOI: 10.3390/microorganisms11092268] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 09/05/2023] [Accepted: 09/07/2023] [Indexed: 09/29/2023] Open
Abstract
Inflammatory bowel disease represents one of the most life-altering gastrointestinal pathologies, with its multifactorial nature and unclear physiopathology. The most relevant clinical forms, ulcerative colitis and Crohn's disease, clinically manifest with mild to severe flares and remission periods that alter the patient's social, familial and professional integration. The chronic inflammatory activity of the intestinal wall determines severe modifications of the local environment, such as dysbiosis, enteric endocrine, nervous and immune system disruptions and intestinal wall permeability changes. These features are part of the gastrointestinal ecosystem that modulates the bottom-to-top signaling to the central nervous system, leading to a neurobiologic imbalance and clinical affective and/or behavioral symptoms. The gut-brain link is a bidirectional pathway and psychological distress can also affect the central nervous system, which will alter the top-to-bottom regulation, leading to possible functional digestive symptoms and local inflammatory responses. In the middle of this neuro-gastrointestinal system, the microbiome is a key player, as its activities offer basic functional support for both relays. The present article presents current scientific information that links the pathophysiology and clinical aspects of inflammatory bowel disease and psychiatric symptomatology through the complex mechanism of the gut-brain axis and the modulatory effects of the gut microbiota.
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Affiliation(s)
| | - Cristina Gabriela Șchiopu
- Department of Psychiatry, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (A.B.); (C.Ș.)
| | - Gabriela Ștefănescu
- Department of Gastroenterology, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (G.-E.G.-B.); (C.M.)
| | - Cătălina Mihai
- Department of Gastroenterology, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (G.-E.G.-B.); (C.M.)
| | - Smaranda Diaconescu
- Department of Pediatrics, University of Medicine Titu Maiorescu, 040441 Bucharest, Romania;
| | | | - Vasile Valeriu Lupu
- Department of Pediatrics, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (V.V.L.)
| | - Ancuța Lupu
- Department of Pediatrics, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (V.V.L.)
| | - Alexandra Boloș
- Department of Psychiatry, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (A.B.); (C.Ș.)
| | - Cristinel Ștefănescu
- Department of Psychiatry, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (A.B.); (C.Ș.)
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Kübler R, Ormel PR, Sommer IEC, Kahn RS, de Witte LD. Gene expression profiling of monocytes in recent-onset schizophrenia. Brain Behav Immun 2023; 111:334-342. [PMID: 37149105 DOI: 10.1016/j.bbi.2023.04.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 04/26/2023] [Accepted: 04/30/2023] [Indexed: 05/08/2023] Open
Abstract
Immune-related mechanisms have been suggested to be involved in schizophrenia. Various studies have shown changes in monocytes isolated from the blood of schizophrenia patients, including changes in monocyte numbers, as well as altered protein and transcript levels of important markers. However, validation of these findings and understanding how these results are related to immune-related changes in the brain and schizophrenia genetic risk factors, is limited. The goal of this study was to better understand changes observed in monocytes of patients with early-onset schizophrenia. Using RNA sequencing, we analyzed gene expression profiles of monocytes isolated from twenty patients with early-onset schizophrenia and seventeen healthy controls. We validated expression changes of 7 out of 29 genes that were differentially expressed in previous studies including TNFAIP3, DUSP2, and IL6. At a transcriptome-wide level, we found 99 differentially expressed genes. Effect sizes of differentially expressed genes were moderately correlated with differential expression in brain tissue (Pearson's r = 0.49). Upregulated genes were enriched for genes in NF-κB and LPS signaling pathways. Downregulated genes were enriched for glucocorticoid response pathways. These pathways have been implicated in schizophrenia before and play a role in regulating the activation of myeloid cells. Interestingly, they are also involved in several non-inflammatory processes in the central nervous system, such as neurogenesis and neurotransmission. Future studies are needed to better understand how dysregulation of the NF-κB and glucocorticoid pathways affects inflammatory and non-inflammatory processes in schizophrenia. The fact that dysregulation of these pathways is also seen in brain tissue, provides potential possibilities for biomarker development.
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Affiliation(s)
- Raphael Kübler
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Paul R Ormel
- Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands
| | - Iris E C Sommer
- Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands; Department of Neuroscience, University Medical Center Groningen, Groningen, the Netherlands
| | - René S Kahn
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands
| | - Lot D de Witte
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.
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Boustany A, Onwuzo S, Zeid HKA, Almomani A, Asaad I. ANTIDEPRESSANT MEDICATIONS ARE ASSOCIATED WITH INCREASED RISK OF HOSPITAL-ACQUIRED CLOSTRIDIOIDES DIFFICILE INFECTION: A POPULATION-BASED STUDY. ARQUIVOS DE GASTROENTEROLOGIA 2023; 60:309-314. [PMID: 37792759 DOI: 10.1590/s0004-2803.230302023-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 06/20/2023] [Indexed: 10/06/2023]
Abstract
WHAT IS ALREADY KNOWN •The rate and severity of Clostridioides difficile infection (CDI) has increased throughout North America, the United Kingdom, and Europe. •Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. What are the new findings: •The risk of Clostridioides difficile infection is higher in patients who are on mirtazapine, nortriptyline, or trazodone. •The prevalence rate of Clostridioides difficile infection in patients who were using antidepressant medications and the ones who did not, increased with age. Background - During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications.Methods - Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results - The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion - In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.
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Affiliation(s)
- Antoine Boustany
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, United States
| | - Somtochukwu Onwuzo
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, United States
| | | | - Ashraf Almomani
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, United States
| | - Imad Asaad
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, United States
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27
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Romano GL, Gozzo L, Maurel OM, Di Martino S, Riolo V, Micale V, Drago F, Bucolo C. Fluoxetine Protects Retinal Ischemic Damage in Mice. Pharmaceutics 2023; 15:pharmaceutics15051370. [PMID: 37242611 DOI: 10.3390/pharmaceutics15051370] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 04/25/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
BACKGROUND To evaluate the neuroprotective effect of the topical ocular administration of fluoxetine (FLX) in a mouse model of acute retinal damage. METHODS Ocular ischemia/reperfusion (I/R) injury in C57BL/6J mice was used to elicit retinal damage. Mice were divided into three groups: control group, I/R group, and I/R group treated with topical FLX. A pattern electroretinogram (PERG) was used as a sensitive measure of retinal ganglion cell (RGC) function. Finally, we analyzed the retinal mRNA expression of inflammatory markers (IL-6, TNF-α, Iba-1, IL-1β, and S100β) through Digital Droplet PCR. RESULTS PERG amplitude values were significantly (p < 0.05) higher in the I/R-FLX group compared to the I/R group, whereas PERG latency values were significantly (p < 0.05) reduced in I/R-FLX-treated mice compared to the I/R group. Retinal inflammatory markers increased significantly (p < 0.05) after I/R injury. FLX treatment was able to significantly (p < 0.05) attenuate the expression of inflammatory markers after I/R damage. CONCLUSIONS Topical treatment with FLX was effective in counteracting the damage of RGCs and preserving retinal function. Moreover, FLX treatment attenuates the production of pro-inflammatory molecules elicited by retinal I/R damage. Further studies need to be performed to support the use of FLX as neuroprotective agent in retinal degenerative diseases.
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Affiliation(s)
- Giovanni Luca Romano
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95100 Catania, Italy
- Center for Research in Ocular Pharmacology-CERFO, University of Catania, 95100 Catania, Italy
| | - Lucia Gozzo
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95100 Catania, Italy
| | - Oriana Maria Maurel
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95100 Catania, Italy
| | - Serena Di Martino
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95100 Catania, Italy
| | - Valentina Riolo
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95100 Catania, Italy
| | - Vincenzo Micale
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95100 Catania, Italy
| | - Filippo Drago
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95100 Catania, Italy
- Center for Research in Ocular Pharmacology-CERFO, University of Catania, 95100 Catania, Italy
| | - Claudio Bucolo
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95100 Catania, Italy
- Center for Research in Ocular Pharmacology-CERFO, University of Catania, 95100 Catania, Italy
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Önal HT, Yetkin D, Ayaz F. Escitalopram's inflammatory effect on the mammalian macrophages and its intracellular mechanism of action. Prog Neuropsychopharmacol Biol Psychiatry 2023; 125:110762. [PMID: 37031947 DOI: 10.1016/j.pnpbp.2023.110762] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 03/29/2023] [Accepted: 04/06/2023] [Indexed: 04/11/2023]
Abstract
The majority of patients with depression are treated with antidepressant drugs that are in the serotonin reuptake inhibitor (SSRI) group. Different studies have been conducted on the effect of treatment with antidepressants on the level of pro-inflammatory cytokines. There have been studies on the effects of escitalopram, an SSRI group antidepressant, on the pro-inflammatory cytokine levels both in vivo and in vitro. The results of these studies do not overlap and therefore the escitalopram's effect on the immune system should be studied in more depth. In this study, we aimed to examine, in detail, the cytokine production amount by escitalopram treatment of the J774.2 macrophage cells and its intracellular mechanism of action by examining the PI3K and p38 pathways. As a result of our study, we observed that Escitalopram caused a significant increase in TNF-α, IL-6, and GM-CSF levels in mammalian macrophage cells, but did not induce IL-12p40 production. We observed that the p38 and PI3K pathways play a role in inflammation in the presence of Escitalopram.
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Affiliation(s)
- Harika Topal Önal
- Medical Laboratory Techniques, Vocational School of Health Services, Toros University, Mersin, Turkey.
| | - Derya Yetkin
- Mersin University Advanced Technology Education Research and Application Center, Mersin, Turkey
| | - Furkan Ayaz
- Science Institute, Faculty of Arts and Science, Department of Biotechnology, Mersin University, Mersin, Turkey; Mersin University Biotechnology Research and Application Center, Mersin University, Mersin, Turkey.
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Markov DD, Dolotov OV, Grivennikov IA. The Melanocortin System: A Promising Target for the Development of New Antidepressant Drugs. Int J Mol Sci 2023; 24:ijms24076664. [PMID: 37047638 PMCID: PMC10094937 DOI: 10.3390/ijms24076664] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/27/2023] [Accepted: 03/30/2023] [Indexed: 04/05/2023] Open
Abstract
Major depression is one of the most prevalent mental disorders, causing significant human suffering and socioeconomic loss. Since conventional antidepressants are not sufficiently effective, there is an urgent need to develop new antidepressant medications. Despite marked advances in the neurobiology of depression, the etiology and pathophysiology of this disease remain poorly understood. Classical and newer hypotheses of depression suggest that an imbalance of brain monoamines, dysregulation of the hypothalamic-pituitary-adrenal axis (HPAA) and immune system, or impaired hippocampal neurogenesis and neurotrophic factors pathways are cause of depression. It is assumed that conventional antidepressants improve these closely related disturbances. The purpose of this review was to discuss the possibility of affecting these disturbances by targeting the melanocortin system, which includes adrenocorticotropic hormone-activated receptors and their peptide ligands (melanocortins). The melanocortin system is involved in the regulation of various processes in the brain and periphery. Melanocortins, including peripherally administered non-corticotropic agonists, regulate HPAA activity, exhibit anti-inflammatory effects, stimulate the levels of neurotrophic factors, and enhance hippocampal neurogenesis and neurotransmission. Therefore, endogenous melanocortins and their analogs are able to complexly affect the functioning of those body’s systems that are closely related to depression and the effects of antidepressants, thereby demonstrating a promising antidepressant potential.
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Affiliation(s)
- Dmitrii D. Markov
- National Research Center “Kurchatov Institute”, Kurchatov Sq. 2, 123182 Moscow, Russia
| | - Oleg V. Dolotov
- National Research Center “Kurchatov Institute”, Kurchatov Sq. 2, 123182 Moscow, Russia
- Faculty of Biology, Lomonosov Moscow State University, Leninskie Gory, 119234 Moscow, Russia
| | - Igor A. Grivennikov
- National Research Center “Kurchatov Institute”, Kurchatov Sq. 2, 123182 Moscow, Russia
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30
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Guillaume M, Endomba FT, Dornier A, Chauvet-Gelinier JC. Association Between Depression Before Hematopoietic Stem Cell Transplantation and Posttransplant Survival: A Systematic Review and Meta-analysis. J Acad Consult Liaison Psychiatry 2023; 64:166-176. [PMID: 36535378 DOI: 10.1016/j.jaclp.2022.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 12/06/2022] [Accepted: 12/11/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND Depressive symptoms are often found in patients undergoing hematopoietic stem cell transplantation (HSCT). However, the impact of depression on overall survival and other outcomes after HSCT has not been systematically reviewed. OBJECTIVE The objective of this review was to determine if depression before HSCT is associated with poor posttransplant outcomes. METHODS We performed a systematic research, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM) guidelines based on several databases (MEDLINE, EMBase, and PsycINFO) for cohort studies on adults undergoing HSCT, comparing overall survival or other outcomes (length of aplasia, infectious complications) between patients with depressive symptoms and controls. For studies reporting overall survival hazard ratios, we conducted a meta-analysis by calculating a 95% confidence interval hazard ratios, and we assessed heterogeneity with the I2 statistic. Study quality was assessed using the Newcastle-Ottawa Quality Assessment scale for cohort studies. RESULTS A total of 18 studies were included in the systematic review (22,235 participants) and 8 in the meta-analysis. There were a variety of depression screening tools, the Hospital Anxiety and Depression Scale (HADS) being the most reported questionnaire. A significant association between depression and overall survival was found in 9 studies, whereas 8 studies shown no association. Depression tended to have an impact on length of aplasia and infectious complications. In the meta-analysis, depression was found to impact significantly overall survival after HSCT with a hazard ratio = 1.07 (95% confidence interval 1.03-1.11). A publication bias was found in the meta-analysis. CONCLUSION Depression seems to have a significant impact on post-HSCT survival and on length of aplasia. A systematic screening of depression before HSCT should be considered, with validated tools such as HADS. Future research needs to be done to measure the impact of depression on HSCT response and understand its physiopathology.
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Affiliation(s)
| | | | - Alexandre Dornier
- Department of Psychiatry, University Hospital of Dijon, Dijon, France
| | - Jean-Christophe Chauvet-Gelinier
- Department of Psychiatry, University Hospital of Dijon, Dijon, France; INSERM LNC UMR1231, University of Burgundy, Dijon, France
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31
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The effect of chronic stress on behaviors, inflammation and lymphocyte subtypes in male and female rats. Behav Brain Res 2023; 439:114220. [PMID: 36414104 DOI: 10.1016/j.bbr.2022.114220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 11/05/2022] [Accepted: 11/18/2022] [Indexed: 11/21/2022]
Abstract
Excessively released proinflammatory mediators from activated macrophages and lymphocytes may contribute to the etiology of depression. However, the relationship between lymphocytes and depression is not fully understood. Although women have higher depression risk than men, sex/gender differences in psychoneuroimmunological mechanisms are still unclear. To explore these two questions, chronic unpredictable mild stress (CUMS) was used to evaluate the changes in behaviors, inflammation and lymphocyte subtypes in adult male and female Wistar rats. Results show that CUMS increased anhedonia and anxiety-like behaviors, along with increased serum corticosterone, hippocampal pro-inflammatory factors, CD11b, IFN-γ, IL-6 and IL-17, but decreased CD4, CD25, CD4/CD8 ratio, GFAP, 5-hydroxytryptamine (5-HT) and NE concentrations, regardless of sex. There was no positive correlation between sucrose preference and blood CD4/CD8 ratio, but a positive correlation between sucrose preference and spleen CD25, sucrose preference and neurotransmitters (NE and 5-HT), spleen CD25 and serum TGF-β1/IL-6 ratio were found, regardless of sex. Females presented higher basal locomotion, blood CD4, CD4/CD8 ratio, serum corticosteroid and IL-6 concentrations, but lower hippocampal norepinephrine (NE) than males. Although CUMS didn't induce significant sex differences, females presented more changes in CD4 and CD8 lymphocytes than male rats. CUMS caused abnormalities in corticosteroid, lymphocytes, cytokines and neurotransmitters, which might be the precursors for inducing depression-like behaviors in both sexes.
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Sidky H, Sahner DK, Girvin AT, Hotaling N, Michael SG, Gersing K. Assessing the Effect of Selective Serotonin Reuptake Inhibitors in the Prevention of Post-Acute Sequelae of COVID-19. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2022.11.09.22282142. [PMID: 36380766 PMCID: PMC9665345 DOI: 10.1101/2022.11.09.22282142] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Importance Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties and therefore may be postulated to be of benefit in patients with PASC, although clinical trial data are lacking. Objectives The main objective was to evaluate whether SSRIs with agonist activity at the sigma-1 receptor lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. A secondary objective was to determine whether potential benefit could be traced to sigma-1 agonism by evaluating the risk of PASC among recipients of SSRIs that are not S1R agonists. Design Retrospective study leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C), a large centralized multi-institutional de-identified EHR database. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code to more comprehensively identify patients likely to have the condition, since the ICD code has come into wide-spread use only recently. Setting Population-based study at US medical centers. Participants Adults (≥ 18 years of age) with a confirmed COVID-19 diagnosis date between October 1, 2021 and April 7, 2022 and at least one follow up visit 45 days post-diagnosis. Of the 17 933 patients identified, 2021 were exposed at baseline to a S1R agonist SSRI, 1328 to a non-S1R agonist SSRI, and 14 584 to neither. Exposures Exposure at baseline (at or prior to COVID-19 diagnosis) to an SSRI with documented or presumed agonist activity at the S1R (fluvoxamine, fluoxetine, escitalopram, or citalopram), an SSRI without agonist activity at S1R (sertraline, an antagonist, or paroxetine, which does not appreciably bind to the S1R), or none of these agents. Main Outcome and Measurement Development of PASC based on a previously validated XGBoost-trained algorithm. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed. Results A 26% reduction in the RR of PASC (0.74 [95% CI, 0.63-0.88]; P = 5 × 10-4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 25% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.75 [95% CI, 0.62 - 0.90]; P = 0.003) compared to SSRI unexposed patients. Conclusions and Relevance SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC. Future prospective studies are warranted.
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Affiliation(s)
- Hythem Sidky
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD
| | - David K. Sahner
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD
| | | | - Nathan Hotaling
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD
| | - Sam G. Michael
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD
| | - Ken Gersing
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD
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Rossi GN, Hallak JEC, Baker G, Dursun SM, Dos Santos RG. The effects of ketamine and classic hallucinogens on neurotrophic and inflammatory markers in unipolar treatment-resistant depression: a systematic review of clinical trials. Eur Arch Psychiatry Clin Neurosci 2023; 273:129-155. [PMID: 35829812 DOI: 10.1007/s00406-022-01460-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/27/2022] [Indexed: 11/03/2022]
Abstract
Although results are still preliminary, ketamine and classical hallucinogens have shown promise in recent years as novel, fast-acting antidepressants, especially for the treatment of unipolar treatment-resistant depression (TRD). Depression also seems to be related to abnormal levels of peripheral inflammatory and neurotrophic biomarkers, which may one day help to diagnose of this disorder. In this context, this systematic review of clinical trials evaluated the current evidence that relates the antidepressant effects of ketamine and classical hallucinogens on TRD with changes in inflammatory and neurotrophic biomarkers. Twelve studies were found (n = 587), 2 with oral ayahuasca (1 mL/kg) and 10 with ketamine (mostly intravenous 0.5 mg/kg) administration. Results for all biomarkers assessed were contradictory and thus inconclusive. Randomized controlled trials with bigger samples and higher statistical power are warranted to clarify if peripheral biomarkers can confidently be used to indicate and measure ketamine's and classical hallucinogens' antidepressant effect. The PROSPERO ID for this study is CRD42021249089.
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Affiliation(s)
- Giordano Novak Rossi
- Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Jaime E C Hallak
- Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.,National Institute for Translational Medicine (INCT-TM), CNPq, São Paulo, Brazil.,Department of Psychiatry (Neurochemical Research Unit) and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada
| | - Glen Baker
- National Institute for Translational Medicine (INCT-TM), CNPq, São Paulo, Brazil.,Department of Psychiatry (Neurochemical Research Unit) and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada
| | - Serdar M Dursun
- National Institute for Translational Medicine (INCT-TM), CNPq, São Paulo, Brazil.,Department of Psychiatry (Neurochemical Research Unit) and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada
| | - Rafael G Dos Santos
- Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil. .,National Institute for Translational Medicine (INCT-TM), CNPq, São Paulo, Brazil. .,Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Hospital das Clínicas, Terceiro Andar, Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, Brazil.
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Donoso F, Cryan JF, Olavarría-Ramírez L, Nolan YM, Clarke G. Inflammation, Lifestyle Factors, and the Microbiome-Gut-Brain Axis: Relevance to Depression and Antidepressant Action. Clin Pharmacol Ther 2023; 113:246-259. [PMID: 35278334 PMCID: PMC10084001 DOI: 10.1002/cpt.2581] [Citation(s) in RCA: 66] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 03/08/2022] [Indexed: 01/27/2023]
Abstract
Depression is considered a major public health concern, where existing pharmacological treatments are not equally effective across all patients. The pathogenesis of depression involves the interaction of complex biological components, such as the immune system and the microbiota-gut-brain axis. Adjunctive lifestyle-oriented approaches for depression, including physical exercise and special diets are promising therapeutic options when combined with traditional antidepressants. However, the mechanisms of action of these strategies are incompletely understood. Accumulating evidence suggests that physical exercise and specific dietary regimens can modulate both the immune system and gut microbiota composition. Here, we review the current information about the strategies to alleviate depression and their crosstalk with both inflammatory mechanisms and the gut microbiome. We further discuss the role of the microbiota-gut-brain axis as a possible mediator for the adjunctive therapies for depression through inflammatory mechanisms. Finally, we review existing and future adjunctive strategies to manipulate the gut microbiota with potential use for depression, including physical exercise, dietary interventions, prebiotics/probiotics, and fecal microbiota transplantation.
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Affiliation(s)
- Francisco Donoso
- Alimentary Pharmabiotic Centre Microbiome Ireland, University College Cork, Cork, Ireland
| | - John F Cryan
- Alimentary Pharmabiotic Centre Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland
| | | | - Yvonne M Nolan
- Alimentary Pharmabiotic Centre Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland
| | - Gerard Clarke
- Alimentary Pharmabiotic Centre Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Psychiatry & Neurobehavioural Science, University College Cork, Cork, Ireland
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Zengeler KE, Shapiro DA, Bruch KR, Lammert CR, Ennerfelt H, Lukens JR. SSRI treatment modifies the effects of maternal inflammation on in utero physiology and offspring neurobiology. Brain Behav Immun 2023; 108:80-97. [PMID: 36343752 PMCID: PMC10291741 DOI: 10.1016/j.bbi.2022.10.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 10/17/2022] [Accepted: 10/29/2022] [Indexed: 11/06/2022] Open
Abstract
Perturbations to the in utero environment can dramatically change the trajectory of offspring neurodevelopment. Insults commonly encountered in modern human life such as infection, toxins, high-fat diet, prescription medications, and others are increasingly linked to behavioral alterations in prenatally-exposed offspring. While appreciation is expanding for the potential consequence that these triggers can have on embryo development, there is a paucity of information concerning how the crucial maternal-fetal interface (MFI) responds to these various insults and how it may relate to changes in offspring neurodevelopment. Here, we found that the MFI responds both to an inflammatory state and altered serotonergic tone in pregnant mice. Maternal immune activation (MIA) triggered an acute inflammatory response in the MFI dominated by interferon signaling that came at the expense of ordinary development-related transcriptional programs. The major MFI compartments, the decidua and the placenta, each responded in distinct manners to MIA. MFIs exposed to MIA were also found to have disrupted sex-specific gene expression and heightened serotonin levels. We found that offspring exposed to MIA had sex-biased behavioral changes and that microglia were not transcriptionally impacted. Moreover, the combination of maternal inflammation in the presence of pharmacologic inhibition of serotonin reuptake further transformed MFI physiology and offspring neurobiology, impacting immune and serotonin signaling pathways alike. In all, these findings highlight the complexities of evaluating diverse environmental impacts on placental physiology and neurodevelopment.
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Affiliation(s)
- Kristine E Zengeler
- Center for Brain Immunology and Glia (BIG), Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA; Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22908, USA; Cell and Molecular Biology Graduate Training Program, University of Virginia, Charlottesville, VA 22908, USA.
| | - Daniel A Shapiro
- Center for Brain Immunology and Glia (BIG), Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA
| | - Katherine R Bruch
- Center for Brain Immunology and Glia (BIG), Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA
| | - Catherine R Lammert
- Center for Brain Immunology and Glia (BIG), Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA; Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22908, USA
| | - Hannah Ennerfelt
- Center for Brain Immunology and Glia (BIG), Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA; Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22908, USA; Cell and Molecular Biology Graduate Training Program, University of Virginia, Charlottesville, VA 22908, USA
| | - John R Lukens
- Center for Brain Immunology and Glia (BIG), Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA; Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22908, USA; Cell and Molecular Biology Graduate Training Program, University of Virginia, Charlottesville, VA 22908, USA.
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Amendt T, Tybulewicz VLJ. Antidepressants cheer up hepatic B1 B cells: Hope for the treatment of autoimmune liver diseases? Front Immunol 2023; 13:1083173. [PMID: 36733387 PMCID: PMC9887017 DOI: 10.3389/fimmu.2022.1083173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 12/16/2022] [Indexed: 01/18/2023] Open
Affiliation(s)
- Timm Amendt
- Institute of Immunology, Ulm University, Ulm, Germany,*Correspondence: Timm Amendt,
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Puangsri P, Jinanarong V, Ninla-Aesong P. Impact of antidepressant treatment on complete blood count parameters and inflammatory ratios in adolescents with major depressive disorder. J Psychiatr Res 2023; 157:26-35. [PMID: 36436425 DOI: 10.1016/j.jpsychires.2022.11.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 10/23/2022] [Accepted: 11/14/2022] [Indexed: 11/18/2022]
Abstract
Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are novel biomarkers of systemic inflammation in depression. This study aims to examines the impact of selective serotonin reuptake inhibitor (SSRI) treatment on complete blood count (CBC) parameters and inflammatory ratios in major depressive disorder (MDD). CBC parameters and inflammatory ratios were examined in a total of 45 drug-naive adolescents with MDD and were compared before and after SSRI treatment for 12 weeks and between responders and nonresponders. Following SSRI treatment in MDD, the red blood cell (RBC) count, hematocrit, and red cell distribution width (RDW) significantly increased. Hemoglobin tended to increase. The MCV, MCH, and MCHC values decreased significantly. White blood cell count, neutrophil percentage, monocyte count, and monocyte and basophil percentages decreased significantly. The percentage of lymphocytes significantly increased. The MLR decreased, whereas the NLR tended to decrease. Platelet count and PLR did not change significantly. A higher platelet count at baseline has been associated with non-response to SSRI treatment in patients with MDD. SSRI treatment increased RBC count, hematocrit, RDW, and lymphocyte percentage, and reduced MLR, and neutrophil and monocyte percentages in responders MDD. We suggest higher platelet counts at baseline as a potential predictor of nonresponders.
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Affiliation(s)
- Pavarud Puangsri
- Department of Clinical Science, School of Medicine, Walailak University, Nakhon Si Thammarat, Thailand.
| | - Vinn Jinanarong
- Prachuap Khiri Khan Hospital, Prachuap Khiri Khan, Thailand.
| | - Putrada Ninla-Aesong
- Department of Preclinical Science, School of Medicine, Walailak University, Nakhon Si Thammarat, Thailand.
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Nakhaee H, Zangiabadian M, Bayati R, Rahmanian M, Ghaffari Jolfayi A, Rakhshanderou S. The effect of antidepressants on the severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis. PLoS One 2022; 17:e0267423. [PMID: 36201406 PMCID: PMC9536564 DOI: 10.1371/journal.pone.0267423] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 09/21/2022] [Indexed: 11/20/2022] Open
Abstract
INTRODUCTION Clinical Depression and the subsequent low immunity is a comorbidity that can act as a risk factor for the severity of COVID-19 cases. Antidepressants such as Selective serotonin reuptake inhibitor and Serotonin-norepinephrine reuptake inhibitors are associated with immune-modulatory effects, which dismiss inflammatory responses and reduce lung tissue damage. The current systematic review and meta-analysis aims to evaluate the effect of antidepressant drugs on the prognosis and severity of COVID-19 in hospitalized patients. METHODS A systematic search was carried out in PubMed/Medline, EMBASE, and Scopus up to June 14, 2022. The following keywords were used: "COVID-19", "SARS-CoV-2", "2019-nCoV", "SSRI", "SNRI", "TCA", "MAOI", and "Antidepressant". A fixed or random-effect model assessed the pooled risk ratio (RR) with 95% CI. We considered P < 0.05 as statistically significant for publication bias. Data were analyzed by Comprehensive Meta-Analysis software, Version 2.0 (Biostat, Englewood, NJ). RESULTS Fourteen studies were included in our systematic review. Five of them were experimental with 2350, and nine of them were observational with 290,950 participants. Eight out of fourteen articles revealed the effect of antidepressants on reducing the severity of COVID-19. Selective serotonin reuptake inhibitors drugs, including Fluvoxamine, Escitalopram, Fluoxetine, and Paroxetine, and among the Serotonin-norepinephrine inhibitors medications Venlafaxine, are reasonably associated with reduced risk of intubation or death. Five studies showed no significant effect, and only one high risk of bias article showed the negative effect of antidepressants on the prognosis of Covid-19. The meta-analysis of clinical trials showed that fluvoxamine could significantly decrease the severity outcomes of COVID-19 (RR: 0.763; 95% CI: 0.602-0.966, I2: 0.0). FINDINGS Most evidence supports that the use of antidepressant medications, mainly Fluvoxamine, may decrease the severity and improve the outcome in hospitalized patients with SARS-CoV-2. Some studies showed contradictory findings regarding the effects of antidepressants on the severity of COVID-19. Further clinical trials should be conducted to clarify the effects of antidepressants on the severity of COVID-19.
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Affiliation(s)
- Hosein Nakhaee
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Moein Zangiabadian
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Bayati
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Rahmanian
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Ghaffari Jolfayi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sakineh Rakhshanderou
- Environmental and Occupational Hazards Control Research Center, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Mustafa G, Zia-ur-Rehman M, Sumrra SH, Ashfaq M, Zafar W, Ashfaq M. A critical review on recent trends on pharmacological applications of pyrazolone endowed derivatives. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2022.133044] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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40
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Spencer HF, Berman RY, Boese M, Zhang M, Kim SY, Radford KD, Choi KH. Effects of an intravenous ketamine infusion on inflammatory cytokine levels in male and female Sprague-Dawley rats. J Neuroinflammation 2022; 19:75. [PMID: 35379262 PMCID: PMC8981848 DOI: 10.1186/s12974-022-02434-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 03/20/2022] [Indexed: 12/29/2022] Open
Abstract
Background Ketamine, a multimodal dissociative anesthetic drug, is widely used as an analgesic following traumatic injury. Although ketamine may produce anti-inflammatory effects when administered after injury, the immunomodulatory properties of intravenous (IV) ketamine in a non-inflammatory condition are unclear. In addition, most preclinical studies use an intraperitoneal (IP) injection of ketamine, which limits its clinical translation as patients usually receive an IV ketamine infusion after injury. Methods Here, we administered sub-anesthetic doses of a single IV ketamine infusion (0, 10, or 40 mg/kg) to male and female Sprague–Dawley rats over a 2-h period. We collected blood samples at 2- and 4-h post-ketamine infusion to determine plasma inflammatory cytokine levels using multiplex immunoassays. Results The 10 mg/kg ketamine infusion reduced spontaneous locomotor activity in male and female rats, while the 40 mg/kg infusion stimulated activity in female, but not male, rats. The IV ketamine infusion produced dose-dependent and sex-specific effects on plasma inflammatory cytokine levels. A ketamine infusion reduced KC/GRO and tumor necrosis factor alpha (TNF-α) levels in both male and female rats, interleukin-6 (IL-6) levels in female rats, and interleukin-10 (IL-10) levels in male rats. However, most cytokine levels returned to control levels at 4-h post-infusion, except for IL-6 levels in male rats and TNF-α levels in female rats, indicating a different trajectory of certain cytokine changes over time following ketamine administration. Conclusions The current findings suggest that sub-anesthetic doses of an IV ketamine infusion may produce sex-related differences in the effects on peripheral inflammatory markers in rodents, and further research is warranted to determine potential therapeutic effects of an IV ketamine infusion in an inflammatory condition.
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Affiliation(s)
- Haley F Spencer
- Program in Neuroscience, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.,Center for the Study of Traumatic Stress, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA
| | - Rina Y Berman
- Center for the Study of Traumatic Stress, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA
| | - Martin Boese
- Daniel K. Inouye Graduate School of Nursing, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA
| | - Michael Zhang
- Center for the Study of Traumatic Stress, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA
| | - Sharon Y Kim
- Program in Neuroscience, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA
| | - Kennett D Radford
- Daniel K. Inouye Graduate School of Nursing, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA
| | - Kwang H Choi
- Program in Neuroscience, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. .,Center for the Study of Traumatic Stress, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. .,Daniel K. Inouye Graduate School of Nursing, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. .,Department of Psychiatry, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
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Abstract
BACKGROUND Recent studies have suggested that microglial activation plays a key role in the pathogenesis of depression. In fact, neuroinflammation is associated with a phenotypic change of microglia, consisting of morphological differences, increased release of cytokines and oxidative stress products, which may contribute to the development and maintenance of depression. Antidepressants, including selective serotonin re-uptake inhibitors and serotonin-norepinephrine reuptake inhibitors, have been shown to act on the immune and oxidative stress mechanisms commonly found to be disrupted in depression. Thus, the inhibition of microglial activation may be one of the mechanisms through which they exert an antidepressant action. AIM This is the first review summarising in vitro and ex vivo studies investigating the effects of different classes of antidepressants on microglia activation, by examining cellular changes and/or via measuring the production of immune and/or oxidative stress signalling molecules, in microglia models of neuroinflammation with either lipopolysaccharide (LPS) or cytokines. A total of 23 studies were identified, 18 using LPS stimulation and 5 using cytokines stimulation. RESULTS Overall, the studies show that antidepressants, such as selective serotonin re-uptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors and tricyclic antidepressants prevented microglial activation, including reduced microglial reactivity and decreased immune and oxidative stress products, in both models. However, specific antidepressants, such as bupropion and agomelatine did not prevent interferon-gamma (IFN-γ)-induced microglial activation; and for other antidepressants, including phenelzine, venlafaxine and sertraline, the results of different studies were inconsistent. CONCLUSIONS Overall, results summarised in this review support the hypothesis that the action of at least certain classes of antidepressants may involve regulation of microglial activation, especially when in presence of increased levels of inflammation.
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Affiliation(s)
- Nicole Mariani
- Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - James Everson
- Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Carmine M Pariante
- Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Alessandra Borsini
- Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
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Caruso G, Grasso M, Fidilio A, Torrisi SA, Musso N, Geraci F, Tropea MR, Privitera A, Tascedda F, Puzzo D, Salomone S, Drago F, Leggio GM, Caraci F. Antioxidant Activity of Fluoxetine and Vortioxetine in a Non-Transgenic Animal Model of Alzheimer's Disease. Front Pharmacol 2022; 12:809541. [PMID: 35002742 PMCID: PMC8740153 DOI: 10.3389/fphar.2021.809541] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 11/17/2021] [Indexed: 12/27/2022] Open
Abstract
Depression is a risk factor for the development of Alzheimer’s disease (AD). A neurobiological and clinical continuum exists between AD and depression, with neuroinflammation and oxidative stress being involved in both diseases. Second-generation antidepressants, in particular selective serotonin reuptake inhibitors (SSRIs), are currently investigated as neuroprotective drugs in AD. By employing a non-transgenic AD model, obtained by intracerebroventricular (i.c.v.) injection of amyloid-β (Aβ) oligomers in 2-month-old C57BL/6 mice, we recently demonstrated that the SSRI fluoxetine (FLX) and the multimodal antidepressant vortioxetine (VTX) reversed the depressive-like phenotype and memory deficits induced by Aβ oligomers rescuing the levels of transforming growth factor-β1 (TGF-β1). Aim of our study was to test FLX and VTX for their ability to prevent oxidative stress in the hippocampus of Aβ-injected mice, a brain area strongly affected in both depression and AD. The long-term intraperitoneal (i.p.) administration of FLX (10 mg/kg) or VTX (5 and 10 mg/kg) for 24 days, starting 7 days before Aβ injection, was able to prevent the over-expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase 2 (Nox2) induced by Aβ oligomers. Antidepressant pre-treatment was also able to rescue the mRNA expression of glutathione peroxidase 1 (Gpx1) antioxidant enzyme. FLX and VTX also prevented Aβ-induced neurodegeneration in mixed neuronal cultures treated with Aβ oligomers. Our data represent the first evidence that the long-term treatment with the antidepressants FLX or VTX can prevent the oxidative stress phenomena related to the cognitive deficits and depressive-like phenotype observed in a non-transgenic animal model of AD.
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Affiliation(s)
- Giuseppe Caruso
- Department of Drug and Health Sciences, University of Catania, Catania, Italy
| | - Margherita Grasso
- Department of Drug and Health Sciences, University of Catania, Catania, Italy.,Oasi Research Institute-IRCCS, Troina, Italy
| | - Annamaria Fidilio
- Department of Drug and Health Sciences, University of Catania, Catania, Italy.,Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | | | - Nicolò Musso
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Federica Geraci
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Maria Rosaria Tropea
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Anna Privitera
- Department of Drug and Health Sciences, University of Catania, Catania, Italy
| | - Fabio Tascedda
- Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy.,Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Daniela Puzzo
- Oasi Research Institute-IRCCS, Troina, Italy.,Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Salvatore Salomone
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Filippo Drago
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Gian Marco Leggio
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Filippo Caraci
- Department of Drug and Health Sciences, University of Catania, Catania, Italy.,Oasi Research Institute-IRCCS, Troina, Italy
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Ketamine used in the therapy of depressive disorders impacts protein profile, proliferation rate, and phagocytosis resistance of enterococci. POSTEP HIG MED DOSW 2022. [DOI: 10.2478/ahem-2022-0047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Abstract
Introduction
A low concentration of ketamine is used to cause an anti-depressive effect. The mechanism of ketamine's action in depression is believed to result, among others, from its anti-inflammatory activity. Despite the fact that only high concentrations of ketamine inhibit bacterial growth, it is clear that even a sub-inhibitory concentration of chemicals may change bacterial properties. Considering the above, in the current study we aimed to evaluate the in vitro influence of ketamine on proliferation of enterococci and their interactions with monocytes.
Materials and Methods
The studied strains were isolated as etiological agents of infection at Medical University of Gdansk. The proliferation and metabolic activity were determined using the FACSVerse flow cytometer after addition of CFDA-SE to bacterial suspension. For the determination of phagocytosis resistance, THP-1 human monocytes cell line was used. Suspension of monocytes which engulfed CFDA-SE–stained bacteria was then stained with propidium iodide to evaluate cytotoxicity of enterococci.
Results
The result of the study showed unexpected response of bacterial cells to ketamine at an early stage of culture. In 57.7% of strains, both proliferation rate and metabolic activity were boosted. This group of strains was also less susceptible to phagocytosis than in culture without ketamine. Different response of isolates to ketamine was also visible in changes of proteins’ profile determined by MALDI-TOF.
Conclusions
The analysis of bacteria at an early stage in the growth curve demonstrated the bacterial diversity in response to ketamine and let us set the hypothesis that microbiome susceptibility to ketamine may be one of the elements which should be taken into consideration when planning the successful pharmacotherapy of depression
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Vargas-Schaffer G, Steverman A, Potvin V. Monitoring Pharmacological Treatment in Patients With Chronic Noncancer Pain. Cureus 2021; 13:e20358. [PMID: 34912657 PMCID: PMC8666110 DOI: 10.7759/cureus.20358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/11/2021] [Indexed: 11/07/2022] Open
Abstract
Chronic pain has been not recognized as a chronic illness, and its far-reaching impacts are often ignored. Chronic noncancer pain (CNCP) is a chronic disease and health care professionals need recommendations on how to monitor treatments, patients and long-term side effects of the different medications used to control CNCP. CNCP patients make up a vulnerable population due to the various associated pathologies and the challenging socio-economic conditions experienced by many of these patients. CNCP is more common among older adults, females, cancer survivors, indigenous peoples, veterans, and populations affected by social inequities and discrimination. These social determinants can lead to a complex interplay between chronic pain, mental illness, and substance use disorders. Given these realities, long-term pharmacological and side effect surveillance is more complex. Follow-up of patients with CNCP is a challenge for physicians, and thus it is important to provide recommendations on how to monitor treatments and long-term side effects of the different medications used to control CNCP.
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Affiliation(s)
- Grisell Vargas-Schaffer
- Anesthesiology and Pain Medicine, Pain Center Centre Hospitalier de l'Université de Montreal (CHUM), Montreal, CAN
| | - Allen Steverman
- Family Medicine, Pain Center Centre Hospitalier de l'Université de Montreal (CHUM), Montreal, CAN
| | - Veronique Potvin
- Anesthesiology, Pain Center Centre Hospitalier de l'Université de Montreal (CHUM), Montreal, CAN
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Muhammad RN, Ahmed LA, Abdul Salam RM, Ahmed KA, Attia AS. Crosstalk Among NLRP3 Inflammasome, ET BR Signaling, and miRNAs in Stress-Induced Depression-Like Behavior: a Modulatory Role for SGLT2 Inhibitors. Neurotherapeutics 2021; 18:2664-2681. [PMID: 34664178 PMCID: PMC8804152 DOI: 10.1007/s13311-021-01140-4] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/05/2021] [Indexed: 12/14/2022] Open
Abstract
Depression is an overwhelming health concern, and many patients fail to optimally respond to available standard therapies. Neuroplasticity and blood-brain barrier (BBB) integrity are the cornerstones of a well-functioning central nervous system, but they are vulnerable to an overly active NLRP3 inflammasome pathway that can also indirectly trigger the release of ET-1 and contribute to the ET system disturbance, which further damages stress resilience mechanisms. Here, the promising yet unexplored antidepressant potential of dapagliflozin (Dapa), a sodium-glucose co-transporter-2 inhibitor, was investigated by assessing its role in the modulation of the NLRP3 inflammasome pathway and ETBR signal transduction, and their impact on neuroplasticity and BBB integrity in an animal model of depression. Dapa (1 mg/kg/day; p.o.) with and without BQ-788 (1 mg/kg/day; i.p.), a specific ETBR blocker, were administered to adolescent male Wistar rats exposed to a 5-week chronic unpredictable stress protocol. The depressive animals demonstrated marked activation of the NLRP3 inflammasome pathway (NF-κB/NLRP3/caspase-1/IL/TNF-α), which was associated with both peripheral and central inflammatory responses. The ET system was disrupted, with noticeable reduction in miR-125a-5p and ETBR gene expression. Cortical ZO-1 expression was downregulated under the influence of NLRP3/TNF-α/miR-501-3p signaling, along with a prominent reduction in hippocampal BDNF and synapsin-1. With ETBR up-regulation being a cornerstone outcome, Dapa administration efficiently created an overall state of resilience, improved histopathological and behavioral variables, and preserved BBB function. These observations were further verified by the results obtained with BQ-788 co-administration. Thus, Dapa may exert its antidepressant action by reinforcing BBB integrity and promoting neuroplasticity through manipulation of the NLRP3/ET-1/ETBR/BDNF/ZO-1 axis, with a significant role for ETBR signaling. Graphical illustration for the proposed mechanisms of the anti-depressant potential of Dapa. Dapa suppressed NLRP3 inflammasome activation and assembly with subsequent inhibition of pro-inflammatory ILs. This results in attenuation of neuro-inflammation, BBB disruption, glial cell activation, TNF-α and ET-1 release, and the enhanced production of neurotrophins. The role of ETBR signaling was emphasized; Dapa possibly augmented ETBR expression, which is thought to boost neurotrophins production. The ETBR blocker, BQ-788, suppressed most of the positive outcomes of Dapa. Finally, miR-125a-5p and miR-501-3p that played major roles in these pathological pathways were modulated by Dapa. It is not yet clear whether Dapa has a direct or rather indirect effect on their expression. BBB, blood-brain barrier; Dapa, dapagliflozin; ET-1, endothelin-1; ETBR, endothelin B receptor; IL, interleukin; NF-κB, nuclear factor kappa B; NLRP3, nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3; TNF-α, tumor necrosis factor-α. Created with BioRender.com.
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Affiliation(s)
- Radwa N Muhammad
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
| | - Lamiaa A Ahmed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
| | - Rania M Abdul Salam
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
- Department of Biology, School of Pharmacy, New Giza University, Giza, Egypt
| | - Kawkab A Ahmed
- Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Amina S Attia
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
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Bonnet U, Claus B, Schaefer M, Kuhn J, Nyhuis P, Scherbaum N, Brüne M, Wakili V, Juckel G. Impact of Psychiatric and Related Somatic Medications on the Duration and Severity of COVID-19: A Retrospective Explorative Multi-center Study from the German Metropolitan Ruhr-area. PHARMACOPSYCHIATRY 2021; 55:30-39. [PMID: 34530483 DOI: 10.1055/a-1559-3904] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Several psychiatric and somatic medications are assumed to improve COVID-19-symptoms. These include antidepressants, antipsychotics, and anticonvulsants as well as anticoagulants, statins, and renin-angiotensin-aldosterone-system (RAAS)-inhibitors for somatic comorbid conditions. All these agents may reduce the hyperinflammatory response to SARS/CoV-2 or the related negative cardio-cerebrovascular outcomes. METHODS In a retrospective longitudinal, multi-center inpatient study, we sought to explore the influence of psychiatric medications on COVID-19, comprising the period from diagnosing SARS/CoV-2-infection via PCR (nasopharyngeal swab) up to the next 21 days. Ninety-six psychiatric inpatients (mean age [SD] 65.5 (20.1), 54% females) were included. The primary outcome was the COVID-19-duration. Secondary outcomes included symptom severity and the presence of residual symptoms. RESULTS COVID-19-related symptoms emerged in 60 (62.5%) patients, lasting 6.5 days on average. Six (6.3%) 56-95 years old patients died from or with COVID-19. COVID-19-duration and residual symptom-presence (n=22, 18%) were not significantly related to any substance. Respiratory and neuro-psychiatric symptom-load was significantly and negatively related to prescription of antidepressants and anticoagulants, respectively. Fatigue was negatively and positively related to RAAS-inhibitors and proton-pump-inhibitors, respectively. These significant relationships disappeared with p-value adjustment owed to multiple testing. The mean total psychiatric burden was not worsened across the study. DISCUSSION None of the tested medications was significantly associated with the COVID-19-duration and -severity up to the end of post-diagnosing week 3. However, there were a few biologically plausible and promising relationships with antidepressants, anticoagulants, and RAAS-inhibitors before p-value adjustment. These should encourage larger and prospective studies to re-evaluate the influence of somatic and psychiatric routine medications on COVID-19-related health outcomes.
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Affiliation(s)
- Udo Bonnet
- Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Evangelisches Krankenhaus Castrop-Rauxel, Academic Teaching Hospital of the University of Duisburg-Essen, Essen, Germany.,LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - BenediktBernd Claus
- Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Evangelisches Krankenhaus Castrop-Rauxel, Academic Teaching Hospital of the University of Duisburg-Essen, Essen, Germany.,PedScience, Datteln, Germany
| | - Martin Schaefer
- Department of Psychiatry, Psychotherapy, Psychoso-matics and Addiction Medicine, Evangelische Kliniken Essen-Mitte, Essen, Germany
| | - Jens Kuhn
- Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Johanniter Hospital Oberhausen, Oberhausen, Germany
| | | | - Norbert Scherbaum
- LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Martin Brüne
- Department of Psychiatry, Ruhr University Bochum, LWL University Hospital, Bochum, Germany
| | - Velat Wakili
- Department of Psychiatry, Psychotherapy, Psychoso-matics and Addiction Medicine, Evangelische Kliniken Essen-Mitte, Essen, Germany
| | - Georg Juckel
- Department of Psychiatry, Ruhr University Bochum, LWL University Hospital, Bochum, Germany
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Transcriptomic signatures of treatment response to the combination of escitalopram and memantine or placebo in late-life depression. Mol Psychiatry 2021; 26:5171-5179. [PMID: 32382137 PMCID: PMC9922535 DOI: 10.1038/s41380-020-0752-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 04/17/2020] [Accepted: 04/22/2020] [Indexed: 12/17/2022]
Abstract
Drugs that target glutamate neuronal transmission, such as memantine, offer a novel approach to the treatment of late-life depression, which is frequently comorbid with cognitive impairment. The results of our recently published double-blind, randomized, placebo-controlled trial of escitalopram or escitalopram/memantine in late-life depression with subjective memory complaints (NCT01902004) indicated no differences between treatments in depression remission, but additional benefits in cognition at 12-month follow-up with combination treatment. To identify pathways and biological functions uniquely induced by combination treatment that may explain cognitive improvements, we generated transcriptional profiles of remission compared with non-remission from whole blood samples. Remitters to escitalopram compared with escitalopram/memantine combination treatment display unique patterns of gene expression at baseline and 6 months after treatment initiation. Functional enrichment analysis demonstrates that escitalopram-based remission associates to functions related to cellular proliferation, apoptosis, and inflammatory response. Escitalopram/memantine-based remission, however, is characterized by processes related to cellular clearance, metabolism, and cytoskeletal dynamics. Both treatments modulate inflammatory responses, albeit via different effector pathways. Additional research is needed to understand the implications of these results in explaining the observed superior effects of combination treatment on cognition observed with prolonged treatment.
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Abadi B, Shahsavani Y, Faramarzpour M, Rezaei N, Rahimi HR. Antidepressants with anti-tumor potential in treating glioblastoma: A narrative review. Fundam Clin Pharmacol 2021; 36:35-48. [PMID: 34212424 DOI: 10.1111/fcp.12712] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 06/13/2021] [Accepted: 06/25/2021] [Indexed: 11/30/2022]
Abstract
Glioblastoma multiforme (GBM) is known as the deadliest form of brain tumor. In addition, its high treatment resistance, heterogeneity, and invasiveness make it one of the most challenging tumors. Depression is a common psychological disorder among patients with cancer, especially GBM. Due to the high occurrence rates of depression in GBM patients and the overlap of molecular and cellular mechanisms involved in the pathogenesis of these diseases, finding antidepressants with antitumor effects could be considered as an affordable strategy for the treatment of GBM. Antidepressants exert their antitumor properties through different mechanisms. According to available evidence in this regard, some of them can eliminate the adverse effects resulting from chemo-radiotherapy in several cancers along with their synergistic effects caused by chemotherapy. Therefore, providing comprehensive insight into this issue would guide scientists and physicians in developing further preclinical studies and clinical trials, in order to evaluate antidepressants' antitumor potential. Considering that no narrative review has been recently published on this issue, specifically on these classes of drugs, we present this article with the purpose of describing the antitumor cellular mechanisms of three classes of antidepressants as follows: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAOIs) in GBM.
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Affiliation(s)
- Banafshe Abadi
- Brain Cancer Research Core (BCRC), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
| | - Yasamin Shahsavani
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran.,Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Mahsa Faramarzpour
- Brain Cancer Research Core (BCRC), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,Department of Physiology and Pharmacology, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Hamid-Reza Rahimi
- Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.,Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
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50
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Sarno E, Moeser AJ, Robison AJ. Neuroimmunology of depression. ADVANCES IN PHARMACOLOGY (SAN DIEGO, CALIF.) 2021; 91:259-292. [PMID: 34099111 DOI: 10.1016/bs.apha.2021.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Depression is one of the leading causes of disability worldwide and a major contributor to the global burden of disease, yet the cellular and molecular etiology of depression remain largely unknown. Major Depressive Disorder (MDD) is associated with a variety of chronic physical inflammatory and autoimmune disorders, and mood disorders may act synergistically with other medical disorders to worsen patient outcomes. Here, we outline the neuroimmune complement, explore the evidence for altered immune system function in MDD, and present some of the potential mechanisms by which immune cells and molecules may drive the onset and course of MDD. These include pro-inflammatory signaling, alterations in the hypothalamic-pituitary-adrenal axis, dysregulation of the serotonergic and noradrenergic neurotransmitter systems, neuroinflammation, and meningeal immune dysfunction. Finally, we discuss the interactions between current antidepressants and the immune system and propose the possibility of immunomodulatory drugs as potential novel antidepressant treatments.
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Affiliation(s)
- Erika Sarno
- Department of Physiology, Michigan State University, East Lansing, MI, United States
| | - Adam J Moeser
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, United States
| | - Alfred J Robison
- Department of Physiology, Michigan State University, East Lansing, MI, United States.
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