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Mashayekhi-Sardoo H, Razazpour F, Hakemi Z, Hedayati-Moghadam M, Baghcheghi Y. Ethanol-Induced Depression: Exploring the Underlying Molecular Mechanisms. Cell Mol Neurobiol 2025; 45:49. [PMID: 40405002 PMCID: PMC12098258 DOI: 10.1007/s10571-025-01569-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 05/12/2025] [Indexed: 05/24/2025]
Abstract
Ethanol consumption is widely recognized for its detrimental effects on mental health, particularly its association with depressive disorders. This narrative review aims to explore the intricate molecular mechanisms underlying ethanol-induced depression, synthesizing findings from preclinical and clinical studies. We begin by providing an overview of the relationship between chronic ethanol consumption and depression, highlighting compelling evidence from diverse populations. Subsequently, we delve into insights from animal models that elucidate the pathophysiological changes triggered by prolonged ethanol exposure. Key mechanisms identified include oxidative stress, which contributes to cellular damage; neuroinflammation, characterized by the activation of glial cells and altered cytokine profiles; and disruptions in neurotrophic factors that impair neuronal growth and survival. Furthermore, we discuss the induction of apoptosis in neural cells and the significant impact of ethanol on neurotransmitter receptor remodeling and regulation, leading to altered synaptic transmission. While substantial progress has been made in understanding these mechanisms, we also acknowledge the limitations of current research methodologies and call for further investigations to translate these findings into effective therapeutic strategies for individuals affected by ethanol-induced depression. This review ultimately underscores the need for a comprehensive understanding of the molecular underpinnings of ethanol's impact on mood disorders, paving the way for improved interventions and preventative measures.
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Affiliation(s)
- Habibeh Mashayekhi-Sardoo
- Bio Environmental Health Hazards Research Center, Jiroft University of Medical Sciences, Jiroft, 7861755765, Iran
- School of Health, Jiroft University of Medical Sciences, Jiroft, Iran
- Student Research Committee, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Fateme Razazpour
- Oral and Dental Diseases Research Center, Kerman University of Medical Science, Kerman, Iran
| | - Zohreh Hakemi
- Student Research Committee, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Mahdiyeh Hedayati-Moghadam
- Student Research Committee, Jiroft University of Medical Sciences, Jiroft, Iran
- Department of Physiology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Yousef Baghcheghi
- Bio Environmental Health Hazards Research Center, Jiroft University of Medical Sciences, Jiroft, 7861755765, Iran.
- Student Research Committee, Jiroft University of Medical Sciences, Jiroft, Iran.
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Fischer IC, Overstreet C, Cabrera-Mendoza B, Qiu D, Krystal JH, Polimanti R, Gelernter J, Pietrzak RH. Optimism moderates the relationship between inflammatory polygenic risk and major depressive disorder in U.S. Military veterans. World J Biol Psychiatry 2025:1-10. [PMID: 40343713 DOI: 10.1080/15622975.2025.2498352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 04/22/2025] [Accepted: 04/23/2025] [Indexed: 05/11/2025]
Abstract
OBJECTIVES Major depressive disorder (MDD) is a leading cause of disability, and chronic inflammation is a contributing factor to its onset and progression. This study examined the relationship between genetic predisposition to inflammation and MDD risk in a nationally representative sample of U.S. military veterans, as well as psychosocial moderators of this association. METHODS A composite polygenic risk score (PRS) for inflammatory biomarkers was derived from the UK Biobank and examined in relation to a positive MDD screen in 1,660 European-American veterans. The analysis adjusted for known correlates of inflammation and MDD, including medical conditions and cumulative trauma burden. RESULTS Each standard deviation increase in the inflammatory PRS was associated with more than two-fold increased odds of screening positive for MDD (OR = 2.51, 95% CI = 1.39-4.54). Interaction analyses revealed that optimism moderated this association; among those in the highest PRS tertile, individuals with high optimism were more than 30 times less likely to screen positive for MDD compared to those with low optimism (0.7% vs. 22.6%). Pathway-based analyses identified enrichment of immune- and brain-related gene sets, highlighting potential biological mechanisms linking inflammation and MDD. CONCLUSIONS Findings suggest genetic risk for inflammation contributes to MDD vulnerability and that optimism may buffer this risk.
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Affiliation(s)
- Ian C Fischer
- U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, VA Connecticut Healthcare System, West Haven, CT, USA
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
| | - Cassie Overstreet
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
- VA Connecticut Healthcare System, West Haven, CT, USA
| | - Brenda Cabrera-Mendoza
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
- VA Connecticut Healthcare System, West Haven, CT, USA
| | - Dan Qiu
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
- VA Connecticut Healthcare System, West Haven, CT, USA
| | - John H Krystal
- U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, VA Connecticut Healthcare System, West Haven, CT, USA
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
| | - Renato Polimanti
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
- VA Connecticut Healthcare System, West Haven, CT, USA
| | - Joel Gelernter
- U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, VA Connecticut Healthcare System, West Haven, CT, USA
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
| | - Robert H Pietrzak
- U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, VA Connecticut Healthcare System, West Haven, CT, USA
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
- Department of Social and Behavioral Sciences, Yale School of Public Health, New Haven, CT, USA
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Zheng Q, Wang T, Wang S, Chen Z, Jia X, Yang H, Chen H, Sun X, Wang K, Zhang L, Fu F. The anti-inflammatory effects of saponins from natural herbs. Pharmacol Ther 2025; 269:108827. [PMID: 40015518 DOI: 10.1016/j.pharmthera.2025.108827] [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: 04/29/2024] [Revised: 11/20/2024] [Accepted: 02/20/2025] [Indexed: 03/01/2025]
Abstract
Inflammation is a protective mechanism that also starts the healing process. However, inflammatory reaction may cause severe tissue damage. The increased influx of phagocytic leukocytes may produce excessive amount of reactive oxygen species, which leads to additional cell injury. Inflammatory response activates the leukocytes and thus induces tissue damage and prolongs inflammation. The inflammation-induced activation of the complement system may also contribute to cell injury. Non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are chief agents for treating inflammation associated with the diseases. However, the unwanted side effects of NSAIDs (e.g., gastrointestinal disturbances, skin reactions, adverse renal effects, cardiovascular side effects) and glucocorticoids (e.g., suppression of immune system, Cushing's syndrome, osteoporosis, hyperglycemia) limit their use in patients. Natural herbs are important sources of anti-inflammatory drugs. The ingredients extracted from natural herbs display anti-inflammatory effects to work through multiple pathways with lower risk of adverse reaction. At present, the main anti-inflammatory natural agents include saponins, flavonoids, alkaloids, polysaccharides, and so on. The present article will review the anti-inflammatory effects of saponins including escin, ginsenosides, glycyrrhizin, astragaloside, Panax notoginseng saponins, saikosaponin, platycodin, timosaponin, ophiopogonin D, dioscin, senegenin.
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Affiliation(s)
- Qinpin Zheng
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, China
| | - Tian Wang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, China
| | - Sensen Wang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, China
| | - Zhuoxi Chen
- School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong, China
| | - Xue Jia
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, China
| | - Hui Yang
- School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong, China
| | - Huijin Chen
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, China
| | - Xin Sun
- School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong, China
| | - Kejun Wang
- School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong, China
| | - Leiming Zhang
- School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong, China.
| | - Fenghua Fu
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, China.
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Ramirez A, Howes S, Chilton R. Ketamine in insulin resistance: Pharmacokinetics, cardiovascular implications and cellular effects on cardiomyocytes. Diabetes Obes Metab 2025; 27:2339-2341. [PMID: 39949188 DOI: 10.1111/dom.16248] [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: 12/22/2024] [Revised: 01/27/2025] [Accepted: 01/28/2025] [Indexed: 04/04/2025]
Abstract
Ketamine, a dissociative anaesthetic, has expanded its clinical use beyond anaesthesia to pain management and treatment-resistant depression. As an N-methyl-d-aspartate receptor antagonist, ketamine disrupts the excitatory neurotransmission via interaction with the opioid, alpha-amino-3-hydroxy-5-methyl-4-isooxazole-propionic acid receptor and serotonin pathways, contributing to its broad therapeutic potential. However, its use is not without risks. In patients with insulin resistance, ketamine's effect on glucose metabolism, mitochondrial function and oxidative stress are exacerbated. This paper explores ketamine's pharmacokinetics, cardiovascular impact and its cellular effects on cardiomyocytes, particularly in insulin-resistant individuals. The findings discussed emphasize the importance of careful administration and monitoring in these vulnerable populations to balance ketamine's therapeutic benefits against its potential risks in patients with underlying metabolic or cardiovascular conditions.
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Affiliation(s)
- Ariana Ramirez
- Cardiology, San Antonio Uniformed Services Health Education Consortium, San Antonio, Texas, USA
| | - Stephanie Howes
- Cardiology, San Antonio Uniformed Services Health Education Consortium, San Antonio, Texas, USA
| | - Robert Chilton
- Division of Cardiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
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Tang L, Wu L, Dai M, Liu N, Liu L. Integrative analysis of signaling and metabolic pathways, immune infiltration patterns, and machine learning-based diagnostic model construction in major depressive disorder. Sci Rep 2025; 15:13519. [PMID: 40253457 PMCID: PMC12009401 DOI: 10.1038/s41598-025-97623-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 04/07/2025] [Indexed: 04/21/2025] Open
Abstract
Major depressive disorder (MDD) is a multifactorial disorder involving genetic and environmental factors, with unclear pathogenesis. This study aims to explore the pathogenic pathway of MDD and its relationship with immune responses and to discover its potential targets by bioinformatics methods. We first applied gene set variation analysis (GSVA) and seven different immune infiltration algorithms to the GSE98793 dataset to determine the differences in signaling pathways, metabolic pathways, and immune cell infiltration between MDD patients and healthy controls. Differentially expressed genes between MDD patients and controls were obtained from five datasets (GSE98793, GSE32280, GSE38206, GSE39653, and GSE52790), and 113 machine learning methods were employed to construct MDD diagnostic models. Based on the constructed MDD diagnostic models, MDD patients were divided into high-risk and low-risk groups. GSVA and immune microenvironment analyses were conducted to investigate the differences between the two groups. Furthermore, potential drugs and therapeutic targets for the high-risk MDD group were explored to provide new insights and directions for the precise treatment of MDD. GSVA and immune infiltration results indicate that patients with MDD exhibit differences from normal individuals in various aspects, including biological processes, signaling pathways, metabolic processes, and immune cells. To investigate the functions and biological significance of differentially expressed genes in MDD patients, we performed GO and KEGG enrichment analyses on the differentially expressed genes from five databases (GSE98793, GSE32280, GSE38206, GSE39653, and GSE52790). By comparing the enrichment results across the five datasets, we found that the cell-killing signaling pathway was consistently present in the enriched signaling pathways of all datasets, suggesting that this pathway may play a crucial role in the pathogenesis of MDD. The random forest algorithm (AUC = 0.788) was selected as the optimal algorithm from 113 machine learning algorithms, leading to the development of a robust and predictive MDD algorithm, highlighting the important role of NPL in MDD. By dividing MDD into high and low-risk subgroups based on diagnostic model scores, enrichment pathways, and immunological results further demonstrated that high-risk MDD is associated with increased levels of reactive oxygen species, inflammation, and numbers of T cells and B cells. Through GSEA scoring, five upregulated pathways in the high-risk MDD group were identified, and multiple potential drugs such as Mibefradil, LY364947, ZLN005, STA- 5326, and vemurafenib were screened. Patients with MDD show differences in signaling pathways, metabolic pathways, and immune mechanisms. By constructing an MDD diagnostic model, we predicted the key genes of MDD and the characteristic pathways associated with a higher risk of MDD. This provides new insights for risk stratification identification and offers new perspectives for the clinical application of precision immunotherapy and drug development.
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Affiliation(s)
- Lei Tang
- Mental Health Center, Affiliated Hospital of North Sichuan Medical College, 1 South Maoyuan Road, 637000, Nanchong, China
- School of Psychiatry, North Sichuan Medical College, Nanchong, China
- Department of Psychiatry, Sleep Medicine Centre, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Liling Wu
- Department of Pharmacy, The Second Clinical School of North Sichuan Medical College, Nanchong Hospital of Beijing Anzhen Hospital CMU (Nanchong Central Hospital), Nanchong, China
| | - Mengqin Dai
- Mental Health Center, Affiliated Hospital of North Sichuan Medical College, 1 South Maoyuan Road, 637000, Nanchong, China
- School of Psychiatry, North Sichuan Medical College, Nanchong, China
| | - Nian Liu
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
| | - Lu Liu
- Mental Health Center, Affiliated Hospital of North Sichuan Medical College, 1 South Maoyuan Road, 637000, Nanchong, China.
- School of Psychiatry, North Sichuan Medical College, Nanchong, China.
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Kim Y, Lee W. Increased risk of herpes zoster associated with stress and sleep deprivation: Evidence from korea health panel survey. J Psychiatr Res 2025; 184:333-339. [PMID: 40086222 DOI: 10.1016/j.jpsychires.2025.03.015] [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: 01/13/2025] [Revised: 02/27/2025] [Accepted: 03/10/2025] [Indexed: 03/16/2025]
Abstract
OBJECTIVE Several studies have reported controversial results regarding the association between mental health factors and the risk of herpes zoster. This study examined the effects of self-rated stress, sleep deprivation, depressive symptoms, and suicidal ideation on the risk of herpes zoster. METHODS Data from the Korea Health Panel Survey (2008-2018) were analyzed. Associations between self-reported mental health factors and herpes zoster were determined using a generalized estimating equation model. Age, sex, socioeconomic status, health behaviors, and comorbidities were adjusted for in the model. The standardized incidence ratios (SIRs) were reported from the sensitivity analysis. RESULTS Of the 78,896 included person-years (mean age, 51.31 ± 16.90; females, n = 43,503 [55.14 %]), 1130 (1.43 %) developed herpes zoster. The adjusted odds ratios (aORs) for the association between severe self-rated stress and herpes zoster were 1.483 (95 % confidence interval [CI]: 1.161-1.895) and for sleep deprivation, 1.194 (95 % CI: 1.038-1.374). When stratified by sex, the association remained significant in females but not in males. For depressive symptoms and suicidal ideation, the adjusted models did not reveal significant associations with herpes zoster infection. In the sensitivity analysis, the SIRs for herpes zoster were higher with severe self-rated stress (1.37, 95 % CI: 1.07-1.68) and sleep deprivation (1.21, 95 % CI: 1.07-1.36). CONCLUSIONS Severe self-rated stress and sleep deprivation were associated with an increased risk of herpes zoster, whereas depressive symptoms and suicidal ideation were not. Further studies are required to confirm these findings and explore additional factors.
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Affiliation(s)
- Youjin Kim
- Department of Preventive Medicine, College of Medicine, Chung-Ang University, Seoul, Republic of Korea
| | - Wanhyung Lee
- Department of Preventive Medicine, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
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Văruț RM, Popescu AIS, Gaman S, Niculescu CE, Niculescu AȘ, Dop D, Stepan MD, Ionovici N, Singer CE, Popescu C. Cyclodextrin-Based Drug Delivery Systems for Depression: Improving Antidepressant Bioavailability and Targeted Central Nervous System Delivery. Pharmaceutics 2025; 17:355. [PMID: 40143019 PMCID: PMC11945394 DOI: 10.3390/pharmaceutics17030355] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/04/2025] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
Cyclodextrin (CD)-based drug delivery systems have emerged as a promising strategy to overcome limitations commonly encountered in antidepressant therapy, including low bioavailability, poor solubility, and suboptimal penetration of the blood-brain barrier. This review synthesizes current evidence demonstrating that complexing various classes of antidepressants-such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and atypical antidepressants-with β-CD or its derivatives significantly enhances drug solubility and stability. In addition, encapsulation with CDs can diminish systemic toxicity and improve pharmacokinetics, thereby helping to optimize dosage regimens and reduce adverse effects. Analysis of published in vitro and in vivo studies indicates that CD formulations not only boost therapeutic efficacy but also enable sustained or targeted release, which is critical for drugs requiring precise plasma and tissue concentrations. When compared to other carriers (e.g., liposomes, polymeric nanoparticles, dendrimers), CD-based systems often stand out for their ease of formulation, biocompatibility, and cost-effectiveness, although limited drug-loading capacity can be a drawback. We recommend expanding in vivo trials to substantiate the clinical benefits of CD-antidepressant complexes, particularly for treatment-resistant cases or specific subpopulations (e.g., elderly and pediatric patients). Additional investigations should also explore hybrid systems-combining CDs with advanced nano- or macroparticles-to amplify their advantages and address any limitations. Ultimately, integrating CDs into antidepressant regimens holds substantial potential to refine therapy outcomes, reduce adverse events, and pave the way for more personalized, effective interventions for depression.
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Affiliation(s)
- Renata Maria Văruț
- Research Methodology Department, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Alin Iulian Silviu Popescu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Simina Gaman
- Department I, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Carmen Elena Niculescu
- Department of Mother and Baby, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (C.E.N.); (D.D.); (M.D.S.); (N.I.); (C.E.S.)
| | - Adrian Ștefan Niculescu
- Department of Orthopedics, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Dalia Dop
- Department of Mother and Baby, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (C.E.N.); (D.D.); (M.D.S.); (N.I.); (C.E.S.)
| | - Mioara Desdemona Stepan
- Department of Mother and Baby, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (C.E.N.); (D.D.); (M.D.S.); (N.I.); (C.E.S.)
| | - Nina Ionovici
- Department of Mother and Baby, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (C.E.N.); (D.D.); (M.D.S.); (N.I.); (C.E.S.)
| | - Cristina Elena Singer
- Department of Mother and Baby, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (C.E.N.); (D.D.); (M.D.S.); (N.I.); (C.E.S.)
| | - Cristina Popescu
- Department of Anatomy, University of Medicine and Pharmacy, Discipline of Anatomy, 200349 Craiova, Romania;
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Li JR, Kao YC, Tsai SJ, Bai YM, Su TP, Chen TJ, Liang CS, Chen MH. Comparative analysis of the risk of severe bacterial infection and septicemia in adolescents and young adults with treatment-resistant depression and treatment-responsive depression - a nationwide cohort study in Taiwan. Eur Child Adolesc Psychiatry 2025:10.1007/s00787-025-02684-y. [PMID: 40056170 DOI: 10.1007/s00787-025-02684-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 02/20/2025] [Indexed: 03/10/2025]
Abstract
Previous studies have shown an association between depression and increased susceptibility to infection in the general population. However, there has been no prior research specifically examining the relationship between treatment-resistant depression (TRD) and severe bacterial infections (SBI) in adolescents and young adults. This retrospective observational cohort study utilized the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2010. It included adolescents (12-19 years of age) and young adults (20-29 years of age) diagnosed with major depressive disorder (MDD), comprising 6958 cases of TRD and 27,832 cases of antidepressant-responsive depression (ARPD). The TRD and ARPD groups were further matched (4:1) by chronological age, age at diagnosis of depression, sex, residence, and family income. The primary outcomes were severe bacterial infections (SBI) and septicemia. Cox regression analysis was conducted to identify the risk of hospitalization due to SBI or septicemia during the follow-up period. Compared with controls, the ARPD group had increased risks of SBI (hazard ratio [HR] with 95% confidence interval [CI]: 3.90, 2.73-5.57) and septicemia (HR, 95% CI: 2.56, 1.34-4.91). Notably, the risks of SBI and septicemia appeared to be further elevated in the TRD group. The TRD group exhibited higher incidences of SBI (HR, 95% CI: 6.99, 4.73-10.34) and septicemia (HR, 95% CI: 2.85, 1.28-6.36) than the control group. Adolescents and young adults with TRD had 6.99-fold and 3.90-fold increased risks of SBI and septicemia compared to individuals without MDD, respectively. Therefore, healthcare providers need to be vigilant when monitoring and implementing preventive measures in this population.
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Affiliation(s)
- Jia-Ru Li
- Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Yu-Chen Kao
- Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, No. 60, Xinmin Road, Beitou District, Taipei City, 112, Taiwan
| | - Shih-Jen Tsai
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ya-Mei Bai
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tung-Ping Su
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Psychiatry, General Cheng Hsin Hospital, Taipei, Taiwan
| | - Tzeng-Ji Chen
- Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Hospital and Health Care Administration, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Family Medicine, Hsinchu Branch, Taipei Veterans General Hospital, Hsinchu, Taiwan
| | - Chih-Sung Liang
- Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
- Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, No. 60, Xinmin Road, Beitou District, Taipei City, 112, Taiwan.
| | - Mu-Hong Chen
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
- Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
- Department of Medical Research, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, 112, Taiwan.
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Dai J, Lin XT, Shen LL, Zhang XW, Ding ZW, Wang J, Fan XW, Ning WD. Immune indicators and depression in adolescents: Associations with monocytes, lymphocytes, and direct bilirubin. World J Psychiatry 2025; 15:101818. [PMID: 39974492 PMCID: PMC11758056 DOI: 10.5498/wjp.v15.i2.101818] [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: 09/28/2024] [Revised: 11/04/2024] [Accepted: 12/17/2024] [Indexed: 01/14/2025] Open
Abstract
BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents. This mental health condition can have severe consequences, including academic failure, social withdrawal, and suicidal behavior. Given the increasing rate of depression in this age group, understanding the underlying biological mechanisms is essential for early detection and intervention. Recent studies have suggested that immune markers play a role in the pathophysiology of depression, prompting further investigation of their potential association with depressive symptoms in adolescents. AIM To investigate the relationship between immune markers (monocytes, lymphocytes, and direct bilirubin) and the incidence and severity of depression among adolescents. METHODS This cross-sectional study recruited 145 adolescent patients with depression [male (M)/female (F) = 38/107] from Jiangbin Hospital in Guangxi, Zhuang and 163 healthy controls (M/F = 77/86) from routine health check-ups. Blood samples were collected after an overnight fast. Depression severity was measured using the Zung Self-Rating Depression Scale. The inclusion criteria were age 12-24 years, diagnosis of depressive disorder (ICD-10), and no recent antidepressant use. The exclusion criteria included psychiatric comorbidities and serious somatic diseases. Key statistical methods included group comparisons and correlation analyses. RESULTS There was a higher prevalence of females in the depression group (P < 0.001). Significant age differences were observed between the groups (Z = 9.43, P < 0.001). The depression group had higher monocyte (Z = 3.43, P < 0.001) and lymphocyte (t = 2.29, P < 0.05) counts, and higher serum direct bilirubin levels (Z = 4.72, P < 0.001). Monocyte count varied significantly according to depression severity, with lower counts in the mild group (Z = -2.90, P < 0.05). A negative correlation between age and lymphocyte counts was observed (ρ = -0.22, P < 0.01). Logistic regression analysis showed that serum direct bilirubin levels significantly predicted depression. CONCLUSION The potential role of elevated levels of immune markers in the early detection of depression in adolescents has been highlighted. Therefore, it is necessary to explore further the relationships between these immune markers and depression.
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Affiliation(s)
- Jian Dai
- Department of Clinical Psychology, Jiangbin Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xiao-Tong Lin
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai 200124, China
| | - Lu-Lu Shen
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai 200124, China
| | - Xi-Wen Zhang
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai 200124, China
| | - Zi-Wen Ding
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai 200124, China
| | - Jing Wang
- Department of Psychological Health, The 980th Hospital of Joint Support Force of China People's Liberation Army, Shijiazhuang 050051, Hebei Province, China
| | - Xi-Wang Fan
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai 200124, China
| | - Wei-Dong Ning
- Department of Psychological Health, The 980th Hospital of Joint Support Force of China People's Liberation Army, Shijiazhuang 050051, Hebei Province, China
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10
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Hu N, Zheng Y, Liu X, Jia J, Feng J, Zhang C, Liu L, Wang X. CircKat6b Mediates the Antidepressant Effect of Esketamine by Regulating Astrocyte Function. Mol Neurobiol 2025; 62:2587-2600. [PMID: 39138759 PMCID: PMC11772408 DOI: 10.1007/s12035-024-04420-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 08/05/2024] [Indexed: 08/15/2024]
Abstract
The abundant expression of circular RNAs (circRNAs) in the central nervous system and their contribution to the pathogenesis of depression suggest that circRNAs are promising therapeutic targets for depression. This study explored the role and mechanism of circKat6b in esketamine's antidepressant effect. We found that intravenous administration of esketamine (5 mg/kg) treatment decreased the circKat6b expression in the astrocytes of hippocampus induced by a chronic unpredictable mild stress (CUMS) mouse model, while the overexpression of circKat6b in the hippocampus significantly attenuated the antidepressant effects of esketamine in depressed mice. RNA-sequencing, RT-PCR, and western blot experiments showed that the stat1 and p-stat1 expression were significantly upregulated in mouse astrocytes overexpressing circKat6b. In the CUMS mouse model, overexpression of circKat6b in the hippocampus significantly reversed the downregulation of p-stat1 protein expression caused by esketamine. Our findings demonstrated that a novel mechanism of the antidepressant like effect of esketamine may be achieved by reducing the expression of circKat6b in the astrocyte of the hippocampus of depressed mice.
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Affiliation(s)
- Na Hu
- Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China
- Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China
| | - Yujie Zheng
- Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China
- Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China
| | - Xueru Liu
- Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China
- Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China
| | - Jing Jia
- Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China
| | - Jianguo Feng
- Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China
| | - Chunxiang Zhang
- Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China
| | - Li Liu
- Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China
- Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China
| | - Xiaobin Wang
- Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China.
- Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan Province, China.
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11
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Li A, Zheng X, Liu D, Huang R, Ge H, Cheng L, Zhang M, Cheng H. Physical Activity and Depression in Breast Cancer Patients: Mechanisms and Therapeutic Potential. Curr Oncol 2025; 32:77. [PMID: 39996878 PMCID: PMC11854877 DOI: 10.3390/curroncol32020077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/21/2025] [Accepted: 01/22/2025] [Indexed: 02/26/2025] Open
Abstract
Breast cancer is a significant traumatic experience that often leads to chronic stress and mental health challenges. Research has consistently shown that physical activity-especially exercise-can alleviate depressive symptoms; however, the specific biological mechanisms underlying these antidepressant effects remain unclear. In this review, we comprehensively summarize the biological mechanisms of depression and the antidepressant mechanisms of physical activity and explore the biological processes through which exercise exerts its antidepressant effects in breast cancer patients. We focus on the impact of physical activity on inflammation, the endocrine system, glutamate, and other aspects, all of which play crucial roles in the pathophysiology of depression. Moreover, we discuss the heterogeneity of depression in breast cancer patients and the complex interactions between its underlying mechanisms. Additionally, we propose that a deeper understanding of these mechanisms in the breast cancer population can guide the design and implementation of exercise-based interventions that maximize the antidepressant benefits of physical activity. Finally, we summarize the current research and propose future research directions.
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Affiliation(s)
- Anlong Li
- Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; (A.L.); (D.L.); (R.H.); (H.G.)
- The Second School of Clinical Medicine, Anhui Medical University, Hefei 230032, China
| | - Xinyi Zheng
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou 510500, China;
- Department of Oncology, Shenzhen Hospital of Southern Medical University, Shenzhen 518000, China
| | - Dajie Liu
- Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; (A.L.); (D.L.); (R.H.); (H.G.)
- The Second School of Clinical Medicine, Anhui Medical University, Hefei 230032, China
| | - Runze Huang
- Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; (A.L.); (D.L.); (R.H.); (H.G.)
- The Second School of Clinical Medicine, Anhui Medical University, Hefei 230032, China
| | - Han Ge
- Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; (A.L.); (D.L.); (R.H.); (H.G.)
- The Second School of Clinical Medicine, Anhui Medical University, Hefei 230032, China
- School of Nursing, Anhui Medical University, Hefei 230032, China
| | - Ling Cheng
- Department of Oncology, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen 518000, China;
| | - Mingjun Zhang
- Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; (A.L.); (D.L.); (R.H.); (H.G.)
- The Second School of Clinical Medicine, Anhui Medical University, Hefei 230032, China
| | - Huaidong Cheng
- Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; (A.L.); (D.L.); (R.H.); (H.G.)
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou 510500, China;
- Department of Oncology, Shenzhen Hospital of Southern Medical University, Shenzhen 518000, China
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12
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Suzuki E, Sueki A, Takahashi H, Ishigooka J, Nishimura K. Association between TNF-α & IL-6 level changes and remission from depression with duloxetine treatment. Int J Neurosci 2024:1-6. [PMID: 39392051 DOI: 10.1080/00207454.2024.2414279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 09/24/2024] [Accepted: 10/04/2024] [Indexed: 10/12/2024]
Abstract
PURPOSE/AIM OF THE STUDY The pathophysiology of major depressive disorder (MDD) involves multiple factors, including inflammatory processes. This study investigated the relationship between changes in the levels of cytokines and remission in patients with MDD following duloxetine treatment. MATERIALS AND METHODS MDD patients were administered duloxetine for 16 weeks. Clinical evaluation and immunological monitoring were performed every 4 weeks. RESULTS Our results indicated that changes in serum levels of TNF-α and IL-6 were associated with remission following duloxetine treatment in MDD patients. There was a slight increase in TNF-α levels in the first four weeks following duloxetine treatment, which correlated significantly with patients who were in remission. Furthermore, patients in remission exhibited an initial increase in IL-6 levels in the first four weeks, followed by a decrease at 16 weeks. CONCLUSIONS These results suggest an important relationship between changes in cytokine levels and remission in patients with major depression after duloxetine treatment.
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Affiliation(s)
- Eriko Suzuki
- Department of Neuropsychiatry, Tokyo Women's Medical University Hospital, Tokyo, Japan
| | - Akitsugu Sueki
- Department of Neuropsychiatry, Tokyo Women's Medical University Hospital, Tokyo, Japan
| | - Hitoshi Takahashi
- Department of Neuropsychiatry, Tokyo Women's Medical University Hospital, Tokyo, Japan
| | - Jun Ishigooka
- Department of Neuropsychiatry, Tokyo Women's Medical University Hospital, Tokyo, Japan
| | - Katsuji Nishimura
- Department of Neuropsychiatry, Tokyo Women's Medical University Hospital, Tokyo, Japan
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13
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Okamoto N, Hoshikawa T, Honma Y, Chibaatar E, Ikenouchi A, Harada M, Yoshimura R. Effect modification of tumor necrosis factor-α on the kynurenine and serotonin pathways in major depressive disorder on type 2 diabetes mellitus. Eur Arch Psychiatry Clin Neurosci 2024; 274:1697-1707. [PMID: 37991535 PMCID: PMC11422469 DOI: 10.1007/s00406-023-01713-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 10/29/2023] [Indexed: 11/23/2023]
Abstract
Major depressive disorder (MDD) is strongly associated with type 2 diabetes mellitus (T2DM). The kynurenine and serotonin pathways, as well as chronic low-grade inflammation, are being considered potential links between them. MDD associated with T2DM is less responsive to treatment than that without T2DM; however, the underlying mechanism remains unknown. We aimed to investigate the effects of inflammatory cytokines on the kynurenine and serotonin pathways in patients with comorbid MDD and T2DM and those with only MDD. We recruited 13 patients with comorbid MDD and T2DM and 27 patients with only MDD. We measured interleukin-6 and tumor necrosis factor-α (TNF-α) levels as inflammatory cytokines and metabolites of the kynurenine pathway and examined the relationship between the two. TNF-α levels were significantly higher in patients with comorbid MDD and T2DM than in those with only MDD in univariate (p = 0.044) and multivariate (adjusted p = 0.036) analyses. TNF-α showed a statistically significant effect modification (interaction) with quinolinic acid/tryptophan and serotonin in patients from both groups (β = 1.029, adjusted p < 0.001; β = - 1.444, adjusted p = 0.047, respectively). Limitations attributed to the study design and number of samples may be present. All patients were Japanese with mild to moderate MDD; therefore, the generalizability of our findings may be limited. MDD with T2DM has more inflammatory depression components and activations of the kynurenine pathway by inflammatory cytokines than MDD without T2DM. Hence, administering antidepressants and anti-inflammatory drugs in combination may be more effective in patients with comorbid MDD and T2DM.
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Affiliation(s)
- Naomichi Okamoto
- Department of Psychiatry, University of Occupational and Environmental Health, 807-8555, Kitakyushu, Fukuoka, 8078555, Japan.
| | - Takashi Hoshikawa
- Department of Psychiatry, University of Occupational and Environmental Health, 807-8555, Kitakyushu, Fukuoka, 8078555, Japan
| | - Yuichi Honma
- Third Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Enkhmurun Chibaatar
- Department of Psychiatry, University of Occupational and Environmental Health, 807-8555, Kitakyushu, Fukuoka, 8078555, Japan
| | - Atsuko Ikenouchi
- Department of Psychiatry, University of Occupational and Environmental Health, 807-8555, Kitakyushu, Fukuoka, 8078555, Japan
- Medical Center for Dementia, University Hospital, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Masaru Harada
- Third Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Reiji Yoshimura
- Department of Psychiatry, University of Occupational and Environmental Health, 807-8555, Kitakyushu, Fukuoka, 8078555, Japan
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14
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Alberti A, Araujo Coelho DR, Vieira WF, Moehlecke Iser B, Lampert RMF, Traebert E, Silva BBD, Oliveira BHD, Leão GM, Souza GD, Dallacosta FM, Kades G, Madeira K, Chupel MU, Grossl FS, Souza R, Hur Soares B, Endrigo Ruppel da Rocha R, da Silva Sipriano E, Fernandes Martins D, Agostinetto L. Factors Associated with the Development of Depression and the Influence of Obesity on Depressive Disorders: A Narrative Review. Biomedicines 2024; 12:1994. [PMID: 39335507 PMCID: PMC11429137 DOI: 10.3390/biomedicines12091994] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Revised: 08/15/2024] [Accepted: 08/16/2024] [Indexed: 09/30/2024] Open
Abstract
Depression affects several aspects of life, including socioeconomic status, relationships, behavior, emotions, and overall health. The etiology of depression is complex and influenced by various factors, with obesity emerging as a significant contributor. This narrative review aims to investigate the factors associated with the development of depression, with a particular focus on the role of obesity. The literature search was conducted on PubMed, Embase, and PsycINFO from May to July 2024. The review highlights the impact of environmental and socioeconomic conditions; lifestyle choices, including physical activity and dietary habits; stress; traumatic experiences; neurotransmitter imbalances; medical and psychological conditions; hormone fluctuations; and epigenetic factors on depression. A key emphasis is placed on the inflammatory processes linked to obesity, which may drive the bidirectional relationship between obesity and depression. The findings suggest that obesity is associated with an increased risk of depression, potentially due to chronic inflammation, neurochemical dysregulation, and the emotional and social challenges related to weight stigma and obesity management. Understanding these interconnected factors is important for developing targeted interventions to address both obesity and depression, leading to improved quality of life for those affected.
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Affiliation(s)
- Adriano Alberti
- Department of Biological and Health Sciences Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça 88132-260, Brazil
- Graduate Program in Environment and Health, University of Planalto Catarinense-UNIPLAC, Lages 88509-900, Brazil
| | | | - Willians Fernando Vieira
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 5508-000, Brazil
- Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-864, Brazil
- Laboratory of Neuroimmune Interface of Pain Research, Faculdade São Leopoldo Mandic, Instituto São Leopoldo Mandic, Campinas 13045-755, Brazil
| | - Betine Moehlecke Iser
- Department of Biological and Health Sciences Posgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Tubarão 88704-900, Brazil
| | - Rose Meiry Fernandez Lampert
- Department of Biological and Health Sciences Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça 88132-260, Brazil
| | - Eliane Traebert
- Department of Biological and Health Sciences Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça 88132-260, Brazil
| | - Bruna Becker da Silva
- Department of Biological and Health Sciences Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça 88132-260, Brazil
| | - Bruna Hoffmann de Oliveira
- Department of Biological and Health Sciences Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça 88132-260, Brazil
| | - Graziela Marques Leão
- Department of Biological and Health Sciences Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça 88132-260, Brazil
| | - Gabriela de Souza
- Department of Biological and Health Sciences Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça 88132-260, Brazil
| | | | - Gabriela Kades
- Department of Biosciences and Health, University of West Santa Catarina, Joaçaba 89600-000, Brazil
| | - Kristian Madeira
- Department of Mathematics and Health Sciences, University of the Extreme South of Santa Catarina (UNESC), Criciúma 88806-000, Brazil
| | - Matheus Uba Chupel
- Hurvitz Brain Sciences, Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada
| | - Fernando Schorr Grossl
- Department of Biosciences and Health, University of West Santa Catarina, Joaçaba 89600-000, Brazil
| | - Renan Souza
- Department of Biosciences and Health, University of West Santa Catarina, Joaçaba 89600-000, Brazil
| | - Ben Hur Soares
- Department of Physical Education and Physiotherapy, University of Passo Fundo, Passo Fundo 99052-900, Brazil
| | - Ricelli Endrigo Ruppel da Rocha
- Department of the Graduate Program in Development and Society-PPGEDS (UNIARP), University of Alto Vale do Rio do Peixe, Caçador 89500-199, Brazil
| | - Erica da Silva Sipriano
- Department of Mathematics and Health Sciences, University of the Extreme South of Santa Catarina (UNESC), Criciúma 88806-000, Brazil
| | - Daniel Fernandes Martins
- Department of Biological and Health Sciences Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça 88132-260, Brazil
| | - Lenita Agostinetto
- Graduate Program in Environment and Health, University of Planalto Catarinense-UNIPLAC, Lages 88509-900, Brazil
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15
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Zhong Q, Lai S, He J, Zhong S, Song X, Wang Y, Zhang Y, Chen G, Yan S, Jia Y. Gender-related alterations of serum trace elements and neurometabolism in the anterior cingulate cortex of patients with major depressive disorder. J Affect Disord 2024; 360:176-187. [PMID: 38723680 DOI: 10.1016/j.jad.2024.05.039] [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: 10/29/2023] [Revised: 04/08/2024] [Accepted: 05/06/2024] [Indexed: 06/04/2024]
Abstract
BACKGROUND It is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. METHODS 109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. RESULTS In individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N-acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. CONCLUSIONS Our findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC.
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Affiliation(s)
- Qilin Zhong
- Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Shunkai Lai
- Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Jiali He
- Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Shuming Zhong
- Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
| | - Xiaodong Song
- Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Ying Wang
- Medical Imaging Center, First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Yiliang Zhang
- Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Guanmao Chen
- Medical Imaging Center, First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Shuya Yan
- Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Yanbin Jia
- Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
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16
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Di Paolo A, Membrino V, Alia S, Nanetti L, Svarca LE, Perrone ML, Aquilanti L, Mazzanti L, Vignini A, Salvolini E, Severini M. Pro-inflammatory cytokine alterations in recent onset anorexia nervosa adolescent female patients before and after 6 months of integrated therapy: A case-control study. J Investig Med 2024; 72:522-531. [PMID: 38641857 DOI: 10.1177/10815589241251702] [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] [Indexed: 04/21/2024]
Abstract
Anorexia nervosa (AN) is a complex disorder affecting mainly, but not only, teenagers. Researchers agree that AN is deeply associated with a pro-inflammatory state following an impaired immune system, resulting from altered levels of cytokines such as IL-1β and TNF-α, also impacted by the frequent depressive states. Thus, this case-control study aimed to evaluate the relationship between patients suffering from AN undergoing specialized eating disorder treatment for AN and pro-inflammatory cytokines. To reach our purpose, we assessed eating-related psychopathology and depressive symptoms and measured serum concentration of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α before and after 6 months of integrated therapy (which included psychopharmacotherapy, psychotherapy, and nutritional treatment), to define whether selected pro-inflammatory cytokines could be considered a pathophysiological marker of the disorder. A sample of 16 young female patients with early diagnosis of AN, and without any previous treatment, and 22 healthy controls matched by age, sex, and socioeconomic status were enrolled. After 6 months of integrated therapy, a significant decrease of all selected pro-inflammatory cytokines was detected. In addition, an improvement in the anxiety-depressant aspects was also noted. In conclusion, the results obtained suggest that pro-inflammatory cytokines are indeed related to the pathophysiology of AN. However, further investigations, involving larger samples of patients with distinct subtypes of AN, are essential to confirm the current findings.
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Affiliation(s)
- Alice Di Paolo
- Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy
| | - Valentina Membrino
- Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy
| | - Sonila Alia
- Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy
| | - Laura Nanetti
- Department of Neuropsychiatry, Children's Hospital "G. Salesi," AOU Ospedali Riuniti Ancona, Italy
| | - Lucia Emanuela Svarca
- Department of Neuropsychiatry, Children's Hospital "G. Salesi," AOU Ospedali Riuniti Ancona, Italy
| | - Massimo Leone Perrone
- Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy
| | - Luca Aquilanti
- Department of Clinical Sciences, Section of Dentistry, Università Politecnica delle Marche, Ancona, Italy
| | - Laura Mazzanti
- Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy
- Fondazione Salesi, Ospedale G. Salesi, Ancona, Italy
| | - Arianna Vignini
- Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy
- Research Center of Health Education and Health Promotion, Università Politecnica delle Marche, Ancona, Italy
| | - Eleonora Salvolini
- Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy
| | - Michele Severini
- Department of Neuropsychiatry, Children's Hospital "G. Salesi," AOU Ospedali Riuniti Ancona, Italy
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17
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Zhang S, Li P, Wang S, Zhu J, Huang Z, Cai F, Freidel S, Ling F, Schwarz E, Chen J. BioM2: biologically informed multi-stage machine learning for phenotype prediction using omics data. Brief Bioinform 2024; 25:bbae384. [PMID: 39126426 PMCID: PMC11316398 DOI: 10.1093/bib/bbae384] [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: 03/06/2024] [Revised: 06/15/2024] [Accepted: 07/24/2024] [Indexed: 08/12/2024] Open
Abstract
Navigating the complex landscape of high-dimensional omics data with machine learning models presents a significant challenge. The integration of biological domain knowledge into these models has shown promise in creating more meaningful stratifications of predictor variables, leading to algorithms that are both more accurate and generalizable. However, the wider availability of machine learning tools capable of incorporating such biological knowledge remains limited. Addressing this gap, we introduce BioM2, a novel R package designed for biologically informed multistage machine learning. BioM2 uniquely leverages biological information to effectively stratify and aggregate high-dimensional biological data in the context of machine learning. Demonstrating its utility with genome-wide DNA methylation and transcriptome-wide gene expression data, BioM2 has shown to enhance predictive performance, surpassing traditional machine learning models that operate without the integration of biological knowledge. A key feature of BioM2 is its ability to rank predictor variables within biological categories, specifically Gene Ontology pathways. This functionality not only aids in the interpretability of the results but also enables a subsequent modular network analysis of these variables, shedding light on the intricate systems-level biology underpinning the predictive outcome. We have proposed a biologically informed multistage machine learning framework termed BioM2 for phenotype prediction based on omics data. BioM2 has been incorporated into the BioM2 CRAN package (https://cran.r-project.org/web/packages/BioM2/index.html).
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Affiliation(s)
- Shunjie Zhang
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
| | - Pan Li
- Center for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, No. 6, 2nd Nanjiang Road, Nansha District, 511462 Guangzhou, China
| | - Shenghan Wang
- Center for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, No. 6, 2nd Nanjiang Road, Nansha District, 511462 Guangzhou, China
| | - Jijun Zhu
- Center for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, No. 6, 2nd Nanjiang Road, Nansha District, 511462 Guangzhou, China
| | - Zhongting Huang
- Center for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, No. 6, 2nd Nanjiang Road, Nansha District, 511462 Guangzhou, China
| | - Fuqiang Cai
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
| | - Sebastian Freidel
- Hector Institute for Artificial Intelligence in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, M7, Mannheim 68161, Germany
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, Mannheim 68159, Germany
| | - Fei Ling
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
| | - Emanuel Schwarz
- Hector Institute for Artificial Intelligence in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, M7, Mannheim 68161, Germany
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, Mannheim 68159, Germany
| | - Junfang Chen
- Center for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, No. 6, 2nd Nanjiang Road, Nansha District, 511462 Guangzhou, China
- Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai, China
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18
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Jia Y, Zhang X, Wang Y, Liu Y, Dai J, Zhang L, Wu X, Zhang J, Xiang H, Yang Y, Zeng Z, Chen Y. Knocking out Selenium Binding Protein 1 Induces Depressive-Like Behavior in Mice. Biol Trace Elem Res 2024; 202:3149-3162. [PMID: 37801218 DOI: 10.1007/s12011-023-03894-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 09/27/2023] [Indexed: 10/07/2023]
Abstract
Selenium binding protein 1 (SELENBP1) is involved in neurologic disorders, such as multiple sclerosis, spinal cord injury, Parkinson's disease, epilepsy, and schizophrenia. However, the role of SELENBP1 in the neurogenesis of depression, which is a neurologic disorder, and the underlying mechanisms of oxidative stress and inflammation in depression remain unknown. In this study, we evaluated the changes in the expression levels of SELENBP1 in the hippocampus of a mouse model of depression and in the serum of human patients with depression using the Gene Expression Omnibus database. These changes were validated using blood samples from human patients with depression and mouse models with chronic unpredictable mild stress (CUMS)-induced depressive-like behavior. We also investigated the effects of SELENBP1 knockout (KO) on inflammation, oxidative stress, and hippocampal neurogenesis in mice with CUMS-induced depression. Our results revealed that SELENBP1 levels was decreased in the blood of human patients with depression and in the hippocampus of mice with CUMS-induced depression. SELENBP1 KO increased CUMS-induced depressive behavior in mice and caused dysregulation of inflammatory cytokines and oxidative stress. This led to a decrease in the numbers of doublecortin- and Ki67-positive cells, which might aggravate CUMS-induced depressive symptoms. These findings suggest that SELENBP1 might be involved in the regulation of neurogenesis in mice with depression and could be served as a potential target for diagnosing and treating depression.
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Affiliation(s)
- Yi Jia
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Cellular Immunotherapy Engineering Research Center of Guizhou Province, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, China.
- Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, 550025, China.
| | - Xin Zhang
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Cellular Immunotherapy Engineering Research Center of Guizhou Province, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, China
- Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, 550025, China
| | - Yongmei Wang
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Cellular Immunotherapy Engineering Research Center of Guizhou Province, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, China
- Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, 550025, China
| | - Yang Liu
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Cellular Immunotherapy Engineering Research Center of Guizhou Province, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, China
- Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, 550025, China
| | - Jie Dai
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Cellular Immunotherapy Engineering Research Center of Guizhou Province, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, China
- Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, 550025, China
| | - Liangliang Zhang
- Prenatal Diagnosis Center, Guizhou Provincial People's Hospital, Guiyang, 550002, Guizhou, China
| | - Xian Wu
- Prenatal Diagnosis Center, Guizhou Provincial People's Hospital, Guiyang, 550002, Guizhou, China
| | - Jie Zhang
- Department of Laboratory, the Second People's Hospital of Guizhou Province, Guiyang, 550004, Guizhou, China
| | - Hongxi Xiang
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Cellular Immunotherapy Engineering Research Center of Guizhou Province, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, China
- Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, 550025, China
| | - Yanping Yang
- Department of Histology and Embryology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, China
| | - Zhu Zeng
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Cellular Immunotherapy Engineering Research Center of Guizhou Province, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, China
- Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, 550025, China
| | - Yulian Chen
- Mental Health Education and Counseling Center for College Students, Guizhou Medical University, Guiyang, 550025, China
- Faculty of Psychology, Beijing Normal University, Beijing, 100875, China
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Stolfi F, Abreu H, Sinella R, Nembrini S, Centonze S, Landra V, Brasso C, Cappellano G, Rocca P, Chiocchetti A. Omics approaches open new horizons in major depressive disorder: from biomarkers to precision medicine. Front Psychiatry 2024; 15:1422939. [PMID: 38938457 PMCID: PMC11210496 DOI: 10.3389/fpsyt.2024.1422939] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 05/28/2024] [Indexed: 06/29/2024] Open
Abstract
Major depressive disorder (MDD) is a recurrent episodic mood disorder that represents the third leading cause of disability worldwide. In MDD, several factors can simultaneously contribute to its development, which complicates its diagnosis. According to practical guidelines, antidepressants are the first-line treatment for moderate to severe major depressive episodes. Traditional treatment strategies often follow a one-size-fits-all approach, resulting in suboptimal outcomes for many patients who fail to experience a response or recovery and develop the so-called "therapy-resistant depression". The high biological and clinical inter-variability within patients and the lack of robust biomarkers hinder the finding of specific therapeutic targets, contributing to the high treatment failure rates. In this frame, precision medicine, a paradigm that tailors medical interventions to individual characteristics, would help allocate the most adequate and effective treatment for each patient while minimizing its side effects. In particular, multi-omic studies may unveil the intricate interplays between genetic predispositions and exposure to environmental factors through the study of epigenomics, transcriptomics, proteomics, metabolomics, gut microbiomics, and immunomics. The integration of the flow of multi-omic information into molecular pathways may produce better outcomes than the current psychopharmacological approach, which targets singular molecular factors mainly related to the monoamine systems, disregarding the complex network of our organism. The concept of system biomedicine involves the integration and analysis of enormous datasets generated with different technologies, creating a "patient fingerprint", which defines the underlying biological mechanisms of every patient. This review, centered on precision medicine, explores the integration of multi-omic approaches as clinical tools for prediction in MDD at a single-patient level. It investigates how combining the existing technologies used for diagnostic, stratification, prognostic, and treatment-response biomarkers discovery with artificial intelligence can improve the assessment and treatment of MDD.
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Affiliation(s)
- Fabiola Stolfi
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Hugo Abreu
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Riccardo Sinella
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Sara Nembrini
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Sara Centonze
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Virginia Landra
- Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy
| | - Claudio Brasso
- Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy
| | - Giuseppe Cappellano
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Paola Rocca
- Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy
| | - Annalisa Chiocchetti
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
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20
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Rivera Gómez AK, Perafán Collazos JF, Prieto JL, Pinzón PV, Ávila González GI, Nino Castaño VE, Dueñas Cuellar RA. Prolonged chronic academic stress and its relationship with cytokine dysregulation in health science students. Stress Health 2024; 40:e3363. [PMID: 38146787 DOI: 10.1002/smi.3363] [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: 05/06/2022] [Revised: 10/20/2023] [Accepted: 12/03/2023] [Indexed: 12/27/2023]
Abstract
Academic stress is a problem that affects students due to a number of factors that are considered stressors. These include academic overload and completion of assignments and exams, exacerbated by such external conditions as family, social and economic problems. Together, these can affect emotional and physical health, which may lead in the long term to developing a number of pathologies, given the alteration of immunological homoeostasis with which they are related. OBJECTIVE To evaluate the effect of academic stress on the production of cytokines IL-6, TNF-α, IL-1β and IL-10 in Morphology students in the Faculty of Health Sciences of the Universidad del Cauca during an academic period. METHODOLOGY A descriptive longitudinal study was carried out with a population of 78 students studying Morphology, among the subjects with the highest academic load in the Physiotherapy, Medicine, Nursing and Phonoaudiology programs in the Faculty. Academic stress was assessed in the students by applying the Academic Stress Questionnaire (ASQ), and through quantification of the IL-6, TNF-α, IL-1β and IL-10 cytokines using the ELISA (Enzyme-linked immunosorbent assay) technique in three "moments" of the academic semester: Moment 1: beginning of the academic semester; Moment 2: week of evaluations of 70% of the semester; Moment 3: week of final exams. RESULTS The students perceived stress as "normal" at Moment 1, while at Moments 2 and 3 it was perceived as "quite a lot", with percentages of 48.7% and 50%, respectively. The predominant stressors were: "methodological deficiencies", "academic overload", and "exams", for the three moments of the study. "Physical exhaustion" was the most prevalent stress response at all three moments, followed by "irascible behaviour" (Moment 2 and 3), and "sleep disturbances" (Moment 3). To cope with the stress, the students resorted mainly to "planning and management of personal resources" in the three moments of the study. A progressive increase in the pro-inflammatory cytokines IL-6 and TNF-α and a decrease in IL-10 were observed at all three moments. A correlation was found between some questions belonging to the "methodological deficiencies", "beliefs about performance", "sleep disturbances", "physical exhaustion" and "irascible behaviour" dimensions with IL-6, IL-1β, TNF-α and IL. -10. CONCLUSION The morphology students suffer increased stress indicators (perceived stress and pro-inflammatory cytokines) throughout the academic period. The "methodological deficiencies", "academic overload" and "exams" stressors, together with "physical exhaustion", "sleep disturbances" and "irascible behaviour", possibly influence the production of the IL-6, TNF-α and IL-10 cytokines.
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Affiliation(s)
- Angie Katherine Rivera Gómez
- Research Group in Immunology and Infectious Diseases, Medicine Program, Department of Pathology, Faculty of Health Sciences, Universidad del Cauca, Popayán, Colombia
| | | | - Jerónimo Londoño Prieto
- Human Body Movement Research Group, Physiotherapy Program, Faculty of Health Sciences, Universidad del Cauca, Popayán, Colombia
| | - Paola Vernaza Pinzón
- Human Body Movement Research Group, Physiotherapy Program, Faculty of Health Sciences, Universidad del Cauca, Popayán, Colombia
| | - Gloria Inés Ávila González
- Research Group in Immunology and Infectious Diseases, Medicine Program, Department of Pathology, Faculty of Health Sciences, Universidad del Cauca, Popayán, Colombia
| | - Victoria Eugenia Nino Castaño
- Research Group in Immunology and Infectious Diseases, Medicine Program, Department of Pathology, Faculty of Health Sciences, Universidad del Cauca, Popayán, Colombia
| | - Rosa Amalia Dueñas Cuellar
- Research Group in Immunology and Infectious Diseases, Medicine Program, Department of Pathology, Faculty of Health Sciences, Universidad del Cauca, Popayán, Colombia
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Xiong Y, Yu Q, Zhi H, Peng H, Xie M, Li R, Li K, Ma Y, Sun P. Advances in the study of the glymphatic system and aging. CNS Neurosci Ther 2024; 30:e14803. [PMID: 38887168 PMCID: PMC11183173 DOI: 10.1111/cns.14803] [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: 10/27/2023] [Revised: 04/26/2024] [Accepted: 05/29/2024] [Indexed: 06/20/2024] Open
Abstract
The glymphatic system is cerebrospinal fluid-brain tissue fluid exchange flow mediated by aquaporin-4 (AQP4) on the end feet of astrocytes for a system, which is capable of rapidly removing brain metabolites and thus maintaining brain homeostasis, and is known as the central immune system. Dysfunction of the glymphatic system causes accumulation of misfolded and highly phosphorylated proteins (amyloid-β and Tau proteins), which destabilizes the proteins, and the body's neuroinflammatory factors are altered causing aging of the immune system and leading to neurodegenerative diseases. Damage to the glymphatic system and aging share common manifestations, as well as unstudied biological mechanisms that are also linked, such as mitochondria, oxidative stress, chronic inflammation, and sleep. In this paper, we first summarize the structure, function, and research methods of the glymphatic system and the relationship between the glymphatic system and the peripheral immune system, and second, sort out and summarize the factors of the glymphatic system in removing metabolites and resolving aging-related diseases and factors affecting aging, to explore its related biological mechanisms, and moreover, to provide a new way of thinking for treating or intervening aging-related diseases.
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Affiliation(s)
- Ying Xiong
- School of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJinanChina
| | - Qingying Yu
- Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical SciencesGuangzhou University of Chinese MedicineGuangzhouChina
| | - Haimei Zhi
- Qilu Hospital of Shandong UniversityJinanChina
| | - Huiyuan Peng
- Department of RehabilitationZhongshan Hospital of Traditional Chinese MedicineZhongshanChina
| | - Mingjun Xie
- School of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJinanChina
| | - Renjun Li
- Department of PsychiatryJinan Mental Health CenterJinanChina
| | - Kejian Li
- Innovative Institute of Chinese Medicine and PharmacyShandong University of Traditional Chinese MedicineJinanChina
| | - Yuexiang Ma
- School of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJinanChina
| | - Peng Sun
- Innovative Institute of Chinese Medicine and PharmacyShandong University of Traditional Chinese MedicineJinanChina
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22
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Monaco F, Vignapiano A, Piacente M, Farina F, Pagano C, Marenna A, Leo S, Vecchi C, Mancuso C, Prisco V, Iodice D, Auricchio A, Cavaliere R, D'Agosto A, Fornaro M, Solmi M, Corrivetti G, Fasano A. Innova4Health: an integrated approach for prevention of recurrence and personalized treatment of Major Depressive Disorder. Front Artif Intell 2024; 7:1366055. [PMID: 38774832 PMCID: PMC11106633 DOI: 10.3389/frai.2024.1366055] [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: 01/05/2024] [Accepted: 04/22/2024] [Indexed: 05/24/2024] Open
Abstract
Background Major Depressive Disorder (MDD) is a prevalent mental health condition characterized by persistent low mood, cognitive and physical symptoms, anhedonia (loss of interest in activities), and suicidal ideation. The World Health Organization (WHO) predicts depression will become the leading cause of disability by 2030. While biological markers remain essential for understanding MDD's pathophysiology, recent advancements in social signal processing and environmental monitoring hold promise. Wearable technologies, including smartwatches and air purifiers with environmental sensors, can generate valuable digital biomarkers for depression assessment in real-world settings. Integrating these with existing physical, psychopathological, and other indices (autoimmune, inflammatory, neuroradiological) has the potential to improve MDD recurrence prevention strategies. Methods This prospective, randomized, interventional, and non-pharmacological integrated study aims to evaluate digital and environmental biomarkers in adolescents and young adults diagnosed with MDD who are currently taking medication. The study implements a sensor-integrated platform built around an open-source "Pothos" air purifier system. This platform is designed for scalability and integration with third-party devices. It accomplishes this through software interfaces, a dedicated app, sensor signal pre-processing, and an embedded deep learning AI system. The study will enroll two experimental groups (10 adolescents and 30 young adults each). Within each group, participants will be randomly allocated to Group A or Group B. Only Group B will receive the technological equipment (Pothos system and smartwatch) for collecting digital biomarkers. Blood and saliva samples will be collected at baseline (T0) and endpoint (T1) to assess inflammatory markers and cortisol levels. Results Following initial age-based stratification, the sample will undergo detailed classification at the 6-month follow-up based on remission status. Digital and environmental biomarker data will be analyzed to explore intricate relationships between these markers, depression symptoms, disease progression, and early signs of illness. Conclusion This study seeks to validate an AI tool for enhancing early MDD clinical management, implement an AI solution for continuous data processing, and establish an AI infrastructure for managing healthcare Big Data. Integrating innovative psychophysical assessment tools into clinical practice holds significant promise for improving diagnostic accuracy and developing more specific digital devices for comprehensive mental health evaluation.
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Affiliation(s)
- Francesco Monaco
- Department of Mental Health, ASL Salerno, Salerno, Italy
- European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
| | - Annarita Vignapiano
- Department of Mental Health, ASL Salerno, Salerno, Italy
- European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
| | - Martina Piacente
- European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
| | - Federica Farina
- European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
| | - Claudio Pagano
- Innovation Technology e Sviluppo (I.T.Svil), Salerno, Italy
| | - Alessandra Marenna
- European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
| | - Stefano Leo
- European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
| | - Corrado Vecchi
- European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
| | - Carlo Mancuso
- Innovation Technology e Sviluppo (I.T.Svil), Salerno, Italy
| | | | - Davide Iodice
- Department of Mental Health, ASL Salerno, Salerno, Italy
| | | | - Roberto Cavaliere
- Ufficio Trasferimento Tecnologico, Università degli Studi di Cassino e del Lazio Meridionale, Cassino, Italy
| | - Amelia D'Agosto
- Istituto Polidiagnostico D'Agosto & Marino, Nocera Inferiore, Italy
| | - Michele Fornaro
- Department of Neuroscience, Reproductive Sciences, and Odontostomatology, Clinical Section of Psychiatry and Psychology, University School of Medicine Federico II, Naples, Italy
| | - Marco Solmi
- Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada
- Department of Mental Health, The Ottawa Hospital, On Track: The Champlain First Episode Psychosis Program, Ottawa, ON, Canada
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
- Department of Child and Adolescent Psychiatry, Charité—Universitätsmedizin, Berlin, Germany
| | - Giulio Corrivetti
- Department of Mental Health, ASL Salerno, Salerno, Italy
- European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
| | - Alessio Fasano
- European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
- Department of Pediatrics, Massachusetts General Hospital for Children, Harvard Medical School, Division of Pediatric Gastroenterology and Nutrition, Boston, MA, United States
- Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MA, United States
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Gedik H, Peterson R, Chatzinakos C, Dozmorov MG, Vladimirov V, Riley BP, Bacanu SA. A novel multi-omics mendelian randomization method for gene set enrichment and its application to psychiatric disorders. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.04.14.24305811. [PMID: 38699366 PMCID: PMC11065030 DOI: 10.1101/2024.04.14.24305811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2024]
Abstract
Genome-wide association studies (GWAS) of psychiatric disorders (PD) yield numerous loci with significant signals, but often do not implicate specific genes. Because GWAS risk loci are enriched in expression/protein/methylation quantitative loci (e/p/mQTL, hereafter xQTL), transcriptome/proteome/methylome-wide association studies (T/P/MWAS, hereafter XWAS) that integrate xQTL and GWAS information, can link GWAS signals to effects on specific genes. To further increase detection power, gene signals are aggregated within relevant gene sets (GS) by performing gene set enrichment (GSE) analyses. Often GSE methods test for enrichment of "signal" genes in curated GS while overlooking their linkage disequilibrium (LD) structure, allowing for the possibility of increased false positive rates. Moreover, no GSE tool uses xQTL information to perform mendelian randomization (MR) analysis. To make causal inference on association between PD and GS, we develop a novel MR GSE (MR-GSE) procedure. First, we generate a "synthetic" GWAS for each MSigDB GS by aggregating summary statistics for x-level (mRNA, protein or DNA methylation (DNAm) levels) from the largest xQTL studies available) of genes in a GS. Second, we use synthetic GS GWAS as exposure in a generalized summary-data-based-MR analysis of complex trait outcomes. We applied MR-GSE to GWAS of nine important PD. When applied to the underpowered opioid use disorder GWAS, none of the four analyses yielded any signals, which suggests a good control of false positive rates. For other PD, MR-GSE greatly increased the detection of GO terms signals (2,594) when compared to the commonly used (non-MR) GSE method (286). Some of the findings might be easier to adapt for treatment, e.g., our analyses suggest modest positive effects for supplementation with certain vitamins and/or omega-3 for schizophrenia, bipolar and major depression disorder patients. Similar to other MR methods, when applying MR-GSE researchers should be mindful of the confounding effects of horizontal pleiotropy on statistical inference.
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24
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Zhu H, Du Z, Lu R, Zhou Q, Shen Y, Jiang Y. Investigating the Mechanism of Chufan Yishen Formula in Treating Depression through Network Pharmacology and Experimental Verification. ACS OMEGA 2024; 9:12698-12710. [PMID: 38524447 PMCID: PMC10955564 DOI: 10.1021/acsomega.3c08350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 01/29/2024] [Accepted: 02/23/2024] [Indexed: 03/26/2024]
Abstract
Objective: To investigate the antidepressant effect and potential mechanism of the Chufan Yishen Formula (CFYS) through network pharmacology, molecular docking, and experimental verification. Methods: The active ingredients and their target genes of CFYS were identified through Traditional Chinese Medicine Systems Pharmacology (TCMSP) and TCM-ID. We obtained the differentially expressed genes in patients with depression from the GEO database and screened out the genes intersecting with the target genes of CFYS to construct the PPI network. The key pathways were selected through STRING and KEGG. Then, molecular docking and experimental verification were performed. Results: A total of 113 effective components and 195 target genes were obtained. After intersecting the target genes with the differentially expressed genes in patients with depression, we obtained 37 differential target genes, among which HMOX1, VEGFA, etc., were the key genes. After enriching the differential target genes by KEGG, we found that the "chemical carcinogenesis-reactive oxygen species" pathway was the key pathway for the CFYS antidepressant effect. Besides, VEGFA might be a key marker for depression. Experimental verification found that CFYS could significantly improve the behavioral indicators of rats with depression models, including improving the antioxidant enzyme activity and increasing VEGFA levels. The results are consistent with the network pharmacology analysis. Conclusions: CFYS treatment for depression is a multicomponent, multitarget, and multipathway complex process, which may mainly exert an antidepressant effect by improving the neuron antioxidant stress response and regulating VEGFA levels.
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Affiliation(s)
- Haohao Zhu
- Mental Health
Center of
Jiangnan University, Wuxi, Jiangsu 214151, China
| | - Zhiqiang Du
- Mental Health
Center of
Jiangnan University, Wuxi, Jiangsu 214151, China
| | - Rongrong Lu
- Mental Health
Center of
Jiangnan University, Wuxi, Jiangsu 214151, China
| | - Qin Zhou
- Mental Health
Center of
Jiangnan University, Wuxi, Jiangsu 214151, China
| | - Yuan Shen
- Mental Health
Center of
Jiangnan University, Wuxi, Jiangsu 214151, China
| | - Ying Jiang
- Mental Health
Center of
Jiangnan University, Wuxi, Jiangsu 214151, China
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25
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Małujło-Balcerska E, Pietras T. Adipocytokines levels as potential biomarkers for discriminating patients with a diagnosis of depressive disorder from healthy controls. J Psychiatr Res 2024; 171:163-170. [PMID: 38290234 DOI: 10.1016/j.jpsychires.2024.01.026] [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: 04/12/2023] [Revised: 01/04/2024] [Accepted: 01/15/2024] [Indexed: 02/01/2024]
Abstract
BACKGROUND Depressive disorder is a complex mental health condition in which the etiopathogenesis involves several factors. Suitable biomarkers for the development of depression have not yet been established. Alterations in cytokines are assumed to be involved in the pathophysiology of depressive disorder. Adipokines (also known as adipocytokines) are important factors that not only regulate the energy balance but also regulate the inflammatory and immune responses. This study investigated the serum levels of adiponectin, leptin, resistin, chemerin, and fetuin A and the possible role of these adipokines in depressive disorder. METHODS We recruited a total of 73 patients diagnosed with recurrent depressive disorder (rDD) and 54 age- and sex-matched healthy controls (HCs). Serum adipocytokines were determined using ELISA kits (R&D, USA). The serum levels of the investigated molecules between depressive patients and HCs were compared, and diagnostic values were evaluated using the receiver operating characteristic (ROC) curve method for discriminating depressive patients from HCs. Correlations between the molecules and clinical variables were also evaluated. RESULTS Patients with rDD had lower levels of serum adiponectin and chemerin and higher levels of serum leptin, resistin and fetuin A (p < 0.05) vs. controls. Moreover, ROC curve analysis showed that the area under the curve (AUC) values of above set of adipocytkines were >0.7, with a sensitivity and specificity over 80% in discriminating patients with rDD from HCs. CONCLUSIONS These results suggest that circulating adipocytokies may hold promise as biomarkers for the diagnosis of rDD.
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Affiliation(s)
| | - Tadeusz Pietras
- Department of Clinical Pharmacology, Medical University of Łódź, Poland; Second Department of Psychiatry, Institute of Psychiatry and Neurology, Warsaw, Poland
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Małujlo-Balcerska E, Pietras T. Systemic concentrations of IL-18, TFG-β, RANTES, ICAM-1 and uPAR as combined pathway-related factors may help in identification of patients suffering from depressive disorder. Arch Med Sci 2024; 20:348-353. [PMID: 38414473 PMCID: PMC10895941 DOI: 10.5114/aoms/178276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 01/04/2024] [Indexed: 02/29/2024] Open
Affiliation(s)
| | - Tadeusz Pietras
- Department of Pharmacology, Medical University of Lodz, Lodz, Poland
- Second Department of Psychiatry, Institute of Psychiatry and Neurology, Warsaw, Poland
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Zhang J, Liu D, Xiang J, Yang M. Combining Glial Fibrillary Acidic Protein and Neurofilament Light Chain for the Diagnosis of Major Depressive Disorder. Anal Chem 2024; 96:1693-1699. [PMID: 38231554 DOI: 10.1021/acs.analchem.3c04825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
Major depressive disorder (MDD) is a prevalent brain disorder affecting more than 2% of the world's population. Due to the lack of well-specific biomarkers, it is difficult to distinguish MDD from other diseases with similar clinical symptoms (such as Alzheimer's disease and cerebral thrombosis). In this work, we provided a strategy to address this issue by constructing a combinatorial biomarker of serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NFL). To achieve the convenient and sensitive detection of two proteins, we developed an electrochemical immunosandwich sensor using two metal-ion-doped carbon dots (Pb-CDs and Cu-CDs) as probes for signal output. Each probe contains approximately 300 Pb2+ or 200 Cu2+, providing excellent signal amplification. This method achieved detection limits of 0.3 pg mL-1 for GFAP and 0.2 pg mL-1 for NFL, lower than most of the reported detection limits. Analysis of real serum samples showed that the concentration ratio of GFAP to NFL, which is associated with the relative degree of brain inflammation and neurodegeneration, is suitable for not only distinguishing MDD from healthy individuals but also specifically distinguishing MDD from Alzheimer's disease and cerebral thrombosis. The good specificity gives the combinatorial GFAP/NFL biomarker broad application prospects in the screening, diagnosis, and treatment of MDD.
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Affiliation(s)
- JinXia Zhang
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
| | - Dan Liu
- Eye Center of Xiangya Hospital, Central South University, Changsha 410083, P. R. China
| | - Juan Xiang
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
| | - Minghui Yang
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
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Sciacchitano S, Carola V, Nicolais G, Sciacchitano S, Napoli C, Mancini R, Rocco M, Coluzzi F. To Be Frail or Not to Be Frail: This Is the Question-A Critical Narrative Review of Frailty. J Clin Med 2024; 13:721. [PMID: 38337415 PMCID: PMC10856357 DOI: 10.3390/jcm13030721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 01/07/2024] [Accepted: 01/22/2024] [Indexed: 02/12/2024] Open
Abstract
Many factors have contributed to rendering frailty an emerging, relevant, and very popular concept. First, many pandemics that have affected humanity in history, including COVID-19, most recently, have had more severe effects on frail people compared to non-frail ones. Second, the increase in human life expectancy observed in many developed countries, including Italy has led to a rise in the percentage of the older population that is more likely to be frail, which is why frailty is much a more common concern among geriatricians compared to other the various health-care professionals. Third, the stratification of people according to the occurrence and the degree of frailty allows healthcare decision makers to adequately plan for the allocation of available human professional and economic resources. Since frailty is considered to be fully preventable, there are relevant consequences in terms of potential benefits both in terms of the clinical outcome and healthcare costs. Frailty is becoming a popular, pervasive, and almost omnipresent concept in many different contexts, including clinical medicine, physical health, lifestyle behavior, mental health, health policy, and socio-economic planning sciences. The emergence of the new "science of frailty" has been recently acknowledged. However, there is still debate on the exact definition of frailty, the pathogenic mechanisms involved, the most appropriate method to assess frailty, and consequently, who should be considered frail. This narrative review aims to analyze frailty from many different aspects and points of view, with a special focus on the proposed pathogenic mechanisms, the various factors that have been considered in the assessment of frailty, and the emerging role of biomarkers in the early recognition of frailty, particularly on the role of mitochondria. According to the extensive literature on this topic, it is clear that frailty is a very complex syndrome, involving many different domains and affecting multiple physiological systems. Therefore, its management should be directed towards a comprehensive and multifaceted holistic approach and a personalized intervention strategy to slow down its progression or even to completely reverse the course of this condition.
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Affiliation(s)
- Salvatore Sciacchitano
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy;
- Unit of Anaesthesia, Intensive Care and Pain Medicine, Sant’Andrea University Hospital, 00189 Rome, Italy; (M.R.); (F.C.)
- Department of Life Sciences, Health and Health Professions, Link Campus University, 00165 Rome, Italy
| | - Valeria Carola
- Department of Dynamic and Clinical Psychology and Health Studies, Sapienza University of Rome, 00189 Rome, Italy; (V.C.); (G.N.)
| | - Giampaolo Nicolais
- Department of Dynamic and Clinical Psychology and Health Studies, Sapienza University of Rome, 00189 Rome, Italy; (V.C.); (G.N.)
| | - Simona Sciacchitano
- Department of Psychiatry, La Princesa University Hospital, 28006 Madrid, Spain;
| | - Christian Napoli
- Department of Surgical and Medical Science and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy;
| | - Rita Mancini
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy;
| | - Monica Rocco
- Unit of Anaesthesia, Intensive Care and Pain Medicine, Sant’Andrea University Hospital, 00189 Rome, Italy; (M.R.); (F.C.)
- Department of Surgical and Medical Science and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy;
| | - Flaminia Coluzzi
- Unit of Anaesthesia, Intensive Care and Pain Medicine, Sant’Andrea University Hospital, 00189 Rome, Italy; (M.R.); (F.C.)
- Department Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, 04100 Latina, Italy
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Jalili S, Shirzad H, Mousavi Nezhad SA. Prediction and Validation of Hub Genes Related to Major Depressive Disorder Based on Co-expression Network Analysis. J Mol Neurosci 2024; 74:8. [PMID: 38198075 DOI: 10.1007/s12031-023-02172-5] [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: 10/18/2023] [Accepted: 11/16/2023] [Indexed: 01/11/2024]
Abstract
Major depressive disorder (MDD) is generally among the most prevalent psychiatric illnesses. Significant advances have occurred in comprehension of the MDD biology. However, it is still essential to recognize new biomarkers for potential targeted treatment of patients with MDD. The present work deals with in-depth comparative computational analyses to obtain new insights, such as gene ontology and pathway enrichment analyses and weighted gene co-expression network analysis (WGCNA) through gene expression dataset. The expression of selected hub-genes was validated in MDD patients using quantitative real-time PCR (RT-qPCR). We found that MDD progression includes the turquoise module genes (p-value = 1e-18, r = 0.97). According to gene enrichment analysis, the cytokine-mediated signaling pathway mostly involves genes in this module. By selection of four candidate hub-genes (IL6, NRG1, TNF, and BDNF), RT-qPCR validation was performed. A significant NRG1 downregulation was revealed by the RT-qPCR outcomes in MDD. In MDD patients, TNF and IL6 expression were considerably higher, and no considerable differences were found in the BDNF expression. Ultimately, based on ROC analyses, IL6, NRG1, and TNF had a higher MDD diagnostic performance. Therefore, our study presents information on the intricate association between MDD development and cytokine-mediated signaling, thus providing new rationales to develop new therapeutic approaches.
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Affiliation(s)
- Shirin Jalili
- Institute of Police Equipment and Technologies, Policing Sciences and Social Studies Research Institute, Tehran, Iran.
| | - Hadi Shirzad
- Research Center for Life & Health Sciences & Biotechnology of the Police, Directorate of Health, Rescue & Treatment, Police Headquarter, Tehran, Iran.
| | - Seyed Amin Mousavi Nezhad
- Research Center for Life & Health Sciences & Biotechnology of the Police, Directorate of Health, Rescue & Treatment, Police Headquarter, Tehran, Iran
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Shirayama Y, Iwata M, Miyano K, Hirose Y, Oda Y, Fujita Y, Hashimoto K. Infusions of beta-hydroxybutyrate, an endogenous NLRP3 inflammasome inhibitor, produce antidepressant-like effects on learned helplessness rats through BDNF-TrkB signaling and AMPA receptor activation, and strengthen learning ability. Brain Res 2023; 1821:148567. [PMID: 37689333 DOI: 10.1016/j.brainres.2023.148567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 08/27/2023] [Accepted: 09/06/2023] [Indexed: 09/11/2023]
Abstract
Beta-hydroxybutyrate (BHB), an endogenous NLRP3 inflammasome inhibitor, has been shown to be associated with the pathophysiology of depression in rodents. However its active mechanism has not been revealed. Herein, we probed both the pathways and brain regions involved in BHB's antidepressant-like effects in a learned helplessness (LH) rat model of depression. A single bilateral infusion of BHB into the cerebral ventricles induced the antidepressant-like effects on the LH rats. The antidepressant-like effects of BHB were blocked by the TrkB inhibitor ANA-12 and the AMPA receptor antagonist NBQX, indicating that the antidepressant-like effects of BHB involve BDNF-TrkB signaling and AMPA receptor activation. Further, infusions of BHB into the prelimbic and infralimbic portions of medial prefrontal cortex, the dentate gyrus of hippocampus, and the basolateral region of amygdala produced the antidepressant-like effects on LH rats. However, infusions of BHB into the central region of amygdala, the CA3 region of hippocampus, and the shell and core regions of nucleus accumbens had no effect. Finally, a single bilateral infusion of BHB into the cerebral ventricles of naive rats strengthened learning ability on repeated active avoidance test where saline-infused animals failed to increase avoidance responses.
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Affiliation(s)
- Yukihiko Shirayama
- Department of Psychiatry, Teikyo University Chiba Medical Center, Ichihara, Japan; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
| | - Masaaki Iwata
- Department of Neuropsychiatry, Faculty of Medicine, Tottori University, Yonago, Japan
| | - Kanako Miyano
- Department of Pain Control Research, The Jikei University School of Medicine, Tokyo, Japan
| | - Yuki Hirose
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Yasunori Oda
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Yuko Fujita
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan
| | - Kenji Hashimoto
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan
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Huang J, Hou X, Li M, Xue Y, An J, Wen S, Wang Z, Cheng M, Yue J. A preliminary composite of blood-based biomarkers to distinguish major depressive disorder and bipolar disorder in adolescents and adults. BMC Psychiatry 2023; 23:755. [PMID: 37845658 PMCID: PMC10580619 DOI: 10.1186/s12888-023-05204-x] [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: 06/13/2023] [Accepted: 09/19/2023] [Indexed: 10/18/2023] Open
Abstract
BACKGROUND Since diagnosis of mood disorder heavily depends on signs and symptoms, emerging researches have been studying biomarkers with the attempt to improve diagnostic accuracy, but none of the findings have been broadly accepted. The purpose of the present study was to construct a preliminary diagnostic model to distinguish major depressive disorder (MDD) and bipolar disorder (BD) using potential commonly tested blood biomarkers. METHODS Information of 721 inpatients with an ICD-10 diagnosis of MDD or BD were collected from the electronic medical record system. Variables in the nomogram were selected by best subset selection method after a prior univariable screening, and then constructed using logistic regression with inclusion of the psychotropic medication use. The discrimination, calibration and internal validation of the nomogram were evaluated by the receiver operating characteristic curve (ROC), the calibration curve, cross validation and subset validation method. RESULTS The nomogram consisted of five variables, including age, eosinophil count, plasma concentrations of prolactin, total cholesterol, and low-density lipoprotein cholesterol. The model could discriminate between MDD and BD with an area under the ROC curve (AUC) of 0.858, with a sensitivity of 0.716 and a specificity of 0.890. CONCLUSION The comprehensive nomogram constructed by the present study can be convenient to distinguish MDD and BD since the incorporating variables were common indicators in clinical practice. It could help avoid misdiagnoses and improve prognosis of the patients.
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Affiliation(s)
- Jieping Huang
- Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China
| | - Xuejiao Hou
- Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China
| | - Moyan Li
- Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China
| | - Yingshuang Xue
- Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China
| | - Jiangfei An
- Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China
| | - Shenglin Wen
- Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China
| | - Zi Wang
- Zhuhai Promotion Association of Mental Health, Zhuhai, 519000, China
| | - Minfeng Cheng
- Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China.
| | - Jihui Yue
- Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China.
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Yang L, Huang Y, Chen F, Wang Y, Su K, Zhao M, Tao W, Liu W. Berberine attenuates depression-like behavior by modulating the hippocampal NLRP3 ubiquitination signaling pathway through Trim65. Int Immunopharmacol 2023; 123:110808. [PMID: 37595491 DOI: 10.1016/j.intimp.2023.110808] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 08/10/2023] [Accepted: 08/13/2023] [Indexed: 08/20/2023]
Abstract
OBJECTIVE Increasing evidence suggests that inflammation appears to play a role in the genesis of depression. Berberine has potent anti-inflammatory effects and potential antidepressant activity, although the mechanism by which it works is yet unclear. Our study aimed to investigate the molecular mechanisms through which berberine treats depression and reduces inflammation. METHODS The CUMS model and behavioral evaluation were utilized in this study to evaluate the efficacy of berberine in the treatment of depression. Berberine's effect on the inflammatory response in CUMS mice was evaluated via ELISA assays and western blotting. Nissl staining was used to observe hippocampal neuronal functional damage. Western blotting, ELISA, ubiquitination tests, and immunoprecipitation were utilized in conjunction with in vitro experiments to study the involvement of Trim65 in the antidepressant effects of berberine. RESULTS The results suggest that berberine effectively alleviates depressive symptoms, suppresses the expression of genes associated with the NLRP3 inflammasome (NLRP3, cleaved caspase-1, ASC, GSDMD-N, Pro-IL-1β, IL-1β, Pro-IL-18, and IL-18), and reduces hippocampal neuronal functional damage in CUMS mice. Further studies showed that knockdown of Trim65 reversed the effects of berberine and increased NLRP3 inflammasome activity. Finally, K285, an important site for Trim65 binding to NLRP3, was identified. CONCLUSION Our study describes the mechanism of berberine limiting NLRP3 inflammasome activity by promoting the conjugation of Trim65 to NLRP3 and NLRP3 ubiquitination, and suggests NLRP3 inflammasome activation as a prospective target for treating inflammation-associated disorders such as depression.
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Affiliation(s)
- Lu Yang
- Nanjing University of Chinese Medicine, Nanjing, 210023, China; Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing, 210014, China
| | - Yuzhen Huang
- Nanjing University of Chinese Medicine, Nanjing, 210023, China; Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing, 210014, China
| | - Fengxi Chen
- Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yan Wang
- Nanjing University of Chinese Medicine, Nanjing, 210023, China; Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing, 210014, China
| | - Kunhan Su
- Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing, 210014, China
| | - Ming Zhao
- Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Weiwei Tao
- Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Wanli Liu
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
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Małujło-Balcerska E, Pietras T. Deiodinase Types 1 and 3 and Proinflammatory Cytokine Values May Discriminate Depressive Disorder Patients from Healthy Controls. J Clin Med 2023; 12:6163. [PMID: 37834806 PMCID: PMC10573790 DOI: 10.3390/jcm12196163] [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: 05/25/2023] [Revised: 09/11/2023] [Accepted: 09/21/2023] [Indexed: 10/15/2023] Open
Abstract
INTRODUCTION Depressive disorders are multifactorial diseases in that a variety of factors may play a role in their etiology, including inflammation and abnormalities in the thyroid hormone (TH) metabolism and levels. The purpose of this study was to evaluate iodothyronine deiodinases (DIOs) and DIO-interacting cytokines as possible biomarkers in the diagnosis of depressive disorders. METHODS This study enrolled 73 patients diagnosed with recurrent depressive disorder (rDD) and 54 controls. The expressions of DIO1, DIO2, DIO3, IL1B, IL6, TNFA, and IFNG genes, encoding three types of DIOs (1, 2, and 3), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, were assessed using the polymerase chain reaction in blood cells and an enzymatic immunoassay method in serum. The levels of examined molecules between patients and controls were compared, and correlations and diagnostic values were evaluated. RESULTS Lower levels of DIO2 and higher levels of IL1B, IL6, and TNFA were found in patients compared to controls. The protein concentrations of DIO1 and DIO2 were lower, while that of DIO3 was higher, in patients than in controls. Serum IL-1β, IL-6, and TNF-α were also higher in patients than in controls. The area under the curve (AUC) of the IL-1β, IL-6, DIO1, and DIO3 proteins was >0.7 for discriminating patients with rDD from controls. CONCLUSIONS The expressions of genes for DIO2, IL-1β, IL-6, and TNF-α may have a role in the estimation of processes present in depressive disorders. We can cautiously claim that DIO1 and DIO3 and pivotal cytokines, mainly IL-1β and IL-6, may play a role in depression diagnosis, and further studies are suggested to explain the exact role of these molecules in larger samples with more precise methods.
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Affiliation(s)
| | - Tadeusz Pietras
- Department of Clinical Pharmacology, Medical University of Łódź, 90-419 Łódź, Poland;
- Second Department of Psychiatry, Institute of Psychiatry and Neurology, 02-957 Warsaw, Poland
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Sumala S, Ekalaksananan T, Pientong C, Buddhisa S, Passorn S, Duangjit S, Janyakhantikul S, Suktus A, Bumrungthai S. The Association of HHV-6 and the TNF-α (-308G/A) Promotor with Major Depressive Disorder Patients and Healthy Controls in Thailand. Viruses 2023; 15:1898. [PMID: 37766304 PMCID: PMC10535374 DOI: 10.3390/v15091898] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 09/04/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023] Open
Abstract
Major depressive disorder (MDD) is a silent global health problem that can lead to suicide. MDD development is suggested to result from numerous risk factors, including genetic factors. A precise tool for MDD diagnosis is currently not available. Recently, inflammatory processes have been identified as being strongly involved in MDD development and the reactivation of human herpesvirus type 6 (HHV-6), upregulating cytokines such as TNF-α, which are associated with MDD. Therefore, this study aimed to determine the association of HHV-6 with genetic factors, especially TNF-α mutation, in MDD patients and their relatives compared to healthy controls. The Patient Health Questionnaire (PHQ-9) was used to evaluate MDD status, and 471 oral buccal samples were investigated for HHV-6 infection and viral copy number by qPCR. TNF-α (-308G/A) gene mutation and the cytokines TNF-α, IL-6, and IL-10 were analyzed by high-resolution melting (HRM) analysis and enzyme-linked immunosorbent assay (ELISA). Whole-exome sequencing of buccal samples was performed to analyze for genetic factors. The results showed significantly higher HHV-6 positivities and viral loads in MDD patients (15/59 (25.67%) and 14,473 ± 16,948 copies/µL DNA) and their relatives (blood relatives 17/36 (47.22%) and 8146 ± 5656 copies/µL DNA); non-blood relatives 7/16 (43.75%) and 20,721 ± 12,458 copies/µL DNA) compared to the healthy population (51/360 (14.17%) and 6303 ± 5791 copies/µL DNA). The TNF-α (-308G/A) mutation showed no significant difference. Surprisingly, 12/26 (46.15%) participants with the TNF-α (-308G/A) mutation showed HHV-6 positivities at higher rates than those with wild-type TNF-α (-308G) (70/267 (26.22%)). HHV-6-positive participants with TNF-α (-308G/A) showed higher levels of TNF-α, IL-6, and IL-10 than those of negative control. Exome analysis revealed that common mutations in immune genes were associated with depression. Therefore, this study unveiled the novel association of inflammatory gene TNF-α (-308G/A) mutations with HHV-6 reactivation, which could represent a combined risk factor for MDD. This result could induce further research on MDD development and clinical applications.
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Affiliation(s)
- Sasiwimon Sumala
- Division of Biotechnology, School of Agriculture and Natural resources, University of Phayao, Phayao 56000, Thailand
| | - Tipaya Ekalaksananan
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Chamsai Pientong
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Surachat Buddhisa
- Department of Medical Technology, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand
| | - Supaporn Passorn
- Division of Biotechnology, School of Agriculture and Natural resources, University of Phayao, Phayao 56000, Thailand
| | - Sureewan Duangjit
- Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand
| | - Somwang Janyakhantikul
- Division of Biopharmacy, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand
| | - Areeya Suktus
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Sureewan Bumrungthai
- HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
- Division of Biopharmacy, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand
- Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand
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Chen X, Wang M, Yu K, Xu S, Qiu P, Lyu Z, Zhang X, Xu Y. Chronic stress-induced immune dysregulation in breast cancer: Implications of psychosocial factors. J Transl Int Med 2023; 11:226-233. [PMID: 37662890 PMCID: PMC10474889 DOI: 10.2478/jtim-2021-0050] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Chronic stress refers to continuous emotional changes and psychological pressure that individuals experience when they are unable to adjust and stabilize the internal environment over an extended period. It can increase the pressure on endocrine mediators and cytokines in the circulation, as well as tissues throughout the hypothalamic-pituitary-adrenaline (HPA) axis and sympathetic nervous system (SNS); thus, evolving the internal environment of the tumor. This review assesses several key issues, involving psychosocial factors, and integrates clinical, cellular, and molecular studies-as well as the latest research progress-to provide a mechanistic understanding regarding breast oncopsychology. We propose that chronic stress contributes to large individual diferences in the prognosis of breast cancer survivors because they change the basic physiological processes of the endocrine and immune systems, which in turn regulate tumor growth. The study of psychological and physiological reactions of breast cancer patients suggests a new idea for psychological intervention and clinical treatment for breast cancer patients.
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Affiliation(s)
- Xiuyun Chen
- Department of Breast Surgery, the First Affiliated Hospital of China Medical University, Shenyang110001, Liaoning Province, China
| | - Mozhi Wang
- Department of Breast Surgery, the First Affiliated Hospital of China Medical University, Shenyang110001, Liaoning Province, China
| | - Keda Yu
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai200032, China
| | - Shouping Xu
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin150081, Heilongjiang Province, China
| | - Pengfei Qiu
- Breast Cancer Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan250117, Shandong Province, China
| | - Zhidong Lyu
- Breast Center, The Affiliated Hospital of Qingdao University, Qingdao266005, Shandong Province, China
| | - Xinwen Zhang
- Center of Implant Dentistry, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease, Shenyang110122, Liaoning Province, China
| | - Yingying Xu
- Department of Breast Surgery, the First Affiliated Hospital of China Medical University, Shenyang110001, Liaoning Province, China
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Mrowietz U, Sümbül M, Gerdes S. Depression, a major comorbidity of psoriatic disease, is caused by metabolic inflammation. J Eur Acad Dermatol Venereol 2023; 37:1731-1738. [PMID: 37184282 DOI: 10.1111/jdv.19192] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 04/26/2023] [Indexed: 05/16/2023]
Abstract
Psoriatic disease is a chronic, systemic immune-mediated inflammatory disorder comprising three major domains, skin, vascular and bone/joint inflammation. It is known for a long time that psoriatic disease is associated with a number of conditions such as hypertension, dyslipidemia, diabetes (metabolic syndrome) and depression. Up to one out of five people with psoriasis show concomitant depression. In the past, this was attributed to psychological stress of suffering from a chronic condition that is often visible and itchy, leading to stigmatization and adding to a significant burden of disease. Recent data provide evidence that depression associated with psoriatic disease is linked to the specific inflammatory pattern with IL-23, IL-17 family cytokines, TNF, IL-6 and IL-8 causing neuroinflammation and subsequently depression or depressive behaviour and/or anxiety. Psoriatic disease shows a distinct pattern of immune cells (e.g. dendritic cells, Th17 cells, neutrophils), mediators (e.g. IL-17A/F, IL-23, TNF) and tissue-related factors in all major domains that is different from other inflammatory dermatoses. There is a striking similarity between the inflammatory pattern in psoriatic disease and neuroinflammation that leads to depression. A number of risk factors have been identified in psoriatic disease, the most important of which are obesity and tobacco smoking. Obesity is known as a major risk factor for depression and anxiety due to its inflammatory signature. Apart from psychotherapy and anti-depressive medication, targeted treatments for psoriasis, including TNF, IL-17 and IL-23 inhibitors, can improve depression/depressive symptoms. The review summarizes the current knowledge about depression as a comorbidity in psoriatic disease.
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Affiliation(s)
- U Mrowietz
- Psoriasis Center at the Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - M Sümbül
- Psoriasis Center at the Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany
| | - S Gerdes
- Psoriasis Center at the Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany
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Mechlińska A, Wiglusz MS, Słupski J, Włodarczyk A, Cubała WJ. Exploring the Relationship between Mood Disorders and Coexisting Health Conditions: The Focus on Nutraceuticals. Brain Sci 2023; 13:1262. [PMID: 37759862 PMCID: PMC10526332 DOI: 10.3390/brainsci13091262] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/26/2023] [Accepted: 08/27/2023] [Indexed: 09/29/2023] Open
Abstract
Major depressive disorder and bipolar disorder are the leading causes of global disability. Approximately 50% of patients fail to attain remission, prompting a pronounced focus on the significance of dietary patterns and specific nutrients within the pathophysiology of mood disorders. The connection between chronic diseases and mood disorders follows a bidirectional pattern: physical ailments are interrelated with affective disorders, and, concurrently, mood symptoms often precede chronic diseases and have the potential to worsen their prognosis. Nutraceuticals affect factors that could potentially impact the onset of mood disorders: monoamines and brain-derived neurotrophic factor (BDNF) concentrations, neuroinflammation, oxidative stress, and sleep quality. Furthermore, mood disorders rarely manifest in isolation. Typically, such patients concurrently experience other mental disorders or somatic comorbidities: obesity, hypertension, diabetes, polycystic ovary syndrome (PCOS), etc., where providing nutritional support is also pertinent. To optimize the therapeutic approach for individuals with mood disorders, incorporating nutritional support may not solely ameliorate symptoms stemming directly from the mental condition, but also indirectly through interventions targeting comorbidities.
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Affiliation(s)
- Agnieszka Mechlińska
- Department of Psychiatry, Faculty of Medicine, Medical University of Gdańsk, Smoluchowskiego 17, 80-214 Gdańsk, Poland; (M.S.W.); (J.S.); (A.W.)
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Chen J, Song W, Zhang W. The emerging role of copper in depression. Front Neurosci 2023; 17:1230404. [PMID: 37609453 PMCID: PMC10440608 DOI: 10.3389/fnins.2023.1230404] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 07/24/2023] [Indexed: 08/24/2023] Open
Abstract
Copper (Cu) is an essential trace element in the brain and serves as an important cofactor for numerous enzymes involved in a wide range of biochemical processes including neurobehavioral, mitochondrial respiration, and antioxidant effects. Recent studies have demonstrated that copper dyshomeostasis is tightly associated with the development of depression by inducing oxidative stress and inflammatory responses. However, these findings have remained controversial so far. Cumulative studies have shown a positive association, while some other studies showed no association and even a negative association between serum/plasma copper level and depression. Based on these conflicted results, the association was speculated to be due to the clinical features of the population, stages of the disease, severity of copper excess, and types of specimens detected in these studies. In addition, there was an inverse association between dietary copper intake and depression. Furthermore, increasing copper intake could influence dietary zinc and iron intake to prevent and treat depression. Thus, copper supplementation may be a good measure to manage depression. This review provided a deeper understanding of the potential applicability of copper in the prevention and treatment of depression.
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Affiliation(s)
| | | | - Wenzhou Zhang
- Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Henan Engineering Research Center for Tumor Precision Medicine and Comprehensive Evaluation, Henan Provincial Key Laboratory of Anticancer Drug Research, Zhengzhou, China
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Abdel-Rasoul AA, Saleh NA, Hosny EN, El-Gizawy MM, Ibrahim EA. Cardamom oil ameliorates behavioral and neuropathological disorders in a rat model of depression induced by reserpine. JOURNAL OF ETHNOPHARMACOLOGY 2023; 308:116254. [PMID: 36781058 DOI: 10.1016/j.jep.2023.116254] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Revised: 02/04/2023] [Accepted: 02/07/2023] [Indexed: 06/18/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Depression is a public health problem. Despite the availability of treatment options, its prevalence is increasing. A high rate of treatment failure is often reported, along with considerable side effects associated with synthetic antidepressants. Therefore, developing effective and safe antidepressants from traditional herbs or natural products as an alternative strategy is warranted to avoid side effects and increase drug efficacy. In traditional medicine, cardamom has traditionally been used to treat conditions like asthma, tooth and gum infections, cataracts, nausea, diarrhea, and even depression and anxiety as well as some problems with the heart, kidneys, and digestive system. AIM OF THE STUDY The current study aimed to evaluate the antidepressant activity of cardamom oil in a rat model of depression induced by reserpine and compare it with the activity of the antidepressant drug fluoxetine. MATERIALS AND METHODS Depression-like symptoms were induced in male rats by daily i. p. injection of reserpine (0.2 mg/kg/d for 15 d followed by 0.1 mg/kg/d for 21 d to maintain the depressive state), and the rats were treated with cardamom oil (oral dose = 200 mg/kg/d) for 21 d along with the maintenance dose of reserpine. We performed behavioral tests (forced swimming test and open-field test) and evaluated biochemical markers of depression. RESULTS Our findings revealed that cardamom oil attenuated depression-like symptoms in reserpine-injected rats by improving the behavioral changes measured by the forced swimming test and the locomotor activities measured by the open-field test. In reserpine-injected rats, cardamom oil exerted antidepressant-like effects by modulating lower levels of brain monoamine neurotransmitters (serotonin, norepinephrine, and dopamine), GSH, and higher oxido-nitrosative stress parameters (malondialdehyde and nitric oxide). Moreover, cardamom oil alleviated depression-like behaviors by lowering monoamine oxidase activity and raising the activities of Na+/K+-ATPase and acetylcholinesterase and levels of a brain-derived neurotrophic factor in the cortex and hippocampus. CONCLUSION We recommend the use of cardamom oil as a safe and reliable treatment or an adjuvant for preventing depression-like symptoms in patients suffering from depression.
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Affiliation(s)
- Alaa A Abdel-Rasoul
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Nabil A Saleh
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Eman N Hosny
- Medical Physiology Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt
| | - Mayada M El-Gizawy
- Medical Physiology Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt
| | - Ehab A Ibrahim
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
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Witkin JM, Golani LK, Smith JL. Clinical pharmacological innovation in the treatment of depression. Expert Rev Clin Pharmacol 2023; 16:349-362. [PMID: 37000975 DOI: 10.1080/17512433.2023.2198703] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2023]
Abstract
INTRODUCTION Deficiencies in standard of care antidepressants are driving novel drug discovery. A new age of antidepressant medications has emerged with the introduction of rapid-acting antidepressants with efficacy in treatment-resistant patients. AREAS COVERED The newly approved medicines and those in clinical development for major depressive disorder (MDD) are documented in this scoping review of newly approved and emerging antidepressants. Compounds are evaluated for clinical efficacy, tolerability, and safety and compared to those of standard of care medicines. EXPERT OPINION A new age of antidepressant discovery relies heavily on glutamatergic mechanisms. New medicines based upon the model of ketamine have been delivered and are in clinical development. Rapid onset and the ability to impact treatment-resistant depression, raises the question of the best first-line medicines for patients. Drugs with improvements in tolerability are being investigated (e.g. mGlu2/3 receptor antagonists, AMPA receptor potentiators, and novel NMDA receptor modulators). Multiple companies are working toward the identification of novel psychedelic drugs where the requirement for psychedelic activity is not fully known. Gaps still exist - methods for matching patients with specific medicines are needed, and medicines for the prevention of MDD and its disease progression need research attention.
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Affiliation(s)
- Jeffrey M Witkin
- Laboratory of Antiepileptic Drug Discovery, Ascension St. Vincent Hospital, Indianapolis, IN, USA
- Departments of Neuroscience and Trauma Research, Ascension St. Vincent Hospital, Indianapolis, IN USA
| | - Lalit K Golani
- Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA
| | - Jodi L Smith
- Laboratory of Antiepileptic Drug Discovery, Ascension St. Vincent Hospital, Indianapolis, IN, USA
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Yu H, Kan J, Tang M, Zhu Y, Hu B. Lipopolysaccharide Preconditioning Restricts Microglial Overactivation and Alleviates Inflammation-Induced Depressive-like Behavior in Mice. Brain Sci 2023; 13:brainsci13040549. [PMID: 37190515 DOI: 10.3390/brainsci13040549] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/20/2023] [Accepted: 03/23/2023] [Indexed: 03/29/2023] Open
Abstract
Overactive microglia and severe neuroinflammation play crucial roles in the development of major depressive disorder. Preconditioning with lipopolysaccharide (LPS) provides protection against severe neuroinflammation. However, administering high doses of LPS to mice triggers depressive symptoms. Therefore, the optimal dose of LPS preconditioning needs to be determined by further experiments. LPS preconditioning is an effective agent in anti-inflammation and neuroprotection, but the mechanism by which LPS preconditioning acts in depression remain unclear. This study finds that the anti-inflammation mechanism of low-dose LPS preconditioning is mainly dependent on G-protein-coupled receptor 84 (GPR84). We use low-dose LPS for preconditioning and re-challenged mice or BV2 microglia with high-dose LPS. In addition, RNA-seq is used to explore underlying changes with LPS preconditioning. Low-dose LPS preconditioning reduces the expression of pro-inflammatory mediators and inhibits microglial activation, as well as suppresses the depressive-like behavior when the mice are re-challenged with high-dose LPS. Further investigation reveals that the tolerance-like response in microglia is dependent on the GPR84. Here, we show that low-dose LPS preconditioning can exert anti-inflammation effects and alleviates inflammation-induced depressive-like behavior in mice. As a potential therapeutic target for depression, LPS preconditioning needs to be given further attention regarding its effectiveness and safety.
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Marin C, Alobid I, Fuentes M, López-Chacón M, Mullol J. Olfactory Dysfunction in Mental Illness. Curr Allergy Asthma Rep 2023; 23:153-164. [PMID: 36696016 PMCID: PMC9875195 DOI: 10.1007/s11882-023-01068-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/13/2023] [Indexed: 01/26/2023]
Abstract
PURPOSE OF REVIEW Olfactory dysfunction contributes to the psychopathology of mental illness. In this review, we describe the neurobiology of olfaction, and the most common olfactory alterations in several mental illnesses. We also highlight the role, hitherto underestimated, that the olfactory pathways play in the regulation of higher brain functions and its involvement in the pathophysiology of psychiatric disorders, as well as the effect of inflammation on neurogenesis as a possible mechanism involved in olfactory dysfunction in psychiatric conditions. RECENT FINDINGS The olfactory deficits present in anxiety, depression, schizophrenia or bipolar disorder consist of specific alterations of different components of the sense of smell, mainly the identification of odours, as well as the qualifications of their hedonic valence (pleasant or unpleasant). Epidemiological findings have shown that both environmental factors, such as air pollutants, and inflammatory disease of the upper respiratory tract, can contribute to an increased risk of mental illness, at least in part, due to peripheral inflammatory mechanisms of the olfactory system. In this review, we describe the neurobiology of olfaction, and the most common olfactory function alterations in several psychiatric conditions and its role as a useful symptom for the differential diagnosis. We also highlight the effect of inflammation on neurogenesis as a possible mechanism involved in olfactory dysfunction in these psychiatric conditions.
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Affiliation(s)
- Concepció Marin
- INGENIO, IRCE, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CELLEX, Department 2B, Villarroel 170, 08036, Barcelona, Catalonia, Spain. .,Centre for Biomedical Investigation in Respiratory Diseases (CIBERES), Health Institute Carlos III, Madrid, Spain.
| | - Isam Alobid
- INGENIO, IRCE, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CELLEX, Department 2B, Villarroel 170, 08036, Barcelona, Catalonia, Spain.,Centre for Biomedical Investigation in Respiratory Diseases (CIBERES), Health Institute Carlos III, Madrid, Spain.,Rhinology Unit and Smell Clinic, ENT Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Mireya Fuentes
- INGENIO, IRCE, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CELLEX, Department 2B, Villarroel 170, 08036, Barcelona, Catalonia, Spain.,Centre for Biomedical Investigation in Respiratory Diseases (CIBERES), Health Institute Carlos III, Madrid, Spain
| | - Mauricio López-Chacón
- INGENIO, IRCE, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CELLEX, Department 2B, Villarroel 170, 08036, Barcelona, Catalonia, Spain.,Centre for Biomedical Investigation in Respiratory Diseases (CIBERES), Health Institute Carlos III, Madrid, Spain.,Rhinology Unit and Smell Clinic, ENT Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Joaquim Mullol
- INGENIO, IRCE, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CELLEX, Department 2B, Villarroel 170, 08036, Barcelona, Catalonia, Spain. .,Centre for Biomedical Investigation in Respiratory Diseases (CIBERES), Health Institute Carlos III, Madrid, Spain. .,Rhinology Unit and Smell Clinic, ENT Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain.
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Ahmad S, Azhar A, Tikmani P, Rafique H, Khan A, Mesiya H, Saeed H. A randomized clinical trial to test efficacy of chamomile and saffron for neuroprotective and anti-inflammatory responses in depressive patients. Heliyon 2022; 8:e10774. [PMID: 36217471 PMCID: PMC9547202 DOI: 10.1016/j.heliyon.2022.e10774] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 07/26/2022] [Accepted: 09/22/2022] [Indexed: 11/24/2022] Open
Abstract
Depression is one of the common psychiatric problems in growing world population caused by long-term stressful events that may trigger the down regulation of neurogenesis. The pathogenesis of depression initially relies on serotonin deficiency which is associated with depressive feelings. Tryptophan (TRP) depletion participate crucial role in inducing depressive symptoms. Long-term reduction of 5-HT may disseminate to high sensitivity of MDD and alters the level of BDNF. Some studies have also revealed the strong association between excessive neuroinflammation and BDNF levels, due the release of pro-inflammatory cytokines. The treatment approach through FDA approved medicine has their own merits and drawbacks. Therefore, herbal alternatives have recently garnered attention for their effectiveness against depression. However, evidence-based synergic effects of antidepressant with different herbal agents are limited. The purpose of this study was to assess the synergistic effects of two well-known herbs, chamomile and saffron, as an adjuvant therapy in patients with mild to moderate depression. The present study was study randomized, open, blinded trial and comprised of 120 participants randomly allocated to control (n = 60) and test (n = 60). After consent, the patient health questionnaire- 9 (PHQ-9) was filled to obtain depression scores. The test participants were received herbal tea sachets twice a day for one month (20 mg Chamomile and 1 mg Saffron/sachet) along with routine medicines, while control participants were received only allopathic medications. Blood samples were taken before and after the treatment. The depressive symptoms improved significantly with both treatments. The effect of herbs enhanced the efficacy of medications and significantly improved PHQ-9 scale and BDNF while reduced the inflammatory markers (CRP) and TRP level in plasma thereby increased the availability of TRP in brain. It has been concluded that the herbal adjuvant therapy produced long term improvement against depression and enhanced the efficacy of allopathic treatment.
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Shvartsur R, Agam G, Uzzan S, Azab AN. Low-Dose Aspirin Augments the Anti-Inflammatory Effects of Low-Dose Lithium in Lipopolysaccharide-Treated Rats. Pharmaceutics 2022; 14:pharmaceutics14050901. [PMID: 35631487 PMCID: PMC9143757 DOI: 10.3390/pharmaceutics14050901] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 04/17/2022] [Accepted: 04/19/2022] [Indexed: 12/23/2022] Open
Abstract
Mounting evidence suggests that immune-system dysfunction and inflammation play a role in the pathophysiology and treatment of mood-disorders in general and of bipolar disorder in particular. The current study examined the effects of chronic low-dose aspirin and low-dose lithium (Li) treatment on plasma and brain interleukin-6 and tumor necrosis factor-α production in lipopolysaccharide (LPS)-treated rats. Rats were fed regular or Li-containing food (0.1%) for six weeks. Low-dose aspirin (1 mg/kg) was administered alone or together with Li. On days 21 and 42 rats were injected with 1 mg/kg LPS or saline. Two h later body temperature was measured and rats were sacrificed. Blood samples, the frontal-cortex, hippocampus, and the hypothalamus were extracted. To assess the therapeutic potential of the combined treatment, rats were administered the same Li + aspirin protocol without LPS. We found that the chronic combined treatment attenuated LPS-induced hypothermia and significantly reduced plasma and brain cytokine level elevation, implicating the potential neuroinflammatory diminution purportedly present among the mentally ill. The combined treatment also significantly decreased immobility time and increased struggling time in the forced swim test, suggestive of an antidepressant-like effect. This preclinical evidence provides a potential approach for treating inflammation-related mental illness.
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Affiliation(s)
- Rachel Shvartsur
- Department of Nursing, School for Community Health Professions, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 8410501, Israel;
- Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 8410501, Israel; (G.A.); (S.U.)
| | - Galila Agam
- Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 8410501, Israel; (G.A.); (S.U.)
| | - Sarit Uzzan
- Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 8410501, Israel; (G.A.); (S.U.)
| | - Abed N. Azab
- Department of Nursing, School for Community Health Professions, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 8410501, Israel;
- Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 8410501, Israel; (G.A.); (S.U.)
- Correspondence: ; Tel.: +972-86-479880; Fax: +972-86-477-683
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Daniel WA, Bromek E, Danek PJ, Haduch A. The mechanisms of interactions of psychotropic drugs with liver and brain cytochrome P450 and their significance for drug effect and drug-drug interactions. Biochem Pharmacol 2022; 199:115006. [PMID: 35314167 DOI: 10.1016/j.bcp.2022.115006] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/11/2022] [Accepted: 03/14/2022] [Indexed: 02/08/2023]
Abstract
Cytochrome P450 (CYP) plays an important role in psychopharmacology. While liver CYP enzymes are responsible for the biotransformation of psychotropic drugs, brain CYP enzymes are involved in the local metabolism of these drugs and endogenous neuroactive substances, such as neurosteroids, and in alternative pathways of neurotransmitter biosynthesis including dopamine and serotonin. Recent studies have revealed a relation between the brain nervous system and cytochrome P450, indicating that CYP enzymes metabolize endogenous neuroactive substances in the brain, while the brain nervous system is engaged in the central neuroendocrine and neuroimmune regulation of cytochrome P450 in the liver. Therefore, the effect of neuroactive drugs on cytochrome P450 should be investigated not only in vitro, but also at in vivo conditions, since only in vivo all mechanisms of drug-enzyme interaction can be observed, including neuroendocrine and neuroimmune modulation. Psychotropic drugs can potentially affect cytochrome P450 via a number of mechanisms operating at the level of the nervous, hormonal and immune systems, and the liver. Their effect on cytochrome P450 in the brain is often different than in the liver and region-dependent. Since psychotropic drugs can affect cytochrome P450 both in the liver and brain, they can modify their own pharmacological effect at both pharmacokinetic and pharmacodynamic level. The article describes the mechanisms by which psychotropic drugs can change the expression/activity of cytochrome P450 in the liver and brain, and discusses the significance of those mechanisms for drug action and drug-drug interactions. Moreover, the brain CYP2D6 is considered as a potential target for psychotropics.
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Affiliation(s)
- Władysława A Daniel
- Department of Pharmacokinetics and Drug Metabolism, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.
| | - Ewa Bromek
- Department of Pharmacokinetics and Drug Metabolism, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland
| | - Przemysław J Danek
- Department of Pharmacokinetics and Drug Metabolism, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland
| | - Anna Haduch
- Department of Pharmacokinetics and Drug Metabolism, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland
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Tateishi H, Mizoguchi Y, Monji A. Is the Therapeutic Mechanism of Repetitive Transcranial Magnetic Stimulation in Cognitive Dysfunctions of Depression Related to the Neuroinflammatory Processes in Depression? Front Psychiatry 2022; 13:834425. [PMID: 35280153 PMCID: PMC8907472 DOI: 10.3389/fpsyt.2022.834425] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 01/28/2022] [Indexed: 12/27/2022] Open
Abstract
The lifetime prevalence of depression is reported to be >10%, and it is an important illness that causes various disabilities over a long period of life. Neuroinflammation process is often reported to be closely linked to the pathophysiology of depression. Approximately one-third of depression is known to be treatment-resistant depression (TRD), in which the symptoms are refractory to adequate treatment. Cognitive dysfunction is one of the most important symptoms of depression that impedes the rehabilitation of patients with depression. Repetitive transcranial magnetic stimulation (rTMS) is a minimally invasive and effective treatment for TRD and is also known to be effective in cognitive dysfunction in depression. Since the details of the therapeutic mechanism of rTMS are still unknown, we have been conducting studies to clarify the therapeutic mechanism of rTMS, especially focusing on cognitive dysfunction in depression. In the present review, we present our latest results and discuss them from the standpoint of the neuroinflammation hypothesis of depression, while citing relevant literature.
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Affiliation(s)
- Hiroshi Tateishi
- Department of Psychiatry, Faculty of Medicine, Saga University, Saga, Japan
| | - Yoshito Mizoguchi
- Department of Psychiatry, Faculty of Medicine, Saga University, Saga, Japan
| | - Akira Monji
- Department of Psychiatry, Faculty of Medicine, Saga University, Saga, Japan
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