{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T20:13:28Z","timestamp":1793218408441,"version":"4.5.0"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Science and Technology of Henan Province","award":["222102310143"],"award-info":[{"award-number":["222102310143"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Major depressive disorder (MDD) is a prevalent psychiatric disorder with a complex pathogenesis influenced by various factors. Recent research has highlighted a significant connection between psychological stress and MDD, with inflammation playing a central role in this relationship. Studies have demonstrated that peripheral immune changes in patients with MDD and in mouse models of social stress are closely linked to depressive symptoms. These findings suggest that targeting peripheral immune factors could represent a novel approach for treating stress-related neuropsychiatric disorders. Stress triggers a cascade of inflammatory responses, leading to disruptions in neurotransmitter metabolism and reduced synaptic plasticity. These changes exacerbate depression and contribute to cognitive decline. This study examines the bidirectional relationship between MDD and stress, focusing on the role of inflammation in this complex interplay. Recent studies have identified specific immune factors that are elevated in the serum of patients with MDD and stress-exposed mice, indicating a mechanism by which peripheral immune responses can affect central nervous system function and behavior. Furthermore, proteins, such as nuclear factor kappa-B (NF-\u03baB), reportedly play a critical role in the regulation of stress hormones and are associated with depressive behaviors. Understanding these mechanisms is essential for advancing diagnostic, intervention, and treatment strategies for MDD.<\/jats:p>","DOI":"10.3390\/cells14090629","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T06:38:37Z","timestamp":1745390317000},"page":"629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inflammatory Factors: A Key Contributor to Stress-Induced Major Depressive Disorder"],"prefix":"10.3390","volume":"14","author":[{"given":"Qian","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baowen","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemin","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxiao","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1159\/000097965","article-title":"Is there a continuity between bipolar and depressive disorders?","volume":"76","author":"Benazzi","year":"2007","journal-title":"Psychother. Psychosom."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ejca.2022.06.058","article-title":"Comparative efficacy of novel combination strategies for unresectable hepatocellular carcinoma: A network metanalysis of phase III trials","volume":"174","author":"Fulgenzi","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1126\/science.aab2358","article-title":"Brain disorders? Precisely","volume":"348","author":"Insel","year":"2015","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1177\/1099800418776082","article-title":"Biological Sex Differences in Depression: A Systematic Review","volume":"20","author":"Labaka","year":"2018","journal-title":"Biol. Res. Nurs."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Micek, A., Jurek, J., Owczarek, M., Guerrera, I., Torrisi, S.A., Castellano, S., Grosso, G., Alshatwi, A.A., and Godos, J. (2023). Polyphenol-Rich Beverages and Mental Health Outcomes. Antioxidants, 12.","DOI":"10.3390\/antiox12020272"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1017\/S0033291721000441","article-title":"The genetic basis of major depression","volume":"51","author":"Kendall","year":"2021","journal-title":"Psychol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1038\/s41588-023-01559-9","article-title":"Phenotype integration improves power and preserves specificity in biobank-based genetic studies of major depressive disorder","volume":"55","author":"Dahl","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/s41562-019-0759-3","article-title":"Genomic prediction of depression risk and resilience under stress","volume":"4","author":"Fang","year":"2020","journal-title":"Nat. Hum. Behav."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1001\/jamapsychiatry.2023.2833","article-title":"Determinants and Outcomes of Suicidal Behavior Among Patients with Major Depressive Disorder","volume":"80","author":"Lundberg","year":"2023","journal-title":"JAMA Psychiatry"},{"key":"ref_10","first-page":"1","article-title":"Cognitive dysfunction: An important feature of major depressive disorder","volume":"2","author":"Corponi","year":"2023","journal-title":"J. Neurons Neurol. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.2522\/ptj.20130597","article-title":"Chronic stress, cortisol dysfunction, and pain: A psychoneuroendocrine rationale for stress management in pain rehabilitation","volume":"94","author":"Hannibal","year":"2014","journal-title":"Phys. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Jentsch, M.C., Burger, H., Meddens, M.B.M., Beijers, L., van den Heuvel, E.R., Meddens, M.J.M., and Schoevers, R.A. (2020). Gender Differences in Developing Biomarker-Based Major Depressive Disorder Diagnostics. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093039"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1146\/annurev-clinpsy-050718-095557","article-title":"Estrogen, Stress, and Depression: Cognitive and Biological Interactions","volume":"15","author":"Albert","year":"2019","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.jad.2023.08.009","article-title":"Premenstrual disorders and gender differences in adolescent mental health","volume":"340","author":"Li","year":"2023","journal-title":"J. Affect. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tian, X., Hu, N., Lu, L., Tan, L., and Li, P. (2024). Gender differences in major depressive disorder at different ages: A REST-meta-MDD project-based study. BMC Psychiatry, 24.","DOI":"10.1186\/s12888-024-06021-6"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/s41467-021-27604-x","article-title":"Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue","volume":"13","author":"Cadoret","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41392-024-01738-y","article-title":"Major depressive disorder: Hypothesis, mechanism, prevention and treatment","volume":"9","author":"Cui","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6835","DOI":"10.1038\/s41467-023-42686-5","article-title":"Transcriptional dissection of symptomatic profiles across the brain of men and women with depression","volume":"14","author":"Mansouri","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/s41398-021-01348-0","article-title":"Mendelian randomization integrating GWAS and eQTL data revealed genes pleiotropically associated with major depressive disorder","volume":"11","author":"Yang","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.metabol.2005.01.007","article-title":"Genes, stress, and depression","volume":"54","author":"Wurtman","year":"2005","journal-title":"Metabolism"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2205486","DOI":"10.1002\/advs.202205486","article-title":"Gene Expression has Distinct Associations with Brain Structure and Function in Major Depressive Disorder","volume":"10","author":"Liu","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/mp.2015.57","article-title":"Gene expression in major depressive disorder","volume":"21","author":"Jansen","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jad.2023.08.113","article-title":"An association study of clock genes with major depressive disorder","volume":"341","author":"Li","year":"2023","journal-title":"J. Affect. Disord."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e519","DOI":"10.1038\/tp.2015.15","article-title":"Identification of genes and gene pathways associated with major depressive disorder by integrative brain analysis of rat and human prefrontal cortex transcriptomes","volume":"5","author":"Malki","year":"2015","journal-title":"Transl. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1017\/S0033291712000955","article-title":"Cortisol and depression: Three questions for psychiatry","volume":"43","author":"Herbert","year":"2013","journal-title":"Psychol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/B978-0-12-800977-2.00005-X","article-title":"Epigenetics of depression","volume":"128","author":"Lolak","year":"2014","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1073\/pnas.1914655117","article-title":"Molecular adaptations of the blood-brain barrier promote stress resilience vs. depression","volume":"117","author":"Dudek","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1038\/s41593-017-0010-3","article-title":"Social stress induces neurovascular pathology promoting depression","volume":"20","author":"Menard","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.pnpbp.2017.11.017","article-title":"Altered neuro-inflammatory gene expression in hippocampus in major depressive disorder","volume":"82","author":"Mahajan","year":"2018","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/acps.12698","article-title":"Peripheral cytokine and chemokine alterations in depression: A meta-analysis of 82 studies","volume":"135","author":"Freitas","year":"2017","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/mp.2017.205","article-title":"Chemokines in depression in health and in inflammatory illness: A systematic review and meta-analysis","volume":"23","author":"Leighton","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.neuron.2018.08.001","article-title":"Defective Inflammatory Pathways in Never-Treated Depressed Patients Are Associated with Poor Treatment Response","volume":"99","author":"Syed","year":"2018","journal-title":"Neuron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1065","DOI":"10.1038\/tp.2017.31","article-title":"Altered peripheral immune profiles in treatment-resistant depression: Response to ketamine and prediction of treatment outcome","volume":"7","author":"Kiraly","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s10555-018-9741-1","article-title":"Stress, inflammation, and eicosanoids: An emerging perspective","volume":"37","author":"Umamaheswaran","year":"2018","journal-title":"Cancer Metastasis Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41398-020-0759-0","article-title":"Stress, inflammation and hippocampal subfields in depression: A 7 Tesla MRI Study","volume":"10","author":"Tannous","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.biopsych.2018.08.018","article-title":"Inflammation: A Proposed Intermediary Between Maternal Stress. and Offspring Neuropsychiatric Risk","volume":"85","author":"Hantsoo","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kouba, B.R., de Araujo Borba, L., Borges de Souza, P., Gil-Mohapel, J., and Rodrigues, A.L.S. (2024). Role of Inflammatory Mechanisms in Major. Depressive Disorder: From Etiology to Potential. Pharmacological Targets. Cells, 13.","DOI":"10.3390\/cells13050423"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41398-022-02175-7","article-title":"Acute stress induces severe neural inflammation and overactivation of glucocorticoid signaling in interleukin-18-deficient mice","volume":"12","author":"Yamanishi","year":"2022","journal-title":"Transl. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jad.2022.04.067","article-title":"Is subthreshold depression in adolescence clinically relevant?","volume":"309","author":"Noyes","year":"2022","journal-title":"J. Affect. Disord."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s12264-021-00638-3","article-title":"Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications","volume":"37","author":"Li","year":"2021","journal-title":"Neurosci. Bull."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1002\/1873-3468.13752","article-title":"The NF-kappaB regulator IkappaBbeta exhibits different molecular interactivity and phosphorylation status from IkappaBalpha in an IKK2-catalysed reaction","volume":"594","author":"Shoji","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.neuron.2018.08.031","article-title":"Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation","volume":"100","author":"Leng","year":"2018","journal-title":"Neuron"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"114426","DOI":"10.1016\/j.expneurol.2023.114426","article-title":"Bergapten alleviates depression-like behavior by inhibiting cyclooxygenase 2 activity and NF-kappaB\/MAPK signaling pathway in microglia","volume":"365","author":"Yan","year":"2023","journal-title":"Exp. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.3389\/fimmu.2019.01511","article-title":"Melatonin Attenuates LPS-Induced Acute Depressive-Like Behaviors and MicroglialNLRP3 Inflammasome Activation Through the SIRT1\/Nrf2 Pathway","volume":"10","author":"Arioz","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.lfs.2018.05.038","article-title":"Perilla aldehyde attenuates CUMS-induced depressive-like behaviors via regulating TXNIP\/TRX\/NLRP3 pathway in rats","volume":"206","author":"Song","year":"2018","journal-title":"Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.bbi.2024.06.008","article-title":"Astrocyte-specific activation of sigma-1 receptors in mPFC mediates the faster onset antidepressant effect by inhibiting NF-kappaB-induced neuroinflammation","volume":"120","author":"Wang","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.immuni.2017.07.025","article-title":"GR Extinguishes Inflamed Chromatin, and NF-kappaB Evacuates","volume":"47","author":"Fasolino","year":"2017","journal-title":"Immunity"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100687","DOI":"10.1016\/j.jbc.2021.100687","article-title":"Repression of transcription by the glucocorticoid receptor: A parsimonious model for the genomics era","volume":"296","author":"Gerber","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"110677","DOI":"10.1016\/j.intimp.2023.110677","article-title":"Aucubin improves chronic unpredictable mild stress-induced depressive behavior in mice via the GR\/NF-kappaB\/NLRP3 axis","volume":"123","author":"Liu","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1182\/blood.2022016040","article-title":"Single-cell multiomics reveal the scale of multilayered adaptations enabling CLL relapse during venetoclax therapy","volume":"140","author":"Thijssen","year":"2022","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ccr.2004.09.003","article-title":"Nuclear factor-kappaB: The enemy within","volume":"6","author":"Aggarwal","year":"2004","journal-title":"Cancer Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.ceb.2003.10.005","article-title":"Dying for NF-kappaB? Control of cell death by transcriptional regulation of the apoptotic machinery","volume":"15","author":"Burstein","year":"2003","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.tim.2016.04.002","article-title":"The Commonalities in Bacterial Effector Inhibition of Apoptosis","volume":"24","author":"Robinson","year":"2016","journal-title":"Trends Microbiol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/9\/629\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:19:50Z","timestamp":1760030390000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/9\/629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,23]]},"references-count":53,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["cells14090629"],"URL":"https:\/\/doi.org\/10.3390\/cells14090629","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,23]]}}}