{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:21:45Z","timestamp":1787498505234,"version":"build-2736575974"},"reference-count":24,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurosciences"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Depression is increasingly recognized as a multisystem disorder involving interconnected neuroinflammatory, neuroendocrine, metabolic and gut\u2013brain mechanisms rather than isolated neurotransmitter abnormalities. Emerging evidence suggests that dysregulation of cytokine activity, hypothalamic\u2013pituitary\u2013adrenal (HPA) axis function, oxidative stress, mitochondrial dysfunction and gut microbiota collectively contribute to depressive pathophysiology. This review aimed to synthesise current evidence on these biological interactions and evaluate the potential role of nutritional modulation in influencing these pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>A PRISMA-informed systematic review was conducted using PubMed, Scopus, Web of Science, Embase, PsycINFO and Google Scholar for studies published between 2010 and 2025. Thirty-five eligible studies were included. The evidence demonstrates a self-reinforcing biological network in which chronic stress activates the HPA axis, leading to glucocorticoid receptor resistance, increased pro-inflammatory cytokines, neuroinflammation, oxidative stress and gut microbiota dysbiosis. These interconnected mechanisms contribute to depressive symptoms and may perpetuate disease progression. Nutritional interventions, including Mediterranean dietary patterns, omega-3 fatty acids, dietary fibre, probiotics, polyphenols and selected micronutrients, consistently showed potential to reduce inflammation, regulate HPA axis activity, improve gut microbial balance and mitigate oxidative stress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Message<\/jats:title>\n                    <jats:p>Depression should be conceptualised as a complex multisystem disorder driven by dynamic interactions among immune, endocrine, metabolic and microbiota-related pathways. Nutritional modulation represents a promising adjunctive strategy capable of targeting these interconnected biological mechanisms. Future longitudinal and interventional studies integrating multi-omics approaches are needed to validate causal pathways and develop personalised nutrition-based interventions for depression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09727531261444529","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T11:30:41Z","timestamp":1786620641000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroinflammation, HPA Axis Dysregulation, Cytokine Activity and Nutritional Modulation in Depression: A PRISMA-compliant Systematic Review"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7240-4782","authenticated-orcid":false,"given":"Saranya","family":"TS","sequence":"first","affiliation":[{"name":"Department of Psychology, School of Social Sciences, Vellore Institute of Technology, Chennai, Tamil Nadu, India"},{"name":"Amity Institute of Behavioural Health and Allied Sciences, Amity University, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eebnem","family":"Y\u00fccel","sequence":"additional","affiliation":[{"name":"Sel\u00e7uk University, Alaeddin Keykubat Campus, Konya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2670-2858","authenticated-orcid":false,"given":"Sandeep Kumar","family":"Gupta","sequence":"additional","affiliation":[{"name":"Mohan Babu University, Tirupati, Andhra Pradesh, India"},{"name":"Symbiosis International University, Pune, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Recep","family":"Y\u00fccel","sequence":"additional","affiliation":[{"name":"K\u0131r\u0131kkale University, K\u0131r\u0131kkale, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumitra","family":"Datta","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_3_6_2_2","unstructured":"World Health Organization. Depression. Geneva: World Health Organization; 2023. Available from: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/depression"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14720"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26041645"},{"issue":"6","key":"e_1_3_6_5_2","first-page":"554","article-title":"Why are depressed patients inflamed? A conceptual review of stress, glucocorticoids, and inflammation","volume":"27","author":"Pariante CM.","year":"2017","unstructured":"Pariante CM. Why are depressed patients inflamed? A conceptual review of stress, glucocorticoids, and inflammation. Mol Psychiatry 2017; 27(6): 554\u2013559.","journal-title":"Mol Psychiatry"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.163"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox14050613"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.31083\/j.jin2203065"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13668-025-00619-2"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-00925-x"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2021.105550"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.847460"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2016.09.007"},{"key":"e_1_3_6_14_2","article-title":"Interleukin-6, hippocampal atrophy, and hypothalamic\u2013pituitary\u2013adrenal axis feedback disruption in depression","author":"Lei Y","year":"2025","unstructured":"Lei Y, , Wang X, , Zhang Y, . 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Hypothalamus\u2013pituitary\u2013adrenal and gut\u2013brain axes in the biological interaction pathway of depression. Front Psychiatry 2025; 19: 1541075.","journal-title":"Front Psychiatry"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom15111556"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2023.1130989"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijtm4010010"},{"issue":"8","key":"e_1_3_6_21_2","article-title":"Hypothalamic\u2013pituitary\u2013adrenal axis: potential mechanisms involved in stress-induced Alzheimer\u2019s disease and depression","volume":"16","author":"Sharan P","year":"2024","unstructured":"Sharan P, and Vellapandian C. Hypothalamic\u2013pituitary\u2013adrenal axis: potential mechanisms involved in stress-induced Alzheimer\u2019s disease and depression. 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