{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T08:31:08Z","timestamp":1791621068510,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AMERI-ASIA MED Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Major depressive disorder (MDD) and its severe subtype, major dysmood disorder (MDMD), are distinguished by activation of inflammatory and growth factor subnetworks, which are associated with recurrence of illness (ROI) and adverse childhood experiences (ACEs). Nerve growth factor (NGF) plays a crucial role in facilitating neuro-immune communications and may regulate the inflammatory response. Methods: The present study examined the effects of ACEs and ROI on culture supernatant NGF, stem cell factor (SCF), stem cell GF (SCGF), hepatocyte GF (HGF), and macrophage colony-stimulating factor (M-CSF), in relation to a neurotoxicity (NT) cytokine profile. Results: NGF levels are lower in MDD (p = 0.003), particularly MDMD (p &lt; 0.001), as compared with normal controls. ROI and ACE were significantly and inversely associated with NGF (\u22640.003) and the NGF\/NT ratio (\u22640.001), whereas there are no effects of ACEs and ROI on SCF, SCGF, HGF, or M-CSF. Lowered NGF (p = 0.003) and the NGF\/NT ratio (p &lt; 0.001) are highly significantly and inversely associated with the severity of the current depression phenome, conceptualized as a latent vector extracted from the current severity of depression, anxiety, and suicidal behaviors. We found that one validated and replicable latent vector could be extracted from NGF, ROI, and the depression phenome, which therefore constitutes a novel ROI-NGF-pathway-phenotype. ACEs explained 59.5% of the variance in the latter pathway phenotype (p &lt; 0.001). Conclusions: The imbalance between decreased NGF and increased neurotoxic cytokines during the acute phase of severe depression may contribute to decreased neuroprotection, increased neuro-affective toxicity, and chronic mild inflammation.<\/jats:p>","DOI":"10.3390\/brainsci13071090","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:47:38Z","timestamp":1689727658000},"page":"1090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Lower Nerve Growth Factor Levels in Major Depression and Suicidal Behaviors: Effects of Adverse Childhood Experiences and Recurrence of Illness"],"prefix":"10.3390","volume":"13","author":[{"given":"Michael","family":"Maes","sequence":"first","affiliation":[{"name":"Sichuan Provincial Center for Mental Health, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China"},{"name":"Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu 610072, China"},{"name":"Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, The Thai Red Cross Society, Bangkok 10330, Thailand"},{"name":"Department of Psychiatry, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"},{"name":"Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muanpetch","family":"Rachayon","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, The Thai Red Cross Society, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketsupar","family":"Jirakran","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, The Thai Red Cross Society, Bangkok 10330, Thailand"},{"name":"Maximizing Thai Children\u2019s Developmental Potential Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pimpayao","family":"Sodsai","sequence":"additional","affiliation":[{"name":"Center of Excellence in Immunology and Immune-Mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atapol","family":"Sughondhabirom","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, The Thai Red Cross Society, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8885","DOI":"10.1007\/s12035-018-1016-x","article-title":"The Compensatory Immune-Regulatory Reflex System (CIRS) in Depression and Bipolar Disorder","volume":"55","author":"Maes","year":"2018","journal-title":"Mol. 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