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Lower Nerve Growth Factor Levels in Major Depression and Suicidal Behaviors: Effects of Adverse Childhood Experiences and Recurrence of Illness

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 cruc...

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Autores principales: Maes, Michael, Rachayon, Muanpetch, Jirakran, Ketsupar, Sodsai, Pimpayao, Sughondhabirom, Atapol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377511/
https://www.ncbi.nlm.nih.gov/pubmed/37509019
http://dx.doi.org/10.3390/brainsci13071090
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author Maes, Michael
Rachayon, Muanpetch
Jirakran, Ketsupar
Sodsai, Pimpayao
Sughondhabirom, Atapol
author_facet Maes, Michael
Rachayon, Muanpetch
Jirakran, Ketsupar
Sodsai, Pimpayao
Sughondhabirom, Atapol
author_sort Maes, Michael
collection PubMed
description 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 < 0.001), as compared with normal controls. ROI and ACE were significantly and inversely associated with NGF (≤0.003) and the NGF/NT ratio (≤0.001), 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 < 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 < 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.
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spelling pubmed-103775112023-07-29 Lower Nerve Growth Factor Levels in Major Depression and Suicidal Behaviors: Effects of Adverse Childhood Experiences and Recurrence of Illness Maes, Michael Rachayon, Muanpetch Jirakran, Ketsupar Sodsai, Pimpayao Sughondhabirom, Atapol Brain Sci Article 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 < 0.001), as compared with normal controls. ROI and ACE were significantly and inversely associated with NGF (≤0.003) and the NGF/NT ratio (≤0.001), 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 < 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 < 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. MDPI 2023-07-18 /pmc/articles/PMC10377511/ /pubmed/37509019 http://dx.doi.org/10.3390/brainsci13071090 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Maes, Michael
Rachayon, Muanpetch
Jirakran, Ketsupar
Sodsai, Pimpayao
Sughondhabirom, Atapol
Lower Nerve Growth Factor Levels in Major Depression and Suicidal Behaviors: Effects of Adverse Childhood Experiences and Recurrence of Illness
title Lower Nerve Growth Factor Levels in Major Depression and Suicidal Behaviors: Effects of Adverse Childhood Experiences and Recurrence of Illness
title_full Lower Nerve Growth Factor Levels in Major Depression and Suicidal Behaviors: Effects of Adverse Childhood Experiences and Recurrence of Illness
title_fullStr Lower Nerve Growth Factor Levels in Major Depression and Suicidal Behaviors: Effects of Adverse Childhood Experiences and Recurrence of Illness
title_full_unstemmed Lower Nerve Growth Factor Levels in Major Depression and Suicidal Behaviors: Effects of Adverse Childhood Experiences and Recurrence of Illness
title_short Lower Nerve Growth Factor Levels in Major Depression and Suicidal Behaviors: Effects of Adverse Childhood Experiences and Recurrence of Illness
title_sort lower nerve growth factor levels in major depression and suicidal behaviors: effects of adverse childhood experiences and recurrence of illness
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377511/
https://www.ncbi.nlm.nih.gov/pubmed/37509019
http://dx.doi.org/10.3390/brainsci13071090
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