Lower nerve growth factor levels in major depression and suicidal behaviors: effects of adverse childhood experiences and recurrence of illness

Abstract

Background: 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 (ACE). 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 ACE 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 ACE 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. ACE 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.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

AMERI-ASIA MED CO, Ltd.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Before participating in this study, all subjects and controls provided written consent. The investigation was conducted in accordance with international and Thai ethical standards and privacy laws. The institutional Review Board of Chulalongkorn University's Faculty of Medicine in Bangkok, Thailand, approved the study (#528/63) in accordance with the International Guidelines for the Protection of Human Subjects as required by the Declaration of Helsinki, The Belmont Report, the CIOMS Guideline, and the International Conference for Harmonization of Good Clinical Practice (ICH-GCP).

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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Data Availability

The dataset generated during and/or analyzed during the current study will be available from the corresponding author (M.M.) upon reasonable request and once the dataset has been fully exploited by the authors.

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