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. 2023 Jul 18;13(7):1090.
doi: 10.3390/brainsci13071090.

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

Michael Maes  1   2   3   4   5   6 , Muanpetch Rachayon  3 , Ketsupar Jirakran  3   7 , Pimpayao Sodsai  8 , Atapol Sughondhabirom  3
Affiliations

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

Michael Maes et al. Brain Sci. .

Abstract

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.

Keywords: biomarkers; inflammation; major depression; mood disorders; neuro-immune.

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Conflict of interest statement

The authors have no conflicts of interest with any commercial or other association in connection with the submitted article.

Figures

Figure 1
Figure 1
Measurements of the growth factors in major dysmood disorder (MDMD) and simple dysmood disorder (SDMD) as compared with healthy controls (set at 0 value). NGF: nerve growth factor; SCF: stem cell factor; SCGF: stem cell growth factor; HGF: hepatocyte growth factor; M-CSF: macrophage colony stimulating factor. GF: composite built using platelet-derived growth factor, vascular endothelial growth factor, and fibroblast growth factor; NT: neurotoxicity: composite of neurotoxic cytokines.
Figure 2
Figure 2
Partial regression of the ratio of nerve growth factor (NGF) on neurotoxicity (NT) and other growth factors [zNGF-z(NT + GF)] on adverse childhood experiences (ACEs).
Figure 3
Figure 3
Partial regression of nerve growth factor (NGF) levels on recurrence of illness (ROI).
Figure 4
Figure 4
Partial regression of the depression phenome (PC_phenome) score on the ratio of nerve growth factor (NGF) to neurotoxicity (NT) and other growth factors (GF) [zNGF-z(NT + GF)].
Figure 5
Figure 5
PLS-SEM model. ACE: Adverse childhood experiences, ROI: recurrence of illness, NGF: nerve growth factor, GF: composite built using platelet-derived growth factor, vascular endothelial growth factor, and fibroblast growth factor; PC_phenome: first factor extracted from current phenome data, HS-SDMD-MDMD: healthy controls—simple dysmood disorder—major dysmood disorder (ordinal scale). ACE is entered as the input variable, the ROI-NGF-phenome latent vector as mediator, and the diagnosis (controls, SDMD and MDMD) as the output. Shown are the path coefficients (with p-value) and loadings (with p values) of the outer model; figures in the blue circles denote explained variance.
See this image and copyright information in PMC

References

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