Novel Insight into Neuroimmune Regulatory Mechanisms and Biomarkers Linking Major Depression and Vascular Diseases: The Dilemma Continues
Abstract
:1. Introduction
2. Role of Inflammation in Depressive Disorder
2.1. Cytokines in MDD Pathophysiology
2.1.1. Tryptophan/Kynurenine Pathway
2.1.2. Hypothalamus–Pituitary–Adrenal (HPA) Axis Pathway
3. Role of Endothelial Function in Depressive Disorder
3.1. Evaluation of Endothelial Function
3.2. Endothelial Dysfunction—Role in MDD-Linked Vascular Pathology
3.2.1. Endothelial Dysfunction and Oxidative Stress
3.2.2. Endothelial Dysfunction and Inflammation
3.2.3. Endothelial Dysfunction and Glucocorticoids
4. Role of Autonomic Nervous System in Depressive Disorder
5. Concluding Remarks and Perspectives
Author Contributions
Funding
Conflicts of Interest
Abbreviations
MDD | Major depressive disorder |
CVD | Cardiovascular disease |
IL | Interleukin |
TNF | Tumor necrosis factor |
WHO | World Health Organization |
IFN | Interferon |
TGF | Transforming growth factor |
CNS | Central nervous system |
MCP | Monocyte chemoattractant protein |
IDO | Indoleamine 2 |
NMDA | N-methyl-D-aspartate |
HPA | Hypothalamic-pituitary-adrenal |
GRs | Glucocorticoid receptors |
ROS | Reactive oxygen species |
RNS | Reactive nitrogen species |
NO | Nitric oxide |
FMD | Flow-mediated dilation |
PAT | Peripheral-artery tonometry |
VWF | von Willebrand factor |
ICAM-1 | Intercellular adhesion molecule-1 |
VCAM-1 | Vascular cell adhesion molecule-1 |
LDL | Low-density lipoprotein |
HDL | High-density lipoprotein |
cGMP | Cyclic guanosine monophosphate |
NADPH | Reduced form of nicotinamide adenine dinucleotide phosphate |
CRP | C-reactive protein |
EPCs | Endothelial progenitor cells |
VEGF | Vascular endothelial growth factor |
ANS | Autonomic nervous system |
SNS | Sympathetic nervous system |
PNS | Parasympathetic nervous system |
HRV | Heart rate variability |
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Recent Studies | Measured Markers | Main Findings |
---|---|---|
Inflammation-Activity Biomarkers | ||
Schmidt et al., 2014 [55] | IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, TNF-γ, TNF-α | Higher levels of IL-2, IL-5, IL-12, IL-13, INF-γ, and TNF-α were found in depressive patients compared with those in non-depressive subjects. |
Haapakoski et al., 2015 [56] | IL-6, IL-1β, TNF-α | Meta-analysis confirmed higher serum IL-6 levels in depressive patients compared with those in non-depressive controls. |
Al-Hakeim et al., 2015 [57] | IL-6, IL-18, TNF-α | Serum levels of IL-6, IL-18, and TNFα were significantly increased in depressive patients compared with those of the control group. |
Muthuramalingam et al., 2016 [58] | IL-6, TNF-α, TGF-β | Depressive patients demonstrated significantly raised baseline levels of TNF-α and IL-6, but no difference in levels of TGF-β compared with healthy controls. |
Goldsmith et al., 2016 [59] | IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, INF-γ | IL-6, IL-10, IL-12, and TNF-α levels were significantly increased, and levels of IFN-γ and IL-4 were significantly decreased without significant differences in IL-1β and IL-2 levels in patients with MDD compared with controls. |
Zou et al., 2018 [60] | IL-1β, IL-6, IL-8, IL-10, TNF-α, TGF-β1 | Increased levels of IL-1β, IL-10, and TNF-α, and decreased IL-8 levels, were found in MDD patients compared with healthy controls. |
Ng et al., 2018 [61] | IL-1β, IL-6, TNF- α | Meta-analysis found elevated peripheral levels of IL-1β and IL-6 without TNF-α in depressive patients compared with controls. |
Gariup et al., 2015 [62] | IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, and TNF-a | Depressive patients (aged 8–17 years) had significantly higher levels of IL-6, IL-8, and IL-1β compared with controls. |
Pallavi et al., 2015 [63] | IL-1β, IL-2, IL-6, IL-10, IL-17, TNF-α, IFN-γ, and TGF-β | Male MDD adolescents had significantly higher levels of IL-2 compared with controls; female MDD adolescents had significantly elevated serum IL-2 and IL-6 compared with their healthy female counterparts. |
Miklowitz et al., 2016 [64] | TNF-α, IL-1β, IL-6, IL-8, and IL-10 | No significant differences in measured cytokines between MDD and controls. |
Perez-Sanchez et al., 2018 [65] | IL-2, IFN-γ, IL-1β, TNF-α, IL-6, IL-12, IL-4, IL-5, IL-13, and IL-10 | Adolescents with MDD at baseline showed significant increases in all mentioned cytokines, except for IL-10, compared with healthy subjects. |
Endothelial-Function Biomarkers | ||
Van Agtmaal et al., 2017 [66] | VCAM, ICAM, E-selectin, VWF | Meta-analysis revealed association between increased levels of all measured peripheral markers and depression. |
Blum et al., 2017 [67] | VCAM-1, VEGF, EPCs | MDD patients had high levels of VCAM-1 and VEGF; significant inhibition of EPCs colonies. |
Baghai et al., 2018 [68] | ICAM-1, P-selectin, E-Selectin | ICAM-1 was significantly elevated in MDD group compared with healthy controls. |
Saleptsis et al., 2019 [69] | P-selectin | Depressive patients had higher levels of P-selectin compared with individuals free of depression. |
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Tonhajzerova, I.; Sekaninova, N.; Bona Olexova, L.; Visnovcova, Z. Novel Insight into Neuroimmune Regulatory Mechanisms and Biomarkers Linking Major Depression and Vascular Diseases: The Dilemma Continues. Int. J. Mol. Sci. 2020, 21, 2317. https://doi.org/10.3390/ijms21072317
Tonhajzerova I, Sekaninova N, Bona Olexova L, Visnovcova Z. Novel Insight into Neuroimmune Regulatory Mechanisms and Biomarkers Linking Major Depression and Vascular Diseases: The Dilemma Continues. International Journal of Molecular Sciences. 2020; 21(7):2317. https://doi.org/10.3390/ijms21072317
Chicago/Turabian StyleTonhajzerova, Ingrid, Nikola Sekaninova, Lucia Bona Olexova, and Zuzana Visnovcova. 2020. "Novel Insight into Neuroimmune Regulatory Mechanisms and Biomarkers Linking Major Depression and Vascular Diseases: The Dilemma Continues" International Journal of Molecular Sciences 21, no. 7: 2317. https://doi.org/10.3390/ijms21072317