Peripheral Markers of Depression

Abstract

Major Depressive Disorder (MDD) is a leading cause of disability worldwide, creating a high medical and socioeconomic burden. There is a growing interest in the biological underpinnings of depression, which are reflected by altered levels of biological markers. Among others, enhanced inflammation has been reported in MDD, as reflected by increased concentrations of inflammatory markers-C-reactive protein, interleukin-6, tumor necrosis factor-α and soluble interleukin-2 receptor. Oxidative and nitrosative stress also plays a role in the pathophysiology of MDD. Notably, increased levels of lipid peroxidation markers are characteristic of MDD. Dysregulation of the stress axis, along with increased cortisol levels, have also been reported in MDD. Alterations in growth factors, with a significant decrease in brain-derived neurotrophic factor and an increase in fibroblast growth factor-2 and insulin-like growth factor-1 concentrations have also been found in MDD. Finally, kynurenine metabolites, increased glutamate and decreased total cholesterol also hold promise as reliable biomarkers for MDD. Research in the field of MDD biomarkers is hindered by insufficient understanding of MDD etiopathogenesis, substantial heterogeneity of the disorder, common co-morbidities and low specificity of biomarkers. The construction of biomarker panels and their evaluation with use of new technologies may have the potential to overcome the above mentioned obstacles.

Keywords: atypical; biomarkers; brain-derived neurotrophic factor (BDNF); depression; inflammatory; interleukins; melancholic; oxidative stress; panels.

Figure 1

Biomarkers can be divided into several subtypes according to their function (top half of the figure, solid lines) or based on when they can be observed (bottom half of the figure, dashed lines).

Figure 2

The summary of the most important depression markers. In bold—those confirmed by a recent umbrella meta-analysis [40]. Abbreviations: 3-HK—3-hydroxykynurenine; 5-HT—serotonin; 8-OHdG—8-hydroxy-2-deoxiguanosine; BDNF—brain-derived neurotrophic factor; CAT—catalase; CRP—C-reactive protein; DA—dopamine; DST—dexamethasone suppression test; FGF-2—fibroblast growth factor-2; GABA—gamma-aminobutyric acid; GDNF—glial cell line derived neurotrophic factor; GH—growth hormone; HDL—high-density lipoprotein; IGF-1—insulin-like growth factor-1; IL-1—interleukin-1; IL-2—interleukin-2; IL-4—interleukin-4; IL-6—interleukin-6; IL-8—interleukin-8; IL-10—interleukin-10; IL-1RA—interleukin-1 receptor antagonist; INF-γ—interferon-γ; KYNA—kynurenic acid; LDL—low-density lipoprotein; MDA—malonylo-dialdehyde; MPO—myeloperoxidase; NA—noradrenaline; NGF—nerve growth factor (NGF); O&NS—oxidative and nitrosative stress; PUFAs—polyunsaturated fatty acids; QA—quinolinic acid; ROS/RNS—reactive oxygen/nitrogen species; sIL-2R—soluble interleukin-2 receptor; SOD—superoxide dismutase; TAC—total antioxidant capacity; TNF-α—tumor necrosis factor-α; VEGF—vascular endothelial growth factor; VGF—VGF nerve growth factor.

Figure 3

Biological systems involved in depression can be assessed on different measurement ‘levels’, called ‘omics’. Note that every system can theoretically be assessed on each ‘omic’ level.

Figure 4

Sources of biological markers used in depression.