Citation

Kalkman HO. Pharmaceuticals (Basel) 2019; 12(3).

Copyright

(Copyright © 2019, MDPI)

DOI

10.3390/ph12030113

PMID

unavailable

Abstract

Inflammation and psychological stress are risk factors for major depression and suicide. Both increase central glutamate levels and activate the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Both factors also affect the function of the chloride transporters, Na-K-Cl-cotransporter-1 (NKCC1) and K-Cl-cotransporter-2 (KCC2), and provoke interleukin-6 (IL-6) trans-signaling. This leads to measurable increases in circulating corticosteroids, catecholamines, anxiety, somatic and psychological symptoms, and a decline in cognitive functions. Recognition of the sequence of pathological events allows the prediction of novel targets for therapeutic intervention. Amongst others, these include blockade of the big-K potassium channel, blockade of the P2X4 channel, TYK2-kinase inhibition, noradrenaline α2B-receptor antagonism, nicotinic α7-receptor stimulation, and the Sgp130Fc antibody. A better understanding of downstream processes evoked by inflammation and stress also allows suggestions for tentatively better biomarkers (e.g., SERPINA3N, MARCKS, or13 C-tryptophan metabolism). © 2019 by the author. Licensee MDPI, Basel, Switzerland.

Language: en

Keywords

human; suicide; Suicide; Review; depression; anxiety; stress; Major depressive disorder; major depression; Ketamine; inflammation; cognitive defect; unclassified drug; signal transduction; nonhuman; mental stress; psychosomatic disorder; corticosteroid; hypothalamus hypophysis adrenal system; vagus nerve stimulation; adrenergic system; physical stress; catecholamine; protein function; adenosine triphosphate; drug targeting; glutamic acid; nicotinic agent; protein analysis; immobilization stress; Vagus nerve; bungarotoxin receptor agonist; catecholamine blood level; corticosteroid blood level; Inflammasome; potassium chloride cotransporter 2; sodium potassium chloride cotransporter 1