H. O. Kalkman Pages 43 - 54 ( 12 )
Background: Accurate prediction of a suicide attempt is a difficult task for clinicians. Inflammatory processes can explain, at least partly, suicidal symptoms such as agitation, anhedonia and hopelessness. Inflammation leads to secretion of mediator proteins, amongst which interleukin-6 (IL6) and arginine vasopressin (AVP) are of particular significance. The levels of both proteins can be monitored in blood.Consequence: Increases in circulating IL6 can also be monitored as C-reactive protein levels, or as soluble IL6-receptor levels. IL6 in the brain increases the activity of the hypothalamic-pituitaryadrenal axis (HPA), and the activity of the L-tryptophan-degrading enzyme indoleamine 2,3- dioxygenase. Inflammation diminishes the levels of tetrahydrobiopterin (BH4), a cofactor for the synthesis of serotonin (5HT), noradrenaline and dopamine. The loss of BH4 can be monitored as an increase in neopterin. The synthesis of 5HT is not only affected by the diminished availability of BH4, but also by an increase in L-tryptophan metabolism. This can be monitored directly in a test with C13-labeled tryptophan, or indirectly by lower output of the metabolite 5-hydroxy-indole acetic acid, by lower circulating tryptophan levels and by a decrease in central melatonin synthesis. Putatively, insufficient levels of serotonin may result in a defective stimulation of aldosterone from the adrenal cortex. Central IL6 and AVP activate the HPA axis in a way that escapes the feed back inhibition by dexamethasone (non-suppression, quantified by high circulating levels of cortisol). Conclusion: It is assumed that a combination of these biomarkers could improve the recognition of an impending suicide act.
Toxoplasma gondii, aggression, 5HT1A receptor, bell-shape response curve, PTSD, Trier social stress test.
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