Inflammatory biomarkers and depression.
Antidepressants, predominantly serotonin- and/or noradrenaline reuptake inhibiting drugs have several shortcomings. The exact pathophysiological mechanisms leading to serotonergic-, noradrenergic- or dopaminergic dysfunction are still unclear. An inflammatory mechanism has been postulated and will be discussed here including possible therapeutic advantages of cyclooxygenase-2 (COX-2) inhibitors. Differences in the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and in the tryptophan-kynurenine metabolism resulting in an increased tryptophan and serotonin degradation and probably in an increased production of quinolinic acid might play a key role in major depression (MD). These differences are associated with an imbalance in the glutamatergic neurotransmission, which may contribute to an overweight of N-methyl-D: -aspartate agonism in MD. The immunological imbalance results in an increased prostaglandin E₂ production and probably also in an increased COX-2 expression. Although there is strong evidence for the view that the interactions of the immune system, IDO, the serotonergic system and the glutamatergic neurotransmission play a key role in MD, several gaps, e.g. the roles of genetics, disease course, sex, different psychopathological states, etc., have to be bridged by intense further research. There were already hints that anti-inflammatory therapy might have beneficial effects in MD. COX-2 inhibitors, however, have been tested in animal models and in preliminary clinical studies showing favourable effects compared to placebo in MD. The effects of COX-2 inhibition in the CNS as well as the different components of the inflammatory system, the kynurenine-metabolism and the glutamatergic neurotransmission, however, still need careful further scientific evaluation including clinical studies in bigger samples of patients.
Müller
Norbert
N
Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Nußbaumstr. 7, 80336 München, Germany. Norbert.Mueller@med.uni-muenchen.de
Myint
Aye-Mu
AM
Schwarz
Markus J
MJ
D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism / Q000627:therapeutic use; D007737:Kynurenine / Q000378:metabolism
D000928:Antidepressive Agents; D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018836:Inflammation Mediators; D007737:Kynurenine