[Immunological aspects of depressive disorders].
Beside the monoaminergic deficiency concept as a pathophysiological correlate of depressive disorder, the role of increased glutamatergic neurotransmission is increasingly being discussed. Causes and interactions of these neurotransmitter disturbances are not fully understood to date. This review presents a concept integrating actual findings of the neurotransmitter dysregulations with immunological and morphological findings in depressive disorder. Several intertwined mechanisms seem to be important: The common cause of serotonin deficiency and increased glutamatergic neurotransmission seems to be the increase of proinflammatory cytokines. Immune activation with increased production of proinflammatory cytokines activate the tryptophan- and serotonin-degradating enzyme indolamine-2,3-dioxygenase (IDO). The increased consumption of serotonin and its precursor tryptophan due to IDO activation may explain the reduced availability of serotonin in depression. In inflammatory somatic disorders, depressive mood is associated with an increase of proinflammatory cytokines and increased consumption of tryptophan. This activation of IDO by proinflammatory cytokines leads to the production of glutamatergic agonists. In the CNS, IDO is activated during inflammatory processes primarily in microglial cells. Therefore the astrocyte:microglial balance in depression is important. The observed decrease of astrocytes in the CNS of depressive patients may contribute to a regulatory fault in the activity of IDO in microglial cells but also can cause an alteration of the glutamatergic neurotransmission. By this mechanism, the dysbalance of the immune response and the astrocyte:microglia dysbalance may contribute to serotonergic deficiency and glutamatergic overproduction in depression. The further search for new antidepressant therapeutic mechanisms should take into regard anti-inflammatory substances, e.g. cyclo-oxygenase-2 (COX-2)-inhibitors.
Müller
N
N
Klinik für Psychiatrie und Psychotherapie, Ludwig-Maximilians-Universität, Nussbaumstrasse 7, 80336 München. Norbert.Mueller@med.uni-muenchen.de
Schwarz
M J
MJ
D000818:Animals; D001921:Brain / Q000276:immunology*; D003866:Depressive Disorder / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology*; D018448:Models, Immunological; D018377:Neurotransmitter Agents / Q000276:immunology*
D007155:Immunologic Factors; D018377:Neurotransmitter Agents