[Immunological treatment options for schizophrenia].
The pathophysiological mechanism leading to dopaminergic dysfunction in schizophrenia is still unclear. Inflammation seems to play a key role. A dysfunction in the activation of the type 1 immune response is associated with decreased activity of the key enzyme of the tryptophan/kynurenine metabolism, indolamine-2.3-dioxygenase (IDO), results in a higher production of kynurenine acid (KYNA)--an N-methyl-D-aspartate antagonist--in the central nervous system (CNS) and decreased glutamatergic neurotransmission. The differential activation of microglial cells and astrocytes, which serve as immune cells in the CNS, contributes to the TH1-TH2 immune imbalance. Antipsychotics, all acting as dopamine D2 receptor antagonists show several shortcomings. The immune effects of antipsychotics rebalance partly the imbalance of the type-1/type-2 immune response and the overproduction of KYNA. The inflammation is associated with higher prostaglandin E2 (PGE2) production and higher cyclo-oxygenase-2 (COX-2) expression. Increasing evidence from clinical studies with COX-2 inhibitors points to an advantageous effect of anti-inflammatory therapy in schizophrenia, especially in the early stages of the disease. Further options of immunomodulatory therapy in schizophrenia are discussed.
Klinik für Psychiatrie und Psychotherapie, Klinikum der LMU München.
N
N
Müller
Klinik für Psychiatrie und Psychotherapie, Klinikum der LMU München.
D
D
Krause
Klinik für Psychiatrie und Psychotherapie, Klinikum der LMU München.
E
E
Weidinger
Institut für Labormedizin, LMU München.
M
M
Schwarz
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation / Q000473:pathology; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D012565:Schizophrenic Psychology
D000893:Anti-Inflammatory Agents