[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.