Immunological aspects of the treatment of depression and schizophrenia

Abstract

Schizophrenia and major depression (MD) have been associated with immune system dysfunction. One example of this is the altered level of cytokines—important inflammatory mediators—in blood, and a proinflammatory immune state has been described in some subgroups of patients. A knock to the immune system in early life might trigger a life-long increased immune reactivity, and infections and autoimmune disorders are now known to be risk factors for development of schizophrenia and MD. Pro- and anti-inflammatory cytokines mediate indoleamine 2,3-dioxygenase activity; this enzyme drives metabolism of tryptophan and kynurenin in the central nervous system and degrades serotonin. Alterations of serotonergic, noradrenergic, and glutamatergic neurotransmission have been associated with low-level neuroinflammation, and anti-inflammatory compounds have a therapeutic benefit in MD and schizophrenia, as shown in meta-analyses. Moreover, antidepressants and antipsychotics have intrinsic immunomodulatory effects. With evidence pointing to the role inflammatory processes play in the pathogenesis of major psychiatric disorders, this review will look at various immunological aspects of treatment of such disorders.