Inflammatory Processes and Psychiatric Disorders

From the psychiatric point of view, it is most intriguing that active immune processes may be involved in the pathogenesis of major psychiatric disorders, as suggested by evidence from recent studies. Specifically, significant alterations of T-cell function, along with activation of the inflammatory response system, appear to be linked to treatment-resistant schizophrenia. Similar processes have also been reported for mood disorders in general. The abnormalities of CNS metabolism observed with functional psychoses and depression might, therefore, arise because genetically modulated inflammatory reactions damage the microvascular system of the brain, with the nature of the infectious agent being less important than the patients’ genetically influenced inflammatory response.

Chronically Elevated Poly-Reactive IgM Levels

The "natural" antibody IgM is in use, for example, as a standard diagnostic test for rheumatoid arthritis, but possesses a low specificity. Since the formation of chronically elevated poly-reactive IgM levels develops years before clinical symptoms occur [Nielen et al. 2006], a genetically predisposed aberrancy of the inflammatory response system has been linked to various complex diseases. In the field of psychiatric disorders, a population-based study of 7,704 patients with a diagnosis of schizophrenia and 192,590 control subjects without psychiatric history has revealed that a parental history of schizophrenia was associated with a 5-fold risk for autoimmune diseases, whereas a parental history of autoimmune diseases increased this risk only slightly, by a factor of 1.45 [Eaton et al. 2006]. More specifically, several antidepressants and antipsychotics show anti-inflammatory effects [e.g., Müller and Schwarz 2006, 2007], while a quantitative (R)-[11C]PK11195 positron emission tomography study demonstrated microglia activation in recent-onset schizophrenia [van Berckel et al. 2008].

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