There has been an increased understanding of the workings of the immune system within the CNS. It is now clear that the immune system in the brain utilizes specialized cells and mechanisms not found in other parts of the body. This difference is best exemplified by the microglia, which are specialized cells within the brain that form during fetal development and are present from birth. While microglia have multiple biological activities, their main function is the monitoring of infections agents and the generation of a controlled immune response.
Microglia are activated following infection with viral, bacterial, fungal, and protozoan agents through a complex and highly refined process of signaling that is mediated by pattern recognition molecules called toll-like receptors. Microglial activation has been documented in a wide range of psychiatric disorders including schizophrenia, bipolar disorder, and autism. Because the pattern of response to infectious agents is similar, microorganisms from widely diverse taxa can cause similar activation of immune processes and, hence, similar clinical pictures.
The list of infectious agents with neuropsychiatric potential includes a diverse set of taxonomic kingdoms including viruses, bacteria, and protozoa, largely overlapping with the microorganisms capable of establishing latency within the brain. The concept that different microorganisms can cause similar clinical disorders represents a divergence from the usual conceptualization of infectious diseases: that each disorder is caused by a specific infectious agent and that each agent has an identifiable clinical effect.
This understanding, derived from Koch’s famous postulates, is useful for the study of many infectious disease. However, this concept has been less useful for the study of complex brain disorders due to the substantial overlap in the immune response to infectious agents within the brain. The role of the immune system also opens the possibility of immune-based therapies for psychiatric disorders, although these are mostly in the stages of development and evaluation.4
Microglial activation can be measured in patients using neuroimaging techniques such as PET scanning. However, the optimal method for employing these scans and their sensitivity and specificity in clinical practice have not yet been defined.5 The pharmacological targeting of microglial activation remains a promising approach in terms of novel therapeutic interventions for a range of psychiatric disorders.6
Dr Yolken is Theodore and Vada Stanley Distinguished Professor of Neurovirology in Pediatrics, Johns Hopkins University, Baltimore, MD; Ms Shwartz is a Psychiatric-Mental Health Nurse Practitioner, Telecare Corporation, Alameda County, CA; and Dr Quanbeck is Associate Medical Director, Cordilleras Mental Health Rehabilitation Center, San Mateo County Health, Redwood City, CA.
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