The Role of Microbes and Autoimmunity in the Pathogenesis of Neuropsychiatric Illness

Mady Hornig


Curr Opin Rheumatol. 2013;25(4):488-495. 

In This Article

Abstract and Introduction


Purpose of review To illustrate how microbes might participate in the pathogenesis of neuropsychiatric illness by triggering the production of autoantibodies that bind to brain targets.

Recent findings Some studies link exposure to infectious agents to development of brain disorders; others have identified autoantibodies in individuals with these conditions without finding evidence of pathogens. Neither line of work demonstrates consistent associations between a specific neuropsychiatric disease and a particular environmental trigger or immune marker. Growing evidence suggests that the microbiome conditions host immunity to microbes and xenobiotics, and regulates autoimmune responses that can affect the central nervous system (CNS). The presence of CNS receptors for cytokines and other immune molecules underscores the importance of brain–immune crosstalk in maintaining normal function. An increased prevalence of familial autoimmunity, exposure to pathogens prenatally and postnatally, and findings of antibrain antibodies is common in disorders as diverse as schizophrenia, obsessive-compulsive disorder and autism, and suggests that differences in exposure timing and genetic vulnerability toward autoimmunity are important determinants of neuropsychiatric outcomes.

Summary Microbes, both pathogenic and commensal, can induce autoantibodies that bind to brain and affect behavior in susceptible hosts. Interventions that correct the microbial balance or diminish autoantibody binding may be effective in diverse neuropsychiatric conditions mediated by autoimmunity.


Many authors assure us that mental alienation is epidemic. It is certain that there are years, when, independently of moral causes, insanity seems suddenly to extend to a great number of individuals. [1]

The causes of most neuropsychiatric illnesses remain stubbornly elusive despite assiduous research into genetic and biochemical factors. Since the time of Hippocrates, these illnesses have been repeatedly attributed to imbalances triggered by infection, diet, xenobiotics and other environmental factors.[2] Failure to establish consistent, unique associations of individual environmental agents with specific neuropsychiatric conditions across populations has led more recently to consideration that host responses to these agents, influenced by genes and maturational status at exposure, are an essential part of the equation. Since the early years of the 20th century, the hunt for microbes, toxins and other causes of 'epidemic' mental illness has been paralleled by the suggestion that autoimmunity may also be implicated. Work related to autoimmune paradigms of any disorder, however, remained submerged under a cloud of impossibility – the concept of 'horror autotoxicus' that persisted until the late 1950s and argued that although an organism might produce antibodies against self-antigens, these autoantibodies were incapable of causing any ill effect.[3] That veil is only very recently being lifted with respect to a potential role for autoimmunity in neuropsychiatric disorders. This shift has occurred as evidence accumulates to support the idea that dysregulated cross-talk between the brain and the immune system is an important contributor to the pathogenesis of conditions as diverse as schizophrenia, mood disorders, autism spectrum disorders (ASDs), obsessive-compulsive disorder (OCD), Tourette syndrome and other tic disorders, attention-deficit hyperactivity disorder (ADHD), anorexia nervosa, narcolepsy, posttraumatic stress disorder and myalgic encephalomyelitis/chronic fatigue syndrome (CFS).[4,5] In addition, intriguing new evidence lends support to the possibility that not only the microbes associated with infectious episodes but also the bacteria of the gut microbiome can foster the production of brain-reactive autoantibodies, and that these microbe-induced antibodies provide the critical link between infection and neuropsychiatric disorders.