The Case for Autoimmunity in the Etiology of Schizophrenia

Abstract

The treatment of schizophrenia has frustrated clinicians for over 50 years. Despite advances in neurotransmitter identification and the development of drugs targeting these transmitters, total remission of the disease is not always achieved. Potential etiologies other than neurotransmitter dysfunction merit consideration. One intriguing concept is the possible contribution of autoimmunity in patients with the disease. This breakdown of self-tolerance has been implicated in patients with other chronic diseases, such as type 1 diabetes mellitus and myasthenia gravis. The literature on autoimmunity as a possible mechanism in the pathogenesis of schizophrenia can be conflicting, but there is a substantial amount of circumstantial, although not conclusive, evidence of immune dysfunction in patients with schizophrenia.

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

“…A protective effect of CMV was previously reported in patients with multiple sclerosis (Zivadinov et al, 2006;Pirko et al, 2012). Although an autoimmune nature of schizophrenia has not been determined (Schattner et al, 1996;Goldsmith and Rogers, 2008), results of some studies are suggestive of the possibility that autoimmune components play a role in etiopathogenic pathways leading to schizophrenia, at least in some subgroups of subjects (Eaton et al, 2006;Goldsmith and Rogers, 2008;Eaton et al, 2010;Chen et al, 2012). Because CMV has an immunosuppressive effect (Rubin, 1989;Zivadinov et al, 2006;Varani et al, 2009), it might ameliorate the autoimmune damage and consequently decrease the likelihood of developing schizophrenia in vulnerable individuals with autoimmune reactions, which are potentially implicated in the etiopathophysiology of schizophrenia.…”

The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease

“…1 Since that time, there have been myriad reports of specific autoimmune responses to self-antigens in psychosis, affective dysregulation, and other behavioral abnormalities. 1–3 Despite these efforts, no autoantibody findings have remained so reproducible or ubiquitous as to become a biomarker for disease.…”

“…1 Since that time, there have been myriad reports of specific autoimmune responses to self-antigens in psychosis, affective dysregulation, and other behavioral abnormalities. 1–3 Despite these efforts, no autoantibody findings have remained so reproducible or ubiquitous as to become a biomarker for disease. 1,4 Recently, a number of syndromes characterized in part by global encephalopathy or even more focal psychiatric changes have been found to result from autoimmune dysfunction, at times with autoantibodies that guide both diagnosis and treatment.…”

“…1–3 Despite these efforts, no autoantibody findings have remained so reproducible or ubiquitous as to become a biomarker for disease. 1,4 Recently, a number of syndromes characterized in part by global encephalopathy or even more focal psychiatric changes have been found to result from autoimmune dysfunction, at times with autoantibodies that guide both diagnosis and treatment. 5,6 Here, we review autoimmune encephalitides caused by antineuronal antibodies that attack proteins involved in synaptic function, and we examine systemic autoimmune diseases that have profound neuropsychiatric components.…”

The emergence of a new science of the mind: immunology benefits the mind

“…The general perception of the role of the immune system has been expanded to include not only host defense but also somatic maintenance and tissue repair. Likewise, the fields of neuroimmunology and psychoneuroimmunology have evolved from disciplines that view the cross-talk between the peripheral immune system and the brain either in terms of how the mind affects the immune system 1 or in terms of how immune system pathologies (such as inflammation) disrupt the mind, 2,3 to fields that appreciate the pivotal role of circulating immune cells in helping sustain the healthy brain. [4][5][6][7] Thus, for example, it has been commonly accepted that mental stress (depending on its severity) either harnesses immune cells to support the body's function (excluding that of the brain) or suppresses healing; 8 however, the possibility that circulating immune cells may actually protect the brain's function from the consequences of stress was only recently recognized.…”