Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia

Severance, Emily G.; Gressitt, Kristin L.; Halling, Meredith; Stallings, Cassie; Origoni, Andrea; Vaughan, Crystal; Khushalani, Sunil; Alaedini, Armin; Dupont, Didier; Dickerson, Faith; Yolken, Robert H.

doi:10.1016/j.nbd.2012.07.005

Cited by 46 publications

(41 citation statements)

References 50 publications

(77 reference statements)

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“…For example, we documented an increased abundance of C1q-containing immune complexes with gluten and casein in individuals with schizophrenia compared to controls [20]. We further found that at time of birth, levels of C1q-related antibodies were elevated in mothers whose children developed psychoses as adults compared to controls [19].…”

Section: The Immune System Brain and Microbiomementioning

confidence: 68%

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Gastroenterology issues in schizophrenia: Why the gut matters

Severance

2016

Eur. psychiatr.

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Genetic and environmental studies implicate immune pathologies in schizophrenia. The body's largest immune organ is the gastrointestinal (GI) tract. Historical associations of GI conditions with mental illnesses predate the introduction of antipsychotics. Current studies of antipsychoticnaïve patients support that gut dysfunction may be inherent to the schizophrenia disease process. Risk factors for schizophrenia (inflammation, food intolerances, Toxoplasma gondii exposure, cellular barrier defects) are part of biological pathways that intersect those operant in the gut. Central to GI function is a homeostatic microbial community that early reports show is disrupted in schizophrenia. Bioactive and toxic products derived from digestion and microbial dysbiosis activate adaptive and innate immunity. Complement C1q, a brain-active systemic immune component, interacts with gut-related schizophrenia risk factors in clinical and experimental animal models. With accumulating evidence supporting newly discovered gut-brain physiological pathways, treatments to ameliorate brain symptoms of schizophrenia should be supplemented with therapies to correct GI dysfunction.

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Section: The Immune System Brain and Microbiomementioning

confidence: 68%

“…Various components of the complement pathway are genetically and biologically linked to schizophrenia [103,20,19,104,105]. For example, we documented an increased abundance of C1q-containing immune complexes with gluten and casein in individuals with schizophrenia compared to controls [20].…”

Section: The Immune System Brain and Microbiomementioning

confidence: 80%

Gastroenterology issues in schizophrenia: Why the gut matters

Severance

2016

Eur. psychiatr.

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“…Matching criteria for offspring included geographic region, date of birth, birth hospital, race, gender and parental history of mental illness. In our previous studies, we found age-associated patterns of C1q-food antibody immune complexes (Severance et al, 2012b); therefore, for the current study, we further restricted the control group based on maternal age. For each identified 1:3 case-control match, we chose the one of three maternal controls who was closest in age to the case mother, with the additional limitation that the age difference could not exceed three years.…”

Section: Methodsmentioning

confidence: 99%

“…C1q was also one of the first immune molecules discovered to have effects on synapse development and function in the brain by mechanisms that are not part of standard immune pathways (Benoit and Tenner, 2011; Bialas and Stevens, 2013; Boulanger, 2009; Fourgeaud and Boulanger, 2007; Stephan et al, 2013; Stevens et al, 2007). In our studies of schizophrenia, we have linked elevated C1q to the presence of IgG antibodies directed against milk caseins and wheat glutens (Severance et al, 2012b), and to inflammatory gut processes in experimental animal models (Severance et al, 2012c). Numerous other accounts also report complement system physiological and genetic aberrations in schizophrenia (Arakelyan et al, 2011; Boyajyan et al, 2008; Havik et al, 2011; Mailian et al, 2005; Mayilyan et al, 2008; Vetlugina et al, 1984; Zakharyan et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Maternal complement C1q and increased odds for psychosis in adult offspring

Severance

Gressitt

Buka

et al. 2014

Schizophrenia Research

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The presence of maternal antibodies to food and infectious antigens may confer an increased risk of developing schizophrenia and psychosis in adult offspring. Complement factor C1q is an immune molecule with multiple functions including clearance of antigen-antibody complexes from circulation and mediation of synaptic pruning during fetal brain development. To determine if maternal C1q was associated with offspring schizophrenia and psychosis, we evaluated 55 matched case-control maternal serum pairs from the National Collaborative Perinatal Project. Sample pairs were composed of mothers whose offspring developed psychoses as adults and those whose offspring were free from psychiatric disease. Matching criteria for offspring included birth date, delivery hospital, race and gender, with further matching based on mother’s age. IgG markers of C1q, bovine milk casein, egg ovalbumin and wheat gluten were measured with enzyme-linked immunosorbent assays. C1q levels were compared to food antigen IgG and to previously generated data for C-reactive protein, adenovirus, herpes simplex viruses, influenza viruses, measles virus and Toxoplasma gondii. C1q was significantly elevated in case mothers with odds ratios of 2.66–6.31 (conditional logistic regressions, p≤0.008–0.05). In case mothers only, C1q was significantly correlated with antibodies to both food and infectious antigens: gluten (R2=0.26, p≤0.004), herpes simplex virus type 2 (R2=0.21, p≤0.02), adenovirus (R2=0.25, p≤0.006). In conclusion, exposure to maternal C1q activity during pregnancy may be a risk factor for the development of schizophrenia and psychosis in offspring. Prenatal measurement of maternal C1q may be an important and convergent screening tool to identify potentially deleterious immune activation from multiple sources.

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“…64 These findings are of interest in light of recent findings indicating polymorphisms in the human complement gene and levels of complement proteins in the blood and cerebrospinal fluid as risk factors for schizophrenia. 65,66 Regarding the schizophrenia protective effect of congenital cortical blindness, this may be similar to the schizophrenia protective effect of rheumatoid arthritis. Such protective effects might be explained if the same or a similar infectious agent caused both conditions; having one condition would thereby confer immunity to getting the second.…”

Section: Complement Activation and Neuronal Connectivitymentioning

confidence: 93%

Schizophrenia and Infections: The Eyes Have It

Torrey

Yolken

2016

SCHBUL

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The visual tract is prominently involved in schizophrenia, as evidenced by perceptual distortions and a type of nystagmus found in many individuals affected. Genetic explanations for these abnormalities have been suggested. This study proposes an alternate explanation based on infection. Several infectious agents thought to be associated with some cases of schizophrenia are known to cause both infection of the fetus and abnormalities of the eye. Toxoplasma gondii is examined in detail, and rubella, cytomegalovirus, varicellazoster virus, and herpes simplex virus more briefly. Careful ophthalmic assessments, including funduscopy and direct examination of tissues for infectious agents, will clarify the role of such agents in ocular aspects of schizophrenia.

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Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia

Cited by 46 publications

References 50 publications

Gastroenterology issues in schizophrenia: Why the gut matters

Gastroenterology issues in schizophrenia: Why the gut matters

Maternal complement C1q and increased odds for psychosis in adult offspring

Schizophrenia and Infections: The Eyes Have It

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