Could schizophrenia be reasonably explained by Dohan's hypothesis on genetic interaction with a dietary peptide overload?

Reichelt, Karl L.; Seim, Anders; Reichelt, Wenche H.

doi:10.1016/s0278-5846(96)00099-1

Cited by 19 publications

(15 citation statements)

References 155 publications

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“…An alternative or additional explanation for the wheat and schizophrenia connection is suggested by Dohan who called these peptides “exorphins” because he felt they resembled the brain-reactive chemicals endorphins, suggestive of a capacity to bind to opioid receptors found throughout the body, but particularly in the brain (Dohan, 1988). Early studies document increased levels of neuroactive food antigen peptides in the bloodstream, CSF and urine in individuals with schizophrenia (Cade et al, 1990; Drysdale et al, 1982; Lindstrom et al, 1986; Reichelt et al, 1981; Reichelt et al, 1996; Reichelt and Stensrud, 1998). The presence of these exorphins has also been found in some analyses of urine samples from children with autism, and in one study, peptide levels correlated with symptom severity scores (Reichelt et al, 2012; Sokolov et al, 2014).…”

Section: Extra-autoimmune Gi Connection To Schizophreniamentioning

confidence: 99%

“…For example, these exorphins may be related to the more general condition known as gluten enteropathy (Kabbani et al, 2014) or alternatively, to the potency potential of the peptide ligands at opioid receptors (Fukudome and Yoshikawa, 1992; Zioudrou et al, 1979). Furthermore, the neuroactive peptides hypothesis is not exclusive to gluten, and Dohan and Reichelt theorized that the digestion of the principal component of bovine milk, casein, also resulted in the production of these exorphins (Reichelt et al, 1996). …”

Section: Extra-autoimmune Gi Connection To Schizophreniamentioning

confidence: 99%

See 1 more Smart Citation

Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling

Severance¹,

Yolken²,

Eaton

2016

Schizophrenia Research

208

149

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Autoimmunity, gastrointestinal (GI) disorders and schizophrenia have been associated with one another for a long time. This paper reviews these connections and provides a context by which multiple risk factors for schizophrenia may be related. Epidemiological studies strongly link schizophrenia with autoimmune disorders including enteropathic celiac disease. Exposure to wheat gluten and bovine milk casein also contribute to non-celiac food sensitivities in susceptible individuals. Co-morbid GI inflammation accompanies humoral immunity to food antigens, occurs early during the course of schizophrenia and appears to be independent from antipsychotic-generated motility effects. This inflammation impacts endothelial barrier permeability and can precipitate translocation of gut bacteria into systemic circulation. Infection by the neurotropic gut pathogen, Toxoplasma gondii, will elicit an inflammatory GI environment. Such processes trigger innate immunity, including activation of complement C1q, which also functions at synapses in the brain. The emerging field of microbiome research lies at the center of these interactions with evidence that the abundance and diversity of resident gut microbiota contribute to digestion, inflammation, gut permeability and behavior. Dietary modifications of core bacterial compositions may explain inefficient gluten digestion and how immigrant status in certain situations is a risk factor for schizophrenia. Gut microbiome research in schizophrenia is in its infancy, but data in related fields suggest disease-associated altered phylogenetic compositions. In summary, this review surveys associative and experimental data linking autoimmunity, GI activity and schizophrenia, and proposes that understanding of disrupted biological pathways outside of the brain can lend valuable information regarding pathogeneses of complex, polygenic brain disorders.

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Section: Extra-autoimmune Gi Connection To Schizophreniamentioning

confidence: 99%

Section: Extra-autoimmune Gi Connection To Schizophreniamentioning

confidence: 99%

Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling

Severance¹,

Yolken²,

Eaton

2016

Schizophrenia Research

208

149

View full text Add to dashboard Cite

show abstract

“…F. Curtis Dohan prolifically disseminated the idea that wheat availability was strongly correlated with hospital rates for schizophrenia, with his interest in this area stimulated by his observations of post-war Europe [54,55]. Mechanistically, Dohan and others have proposed that gluten is broken down into bioactive opioid receptor peptides that may penetrate the GI and brain structural barriers [56,57]. Implicated by these reports is a separate condition, gluten intolerance or sensitivity that does not have the same autoantigenic profile as celiac disease, but which has also been shown to have associations with schizophrenia [58].…”

Section: Diet-based Immune Sensitivitymentioning

confidence: 99%

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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“…It also fit our data on depression [8] where increased levels of peptides were found and also opioids. Given the fact that there is a strong genetic input in the schizophrenias [36] it is unavoidable that there must be chemical changes [37]. Since opioids decrease dopaminergic uptake into synaptosomes and cause in vivo dopaminergic hyperactivity [1] the exorphins found may by causing increased dopaminergic function, relate certain food proteins to psychosis.…”

Section: Resultsmentioning

confidence: 99%

Exorphins in urine from schizoaffective psychotics

Tveiten¹,

Reichelt²

2012

OJPsych

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Hyperpeptiduria and opioid excess have been reported in schizophrenia. According to Prof. Dr. L. Lindström, Sweden opioids may explain the pathophysiology of this syndrome. Therefore it is critical to elucidate the presence and nature of opioids in schizophrenia and diagnostic sub groups. First morning urine from untreated schizoaffective patients (ICD-10: F 25.1) was separated on HPLC and peaks that elute where different opioid standards appear, freeze dried, re-dissolved in methanol/water (50/50) and 10 mM formic acid. Mass spectrometry and MS/MS or fragmentation mass spectrometry was performed. We found fragmentation pattern of beta-casomorphin 1 -3 and 1 -4 (bovine) identical to synthetic standards from Bachem. The aggregation tendency of peptides was much in evidence. The reported exorphins were found in the urine from 8 of 12 untreated schizoaffective patients.

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Could schizophrenia be reasonably explained by Dohan's hypothesis on genetic interaction with a dietary peptide overload?

Cited by 19 publications

References 155 publications

Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling

Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling

Gastroenterology issues in schizophrenia: Why the gut matters

Exorphins in urine from schizoaffective psychotics

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