Urinary peptides in schizophrenia and depression

Reichelt, Karl L.; Edminson, Paul D.; Toft, Kim Gunnar

doi:10.1002/smi.2460010307

Cited by 13 publications

(6 citation statements)

References 84 publications

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“…We here report on the urinary state in severe depression only. We have previously found a lack of peptides during mania/hypomania [ 6 ].…”

Section: Methodsmentioning

confidence: 99%

“…The disease takes time to develop, which probably points to unknown substances increasing and, or decreasing until they reach a critical level. We have previously found increased low molecular weight peptides (fragments of proteins) in urine from patients with depression [ 5 , 6 ] diagnosed according to The Diagnostic Manual of Mental Disorder, 3 rd edition (DSMIII). A peptide fraction was found that stimulated the uptake of serotonin (5-HT) into platelets [ 7 ] Compounds with opioid activity were also found.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Towards a possible aetiology for depressions?

Liu¹,

Heiberg

Reichelt³

2007

Behav Brain Funct

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“…We here report on the urinary state in severe depression only. We have previously found a lack of peptides during mania/hypomania [ 6 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Towards a possible aetiology for depressions?

Liu¹,

Heiberg

Reichelt³

2007

Behav Brain Funct

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“…Less specifically, methods might be developed that measure the concentration of gluten peptides in body fluids. Reichelt et al (1985) reported that small peptides—some possibly from gluten—are greatly increased in the urine of individuals with schizophrenia and untreated celiac disease. Measurements before and after an oral dose of gluten might be developed into a test for those with the genotypes for the gluten-evoked disorders.…”

Section: Evidence Pro and Con—and Ways Of Testing The Modelmentioning

confidence: 99%

Genetic Hypothesis of Idiopathic Schizophrenia: Its Exorphin Connection

Dohan

1988

Schizophrenia Bulletin

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This brief overview proposes a testable oligogenic model of the inheritance of susceptibility to idiopathic schizophrenia: "abnormal" genes at each of a few complementary loci. The model is based on my assumptions as to the likely genetic abnormalities at possibly four or five interacting loci that would permit exorphins, the opioid peptides from some food proteins, especially glutens and possibly caseins, to go from gut to brain and cause symptoms of schizophrenia. Exorphins may reach the brain cerebrospinal fluid (CSF) in harmful amounts because of their genetically increased, receptor-mediated transcellular passage across the gut epithelial barrier plus decreased catabolism by genetically defective enzymes. A schizophrenia-specific, genetically enhanced affinity for exorphins by opioid receptors influencing dopaminergic and other neurons would permit sustained dysfunction at low CSF exorphin concentrations. Tests of each postulated genetic abnormality are suggested. This model is supported by a variety of evidence, including a significant effect of gluten or its absence on relapsed schizophrenic patients, the high correlation of changes in first admission rates for schizophrenia with changes in grain consumption rates, and the rarity of cases of schizophrenia where grains and milk are rare.

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“…The proteins, gluten and casein, are hydrolyzed in the GI tract into hundreds to thousands of peptides, some of which have been shown to have opioid-like properties and are referred to as exorphins (Boutrou et al, 2013; Dohan, 1988a; Dohan, 1979, 1980, 1988b; Prandi et al, 2014; Reichelt, 1991, 1994; Reichelt et al, 1985; Reichelt et al, 1981; Reichelt et al, 1995; Reichelt et al, 2012). The immunomodulatory potential of these exorphins is not well-understood, with observations that among the repertoire of digested peptides, some have pro-inflammatory and others have anti-inflammatory effects (Aihara et al, 2014; Barnett et al, 2014; Haq et al, 2014; Kaminski et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

Severance¹,

Gressitt²,

Alaedini³

et al. 2015

Brain, Behavior, and Immunity

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Schizophrenia is a complex brain disorder that may be accompanied by idiopathic inflammation. Classic central nervous system (CNS) inflammatory disorders such as viral encephalitis or multiple sclerosis can be characterized by incongruent serum and cerebrospinal fluid (CSF) IgG due in part to localized intrathecal synthesis of antibodies. The dietary antigens, wheat gluten and bovine milk casein, can induce a humoral immune response in susceptible individuals with schizophrenia, but the correlation between the food-derived serological and intrathecal IgG response is not known. Here, we measured IgG to wheat gluten and bovine milk casein in matched serum and CSF samples from 105 individuals with first-episode schizophrenia (n=75 antipsychotic-naïve), and 61 controls. We found striking correlations in the levels of IgG response to dietary proteins between serum and CSF of schizophrenia patients, but not controls (schizophrenia, R2=0.34–0.55, p≤0.0001; controls R2=0.05–0.06, p>0.33). A gauge of blood-CSF barrier permeability and CSF flow rate, the CSF-to-serum albumin ratio, was significantly elevated in cases compared to controls (p≤0.001–0.003). Indicators of intrathecal IgG production, the CSF IgG index and the specific Antibody Index, were not significantly altered in schizophrenia compared to controls. Thus, the selective diffusion of bovine milk casein and wheat gluten antibodies between serum and CSF in schizophrenia may be the function of a low-level anatomical barrier dysfunction or altered CSF flow rate, which may be transient in nature.

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Urinary peptides in schizophrenia and depression

Cited by 13 publications

References 84 publications

Towards a possible aetiology for depressions?

Towards a possible aetiology for depressions?

Genetic Hypothesis of Idiopathic Schizophrenia: Its Exorphin Connection

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

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