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.