Gene, gut and schizophrenia: the meeting point for the gene–environment interaction in developing schizophrenia

Abstract

Both schizophrenia and celiac disease involve a genetic component. Several lines of evidence have shown a genetic relationship between these two conditions. Celiac disease is characterized by damage to the microscopic finger-like projections called villi, which line the small intestine and play a significant role in digestion, due to an inflammatory condition caused by a reaction to wheat gluten or related rye and barley proteins. Celiac disease represents not only malabsorption leading to a poor nutritional condition but also an alteration of gut permeability. Individuals with a history of a childhood celiac condition have a raised risk of developing schizophrenia. Psychotic symptoms often occur in adult celiac disease. It can be hypothesized that apart from malnutrition, the meeting point for the gene-environment interaction may be an alteration in gut permeability, in which the gut may lose its capacity to block exogenous psychosis-causing substances that may enter the body thus causing the development of schizophrenia and other mental conditions. To support this hypothesis, the conditional test was conducted to look at the combined effect of the CLDN5 gene involved in forming permeability barriers and the DQB1 gene that has been found to be associated with celiac disease. The results demonstrate that these two genes possibly work together in conferring a susceptibility to schizophrenia.