Identification of candidate genes for schizophrenia based on natural resistance to infectious diseases

Background: Identification of candidate genes for schizophrenia may be more successful than genome screens as the latter have not found consistent linkages. Objective: To assist in the gene search, a model of schizophrenia based on resistance to infectious diseases, rather than susceptibility, is proposed. The theory blends the geography of schizophrenia with the assumption that genes that cause schizophrenia likely evolved and persist from selection pressure. The theory includes the notion that schizophrenia enhances biological survival at the cost of psychological and social functioning. Method: To demonstrate the utility of using this model, the Medline literature was searched for resistance genes, mostly identified in mice. Results: Based on homologous locations in the human genome, these resistance genes are shown to be located in human chromosome regions linked significantly, in at least one genome screen, with schizophrenia or some physiologically related function or condition associated with schizophrenia. Conclusions: The infectious disease resistance theory of schizophrenia is offered as a viable model for understanding the origins of schizophrenia. The theory also allows for the inclusion of persistent infections seasonal variability and translational pathophysiology to contribute to the etiology of schizophrenia.