Schizophrenia: the teratogenic antibody hypothesis

Disease discordance of 50% in monozygotic twins implicates genetic and envi ronmental factors in the aetiology of schizophrenia. Autoimmune diseases ar e HLA associated and are thought to occur when a genetically predisposed in dividual is exposed to an essential, probably viral, environmental trigger. We have reported an excess of autoimmune diseases in the first degree rela tives of schizophrenic patients, an excess of second trimester influenza in fections in the mothers of schizophrenic patients, and a deficiency of HLA DRB1*04 alleles in the mothers of schizophrenic patients and in schizophren ic patients themselves. We have therefore hypothesised that maternal immuno genetic predisposition interacts with the influenza virus to cause neurodev elopmental lesions which manifest in adulthood as schizophrenia. Our work r aises the possibility of an (immuno)genetic predisposition to schizophrenia at pedigree, maternal, and proband level.