Tumor necrosis factor receptor-II: heritability and effect on brain morphology in schizophrenia

A growing body of research suggests the involvement of immune system factor s in central nervous system development and in pathophysiology related to s chizophrenia.(1,2) 2 We therefore investigated the Tumor Necrosis Factor Re ceptor-II (TNF-RII), a TNF alpha receptor expressed in fetal brain, as a ca ndidate disease gene for schizophrenia. We also investigated the relationsh ip between TNF-RII and adult brain morphology, The study sample consisted o f 140 probands diagnosed with schizophrenia or schizophreniform disorder, 1 97 parents of the probands (a subset of which formed 62 proband-parent trio s), and 46 psychiatrically normal control subjects. A bi-allelic TNF-RII po lymorphism was examined for evidence of association, with none being found between this polymorphism and schizophrenia. Subjects with schizophrenia ho mozygous for allele 1, however, had larger Ventricles and smaller frontal r obes than subjects with at least one copy of allele 2. On follow-up testing , they also had an earlier, less variable age of onset for their illness. W e found no support, therefore, for TNF-RII as a disease susceptibility gene for schizophrenia. The gene may, however, modify phenotypic aspects of the disease such as brain morphology and age of onset of illness.