Potential role of lymphotoxin-alpha (tumor necrosis factor-beta) in the development of schizophrenia

Immune hypothesis of schizophrenia fits well with the supposed interaction between genetic and environmental factors in understanding its complicated pathogenesis that is not be able to be explained by any one supposed hypothesis. Prenatal infections have been also suggested to be associated with schizophrenia in which cytokines may play a critical role in the translation of prenatal infection to develop schizophrenia. Moreover, antipsychotics are known to have direct or indirect effects on the immune system. Among cytokines, the immunomodulatory functions of lymphotoxin-alpha (tumor necrosis factor (TNF)-beta) is well known and could come up with the pathophysiology of schizophrenia. It affects and modulates production of other cytokines such as TNF-alpha and IL-6 which are consistently proposed to be involved in the development of schizophrenia. TNF-beta is also crucial to prevent prenatal infections. In addition, TNF-beta is effective in the protection of neuronal cells against glutamate and NMDA toxicity which is considered a neurodevelopmental hypothesis of schizophrenia. Moreover, it was also found to be associated with the regulation of glial cells and stimulation of the synthesis and secretion of nerve growth factors (NGFs) in the CNS. Finally, TNF-beta gene is located on the short arm of chromosome 6 (6p21.1-6p21.3), where is a possible susceptibility locus for schizophrenia. Therefore, TNF-beta may provide a new insight for understanding schizophrenia, providing a more systematic organization of immunological contributing factors to the development of schizophrenia.