Immunity and schizophrenia: autoimmunity, cytokines, and immune responses.

As is evident from the present account, there is no single or persuasive argument that signals emanating from the immune system are directly involved in the etiology of schizophrenia. We do not even know if we are dealing with a single disorder with a single causality; almost certainly we are not. The precise etiology of schizophrenia, as with so many neurological disorders, remains obscure. However, there is abundant evidence in schizophrenia of mutual dysregulation of neuronal function and immune system activity. Although this evidence is not always consistent, a pattern emerges suggesting aspects of immune activity being involved in the pathology of neuronal development that characterizes schizophrenia. Exposure to infective agents, HLA associations, autoimmune associations, disturbances in lymphocyte populations, and cytokine imbalances with a skew toward Th2 activity are supportive of this view. That the evidence is not always consistent is a testament to the complexity and heterogeneity of the disorder, to confounding by antipsychotics that themselves are immunomodulatory, and to the multifaceted nature, with all its checks and balances, of the immune system itself.