Schizophrenia, autoimmunity and immune system dysregulation: A comprehensive model updated and revisited

Recent investigation suggests a strong relationship between immunological effects and the pathophysiology of schizophrenia. Two prevalent approaches exist to this association. First, is more empirical a-priori research investigating immunological changes prevalent in schizophrenia and the second approach is more hypothesis-driven with analysis of immunological changes in schizophrenia based on known irregularities of the illness. The former approach is based upon three predominant lines of investigation including observations of a diffuse non-specific over-activation of the immunological response system, of a T-helper cell type 1 immune activation and of a T-helper cell type 2 immune activation in subgroups of schizophrenia patients. These last two theories suggest that a subgroup of patients with schizophrenia may demonstrate features of an autoimmune process, a theory supported by a growing database of investigation. The latter approach notes that many observations of immune dysregulation in schizophrenia overlap with central etiopathophysiological mechanisms as well as with clinical manifestations of the illness. Immunotherapy offers the opportunity to modify or re-balance the immune system and may become useful in management of the illness. Given that autoimmune mechanisms could interrupt neurotransmission, any process interfering with this disruption including therapeutic antibodies to involved cytokines, or with various other natural autoantibodies or immune system regulators, may become useful in the augmentative management of the illness. (c) 2006 Elsevier Ltd. All rights reserved.