ABSTRACT
Autoantibodies that bind the N-methyl-D-aspartate receptor (NMDAR) may underlie glutamate receptor hypofunction and related cognitive impairment found in schizophrenia. Exposure to neurotropic pathogens can foster an autoimmune-prone environment and drive systemic inflammation leading to endothelial barrier defects. In mouse model cohorts, we demonstrate that infection with the protozoan parasite, Toxoplasma gondii, caused sustained elevations of IgG class antibodies to the NMDAR in conjunction with compromised blood-gut and blood-brain barriers. In human cohorts, NMDAR IgG and markers of barrier permeability were significantly associated with T. gondii exposure in schizophrenia compared with controls and independently of antipsychotic medication. Combined T. gondii and NMDAR antibody seropositivity in schizophrenia resulted in higher degrees of cognitive impairment as measured by tests of delayed memory. These data underscore the necessity of disentangling the heterogeneous pathophysiology of schizophrenia so that relevant subsets eligible for NMDAR-related treatment can be identified. Our data aid to reconcile conflicting reports regarding a role of pathological NMDAR autoantibodies in this disorder.
Subject(s)
Autoantibodies/immunology , Receptors, N-Methyl-D-Aspartate/immunology , Schizophrenia/immunology , Adult , Animals , Autoimmunity , Female , Humans , Male , Mice , Middle Aged , Toxoplasma/immunology , Young AdultABSTRACT
The authors used a battery of cognitive and social functioning measures to evaluate stable outpatients with schizophrenia (n=74) and bipolar I disorder (n=26) who were receiving care at community and rehabilitation programs. The groups did not differ significantly on 36 of 41 measures. For most variables, comparisons between groups yielded effect sizes of <0.5. These results suggest that individuals with bipolar I disorder receiving community and rehabilitation services have many social and cognitive deficits that are as severe as those in schizophrenia.
