Abstract Body

The epidemiological studies show mixed results for the role of Toxoplasma gondii in schizophrenia, Alzheimer’s disease, and Parkinson’s disease. Our studies suggest that differences in Toxoplasma strain type and infection stage may account for these discrepancies. Toxoplasma has many strain types, with virulence being the most notable difference. Following exposure to Toxoplasma, there is marked variation in human response ranging from resolved to persistent infection. We have found that maternal infection with virulent type I strains increased the risk of psychosis in offspring. Pregnant women who were Toxoplasma-seropositive are at risk for dysphoric mood states of depression and anxiety, of which type I-infected had the highest scores. Our studies also suggest that the presence of tissue cysts is associated with clinical manifestations. In HIV+ individuals, tissue cysts showed predictive value on the occurrence of toxoplasmic encephalitis. In animal models of chronic infection, there are multiple neuropathologies. We found that persistent infection leads to cortical neurodegeneration, NMDAR autoantibody generation, and behavioral changes. Neurodegeneration occurs in specific regions of the prefrontal cortex. NMDAR autoantibodies have been postulated to play a role in the pathogenesis of NMDAR hypofunction. The presence of tissue cysts is associated with the elevation of NMDAR autoantibodies. Several behavioral abnormalities were discovered, such as reduced locomotor and exploratory activity, impaired object recognition memory, and lack of motor activation to amphetamine. These studies have provided mechanistic explanations for the link between Toxoplasma infection and psychiatric disorders.