TABLE 3.

Potential linkages between T. canis infections and neuropsychiatric disorders

Neuropsychiatric disorder	Possible mechanisms	Type of studies	Possible causal relationships	References
Seizure	Increased proinflammatory cytokine expression and BBB dysfunction	Human/animal studies	Three large-scale studies provided evidence for a positive association between T. canis seropositivity and seizure.	71–73, 153–159, 200, 208
Schizophrenia	Increased or decreased dopamine expression	Animal studies	Epidemiological studies indicated that the schizophrenia group had a higher seroprevalence of T. canis infection than healthy individuals. Increased or decreased dopamine expression was observed in the T. canis-infected mouse brain.	97, 166–170, 173–178
Cognitive deficits	CNS inflammation causes amyloid neuritic plaque formation	Human/animal studies	Several epidemiological studies indicated significant cognitive deficits in T. canis-seropositive children compared with seronegative controls.	170, 179–189, 199
Idiopathic Parkinson's disease (IPD)	CNS inflammation causes dopaminergic neuronal degeneration	Animal studies	Insignificantly higher seroprevalence of T. canis infection in patients with IPD than in controls. Significantly decreased GABA and DP levels were found in T. canis-infected mice compared with uninfected mice.	170, 192–195
Dementia	CNS inflammation causes amyloid neuritic plaque formation	Human studies	An elderly German woman with a long history of depression and cognitive decline showed reactive antibodies against T. canis antigen in CSF.	75, 179, 180
Alzheimer's disease	CNS inflammation causes amyloid neuritic plaque formation	Human/animal studies	Significantly increased proinflammatory cytokines and insoluble β-amyloid levels were found in brains of T. canis-infected mice compared with uninfected mice.	170, 196, 200, 208