The basic underlying neurobiological defect in TS is unknown. Most investigators concur that the disorder results from abnormalities within cortical-striatal-thalamo-cortical pathways.20,21 The precise localization, whether cortical or striatal, however, remains controversial.
Recent neuroimaging studies suggest small volumes in the caudate and possibly compensatory increases in prefrontal cortices, the later contributing to persistence of symptoms.22
Other studies have shown larger volumes of the hippocampus and amygdala, regions that send projections to the ventromedial striatum.23
Smaller area measurements of the midsaggital corpus callosum in TS have correlated with impaired forced-left ear attention performance.24
Abnormalities of neurotransmitters, which convey messages between brain neurons, are thought to have a prominent pathological role in TS.
Abnormalities of dopamine markers in postmortem frontal lobe 25 and PET studies showing excessive neurotransmitter release26,27 support a role for dopamine.
Other investigators, however, emphasize the importance of serotonin.27,28
Lower serum ferritin and iron levels in patients with TS, although within the normal range, have been proposed to have a possible role in the pathophysiology of this disorder.29
