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Abstract

While the implication of a dysfunctional dopaminergic system in Tourette syndrome (TS) is well established, the underlying pathophysiological mechanisms remain unclear. Apart from neurotransmitters, disturbed iron homeostasis and iron regulatory mechanisms are also suspected. Iron is a trace element of fundamental biological importance and is involved in the synthesis and metabolism of dopamine and its receptors and transporters. The goal of the current pre-registered, multi-modal, cross-sectional study was to investigate the relationship between potential iron homeostasis imbalances and dopaminergic system disturbances in patients with TS. Susceptibility-sensitive MRI at 7 Tesla was used to obtain surrogate measures for local brain iron in 25 patients with TS (age 30 ± 9 years, 6 female) and 40 matched control subjects. Additionally, dopamine D1 receptor availability was investigated with [11C]SCH23390 PET in a subgroup of 20 patients and 20 controls. Significantly reduced sub-cortical magnetic susceptibility, indicating reduced iron levels, was observed in TS patients in the caudate, pallidum, sub-thalamic nucleus, thalamus, red nucleus and substantia nigra. These reductions were accompanied by significant reductions of the [11C]SCH23390 binding potential indicating reduced availability of D1 receptors in the dorsal striatum. The D1 receptor abnormality correlated with tic severity. These results point to alterations of intra-synaptic dopamine release and reduced striatal D1 receptor binding, supporting the notion of disruption in multiple functional elements of the dopaminergic system. Such dopaminergic abnormalities appear to be associated with disturbances in iron homeostasis.