In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers

Introduction: We used positron emission tomography (PET) to assess dopaminergic and serotonergic terminal density in three subjects carrying a mutation in the DCT1 gene, two clinically affected with Perry syndrome. Methods: All subjects had brain imaging using 18F-6-fluoro-l-dopa (FDOPA, dopamine synthesis and storage), (+)-11C-dihydrotetrabenazine (DTBZ, vesicular monoamine transporter type 2), and 11C-raclopride (RAC, dopamine D2/D3 receptors). One subject also underwent PET with 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB, serotonin transporter). Results: FDOPA-PET and DTBZ-PET in the affected individuals showed a reduction of striatal tracer uptake. Also, RAC-PET showed higher uptake in these area. DASB-PET showed significant uptake changes in left orbitofrontal cortex, bilateral anterior insula, left dorsolateral prefrontal cortex, left orbitofrontal cortex, left posterior cingulate cortex, left caudate, and left ventral striatum. Conclusions: Our data showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the DCTN1 gene.