PT - JOURNAL ARTICLE AU - Juho Joutsa AU - Jarkko Johansson AU - Marko Petteri Seppänen AU - Tommi Noponen AU - Valtteri Kaasinen TI - Dorsal-to-ventral shift in midbrain dopaminergic projections and increased thalamic/raphe serotonergic function in early Parkinson's disease AID - 10.2967/jnumed.115.153734 DP - 2015 May 01 TA - Journal of Nuclear Medicine PG - jnumed.115.153734 4099 - http://jnm.snmjournals.org/content/early/2015/05/06/jnumed.115.153734.short 4100 - http://jnm.snmjournals.org/content/early/2015/05/06/jnumed.115.153734.full AB - Loss of nigrostriatal neurons leading to dopamine depletion in the dorsal striatum is the pathological hallmark of Parkinson’s disease contributing to the primary motor symptoms of the disease. However, Parkinson pathology is more widespread in the brain affecting also other dopaminergic pathways and neurotransmitter systems but these changes are less well characterized. This study aimed to investigate the mesencephalic sriatal and extrastriatal dopaminergic projections together with extrastriatal serotonin transporter binding in PD. Methods: Two hundred sixteen patients with Parkinson’s disease and 204 control patients (patients without neurodegenerative parkinsonism syndromes and normal SPECT imaging) were investigated with SPECT using the dopamine/serotonin transporter ligand [123I]FP-CIT in the clinical setting. The group differences and midbrain correlations were analyzed voxel-by-voxel over the entire brain. Results: We found that Parkinson patients had lower [123I]FP-CIT uptake in the striatum and ventral midbrain but higher uptake in the thalamus and raphe nuclei compared to control patients. In patients with Parkinson’s disease, the correlation of the midbrain tracer uptake was shifted from the putamen to widespread corticolimbic areas. All findings were highly significant at the voxel-level FWE-corrected P<0.05. Conclusion: Our findings show that Parkinson’s disease is associated not only with the degeneration of the nigrostriatal dopamine neurotransmission, but also with a parallel shift towards mesolimbic and mesocortical function. Furthermore, Parkinson’s disease patients seem to have upregulation of brain serotonin transporter function at the early phase of the disease.