Leonidas Stefanis, Alexia Polissidis and colleagues recently published a study in Movement Disorders

The overarching aim of our lab’s research program is to elucidate the pathogenesis and pathophysiology of Parkinson’s disease and related synucleinopathies. The predominantly neuronal protein, alpha-synuclein, is central to our research as it is notoriously implicated in the pathogenesis of Parkinson’s disease at the genetic, biochemical and pathological level. On the other hand, psychosis is a common and debilitating feature of Parkinson's Disease. In the present publication, we demonstrate for the first time a link between aberrant alpha‐synuclein expression and Parkinson's disease psychosis in a transgenic rat model, and provide evidence that this psychotic-like phenotype is due to a paradoxical prodromal hyperdopaminergic state, prior to the well appreciated degeneration of the dopaminergic system. The reported phenotype coincides with the latest clinical findings that suggest that in Parkinson's Disease a premotor hyperdopaminergic state may occur, while at the same time, premotor psychotic symptoms are increasingly being recognized.

Psychosis-Like Behavior and Hyperdopaminergic Dysregulation in Human α-Synuclein BAC Transgenic Rats.
Polissidis A, Koronaiou M, Kollia V, Koronaiou E, Nakos-Bimpos M, Bogiongko M, Vrettou S, Karali K, Casadei N, Riess O, Sardi SP, Xilouri M, Stefanis L.
Mov Disord. 2020 Nov 17. doi: 10.1002/mds.28383.

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