Non-Motor Symptoms and Neuropsychiatric Features in Parkinson’s Disease: From Prodromal Indicators to Therapeutic Targets

Parkinson’s disease (PD) has traditionally been defined by its motor symptoms and nigrostriatal dopaminergic degeneration, yet a growing body of research highlights the central importance of non-motor manifestations and dysfunctions of other neural pathways and neurotransmitter systems. Symptoms such as pain, sleep disturbances, autonomic dysfunction, and affective symptoms (like apathy, anhedonia, depression, and anxiety) often arise in the prodromal phase, before the onset of motor deficits. Frequently underdiagnosed and undertreated, these non-motor features can significantly diminish patients’ quality of life and complicate disease management. Progress has been made in understanding their links to neurodegenerative changes and dysfunctions in different neurotransmitter systems (including the dopaminergic, serotonergic, cholinergic, histaminergic, glutamatergic, and noradrenergic systems) and neural circuits (such as the mesolimbic and mesocortical circuits implicated in affective symptoms). Nevertheless, much remains to be understood about their etiology, their interactions, their influence on PD progression, and the optimal therapeutic strategies for this complex symptom burden.This Research Topic aims to deepen our understanding of the pathogenetic mechanisms and clinical manifestations of non-motor symptoms in Parkinson’s disease, including pain, sleep disorders, autonomic dysfunction, and cognitive, behavioral, and neuropsychiatric features. We aim to identify more precise therapeutic targets, discover additional biomarkers for patient phenotyping, and develop personalized therapeutic interventions that could potentially slow disease progression. A particular focus on apathy (which affects about 70% of PD patients) is vital, as it serves as an independent predictor of poor outcomes, lower treatment adherence, and reduced quality of life. To gather further insights within the non-motor features of PD, we welcome submissions across a diverse range of manuscript types supported by the journal - including Original Research, Brief Research Reports, Perspectives, Protocols, Mini-Reviews, and more - exploring, but not limited to, the following themes:- Early detection, longitudinal monitoring, and management of non-motor symptoms: novel diagnostic tools, biomarkers, prognostic indicators, and therapeutic strategies across prodromal and progressive disease stages- Anatomical imaging studies for circuit characterization in prodromal PD.- Pain in PD: subtypes, central and peripheral mechanisms, clinical assessment tools, and pharmacological, interventional, and non-pharmacological therapeutic approaches- The interplay between pain, motor fluctuations, and other non-motor symptoms, and its impact on quality of life and decision-making- Mechanistic insights and interventions for apathy and related affective symptoms- Reward and motivation dysfunction in hypodopaminergic and hyperdopaminergic states- Neuropsychological features associated with motivational disorders and their implications for rehabilitative approaches in PD- Non-motor fluctuations: clinical spectrum (from anxiety and panic attacks to mood swings and confusion) and their role in addictive behaviors such as dopamine dysregulation syndrome (DDS)- The gut-brain axis and serotonergic involvement in PD- The noradrenergic neurotransmission in PD and its implication in non-motor symptoms and prodromal phase. Interactions with the inflammatory system and neuroprotective functions- Neuroinflammation as a driver of prodromal and established non-motor features- Implication of PARP-1 in PD pathogenesis and treatment: its interactions with alpha synuclein, implication in neuroinflammation, mitochondria dysfunctions, and dysfunctions in autophagy. - Cholinergic system alterations and therapeutic development - Animal models for non-motor and prodromic symptoms of PD- In vitro models: cell-based models of PD for studying mechanisms underlying non-motor symptoms and for phenotypic screening in drug discovery.- iPSC modelling of PD focused on non-motor phenotypes, for mechanistic probing, drug screening, diagnosis, personalized medicine, phenotyping of patients, and therapy.- Patient stratification, phenotype-specific interventions, and a precision medicine approachArticles accepted after peer review will be published and appear online as soon as approved for publication.Sign up now to participate in this exciting Research Topic. Topic editors: Cristina Cosi, Chiara Siri, Veronica Andrea Bruno, Eleonora Fiorenzato Source: https://www.frontiersin.org/research-topics/73950/non-motor-symptoms-and-neuropsychiatric-features-in-parkinsons-disease-from-prodromal-indicators-to-therapeutic-targets