Disentangling gray matter atrophy and its neurotransmitter architecture in drug-naïve Parkinson’s disease: an atlas-based correlation analysis

Parkinson's disease is characterized by multiple neurotransmitter systems beyond the traditional dopaminergic pathway, yet their influence on volumetric alterations is not well comprehended. We included 72 de novo, drug-naïve Parkinson's disease patients and 61 healthy controls. Voxel-wise gray matter volume was evaluated between Parkinson's disease and healthy controls, as well as among Parkinson's disease subgroups categorized by clinical manifestations. The Juspace toolbox was utilized to explore the spatial relationship between gray matter atrophy and neurotransmitter distribution. Parkinson's disease patients exhibited widespread GM atrophy in the cerebral and cerebellar regions, with spatial correlations with various neurotransmitter receptors (FDR-P < 0.05). Cognitively impaired Parkinson's disease patients showed gray matter atrophy in the left middle temporal atrophy, which is associated with serotoninergic, dopaminergic, cholinergic, and glutamatergic receptors (FDR-P < 0.05). Postural and gait disorder patients showed atrophy in the right precuneus, which is correlated with serotoninergic, dopaminergic, gamma-aminobutyric acid, and opioid receptors (FDR-P < 0.05). Patients with anxiety showed atrophy in the right superior orbital frontal region; those with depression showed atrophy in the left lingual and right inferior occipital regions. Both conditions were linked to serotoninergic and dopaminergic receptors (FDR-P < 0.05). Parkinson's disease patients exhibited regional gray matter atrophy with a significant distribution of specific neurotransmitters, which might provide insights into the underlying pathophysiology of clinical manifestations and develop targeted intervention strategies.