Abstract
Depression is a common non-motor symptom of Parkinson's disease (PD), with poorly understood mechanisms. To explore whether there are dysregulated metabolic pathways among PD patients with depression, we analyzed serum samples of PD patients from a population-based case-control study (total n = 635) and performed metabolome-wide association and pathway analyses of depression in PD. We identified 212 metabolomic features associated with having ever received a depression diagnosis before PD and 213 features with higher Geriatric Depression Scale (GDS) scores (129 were annotated). Metabolic features we identified belonged to 14 pathways: glycerophospholipid metabolism for both outcomes and tryptophan, tyrosine, folate, biopterin, and sialic acid metabolism for those with higher GDS scores. An association with 6-hydroxy-1H-indole-3acetamide we observed likely indicates recent antidepressant treatment. These findings suggest that dysregulation in lipid and amino acid pathways, including tryptophan and tyrosine metabolism involved in neurotransmitter synthesis, may reflect altered neurochemical signaling and systemic metabolic changes related to depression in PD.