Mental Health
Metabolomic profiles of depression in Parkinson’s disease patients Yuyuan Lin* Yuyuan Lin Kimberly C. Paul Dean Jones Douglas I. Walker Aline Duarte Folle Irish Del Rosario Yu Yu Keren Zhang Adrienne M. Keener Jeff Bronstein Beate Ritz
Objectives: Depression is a common non-motor symptom of Parkinson’s disease (PD). While mechanisms for this are poorly understood, it has recently been suggested that the gut microbiome affects depression and also PD risk. Here we applied high resolution, untargeted metabolomics to explore whether there are dysregulated metabolic pathways possibly suggesting an influence from the gut microbiome in PD patients with depression.
Methods: We performed a metabolome-wide association analysis using serum samples of PD patients from a population-based case control study (total n = 635). Metabolomic profiling was done using liquid chromatography with mass spectrometry (LC-MS). We did two analyses using different depression outcomes, first depression diagnosis before baseline, and second, the Geriatric Depression Scale (GDS) score at baseline interview.
Results: 4762 metabolomic features were detected from the LC-MS after data cleaning. Using partial least square models and a threshold of VIP ≥ 2, we identified 223 metabolomic features associated with depression diagnosis and 212 with a high GDS score. Among all significant features, 127 were successfully annotated. The leading metabolite categories identified were lipids/lipid-like molecules and amino acids and derivatives. The strongest association with both outcomes was seen for 6-Hydroxy-1H-indole-3acetamide (VIP = 8.59 depression diagnosis; VIP = 3.24 for GDS score). In the pathway analysis, 10 metabolic pathways were highlighted using the Mummichog package. The majority was related to amino acids and lipids metabolism, including tryptophan and tyrosine metabolism.
Conclusions: Our study highlighted perturbation and dysregulated pathways related to gut microbial metabolism associated with depression in PD, suggesting possible links between the gut microbial flora and depression in PD patients.