biostudies-literatureBrazdis RMDeutsche ForschungsgemeinschaftFederal Ministry of Education and ResearchIZKF3219https://www.ebi.ac.uk/biostudies/studies/S-EPMC10970259biostudies-literatureUnknown25(6)Due to the high comorbidity of Parkinson's disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (<i>SNCA</i>), lysosomal enzyme β-glucocerebrosidase (<i>GBA1</i>), and UDP-glucose ceramide glucosyltransferase (<i>UGCG</i>) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated <i>n</i> = 63, medicated <i>n</i> = 66) and controls (remitted MDD <i>n</i> = 39, healthy subjects <i>n</i> = 61). We observed that expression levels of <i>SNCA</i> (<i>p</i> = 0.036), <i>GBA1</i> (<i>p</i> = 0.014), and <i>UGCG</i> (<i>p</i> = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of <i>GBA1</i> and <i>UGCG</i> decreased in medicated patients during three weeks of therapy. Additionally, in subgroups, expression was positively correlated with the severity of depression and anxiety. Furthermore, we identified correlations between the gene expression levels and PD-related laboratory parameters. Our findings suggest that <i>SNCA</i>, <i>GBA1</i>, and <i>UGCG</i> analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.International journal of molecular sciencesPeripheral Upregulation of Parkinson's Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression.PMC10970259GRK2162/270949263Clinician Scientist ProgrammeKO 947/13 to J.K01EE1401C to J.Kvon Zimmermann CLenz BBrazdis RMKornhuber JMuhle CfalsePeripheral Upregulation of Parkinson's Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression.Due to the high comorbidity of Parkinson's disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (<i>SNCA</i>), lysosomal enzyme β-glucocerebrosidase (<i>GBA1</i>), and UDP-glucose ceramide glucosyltransferase (<i>UGCG</i>) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated <i>n</i> = 63, medicated <i>n</i> = 66) and controls (remitted MDD <i>n</i> = 39, healthy subjects <i>n</i> = 61). We observed that expression levels of <i>SNCA</i> (<i>p</i> = 0.036), <i>GBA1</i> (<i>p</i> = 0.014), and <i>UGCG</i> (<i>p</i> = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of <i>GBA1</i> and <i>UGCG</i> decreased in medicated patients during three weeks of therapy. Additionally, in subgroups, expression was positively correlated with the severity of depression and anxiety. Furthermore, we identified correlations between the gene expression levels and PD-related laboratory parameters. Our findings suggest that <i>SNCA</i>, <i>GBA1</i>, and <i>UGCG</i> analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.2024-01-01T00:00:00Z2024 Mar2025-04-04T23:53:45.95Z2025-04-04T23:53:45.95ZS-EPMC109702593854219310.3390/ijms25063219