Peripheral 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 (SNCA), lysosomal enzyme β-glucocerebrosidase (GB...

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Published inInternational journal of molecular sciences Vol. 25; no. 6; p. 3219
Main Authors Brazdis, Razvan-Marius, von Zimmermann, Claudia, Lenz, Bernd, Kornhuber, Johannes, Mühle, Christiane
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 12.03.2024
MDPI
Subjects
alpha-Synuclein - genetics
alpha-Synuclein - metabolism
Analysis
Anxiety
Body mass index
Cellulose
Comorbidity
Depression
Depressive Disorder, Major - genetics
Development and progression
Disease
Enzymes
Females
Gene Expression
Genes
Glucosylceramidase - genetics
Glucosylceramidase - metabolism
Glucosyltransferases
Health risk assessment
Humans
Major depressive disorder
Males
Membrane lipids
Mental depression
Metabolism
Mutation
Parkinson Disease - metabolism
Psychosis
Signal transduction
Sphingolipids
Up-Regulation
Germany
UGCG
anxiety
PD
affective disorder
major depressive disorder
GBA1
MDD
biomarker
gene expression
SNCA
Online AccessGet full text
ISSN1422-0067
1661-6596
1422-0067
DOI10.3390/ijms25063219

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Abstract 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 (SNCA), lysosomal enzyme β-glucocerebrosidase (GBA1), and UDP-glucose ceramide glucosyltransferase (UGCG) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated n = 63, medicated n = 66) and controls (remitted MDD n = 39, healthy subjects n = 61). We observed that expression levels of SNCA (p = 0.036), GBA1 (p = 0.014), and UGCG (p = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of GBA1 and UGCG 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 SNCA, GBA1, and UGCG analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.
AbstractList 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 (SNCA), lysosomal enzyme β-glucocerebrosidase (GBA1), and UDP-glucose ceramide glucosyltransferase (UGCG) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated n = 63, medicated n = 66) and controls (remitted MDD n = 39, healthy subjects n = 61). We observed that expression levels of SNCA (p = 0.036), GBA1 (p = 0.014), and UGCG (p = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of GBA1 and UGCG 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 SNCA, GBA1, and UGCG analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.
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 (SNCA), lysosomal enzyme β-glucocerebrosidase (GBA1), and UDP-glucose ceramide glucosyltransferase (UGCG) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated n = 63, medicated n = 66) and controls (remitted MDD n = 39, healthy subjects n = 61). We observed that expression levels of SNCA (p = 0.036), GBA1 (p = 0.014), and UGCG (p = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of GBA1 and UGCG 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 SNCA, GBA1, and UGCG analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.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 (SNCA), lysosomal enzyme β-glucocerebrosidase (GBA1), and UDP-glucose ceramide glucosyltransferase (UGCG) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated n = 63, medicated n = 66) and controls (remitted MDD n = 39, healthy subjects n = 61). We observed that expression levels of SNCA (p = 0.036), GBA1 (p = 0.014), and UGCG (p = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of GBA1 and UGCG 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 SNCA, GBA1, and UGCG analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.
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 ( ), lysosomal enzyme β-glucocerebrosidase ( ), and UDP-glucose ceramide glucosyltransferase ( ) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated = 63, medicated = 66) and controls (remitted MDD = 39, healthy subjects = 61). We observed that expression levels of ( = 0.036), ( = 0.014), and ( = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of and 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 , , and analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.
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 ( SNCA ), lysosomal enzyme β-glucocerebrosidase ( GBA1 ), and UDP-glucose ceramide glucosyltransferase ( UGCG ) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated n = 63, medicated n = 66) and controls (remitted MDD n = 39, healthy subjects n = 61). We observed that expression levels of SNCA ( p = 0.036), GBA1 ( p = 0.014), and UGCG ( p = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of GBA1 and UGCG 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 SNCA , GBA1 , and UGCG analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.
Audience Academic
Author Lenz, Bernd
von Zimmermann, Claudia
Kornhuber, Johannes
Brazdis, Razvan-Marius
Mühle, Christiane
AuthorAffiliation 2 Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (CIMH), Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
1 Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen and Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; razvanmarius.brazdis@uk-erlangen.de (R.-M.B.); bernd.lenz@zi-mannheim.de (B.L.); johannes.kornhuber@uk-erlangen.de (J.K.)
AuthorAffiliation_xml – name: 1 Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen and Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany; razvanmarius.brazdis@uk-erlangen.de (R.-M.B.); bernd.lenz@zi-mannheim.de (B.L.); johannes.kornhuber@uk-erlangen.de (J.K.)
– name: 2 Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (CIMH), Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
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Keywords UGCG
anxiety
PD
affective disorder
major depressive disorder
GBA1
MDD
biomarker
gene expression
SNCA
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SSID ssj0023259
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Snippet Due to the high comorbidity of Parkinson’s disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we...
Due to the high comorbidity of Parkinson's disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we...
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SourceType Open Access Repository
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StartPage 3219
SubjectTerms alpha-Synuclein - genetics
alpha-Synuclein - metabolism
Analysis
Anxiety
Body mass index
Cellulose
Comorbidity
Depression
Depressive Disorder, Major - genetics
Development and progression
Disease
Enzymes
Females
Gene Expression
Genes
Glucosylceramidase - genetics
Glucosylceramidase - metabolism
Glucosyltransferases
Health risk assessment
Humans
Major depressive disorder
Males
Membrane lipids
Mental depression
Metabolism
Mutation
Parkinson Disease - metabolism
Psychosis
Signal transduction
Sphingolipids
Up-Regulation
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Title Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression
URI https://www.ncbi.nlm.nih.gov/pubmed/38542193
https://www.proquest.com/docview/3003241431
https://www.proquest.com/docview/3014009047
https://pubmed.ncbi.nlm.nih.gov/PMC10970259
Volume 25
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