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Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder

BACKGROUND: The retrograde endocannabinoid (eCB) pathway is closely associated with the etiology of major depressive disorder (MDD) at both pathophysiological and genetic levels. This study aimed to investigate the potential role of genetic mutations in the eCB pathway and underlying mechanisms in H...

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Autores principales: Xu, Huifang, Li, Tongtong, Gong, Qiyong, Xu, Haizhen, Hu, Yongbo, Lü, Wenqi, Yang, Xin, Li, Jin, Xu, Wenming, Kuang, Weihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165312/
https://www.ncbi.nlm.nih.gov/pubmed/37168668
http://dx.doi.org/10.3389/fneur.2023.1153509
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author Xu, Huifang
Li, Tongtong
Gong, Qiyong
Xu, Haizhen
Hu, Yongbo
Lü, Wenqi
Yang, Xin
Li, Jin
Xu, Wenming
Kuang, Weihong
author_facet Xu, Huifang
Li, Tongtong
Gong, Qiyong
Xu, Haizhen
Hu, Yongbo
Lü, Wenqi
Yang, Xin
Li, Jin
Xu, Wenming
Kuang, Weihong
author_sort Xu, Huifang
collection PubMed
description BACKGROUND: The retrograde endocannabinoid (eCB) pathway is closely associated with the etiology of major depressive disorder (MDD) at both pathophysiological and genetic levels. This study aimed to investigate the potential role of genetic mutations in the eCB pathway and underlying mechanisms in Han Chinese patients with MDD. METHODS: A total of 96 drug-naïve patients with first-episode MDD and 62 healthy controls (HCs) were recruited. Whole-exome sequencing was performed to identify the gene mutation profiles in patients with MDD. Results were filtered to focus on low-frequency variants and rare mutations (minor allele frequencies <0.05) related to depressive phenotypes. Enrichment analyses were performed for 146 selected genes to examine the pathways in which the most significant enrichment occurred. A protein–protein interaction (PPI) network analysis was performed to explore the biological functions of the eCB pathway. Finally, based on current literature, a preliminary analysis was conducted to explore the effect of genetic mutations on the function of this pathway. RESULTS: Our analysis identified 146 (15.02%) depression-related genetic mutations in patients with MDD when compared with HCs, and 37 of the mutations were enriched in the retrograde eCB signaling pathway. Seven hub genes in the eCB pathway were closely related to mitochondrial function, including Complex I genes (NDUFS4, NDUFV2, NDUFA2, NDUFA12, NDUFB11) and genes associated with protein (PARK7) and enzyme (DLD) function in the regulation of mitochondrial oxidative stress. CONCLUSION: These results indicate that genetic mutations in the retrograde eCB pathway represent potential etiological factors associated with the pathogenesis of MDD.
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spelling pubmed-101653122023-05-09 Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder Xu, Huifang Li, Tongtong Gong, Qiyong Xu, Haizhen Hu, Yongbo Lü, Wenqi Yang, Xin Li, Jin Xu, Wenming Kuang, Weihong Front Neurol Neurology BACKGROUND: The retrograde endocannabinoid (eCB) pathway is closely associated with the etiology of major depressive disorder (MDD) at both pathophysiological and genetic levels. This study aimed to investigate the potential role of genetic mutations in the eCB pathway and underlying mechanisms in Han Chinese patients with MDD. METHODS: A total of 96 drug-naïve patients with first-episode MDD and 62 healthy controls (HCs) were recruited. Whole-exome sequencing was performed to identify the gene mutation profiles in patients with MDD. Results were filtered to focus on low-frequency variants and rare mutations (minor allele frequencies <0.05) related to depressive phenotypes. Enrichment analyses were performed for 146 selected genes to examine the pathways in which the most significant enrichment occurred. A protein–protein interaction (PPI) network analysis was performed to explore the biological functions of the eCB pathway. Finally, based on current literature, a preliminary analysis was conducted to explore the effect of genetic mutations on the function of this pathway. RESULTS: Our analysis identified 146 (15.02%) depression-related genetic mutations in patients with MDD when compared with HCs, and 37 of the mutations were enriched in the retrograde eCB signaling pathway. Seven hub genes in the eCB pathway were closely related to mitochondrial function, including Complex I genes (NDUFS4, NDUFV2, NDUFA2, NDUFA12, NDUFB11) and genes associated with protein (PARK7) and enzyme (DLD) function in the regulation of mitochondrial oxidative stress. CONCLUSION: These results indicate that genetic mutations in the retrograde eCB pathway represent potential etiological factors associated with the pathogenesis of MDD. Frontiers Media S.A. 2023-04-20 /pmc/articles/PMC10165312/ /pubmed/37168668 http://dx.doi.org/10.3389/fneur.2023.1153509 Text en Copyright © 2023 Xu, Li, Gong, Xu, Hu, Lü, Yang, Li, Xu and Kuang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Xu, Huifang
Li, Tongtong
Gong, Qiyong
Xu, Haizhen
Hu, Yongbo
Lü, Wenqi
Yang, Xin
Li, Jin
Xu, Wenming
Kuang, Weihong
Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder
title Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder
title_full Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder
title_fullStr Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder
title_full_unstemmed Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder
title_short Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder
title_sort genetic variations in the retrograde endocannabinoid signaling pathway in chinese patients with major depressive disorder
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165312/
https://www.ncbi.nlm.nih.gov/pubmed/37168668
http://dx.doi.org/10.3389/fneur.2023.1153509
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