Genetic and molecular basis of abnormal BOLD signaling variability in patients with major depressive disorder after electroconvulsive therapy

Abstract Electroconvulsive therapy (ECT) is an effective and rapid neuromodulatory intervention for treatment-resistant major depressive disorders (MDD). However, the precise mechanisms underlying their efficacies remain unclear. Resting-state functional magnetic resonance imaging (fMRI) data were c...

Full description

Saved in:
Bibliographic Details
Main Authors: Siyu Fan, Yulin Zhang, Rui Qian, Jie Hu, Hao Zheng, Wentao Dai, Yang Ji, Yue Wu, Xiaohui Xie, Si Xu, Gong-Jun Ji, Yanghua Tian, Kai Wang
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-025-03330-6
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850153495208919040
author Siyu Fan
Yulin Zhang
Rui Qian
Jie Hu
Hao Zheng
Wentao Dai
Yang Ji
Yue Wu
Xiaohui Xie
Si Xu
Gong-Jun Ji
Yanghua Tian
Kai Wang
author_facet Siyu Fan
Yulin Zhang
Rui Qian
Jie Hu
Hao Zheng
Wentao Dai
Yang Ji
Yue Wu
Xiaohui Xie
Si Xu
Gong-Jun Ji
Yanghua Tian
Kai Wang
author_sort Siyu Fan
collection DOAJ
description Abstract Electroconvulsive therapy (ECT) is an effective and rapid neuromodulatory intervention for treatment-resistant major depressive disorders (MDD). However, the precise mechanisms underlying their efficacies remain unclear. Resting-state functional magnetic resonance imaging (fMRI) data were collected from 84 individuals with MDD and healthy controls before and after ECT, and coefficient of variation of the BOLD signal (CVBOLD) analysis was combined with region of interest (ROI) functional connectivity (FC) analysis. To assess the reliability of the antidepressant mechanism of ECT, we analyzed the changes in CVBOLD in a separate cohort consisting of 35 patients with MDD who underwent ECT. Moreover, transcriptomic and neurotransmitter receptor data were used to reveal the genetic and molecular bases of the changes in CVBOLD. Patients with MDD who underwent ECT demonstrated increased CVBOLD in the left angular cortex and left precuneus. Following ECT, an increase in FC between the left precuneus and right lingual lobes was associated with improvements in Hamilton Depression Rating Scale (HAMD) scores. validation analysis consistently demonstrated similar changes in CVBOLD in two independent cohorts of patients with MDD. Moreover, these changes in CVBOLD were closely associated with thyroid hormone synthesis, oxidative phosphorylation, endocytosis, and the insulin signaling pathway, and were significantly correlated with the receptor/transporter density of serotonin and dopamine. These findings suggest that ECT modulates abnormal functions in the left angular cortex and left precuneus, leading to widespread changes in functional connectivity and neuroplasticity, especially in the default mode network, and exerts an antidepressant effect.
format Article
id doaj-art-84405e7e8f784a75bb07c68a20ba2ac1
institution OA Journals
issn 2158-3188
language English
publishDate 2025-04-01
publisher Nature Publishing Group
record_format Article
series Translational Psychiatry
spelling doaj-art-84405e7e8f784a75bb07c68a20ba2ac12025-08-20T02:25:41ZengNature Publishing GroupTranslational Psychiatry2158-31882025-04-011511910.1038/s41398-025-03330-6Genetic and molecular basis of abnormal BOLD signaling variability in patients with major depressive disorder after electroconvulsive therapySiyu Fan0Yulin Zhang1Rui Qian2Jie Hu3Hao Zheng4Wentao Dai5Yang Ji6Yue Wu7Xiaohui Xie8Si Xu9Gong-Jun Ji10Yanghua Tian11Kai Wang12Department of Neurology, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Neurology, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Neurology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Neurology, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Neurology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Neurology, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Neurology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Psychology and Sleep Medicine, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Neurology, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Neurology, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Psychology and Sleep Medicine, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Neurology, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Neurology, the First Affiliated Hospital of Anhui Medical UniversityAbstract Electroconvulsive therapy (ECT) is an effective and rapid neuromodulatory intervention for treatment-resistant major depressive disorders (MDD). However, the precise mechanisms underlying their efficacies remain unclear. Resting-state functional magnetic resonance imaging (fMRI) data were collected from 84 individuals with MDD and healthy controls before and after ECT, and coefficient of variation of the BOLD signal (CVBOLD) analysis was combined with region of interest (ROI) functional connectivity (FC) analysis. To assess the reliability of the antidepressant mechanism of ECT, we analyzed the changes in CVBOLD in a separate cohort consisting of 35 patients with MDD who underwent ECT. Moreover, transcriptomic and neurotransmitter receptor data were used to reveal the genetic and molecular bases of the changes in CVBOLD. Patients with MDD who underwent ECT demonstrated increased CVBOLD in the left angular cortex and left precuneus. Following ECT, an increase in FC between the left precuneus and right lingual lobes was associated with improvements in Hamilton Depression Rating Scale (HAMD) scores. validation analysis consistently demonstrated similar changes in CVBOLD in two independent cohorts of patients with MDD. Moreover, these changes in CVBOLD were closely associated with thyroid hormone synthesis, oxidative phosphorylation, endocytosis, and the insulin signaling pathway, and were significantly correlated with the receptor/transporter density of serotonin and dopamine. These findings suggest that ECT modulates abnormal functions in the left angular cortex and left precuneus, leading to widespread changes in functional connectivity and neuroplasticity, especially in the default mode network, and exerts an antidepressant effect.https://doi.org/10.1038/s41398-025-03330-6
spellingShingle Siyu Fan
Yulin Zhang
Rui Qian
Jie Hu
Hao Zheng
Wentao Dai
Yang Ji
Yue Wu
Xiaohui Xie
Si Xu
Gong-Jun Ji
Yanghua Tian
Kai Wang
Genetic and molecular basis of abnormal BOLD signaling variability in patients with major depressive disorder after electroconvulsive therapy
Translational Psychiatry
title Genetic and molecular basis of abnormal BOLD signaling variability in patients with major depressive disorder after electroconvulsive therapy
title_full Genetic and molecular basis of abnormal BOLD signaling variability in patients with major depressive disorder after electroconvulsive therapy
title_fullStr Genetic and molecular basis of abnormal BOLD signaling variability in patients with major depressive disorder after electroconvulsive therapy
title_full_unstemmed Genetic and molecular basis of abnormal BOLD signaling variability in patients with major depressive disorder after electroconvulsive therapy
title_short Genetic and molecular basis of abnormal BOLD signaling variability in patients with major depressive disorder after electroconvulsive therapy
title_sort genetic and molecular basis of abnormal bold signaling variability in patients with major depressive disorder after electroconvulsive therapy
url https://doi.org/10.1038/s41398-025-03330-6
work_keys_str_mv AT siyufan geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy
AT yulinzhang geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy
AT ruiqian geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy
AT jiehu geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy
AT haozheng geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy
AT wentaodai geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy
AT yangji geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy
AT yuewu geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy
AT xiaohuixie geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy
AT sixu geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy
AT gongjunji geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy
AT yanghuatian geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy
AT kaiwang geneticandmolecularbasisofabnormalboldsignalingvariabilityinpatientswithmajordepressivedisorderafterelectroconvulsivetherapy