Dataset Information

Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder.

ABSTRACT:

Background

Although electroconvulsive therapy (ECT) is an effective treatment for depression, ECT cognitive impairment remains a major concern. The neurobiological underpinnings and mechanisms underlying ECT antidepressant and cognitive impairment effects remain unknown. This investigation aims to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks and assesses whether they are associated with the ECT-induced electric field (E-field) with an optimal pulse amplitude estimation.

Methods

A single site clinical trial focused on amplitude (600, 700, and 800 mA) included longitudinal multimodal imaging and clinical and cognitive assessments completed before and immediately after the ECT series (n = 54) for late-life depression. Another two independent validation cohorts (n = 84, n = 260) were included. Symptom and cognition were used as references to supervise fMRI and sMRI fusion to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks. Correlations between ECT-induced E-field within these two networks and clinical and cognitive outcomes were calculated. An optimal pulse amplitude was estimated based on E-field within antidepressant-response and cognitive-impairment networks.

Results

Decreased function in the superior orbitofrontal cortex and caudate accompanied with increased volume in medial temporal cortex showed covarying functional and structural alterations in both antidepressant-response and cognitive-impairment networks. Volume increases in the hippocampal complex and thalamus were antidepressant-response specific, and functional decreases in the amygdala and hippocampal complex were cognitive-impairment specific, which were validated in two independent datasets. The E-field within these two networks showed an inverse relationship with HDRS reduction and cognitive impairment. The optimal E-filed range as [92.7-113.9] V/m was estimated to maximize antidepressant outcomes without compromising cognitive safety.

Conclusions

The large degree of overlap between antidepressant-response and cognitive-impairment networks challenges parameter development focused on precise E-field dosing with new electrode placements. The determination of the optimal individualized ECT amplitude within the antidepressant and cognitive networks may improve the treatment benefit-risk ratio.

Trial registration

ClinicalTrials.gov Identifier: NCT02999269.

SUBMITTER: Qi S

PROVIDER: S-EPMC9733153 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder.

Qi Shile S Calhoun Vince D VD Zhang Daoqiang D Miller Jeremy J Deng Zhi-De ZD Narr Katherine L KL Sheline Yvette Y McClintock Shawn M SM Jiang Rongtao R Yang Xiao X Upston Joel J Jones Tom T Sui Jing J Abbott Christopher C CC

BMC medicine 20221208 1

<h4>Background</h4>Although electroconvulsive therapy (ECT) is an effective treatment for depression, ECT cognitive impairment remains a major concern. The neurobiological underpinnings and mechanisms underlying ECT antidepressant and cognitive impairment effects remain unknown. This investigation aims to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks and assesses whether they are associated with the ECT-induced electric field (E-field) with an optimal pu ...[more]

PMID: 36482369

Similar Datasets

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Project description:There is compelling evidence that epigenetic factors contribute to the manifestation of depression, in which microRNA132 (miR-132) is suggested to play a pivotal role in the pathogenesis and neuronal mechanisms underlying the symptoms of depression. Additionally, several depression-associated genes [MECP2, ARHGAP32 (p250GAP), CREB, and period genes] were experimentally validated as miR-132 targets. However, most studies regarding miR-132 in major depressive disorder are based on post-mortem, animal models or genetic comparisons. This work will be the first attempt to investigate how miR-132 dysregulation may impact covariation of multimodal brain imaging data in 81 unmedicated major depressive patients and 123 demographically-matched healthy controls, as well as in a medication-naïve subset of major depressive patients. MiR-132 values in blood (patients > controls) was used as a prior reference to guide fusion of three MRI features: fractional amplitude of low frequency fluctuations, grey matter volume, and fractional anisotropy. The multimodal components correlated with miR-132 also show significant group difference in loadings. Results indicate that (i) higher miR-132 levels in major depressive disorder are associated with both lower fractional amplitude of low frequency fluctuations and lower grey matter volume in fronto-limbic network; and (ii) the identified brain regions linked with increased miR-132 levels were also associated with poorer cognitive performance in attention and executive function. Using a data-driven, supervised-learning method, we determined that miR-132 dysregulation in major depressive disorder is associated with multi-facets of brain function and structure in fronto-limbic network (the key network for emotional regulation and memory), which deepens our understanding of how miR-132 dysregulation in major depressive disorders contribute to the loss of specific brain areas and is linked to relevant cognitive impairments.

Project description:ImportanceElectroconvulsive therapy (ECT) is indicated for severe depression, including depression with psychosis, catatonia, and/or an elevated suicide risk. However, the association of ECT with suicide risk is uncertain.ObjectiveTo determine the association between ECT and the risk of suicide in patients with unipolar major depressive disorder.Design, setting, and participantsThis registry-based cohort study used patient data from Swedish national registers. Patients with a record of inpatient care between January 1, 2012, and October 31, 2018, for moderate depression, severe depression, or severe depression with psychosis were included in the study. Propensity score matching (1:1) was used to balance risk factors for suicide at baseline between patients treated with and without ECT during the inpatient episode.ExposuresData from the Swedish National Quality Register for ECT and the Swedish National Inpatient Register were combined to identify patients who had received ECT during the inpatient episode. National registers were used to identify risk factors for suicide.Main outcomes and measuresSuicide within 3 and 12 months of admission to inpatient care was analyzed. Cox regression analyses were used to adjust for confounders.ResultsThe study included 28 557 patients (mean [SD] age, ECT group, 55.9 [18.4] years; non-ECT group, 45.2 [19.2] years; 15 856 women [55.5%]). In the matched sample of 5525 patients in each group, 62 patients (1.1%) in the ECT group and 90 patients (1.6%) in the non-ECT group died of suicide within 12 months (hazard ratio [HR], 0.72; 95% CI, 0.52-0.99). Electroconvulsive therapy was significantly associated with a decreased risk of suicide in patients with psychotic features (HR, 0.20; 95% CI, 0.08-0.54) and those aged 45 to 64 years (HR, 0.54; 95% CI, 0.30-0.99) or 65 years or older (HR, 0.30; 95% CI, 0.15-0.59), but not in patients aged 44 years or younger (HR, 1.22; 95% CI, 0.68-2.16).Conclusions and relevanceThe results of this cohort study support the continued use of ECT to reduce suicide risk in hospitalized patients who are severely depressed, especially those who are older than 45 years and those with a psychotic subtype.

Dataset Information

Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder.

Background

Methods

Results

Conclusions

Trial registration

Publications

Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets