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Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder.

ABSTRACT: To date, electroconvulsive therapy (ECT) is the most potent treatment in severe depression. Although ECT has been successfully applied in clinical practice for over 70 years, the underlying mechanisms of action remain unclear. We used functional MRI and a unique data-driven analysis approach to examine functional connectivity in the brain before and after ECT treatment. Our results show that ECT has lasting effects on the functional architecture of the brain. A comparison of pre- and posttreatment functional connectivity data in a group of nine patients revealed a significant cluster of voxels in and around the left dorsolateral prefrontal cortical region (Brodmann areas 44, 45, and 46), where the average global functional connectivity was considerably decreased after ECT treatment (P < 0.05, family-wise error-corrected). This decrease in functional connectivity was accompanied by a significant improvement (P < 0.001) in depressive symptoms; the patients' mean scores on the Montgomery Asberg Depression Rating Scale pre- and posttreatment were 36.4 (SD = 4.9) and 10.7 (SD = 9.6), respectively. The findings reported here add weight to the emerging "hyperconnectivity hypothesis" in depression and support the proposal that increased connectivity may constitute both a biomarker for mood disorder and a potential therapeutic target.

SUBMITTER: Perrin JS

PROVIDER: S-EPMC3325678 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder.

Perrin Jennifer S JS Merz Susanne S Bennett Daniel M DM Currie James J Steele Douglas J DJ Reid Ian C IC Schwarzbauer Christian C

Proceedings of the National Academy of Sciences of the United States of America 20120319 14

To date, electroconvulsive therapy (ECT) is the most potent treatment in severe depression. Although ECT has been successfully applied in clinical practice for over 70 years, the underlying mechanisms of action remain unclear. We used functional MRI and a unique data-driven analysis approach to examine functional connectivity in the brain before and after ECT treatment. Our results show that ECT has lasting effects on the functional architecture of the brain. A comparison of pre- and posttreatme ...[more]

PMID: 22431642

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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.

Project description:Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal ideation in MDD patients.

Project description:Although large genome-wide association studies (GWAS) of major depressive disorder (MDD) have identified many significant loci, the SNP-based heritability remains notably low, which might be due to etiological heterogeneity in existing samples. Here, we test the utility of targeting the severe end of the MDD spectrum through genome-wide SNP genotyping of 2725 cases who received electroconvulsive therapy (ECT) for a major depressive episode (MDE) and 4035 controls. A subset of cases (n = 1796) met a narrow case definition (MDE occurring in the context of MDD). Standard GWAS quality control procedures and imputation were conducted. SNP heritability and genetic correlations with other traits were estimated using linkage disequilibrium score regression. Results were compared with MDD cases of mild-moderate severity receiving internet-based cognitive behavioral therapy (iCBT) and summary results from the Psychiatric Genomics Consortium (PGC). The SNP-based heritability was estimated at 29-34% (SE: 6%) for the narrow case definition, considerably higher than the 6.5-8.0% estimate in the most recent PGC MDD study. Our severe MDE cases had smaller genetic correlations with neurodevelopmental disorders and neuroticism than PGC MDD cases but higher genetic risk scores for bipolar disorder than iCBT MDD cases. One genome-wide significant locus was identified (rs114583506, P = 5e-8) in an intron of HLA-B in the major histocompatibility locus on chr6. These results indicate that individuals receiving ECT for an MDE have higher burden of common variant risk loci than individuals with mild-moderate MDD. Furthermore, severe MDE shows stronger relations with other severe adult-onset psychiatric disorders but weaker relations with personality and stress-related traits than mild-moderate MDD. These findings suggest a different genetic architecture at the severest end of the spectrum, and support further study of the severest MDD cases as an extreme phenotype approach to understand the etiology of MDD.

Dataset Information

Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder.

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Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder.

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