Hippocampal structural and functional changes associated with electroconvulsive therapy response.
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ABSTRACT:
SUBMITTER: Abbott CC
PROVIDER: S-EPMC4259994 | biostudies-other | 2014 Nov
REPOSITORIES: biostudies-other
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Project description:BackgroundDepressive episodes (DEPs), characterized by abnormalities in cognitive functions and mood, are a leading cause of disability. Electroconvulsive therapy (ECT), which involves a brief electrical stimulation of the anesthetized brain, is one of the most effective treatments used in patients with DEP due to its rapid efficacy.MethodsIn this work, we investigated how dynamic brain functional connectivity responds to ECT and whether the dynamic responses are associated with treatment outcomes and side effects in patients. We applied a fully automated independent component analysis-based pipeline to 110 patients with DEP (including diagnosis of unipolar depression or bipolar depression) and 60 healthy control subjects. The dynamic functional connectivity was analyzed by a combination of the sliding window approach and clustering analysis.ResultsFive recurring connectivity states were identified, and patients with DEPs had fewer occurrences in one brain state (state 1) with strong positive and negative connectivity. Patients with DEP changed the occupancy of two states (states 3 and 4) after ECT, resulting in significantly different occurrences of one additional state (state 3) compared with healthy control subjects. We further found that patients with DEP had diminished global metastate dynamism, two of which recovered to normal after ECT. The changes in dynamic connectivity characteristics were associated with the changes in memory recall and Hamilton Depression Rating Scale of DEP after ECT.ConclusionsThese converging results extend current findings on subcortical-cortical dysfunction and dysrhythmia in DEP and demonstrate that ECT might cause remodeling of brain functional dynamics that enhance the neuroplasticity of the diseased brain.
| S-EPMC8783932 | biostudies-literature
Project description:Electroconvulsive therapy (ECT) has been repeatedly linked to hippocampal plasticity. However, it remains unclear what role hippocampal plasticity plays in the antidepressant response to ECT. This magnetic resonance imaging (MRI) study tracks changes in separate hippocampal subregions and hippocampal networks in patients with depression (n = 44, 23 female) to determine their relationship, if any, with improvement after ECT. Voxelwise analyses were restricted to the hippocampus, amygdala, and parahippocampal cortex, and applied separately for responders and nonresponders to ECT. In analyses of arterial spin-labeled (ASL) MRI, nonresponders exhibited increased cerebral blood flow (CBF) in bilateral anterior hippocampus, while responders showed CBF increases in right middle and left posterior hippocampus. In analyses of gray matter volume (GMV) using T1-weighted MRI, GMV increased throughout bilateral hippocampus and surrounding tissue in nonresponders, while responders showed increased GMV in right anterior hippocampus only. Using CBF loci as seed regions, BOLD-fMRI data from healthy controls (n = 36, 19 female) identified spatially separable neurofunctional networks comprised of different brain regions. In graph theory analyses of these networks, functional connectivity within a hippocampus-thalamus-striatum network decreased only in responders after two treatments and after index. In sum, our results suggest that the location of ECT-related plasticity within the hippocampus may differ according to antidepressant outcome, and that larger amounts of hippocampal plasticity may not be conducive to positive antidepressant response. More focused targeting of hippocampal subregions and/or circuits may be a way to improve ECT outcome.
| S-EPMC7415508 | biostudies-literature
Project description:IntroductionReduced hippocampal volume is one of the most consistent morphological findings in Major Depressive Disorder (MDD). Electroconvulsive therapy (ECT) is the most effective therapy for MDD, yet its mechanism of action remains poorly understood. Animal models show that ECT induces several neuroplastic processes, which lead to hippocampal volume increases. We conducted a meta-analysis of ECT studies in humans to investigate its effects on hippocampal volume.MethodsPubMed was searched for studies examining hippocampal volume before and after ECT. A random-effects model was used for meta-analysis with standardized mean difference (SMD) of the change in hippocampal volume before and after ECT as the primary outcome. Nine studies involving 174 participants were included.ResultsTotal hippocampal volumes increased significantly following ECT compared to pre-treatment values (SMD=1.10; 95% CI 0.80-1.39; z=7.34; p<0.001; k=9). Both right (SMD=1.01; 95% CI 0.72-1.30; z=6.76; p<0.001; k=7) and left (SMD=0.87; 95% CI 0.51-1.23; z=4.69; p<0.001; k=7) hippocampal volumes were also similarly increased significantly following ECT. We demonstrated no correlation between improvement in depression symptoms with ECT and change in total hippocampal volume (beta=-1.28, 95% CI -4.51-1.95, z=-0.78, p=0.44).ConclusionWe demonstrate fairly consistent increases in hippocampal volume bilaterally following ECT treatment. The relationship among these volumetric changes and clinical improvement and cognitive side effects of ECT should be explored by larger, multisite studies with harmonized imaging methods.
| S-EPMC5627663 | biostudies-literature
Project description:BackgroundElectroconvulsive therapy (ECT) is the treatment of choice for severe mental illness including treatment-resistant depression (TRD). Increases in volume of the hippocampus and amygdala following ECT have consistently been reported.AimsTo investigate neuroplastic changes after ECT in specific hippocampal subfields and amygdala nuclei using high-resolution structural magnetic resonance imaging (MRI) (trial registration: clinicaltrials.gov - NCT02379767).MethodMRI scans were carried out in 14 patients (11 women, 46.9 years (s.d. = 8.1)) with unipolar TRD twice before and once after a series of right unilateral ECT in a pre-post study design. Volumes of subcortical structures, including subfields of the hippocampus and amygdala, and cortical thickness were extracted using FreeSurfer. The effect of ECT was tested using repeated-measures ANOVA. Correlations of imaging and clinical parameters were explored.ResultsIncreases in volume of the right hippocampus by 139.4 mm3 (s.d. = 34.9), right amygdala by 82.3 mm3 (s.d. = 43.9) and right putamen by 73.9 mm3 (s.d. = 77.0) were observed. These changes were localised in the basal and lateral nuclei, and the corticoamygdaloid transition area of the amygdala, the hippocampal-amygdaloid transition area and the granule cell and molecular layer of the dentate gyrus. Cortical thickness increased in the temporal, parietal and insular cortices of the right hemisphere.ConclusionsFollowing ECT structural changes were observed in hippocampal subfields and amygdala nuclei that are specifically implicated in the pathophysiology of depression and stress-related disorders and retain a high potential for neuroplasticity in adulthood.Declaration of interestS.K. has received grants/research support, consulting fees and/or honoraria within the past 3 years from Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Celegne GmbH, Eli Lilly, Janssen-Cilag Pharma GmbH, KRKA-Pharma, Lundbeck A/S, Neuraxpharm, Pfizer, Pierre Fabre, Schwabe and Servier. R.L. received travel grants and/or conference speaker honoraria from Shire, AstraZeneca, Lundbeck A/S, Dr. Willmar Schwabe GmbH, Orphan Pharmaceuticals AG, Janssen-Cilag Pharma GmbH, and Roche Austria GmbH.
| S-EPMC6383756 | biostudies-literature
Project description:Electroconvulsive therapy (ECT) is considered a treatment option in patients with drug-resistant schizophrenia (SZ). However, approximately one-third of patients do not benefit from ECT in the clinic. Thus, it is critical to investigate differences between ECT responders and non-responders. Accumulated evidence has indicated that one region of ECT action is the hippocampus, which also plays an important role in SZ pathophysiology. To date, no studies have investigated differences in ECT effects in the hippocampus between treatment responders and non-responders. This study recruited twenty-one SZ patients treated for four weeks with ECT (MSZ, n = 21) and twenty-one SZ patients who received pharmaceutical therapy (DSZ, n = 21). The MSZ group was further categorized into responders (MSR, n = 10) or non-responders (MNR, n = 11) based on treatment outcomes by the criterion of a 50% reduction in the Positive and Negative Syndrome Scale total scores. Using structural and resting-state functional MRI, we measured the hippocampal volume and functional connectivity (FC) in all SZ patients (before and after treatment) and 23 healthy controls. In contrast to pharmaceutical therapy, ECT induced bilateral hippocampal volume increases in the MSZ. Both the MSR and MNR exhibited hippocampal expansion after ECT, whereas a lower baseline volume in one of hippocampal subfield (hippocampus-amygdala transition area) was found in the MNR. After ECT, increased FC between the hippocampus and brain networks associated with cognitive function was only observed in the MSR. The mechanism of action of ECT in schizophrenia is complex. A combination of baseline impairment level, ECT-introduced morphological changes and post-ECT FC increases in the hippocampus may jointly contribute to the post-ECT symptom improvements in patients with SZ.
| S-EPMC6861644 | biostudies-literature
Project description:Electroconvulsive therapy (ECT) is a quick-acting and powerful antidepressant treatment considered to be effective in treating severe and pharmacotherapy-resistant forms of depression. Recent studies have suggested that epigenetic mechanisms can mediate treatment response and investigations about the relationship between the effects of ECT and DNA methylation have so far largely taken candidate approaches. In the present study, we examined the effects of ECT on the methylome associated with response in depressed patients (n = 34), testing for differentially methylated CpG sites before the first and after the last ECT treatment. We identified one differentially methylated CpG site associated with the effect of ECT response (defined as >50% decrease in Hamilton Depression Rating Scale score, HDRS), TNKS (q < 0.05; p = 7.15 × 10-8). When defining response continuously (ΔHDRS), the top suggestive differentially methylated CpG site was in FKBP5 (p = 3.94 × 10-7). Regional analyses identified two differentially methylated regions on chromosomes 8 (Šídák's p = 0.0031) and 20 (Šídák's p = 4.2 × 10-5) associated with ΔHDRS. Functional pathway analysis did not identify any significant pathways. A confirmatory look at candidates previously proposed to be involved in ECT mechanisms found CpG sites associated with response only at the nominally significant level (p < 0.05). Despite the limited sample size, the present study was able to identify epigenetic change associated with ECT response suggesting that this approach, especially when involving larger samples, has the potential to inform the study of mechanisms involved in ECT and severe and treatment-resistant depression.
| S-EPMC8179923 | biostudies-literature
Project description:BackgroundSeizure duration has long been measured as a potential marker of ECT treatment efficacy, with concern that short seizures may be clinically ineffective. Relatively small studies have documented a trend towards shorter seizures during acute course ECT, but data from large cohorts would help provide normative data on seizure duration changes during treatment.ObjectiveThis study analyzes the effects of age, sex, ECT dose, and treatment number on the duration of electrographic seizures during acute course ECT in a large single-center cohort.MethodsA single-center retrospective chart review was conducted of adult patients receiving a first course of ECT from 2000 to 2017 at a large freestanding psychiatric hospital.Results3648 patients met inclusion criteria, receiving 32,879 acute course ECT treatments. There was a shortening of mean ECT seizure duration over the acute course, with the greatest decrease in duration over the first 3 treatments but continuing decreases over the entire acute course. Older age, higher ECT dose, and increasing treatment number were all associated with shorter seizures, while sex was not significantly associated. Increasing treatment dose was associated with shorter seizures relative to no dose increase, with those patients receiving the highest cumulative doses also having the shortest cumulative seizure time.ConclusionsAmong patients undergoing acute-course ECT treatment, seizure duration decreased over the treatment course, and increases in applied electrical charge were associated with shorter seizures.
| S-EPMC8316429 | biostudies-literature
Project description:While biomarkers have been used to define pathophysiological types and to optimize treatment in many areas of medicine, in psychiatry such biomarkers remain elusive. Based on previously described abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function in severe forms of depression, we hypothesized that the temporal trajectory of basal cortisol levels would vary among individuals with depression due to heterogeneity in pathophysiology, and that cortisol trajectories that reflect elevated or increasing HPA activity would predict better response to electroconvulsive therapy (ECT). To test that hypothesis, we sampled scalp hair from 39 subjects with treatment-resistant depression just before ECT. Cortisol trajectory over the 12 weeks preceding ECT was reconstructed from cortisol concentrations in sequential hair segments. Cortisol trajectories varied widely between individuals, and exploratory analyses of clinical features revealed associations with melancholia and global severity. ECT non-responders showed a decreasing trajectory (mean change -25%, 95%-CI = [-1%,-43%]) during the 8 weeks preceding ECT (group-by-time interaction, p = 0.004). The association between cortisol trajectory and subsequent ECT response was independent of clinical features. A classification algorithm showed that cortisol trajectory predicted ECT response with 80% accuracy, suggesting that this biomarker might be developed into a clinically useful test for ECT-responsive depression. In conclusion, cortisol trajectory mapped onto symptoms of melancholia and independently predicted response to ECT in this severely depressed sample. These findings deserve to be replicated in a larger sample. Cortisol trajectory holds promise as a reliable, noninvasive, inexpensive biomarker for psychiatric disorders.
| S-EPMC6457450 | biostudies-literature
Project description:BackgroundObesity is a frequent somatic comorbidity of major depression, and it has been associated with worse clinical outcomes and brain structural abnormalities. Converging evidence suggests that electroconvulsive therapy (ECT) induces both clinical improvements and increased subcortical grey matter volume in patients with depression. However, it remains unknown whether increased body weight modulates the clinical response and structural neuroplasticity that occur with ECT.MethodsTo address this question, we conducted a longitudinal investigation of structural MRI data from the Global ECT-MRI Research Collaboration (GEMRIC) in 223 patients who were experiencing a major depressive episode (10 scanning sites). Structural MRI data were acquired before and after ECT, and we assessed change in subcortical grey matter volume using FreeSurfer and Quarc.ResultsHigher body mass index (BMI) was associated with a significantly lower increase in subcortical grey matter volume following ECT. We observed significant negative associations between BMI and change in subcortical grey matter volume, with pronounced effects in the thalamus and putamen, where obese participants showed increases in grey matter volume that were 43.3% and 49.6%, respectively, of the increases found in participants with normal weight. As well, BMI significantly moderated the association between subcortical grey matter volume change and clinical response to ECT. We observed no significant association between BMI and clinical response to ECT.LimitationsBecause only baseline BMI values were available, we were unable to study BMI changes during ECT and their potential association with clinical and grey matter volume change.ConclusionFuture studies should take into account the relevance of body weight as a modulator of structural neuroplasticity during ECT treatment and aim to further explore the functional relevance of this novel finding.
| S-EPMC8410473 | biostudies-literature
Project description:Electroconvulsive therapy (ECT) works rapidly and has been widely used to treat depressive disorders (DEP). However, identifying biomarkers predictive of response to ECT remains a priority to individually tailor treatment and understand treatment mechanisms. This study used a connectome-based predictive modeling (CPM) approach in 122 patients with DEP to determine if pre-ECT whole-brain functional connectivity (FC) predicts depressive rating changes and remission status after ECT (47 of 122 total subjects or 38.5% of sample), and whether pre-ECT and longitudinal changes (pre/post-ECT) in regional brain network biomarkers are associated with treatment-related changes in depression ratings. Results show the networks with the best predictive performance of ECT response were negative (anti-correlated) FC networks, which predict the post-ECT depression severity (continuous measure) with a 76.23% accuracy for remission prediction. FC networks with the greatest predictive power were concentrated in the prefrontal and temporal cortices and subcortical nuclei, and include the inferior frontal (IFG), superior frontal (SFG), superior temporal (STG), inferior temporal gyri (ITG), basal ganglia (BG), and thalamus (Tha). Several of these brain regions were also identified as nodes in the FC networks that show significant change pre-/post-ECT, but these networks were not related to treatment response. This study design has limitations regarding the longitudinal design and the absence of a control group that limit the causal inference regarding mechanism of post-treatment status. Though predictive biomarkers remained below the threshold of those recommended for potential translation, the analysis methods and results demonstrate the promise and generalizability of biomarkers for advancing personalized treatment strategies.
| S-EPMC7229344 | biostudies-literature