ECT Response Research Articles

The influence of age on ECT efficacy in depression, mania, psychotic depression and schizophrenia: A transdiagnostic analysis

AimECT use is variable across age groups. We aim to investigate the effect of age on ECT response among patients with depression, psychotic depression, mania and schizophrenia. MethodsOur retrospective observational study included patients from the Institute of Mental Health (Singapore) who were initiated on ECT (March 2017–February 2023). MADRS and BPRS scores were assessed 1–2 days before the first ECT and after the 6th session. The association between age group and ECT response was analyzed by ANOVA and generalized linear regression. A one-way sensitivity analysis was performed with age as a continuous variable. Results166 (15.7%) patients were “young-age (≤26 years)”, 634 (60%) patients were in the “middle-age (27–59 years)” group and 256 (24.3%) were “old-age (≥60 years)”. The association between older age and post-ECT improvement in patients with depression was significant in the categorical age analysis but it did not persist in the sensitivity analysis. No significant association between age and ECT response was noted in patients with bipolar disorder and schizophrenia as evidenced by both categorical and continuous age analyses. In a small subgroup with psychotic depression, younger patients improved significantly more than older patients post-ECT. ConclusionPatients with unipolar or bipolar depression, mania, or schizophrenia, regardless of age, respond favourably to ECT. Other associated factors such as psychomotor and psychotic symptoms, disease severity and number of failed pharmacotherapies should be considered in predicting ECT response. Younger patients with psychotic depression may respond better to ECT.

Adherence to clinical practice guidelines for using electroconvulsive therapy in elderly depressive patients

ObjectivesElectroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines.MethodsIn this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests.ResultsWe identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT.ConclusionEven if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

The utility of the Sydney Melancholia Prototype Index (SMPI) for predicting response to electroconvulsive therapy in depression: A CARE Network study

An enhanced understanding of clinical predictors of positive ECT outcome could assist with the decision to prescribe ECT for select patients. Reliable predictors of ECT response such as psychotic symptoms and age have been identified, however, studies of melancholia and ECT response have been inconsistent. The Sydney Melancholia Prototype Index (SMPI) is a clinical measure designed to differentiate melancholic and non-melancholic depression. This study aimed to investigate whether melancholic depression (as measured by the clinician rated version of the SMPI) predicted a better response to ECT than non-melancholic depression. The study included data collated from four participating sites in the Clinical Alliance for ECT and Related treatments (CARE) network. The primary outcome was response (>50% improvement) on the Montgomery Asberg Depression Rating Scale (MADRS) and the secondary outcome was raw change in MADRS score. Of the 329 depressed patients included in the study, 81% had melancholic features and 76% met criteria for clinical response. SMPI defined melancholia was associated with older age, higher pre-treatment mood scores and presence of psychosis. Melancholia as defined by the SMPI, however, did not significantly predict either clinical response or overall mood improvement with ECT in multivariate analyses. Instead, older age, greater pre-treatment depression severity and the use of bifrontal compared to right unilateral ultrabrief ECT were significant predictors of mood improvement. Path analysis showed that higher pre-treatment mood score and older age were independently associated with mood improvement with ECT.

White matter changes following electroconvulsive therapy for depression: a mega-analysis

IntroductionElectroconvulsive therapy (ECT) is proposed to exert an effect on white matter (WM) microstructure, but the limited power of previous studies made it difficult to highlight consistent patterns of change in diffusion metrics.ObjectivesWe initiated a multi-site mega-analysis and sought to address whether changes in WM microstructure occur following ECT.Methods To this end, diffusion tensor imaging (DTI) data (n=58) from 4 different sites were harmonized before pooling them by using ComBat, a batch-effect correction tool that removes inter-site technical variability, preserves inter-site biological variability and maximizes statistical power. Downstream statistical analyses aimed to quantify changes in Fractional anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD) and Axial Diffusivity (AD), by employing whole-brain, tract-based spatial statistics (TBSS).ResultsECT increases FA in the right splenium of the corpus callosum and the left cortico-spinal tract. Both the left superior longitudinal fasciculus and the right inferior fronto-occipital fasciculus showed increases in AD. Increases in MD and RD could be observed in overlapping white matter structures of both hemispheres. Finally, responders showed significantly smaller FA values in the left forceps major and smaller AD values in the right uncinate fasciculus compared with non-responders.ConclusionsThis is the first and largest multi-site mega-analysis to demonstrate that ECT normalizes altered WM microstructure in important brain circuits that are implicated in the pathophysiology of depression. Furthermore, responders appear to present a more decreased WM integrity at baseline, which if replicated could serve as a biomarker for ECT response.DisclosureNo significant relationships.

Electrochemotherapy of Primary Colon Rectum Cancer and Local Recurrence: Case Report and Prospective Analysis

Purpose: Surgery, radiotherapy, and oncological treatment (chemotherapy and antineoplastic antibodies) are standard treatments of rectal cancer. ECT has shown its effectiveness and suitability in deep solid tumors conducted in both preclinical and clinical studies. We show here an update and preliminary results with locally advanced rectum cancer (LARC) treated with ECT. Methods: Two patients with major clinical response to restaging after neoadjuvant treatment for LARC were subjected to ECT 12 weeks after completing chemo-radiation therapy. One patient was subjected to ECT on a colorectal local recurrence formed after neoadjuvant treatment for LARC and surgery. Computed Tomography and Magnetic Resonance Imaging were used to assess ECT response. Results: The results showed stable disease in two of the three patients treated, while one patient achieved a complete response. The local control of disease is maintained in the patient follow-up. For each patient, a reduction in pain was observed and for the patient with local recurrence, a reduction in bleeding present before ECT was also achieved. Conclusion: Preliminary results showed that ECT is a safe and effective treatment in patients with a major clinical response or local recurrence after neoadjuvant therapy for LARC and allows a reduction in pain and bleeding with a consequent improvement to quality of life.

Individual response to electroconvulsive therapy is not correlated between multiple treatment courses

ObjectivesElectroconvulsive therapy (ECT) effectively treats depressive disorders, but many patients will have subsequent relapses. While some guidelines suggest prior response to ECT is an indication for ECT in a subsequent mood episode, it is unknown whether response to ECT is correlated between treatment courses. This study explores whether response to ECT at a first treatment correlates with response to treatment in a second independent ECT course. MethodsSingle-center retrospective cohort of patients receiving two different ECT treatment courses between 2011 and 2020 and who self-reported depression symptoms using the Quick Inventory of Depressive Symptomatology (QIDS) at baseline and following treatment #5. Results286 patients received two independent ECT series during the study period, of whom 153 received at least 5 treatments in both series. Patients had similar QIDS scores at the start of each treatment series (Pearson's correlation, r = 0.58, p <0.001), but the change in QIDS following 5 ECT treatments was not correlated between series for individual patients (Pearson's correlation, r = 0.083, p = 0.31). In multivariate analyses, change in QIDS was similar for both treatment series, but patients were less likely to receive 5 treatments in the second treatment series. Limitationsretrospective cohort cannot control for factors influencing access to repeat ECT treatment ConclusionsWhile on average final QIDS score was the same following two independent treatment courses, for individual patients the change in depression symptoms was not correlated between treatment series. Further research is needed to identify factors that may predict longitudinal ECT response.

Deiodinase variation and liothyronine treatment interaction to accelerate ECT response in major depression: Pilot data and implications for thyroid pharmacogenomic testing in mood disorders

BackgroundConcurrent liothyronine treatment has been shown to accelerate time to response in patients treated for major depression. However, the relationship between genetic variation in deiodinase and T3 treatment response has received little investigation. MethodsThis is a post-hoc analysis of a randomized, double-blind, placebo-controlled trial of concurrent liothyronine (T3-Cytomel®, n = 23; mean dose 46.3 ± 3.3 mcg) in patients with major depression where a clinical recommendation was made to pursue ECT. The primary outcome measure was time to 50% reduction in depressive symptoms. Multivariable linear models were used to examine effect of T3 and placebo and genetic variants as predictors of change in HAMD24 and number of ECT treatments. ResultsSurvival analysis did not show a significant effect for the T3 + ECT group achieving a faster time to response compared to placebo + ECT (p + ECT). Survival analysis for RUL lead placement alone showed a significant effect for the T3 + ECT group achieving a faster time to response compared to p + ECT (p = 0.01) with significantly fewer ECT treatments (p = 0.03). Carriers of the functional SNP rs11206244 gene DI01-C785T minor allele (TT and CT) vs. non-carriers (CC), showed fewer ECT treatments in the T3 + ECT group, compared to p + ECT (5.3 ± 1.0 vs. 8.3 ± 2.1, p = 0.045). ConclusionsThese pilot data identify clinically relevant genetic variation in DI01- C785T contributing to an accelerated response time, but not an overall greater symptom reduction. Exogenous T3 supplementation may be therapeutic by attenuating a baseline DI01 relative functional deficit which functionally reduces peripheral conversion of T4 to biologically active T3. Further work is encouraged to assess genetic variation of thyroid deiodinase enzymes in larger samples of depressed patients to better optimize accelerating strategies to ECT and more broadly, thyroid augmentation strategies in major depressive and bipolar disorders.

Habenula and left angular gyrus circuit contributes to response of electroconvulsive therapy in major depressive disorder.

The habenula (Hb), one of the hottest structures in depression, has been widely demonstrated to be involved in the neurobiology of depression. Although the structural and functional abnormalities of Hb have been reported in major depressive disorders (MDD) patients, the role of Hb in treatment response in MDD remains unclear. In this study, resting-state functional connectivity (RSFC) and Granger causality analysis (GCA) were performed to investigate the intrinsic and causal changes of Hb in MDD after ECT. Moreover, support vector classification was applied to find out whether the changed functional and causal connections of Hb can effectively distinguish the MDD patients from healthy controls. The RSFC and GCA identified increased RSFC strength between bilateral Hb and left angular gyrus (AG), decreased causal connectivity strength from left AG to left Hb, from right Hb to left AG, and bidirectional interactions between left and right Hb in MDD patients after ECT. The changed causal connectivities from left AG to left Hb, and from right Hb to left AG were correlated with the changed depression symptoms and impaired delay memory recall performances. Furthermore, the functional and causal connectivities between left AG and bilateral Hb could serve as a biomarker to differentiate MDD from HCs. These results provided new evidence for the importance of Hb in depression and revealed that the interactions between Hb and left AG contribute to ECT response in MDD. Our findings will facilitate the future treatment of depression with the target of Hb in MDD and other brain disorders.

Long term response of electrochemotherapy with reduced dose of bleomycin in elderly patients with head and neck non-melanoma skin cancer

BackgroundElectrochemotherapy (ECT) is a local cancer treatment based on electroporation where the electric field is used to enhance cell membrane permeability and thereby facilitating the transition of chemotherapeutic agents into the cell. For the treatment of non-melanoma skin cancer, a standard dosage of 15,000 IU/m2 bleomycin (BLM) is used. The aim of the present study was to evaluate the long-term ECT response in the group of elderly patients with non-melanoma skin cancer treated with a reduced dose of BLM in comparison to the outcome in the patients treated with the standard dose of BLM.Patients and methodsTwenty-eight patients older than 65 years, with a total of 52 non-melanoma skin lesions were included in the study. Twelve patients (24 lesions) in the experimental group received a reduced dose of BLM (10,000 IU/m2), 16 patients (28 lesions) were treated with a standard dose of BLM (15,000 IU/m2).ResultsNo statistically significant difference in tumor control was observed between both groups. In the experimental group, tumors recurred in 39.0% of treated lesions in a median follow-up time of 28 months. In the control group, the recurrence rate of treated lesions was 15.4% in a median follow-up time of 40 months.ConclusionsECT with a reduced dose of BLM is a feasible treatment option for elderly patients with equal efficacy to standard dose treatment and should be considered as a treatment modality in advanced aged patients with comorbidities, where overall life expectancy is poor.

Disturbance of Oxidative Stress Parameters in Treatment-Resistant Bipolar Disorder and Their Association With Electroconvulsive Therapy Response.

ObjectiveElectroconvulsive therapy (ECT) is an effective option for treatment-resistant bipolar disorder (trBD). However, the mechanisms of its effect are unknown. Oxidative stress is thought to be involved in the underpinnings of BD. Our study is the first, to our knowledge, to report the association between notable oxidative stress parameters (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and malondialdehyde [MDA]) levels and ECT response in trBD patients.MethodsA total 28 trBD patients and 49 controls were recruited. Six-week ECT and naturalistic follow-up were conducted. SOD, GSH-Px, CAT, and MDA levels were measured by enzyme-linked immunosorbent assay, and the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale were administered at baseline and the end of the 6th week. MANCOVA, ANCOVA, 2 × 2 ANCOVA, and a multiple regression model were conducted.ResultsSOD levels were lower in both trBD mania and depression (P = .001; P = .001), while GSH-Px (P = .01; P = .001) and MDA (P = .001; P = .001) were higher in both trBD mania and depression compared with controls. CAT levels were positively associated with 17-item Hamilton Depression Rating Scale scores in trBD depression (radjusted = 0.83, P = .005). MDA levels in trBD decreased after 6 weeks of ECT (P = .001). Interestingly, MDA levels decreased in responders (P = .001) but not in nonresponders (P > .05).ConclusionsOur study indicates that decreased SOD could be a trait rather than a state in trBD. Oxidative stress levels are associated with illness severity and ECT response. This suggests that the mechanism of oxidative stress plays a crucial role in the pathophysiology of trBD.

Adherence to treatment guidelines in clinical practice for using electroconvulsive therapy in major depressive episode

BackgroundECT is the most effective treatment of major depressive episode (MDE) but remains a neglected treatment. The French Society for Biological Psychiatry and Neuropsychopharmacology aimed to determine whether prescribing practice of ECT followed guidelines recommendations. MethodsThis multicenter, retrospective study included adult patients with major depressive disorder (MDD) or bipolar disorder (BD), who have been treated with ECT for MDE. Duration of MDE and number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. ResultsSeven hundred and forty-five individuals were included. The mean duration of MDE before ECT was 10.1 months and the mean number of lines of treatment before ECT was 3.4. It was significantly longer for MDD single episode than recurrent MDD and BD. The presence of first-line indications for using ECT was significantly associated to shorter duration of MDE (9.1 vs 13.1 months, p<0.001) and lower number of lines of treatment before ECT (3.3 vs 4.1, p<0.001). LimitationsThis is a retrospective study and not all facilities practicing ECT participated that could limit the extrapolation of the results. Conclusion: Compared to guidelines, ECT was not used as first-line strategy in clinical practice. The presence of first-line indications seemed to reduce the delay before ECT initiation. The improvements of knowledge and access of ECT are needed to decrease the gap between guidelines and clinical practice.

Prediction of individual responses to electroconvulsive therapy in patients with schizophrenia: Machine learning analysis of resting-state electroencephalography

BackgroundElectroconvulsive therapy (ECT) has strong efficacy in patients with treatment refractory schizophrenia. However, access to ECT has been limited by high costs, professional labor, treatment duration, and significant adverse effects. To provide support for the decision to perform ECT, we aimed to predict individual responses to ECT among patients with schizophrenia using machine learning analysis of resting-state electroencephalography (EEG). MethodsForty-seven patients diagnosed with schizophrenia or schizoaffective disorder with EEG recordings before the course of ECT were treated at Seoul National University Hospital. Among these patients, 29 were responders who showed scores of 3 or less on the Clinical Global Impression Severity scale after the course of ECT. Transfer entropy (TE), which represents information flow, was extracted from baseline EEG data and used as a feature. Feature selection was performed with four methods, including Random Subset Feature Selection (RSFS). The random forest classifier was used to predict individual ECT responses. ResultsThe averaged TE, especially in frontal regions, was higher in ECT responders than in nonresponders. A predictive model using the RSFS method classified ECT responders and nonresponders with 85.3% balanced accuracy, 85.2% accuracy, 88.7% sensitivity, and 81.8% specificity. The positive predictive value was 82.6%, and the negative predictive value was 88.2%. ConclusionsThe results of the current study suggest that higher effective connectivity in frontal areas may be associated with a favorable ECT response. Furthermore, personalized decisions to perform ECT in clinical practice could be augmented by resting-state EEG biomarkers of the ECT response in schizophrenia patients.

Electroconvulsive therapy in bipolar depression - effectiveness and prognostic factors.

ObjectiveElectroconvulsive therapy (ECT) is used in patients with severe forms of bipolar depression. ECT is effective but not all patients respond. The aim of this study was to determine prognostic factors for response to ECT in patients hospitalized for bipolar depression.MethodsData were obtained from several national Swedish registers. All patients with bipolar depression treated with ECT in any hospital in Sweden between 2011 and 2016 for whom information about ECT response was available were included (n = 1251). Response was defined as a score on the Clinical Global Impression – Improvement scale of one or two. Univariate and multivariate logistic regression were conducted to investigate associations between socio‐demographic and clinical factors and response.ResultsResponse was achieved in 80.2% patients. Older age was associated with higher response rate to ECT. Patients with comorbid obsessive‐compulsive disorder or personality disorder, and patients previously treated with lamotrigine had lower response rate.ConclusionElectroconvulsive therapy for bipolar depression was associated with very high response rates. The strongest prognostic factors were higher age, absence of comorbid obsessive‐compulsive disorder or personality disorder, and less prior pharmacologic treatment.

Neurostimulation for depression: Evidence from preclinical models

Because most patients fail to enter remission with the first line treatment, there is a need to develop new therapeutic strategies and reliable treatment response predictors to guide personalized antidepressant strategies. Various neurostimulation modalities for depression have been developed (i.e., tDCS, rTMS, DBS, US, ECT). However, few data are available regarding the mechanisms by which neurostimulation induces remission of depressive-like states. This symposium will explore evidence from preclinical models about neurostimulation for depression. Preclinical research on tDCS allowed to mimic its antidepressant effect in several mouse models of depression and identified some of the mechanisms underlying this behavioural effect, including the involvement of inflammatory processes. New data compared the effects of chronic fluoxetine with the ones of rTMS on the infra limbic cortex in mice that were subjected to unpredictable chronic mild stress (UCMS, a model of depression). We will present some methodological data on the modelization of the effects of rTMS, how the rTMS counteracts the UCMS-induced depressive behaviours, and determine the underlying cellular and molecular mechanisms focusing on the modification of the function of specific brain areas from the corticolimbic circuits, hippocampal neurogenesis and the metabolomics signatures. ECT is known as the most effective approach for treatment resistant depression. We aim to profile a diverse array of biomarkers that contribute to ECT response, so as to provide guidance for therapeutic interventions. Neurostimulation using ultrasound (US) waves has been recently introduced as a potential physical non-invasive method for brain tissue stimulation. Here, we will present data on the efficacy of ultrasound neurostimulation of the anterior cingulate cortex in UCMS model of depression, and its effects on behaviour (nest-building, anxiety), brain metabolic activity in different brain regions, and metabolomic profile in cortical and subcortical regions.

Prediction of electroconvulsive therapy response and remission in major depression: meta-analysis

Electroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates. Aims To investigate the predictive value of age, depression severity, psychotic and melancholic features for ECT response and remission in major depression. A meta-analysis was conducted according to the PRISMA statement. A literature search identified recent studies that reported on at least one of the potential predictors. Of the 2193 articles screened, 34 have been included for meta-analysis. Presence of psychotic features is a predictor of ECT remission (odds ratio (OR) = 1.47, P = 0.001) and response (OR = 1.69, P < 0.001), as is older age (standardised mean difference (SMD) = 0.26 for remission and 0.35 for response (P < 0.001)). The severity of depression predicts response (SMD = 0.19, P = 0.001), but not remission. Data on melancholic symptoms were inconclusive. ECT is particularly effective in patients with depression with psychotic features and in elderly people with depression. More research on both biological and clinical predictors is needed to further evaluate the position of ECT in treatment protocols for major depression. Declaration of interest None.

Local functional connectivity density is closely associated with the response of electroconvulsive therapy in major depressive disorder

BackgroundElectroconvulsive therapy (ECT) has been demonstrated to be an effective treatment of major depressive disorder (MDD). However, the neuroanatomical basis of response to ECT is still largely unknown. MethodsIn present study, we used functional connectivity density (FCD) and resting-state functional connectivity (RSFC) to identify the relationship between the changes of resting-state activities and ECT responses in 23 MDD patients before and after ECT. In addition, the identified neural indices as classification characteristics were entered into multivariate pattern analysis using linear support vector machine (SVM) to classify 23 MDD patients before ECT from 25 gender, age and years of education matched healthy controls. ResultsWe found that the changes of local FCD (lFCD), not long-range FCD, of the left pre-/postcentral gyrus (Pre-/postCG), left superior temporal gyrus (STG), and right STG were significantly correlated with the changes of Hamilton Rating Scale for Depression (HRSD) scores in MDD patients before and after ECT. The subsequent functional connectivity analysis revealed significantly decreased functional connectivity between right STG and right intraparietal sulcus (IPS) in MDD after ECT in spite of no correlation with HRSD scores. Finally, SVM-based classification achieved an accuracy of 72.92% with a sensitivity of 73.91% and a specificity of 72% by leave-one-out cross-validation. ConclusionsOur findings indicated that Pre-/postCG and bilateral STG play an important role in response of ECT in MDD patients, and the lFCD in these areas may serve as a biomarker for predicting ECT response.

56. Connectomic Correlates of ECT Treatment and Response

56. Connectomic Correlates of ECT Treatment and Response

Structural-functional brain changes in depressed patients during and after electroconvulsive therapy.

Electroconvulsive therapy (ECT) is a non-pharmacological treatment that is effective in treating severe and treatment-resistant depression. Although the efficacy of ECT has been demonstrated to treat major depressive disorder (MDD), the brain mechanisms underlying this process remain unclear. Structural-functional changes occur with the use of ECT as a treatment for depression based on magnetic resonance imaging (MRI). For this reason, we have tried to identify the changes that were identified by MRI to try to clarify some operating mechanisms of ECT. We focus to brain changes on MRI [structural MRI (sMRI), functional MRI (fMRI) and diffusion tensor imging (DTI)] after ECT. A systematic search of the international literature was performed using the bibliographic search engines PubMed and Embase. The research focused on papers published up to 30 September 2015. The following Medical Subject Headings (MESH) terms were used: electroconvulsive therapy AND (MRI OR fMRI OR DTI). Papers published in English were included. Four authors searched the database using a predefined strategy to identify potentially eligible studies. There were structural changes according to the sMRI performed before and after ECT treatment. These changes do not seem to be entirely due to oedema. This investigation assessed the functional network connectivity associated with the ECT response in MDD. ECT response reverses the relationship from negative to positive between the two pairs of networks. We found structural-functional changes in MRI post-ECT. Because of the currently limited MRI data on ECT in the literature, it is necessary to conduct further investigations using other MRI technology.

Electroconvulsive therapy and structural neuroplasticity in neocortical, limbic and paralimbic cortex.

Electroconvulsive therapy (ECT) is a highly effective and rapidly acting treatment for severe depression. To understand the biological bases of therapeutic response, we examined variations in cortical thickness from magnetic resonance imaging (MRI) data in 29 patients scanned at three time points during an ECT treatment index series and in 29 controls at two time points. Changes in thickness across time and with symptom improvement were evaluated at high spatial resolution across the cortex and within discrete cortical regions of interest. Patients showed increased thickness over the course of ECT in the bilateral anterior cingulate cortex (ACC), inferior and superior temporal, parahippocampal, entorhinal and fusiform cortex and in distributed prefrontal areas. No changes across time occurred in controls. In temporal and fusiform regions showing significant ECT effects, thickness differed between patients and controls at baseline and change in thickness related to therapeutic response in patients. In the ACC, these relationships occurred in treatment responders only, and thickness measured soon after treatment initiation predicted the overall ECT response. ECT leads to widespread neuroplasticity in neocortical, limbic and paralimbic regions and changes relate to the extent of antidepressant response. Variations in ACC thickness, which discriminate treatment responders and predict response early in the course of ECT, may represent a biomarker of overall clinical outcome. Because post-mortem studies show focal reductions in glial density and neuronal size in patients with severe depression, ECT-related increases in thickness may be attributable to neuroplastic processes affecting the size and/or density of neurons and glia and their connections.

Structural Plasticity of the Hippocampus and Amygdala Induced by Electroconvulsive Therapy in Major Depression

BackgroundElectroconvulsive therapy (ECT) elicits a rapid and robust clinical response in patients with refractory depression. Neuroimaging measurements of structural plasticity relating to and predictive of ECT response may point to the mechanisms underlying rapid antidepressant effects and establish biomarkers to inform other treatments. Here, we determine the effects of diagnosis and of ECT on global and local variations of hippocampal and amygdala structures in major depression and predictors of ECT-related clinical response. MethodsLongitudinal changes in hippocampal and amygdala structures were examined in patients with major depression (N = 43, scanned three times: prior to ECT, after the second ECT session, and within 1 week of completing the ECT treatment series), referred for ECT as part of their standard clinical care. Cross-sectional comparisons with demographically similar controls (N = 32, scanned twice) established effects of diagnosis. ResultsPatients showed smaller hippocampal volumes than controls at baseline (p < .04). Both the hippocampal and the amygdala volumes increased with ECT (p < .001) and in relation to symptom improvement (p < .01). Hippocampal volume at baseline predicted subsequent clinical response (p < .05). Shape analysis revealed pronounced morphometric changes in the anterior hippocampus and basolateral and centromedial amygdala. All structural measurements remained stable across time in controls. ConclusionsECT-induced neuroplasticity in the hippocampus and amygdala relates to improved clinical response and is pronounced in regions with prominent connections to ventromedial prefrontal cortex and other limbic structures. Smaller hippocampal volumes at baseline predict a more robust clinical response. Neurotrophic processes including neurogenesis shown in preclinical studies may underlie these structural changes.