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Background: Increased gray matter volume (GMV) following electroconvulsive therapy (ECT) has been well-documented, with limited studies reporting a subsequent decrease in GMV afterwards. Objective: This study characterized the reversion pattern of GMV after ECT and its association with clinical depression outcome, using multi-site triple time-point data from the Global ECT-MRI Research Collaboration (GEMRIC). Methods: 86 subjects from the GEMRIC database were included, and GMV in 84 regions-of-interest (ROI) was obtained from automatic segmentation of T1 MRI images at three timepoints: pre-ECT (T0), within one-week post-ECT (T1), and one to six months post-ECT (T2). RM-ANOVAs were used to assess longitudinal changes and LMM analyses explored associations between GMV changes and demographical and clinical characteristics. Results: 63 of the 84 ROIs showed a significant increase-and-decrease pattern (RM-ANOVA, Bonferroni corrected p

Introduction Electroconvulsive therapy (ECT) is an evidence-based treatment for difficult-to-treat depression, in which an electrical stimulus is applied via right unilateral (RUL) (Fig 1) or bitemporal (BT) electrodes (Fig 2). Current guidelines recommend to start ECT with RUL placement, except for cases where rapid response is needed. BT ECT has the reputation of exerting a stronger and faster antidepressive effect, but is associated with more pronounced cognitive side effects, as compared to RUL ECT. Recent studies, however, suggest comparable outcomes. In patients responding to ECT, most of the improvement in depressive symptom severity is witnessed early in the treatment course. In case of non-response, it is common practice to switch from RUL to BT electrode placement, although scientific evidence is lacking. As an answer to this research gap, the ChaT-trial was designed: a randomized controlled trial (RCT) to address which treatment strategy (either continue RUL ECT or switch to BT ECT) speeds up recovery with the least impact on cognitive function, in case of early non-response after 4 ECT sessions. Objectives 1) To compare the antidepressant efficacy and cognitive effects of continuing RUL ECT vs switching to BT ECT. 2) To assess group and subject-specific trajectories of depressive symptom severity and neurocognitive performance during the acute ECT course and up to 3 months post-treatment. Methods This multi-center double-blind RCT includes adult patients with a uni- or bipolar depression. In case of non-response (

Background: The recent network perspective of depression conceptualizes depression as a dynamic network of causally related symptoms, that contrasts with the traditional view of depression as a discrete latent entity that causes all symptoms. Electroconvulsive therapy (ECT) is an effective treatment for severe depression, but little is known about the temporal trajectories of symptom improvement during a course of ECT. Objective: To gain insight into the dynamics of depressive symptoms in individuals treated with ECT. Methods: The Quick Inventory of Depressive Symptomatology (QIDS) was used to assess symptoms twice a week in 68 participants with a unipolar or bipolar depression treated with ECT, with an average of 12 assessments per participant. Dynamic time warping (DTW) was used to analyze individual time series data, which were subsequently aggregated to calculate a directed symptom network and the in- and out-strength for each symptom. Results: Participants had a mean age of 49.6 (SD = 12.8) and 60% were female. Somatic symptoms (e.g., decreased weight) and suicidal ideation showed the highest out-strength values, indicating that their improvement tended to precede improvements in mood symptoms, which showed high in-strength. Sad mood had the highest in-strength, and thus appeared to be the last symptom to improve during ECT treatment (p

Background: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depressive disorders. A recent multi-center study found no consistent changes in correlation-based (undirected) resting-state connectivity after ECT. Effective (directed) connectivity may provide more insight into the working mechanism of ECT. Objective: We investigated whether there are consistent changes in effective resting-state connectivity. Methods: This multi-center study included data from 189 patients suffering from severe unipolar depression and 59 healthy control participants. Longitudinal data were available for 81 patients and 24 healthy controls. We used dynamic causal modeling for resting-state functional magnetic resonance imaging to determine effective connectivity in the default mode, salience and central executive networks before and after a course of ECT. Bayesian general linear models were used to examine differences in baseline and longitudinal effective connectivity effects associated with ECT and its effectiveness. Results: Compared to controls, depressed patients showed many differences in effective connectivity at baseline, which varied according to the presence of psychotic features and later treatment outcome. Additionally, effective connectivity changed after ECT, which was related to ECT effectiveness. Notably, treatment effectiveness was associated with decreasing and increasing effective connectivity from the posterior default mode network to the left and right insula, respectively. No effects were found using correlation-based (undirected) connectivity. Conclusions: A beneficial response to ECT may depend on how brain regions influence each other in networks important for emotion and cognition. These findings further elucidate the working mechanisms of ECT and may provide directions for future non-invasive brain stimulation research.

Abstract ECT is proposed to exert a therapeutic effect on WM microstructure, but the limited power of previous studies made it difficult to highlight consistent patterns of change in diffusion metrics. We initiated a multicenter analysis and sought to address whether changes in WM microstructure occur following ECT. 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). ECT increased FA in the right splenium of the corpus callosum and the left cortico-spinal tract. AD in the left superior longitudinal fasciculus and the right inferior fronto-occipital fasciculus was raised. Increases in MD and RD could be observed in overlapping white matter structures of both hemispheres. At baseline, responders showed significantly smaller FA values in the left forceps major and smaller AD values in the right uncinate fasciculus compared with non-responders. By harmonizing multicenter data, we demonstrate that ECT modulates 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 could point toward a specific subtype of patients, characterized by a more altered neuroplasticity, who are especially sensitive to the potent neuroplastic effects of ECT.

Background: Electroconvulsive therapy (ECT) is provided for patients with severe and often life-threatening illness, who lack decision making capacity to consent to treatment (DMC-T) in clinical settings. Objective: The aim of this study is to summarize previous studies investigating clinical outcomes of ECT in patients lacking DMC-T. Methods: A systematic review and meta-analysis of studies reporting clinical outcomes of ECT in patients lacking DMC-T with any psychiatric diagnoses was conducted. The primary outcome was clinical improvement. Secondary outcomes were cognitive outcomes and six month readmission rate. Hedges’ g and odds ratios were calculated using a random-effects model. The protocol was registered in Open Science Framework (https://osf.io/rxjkm). Results: Of 3552 identified articles, 41 studies (n = 1299) were included. Approximately 80% of patients lacking DMC-T responded to ECT, and part of the patients regained capacity to consent and consented to further treatment with ECT. A total of seven studies (n = 1081) were included for meta-analysis. Patients without DMC-T showed superior clinical improvement and less cognitive side effects compared with those with DMC-T, whereas the groups did not show any difference in readmission rate. Several clinical characteristics at baseline and ECT techniques were significantly different between the groups. Conclusion: ECT is equally, if not superiorly, effective in patients lacking DMC-T compared to patients with DMC-T. ECT can potentially enhance patients’ autonomy, without increasing the risk of cognitive side effects. These results support the clinical and ethical legitimacy of ECT provision for patients with the most severe illness who lack DMC-T at start of treatment.

Recent longitudinal neuroimaging studies in patients with electroconvulsive therapy (ECT) suggest local effects of electric stimulation (lateralized) occur in tandem with global seizure activity (generalized). We used electric field (EF) modeling in 151 ECT treated patients with depression to determine the regional relationships between EF, unbiased longitudinal volume change, and antidepressant response across 85 brain regions. The majority of regional volumes increased significantly, and volumetric changes correlated with regional electric field (t = 3.77, df = 83, r = 0.38, p=0.0003). After controlling for nuisance variables (age, treatment number, and study site), we identified two regions (left amygdala and left hippocampus) with a strong relationship between EF and volume change (FDR corrected p

Objectives: We aimed to review and summarise the existing human literature on the association between lithium and hyperparathyroidism. Methods: A systematic literature search was carried out according to PRISMA guidelines (last search 27 February 2024), using MEDLINE, Web of Science, Embase and the Cochrane Library. A meta-analysis was performed to determine the prevalence of lithium-associated hypercalcemia (LAHca) in lithium-treated patients. Results: The pooled prevalence of LAHca based on total calcium and ionised calcium was comparable, at 3.17% and 4.23%, respectively. Calcium, and PTH if the patient is hypercalcaemic, is insufficiently measured in lithium-treated patients in clinical practice. Lithium use is associated with higher calcium and PTH levels, as well as a higher incidence of hyperparathyroidism. There is a high prevalence of multiglandular disease in lithium-associated hyperparathyroidism (LAH), with a pooled prevalence of 51.28%. Parathyroid surgery and cinacalcet are effective treatments for LAH. Regarding lithium discontinuation, there is anecdotal but conflicting evidence suggesting that it can result in the resolution of LAH in selected cases. Conclusions: Lithium treatment increases the risk of hyperparathyroidism, a treatable complication with a pooled prevalence of around 4%, compared to 0.5% in the healthy population. [ABSTRACT FROM AUTHOR]

Lifelong movement and physical activity (PA) patterns develop during early childhood. Therefore, educators (teachers and practitioners) in early childhood education and care (ECEC) should provide opportunities to support children’s play, PA, and movement development. The World Health Organization (2019) offers new recommendations for PA, for children under five years. The guidelines do not specify the ways ECEC staff can support PA through play. Therefore, this paper investigates, how physical play (PP) is enacted globally. An international policy and practice analysis of twelve countries, (Australia [Victoria], Belgium [Flanders], Canada [Alberta], China, Finland, Ireland, Italy, Portugal, Spain, Sweden, UK [England] and USA) was completed by analyzing the ECEC curricula and their implementation in different cultural contexts. A content analysis was undertaken by AIESEP Early Years SIG experts revealing that PP was not clearly defined. When defined, it was described as PA, and important for children’s holistic development. The majority of curricula did not state the length/time for PP. Three main strategies for implementing PP were found: a) pedagogical framework; b) active learning methods; and c) motor development. This international analysis highlights the global need for better ECEC staff support in acknowledging and implementing PP to aid children’s overall development, PA and wellbeing.

BackgroundHippocampal enlargements are commonly reported after electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT-induced hippocampal volume change relates to dose (number of ECT sessions and electrode placement) and acts as a biomarker of clinical outcome.MethodsLongitudinal neuroimaging and clinical data from 10 independent sites participating in the Global ECT-Magnetic Resonance Imaging Research Collaboration (GEMRIC) were obtained for mega-analysis. Hippocampal volumes were extracted from structural magnetic resonance images, acquired before and after patients (n = 281) experiencing a major depressive episode completed an ECT treatment series using right unilateral and bilateral stimulation. Untreated nondepressed control subjects (n = 95) were scanned twice.ResultsThe linear component of hippocampal volume change was 0.28% (SE 0.08) per ECT session (p < .001). Volume change varied by electrode placement in the left hippocampus (bilateral, 3.3 ± 2.2%, d = 1.5; right unilateral, 1.6 ± 2.1%, d = 0.8; p < .0001) but not the right hippocampus (bilateral, 3.0 ± 1.7%, d = 1.8; right unilateral, 2.7 ± 2.0%, d = 1.4; p = .36). Volume change for electrode placement per ECT session varied similarly by hemisphere. Individuals with greater treatment-related volume increases had poorer outcomes (Montgomery-Åsberg Depression Rating Scale change -1.0 [SE 0.35], per 1% volume increase, p = .005), although the effects were not significant after controlling for ECT number (slope -0.69 [SE 0.38], p = .069).ConclusionsThe number of ECT sessions and electrode placement impacts the extent and laterality of hippocampal enlargement, but volume change is not positively associated with clinical outcome. The results suggest that the high efficacy of ECT is not explained by hippocampal enlargement, which alone might not serve as a viable biomarker for treatment outcome.

Introduction There have been important advances in the use of electroconvulsive therapy (ECT) to treat major depressive episodes. These include variations to the type of stimulus the brain regions stimulated, and the stimulus parameters (eg, stimulus duration/pulse width). Our aim is to investigate ECT types using a network meta-analysis (NMA) approach and report on comparative treatment efficacy, cognitive side effects and acceptability.Method We will conduct a systematic review to identify randomised controlled trials that compared two or more ECT protocols to treat depression. This will be done using the following databases: Embase, MEDLINE PubMed, Web of Science, Scopus, PsycINFO, Cochrane CENTRAL and will be supplemented by personal contacts with researchers in the field. All authors will be contacted to provide missing information. Primary outcomes will be symptom severity on a validated continuous clinician-rated scale of depression, cognitive functioning measured using anterograde verbal recall, and acceptability calculated using all-cause drop-outs. Secondary outcomes will include response and remission rates, autobiographical memory following a course of ECT, and anterograde visuospatial recall.Bayesian random effects hierarchical models will compare ECT types. Additional meta-regressions may be conducted to determine the impact of effect modifiers and patient-specific prognostic factors if sufficient data are available.Discussion This NMA will facilitate clinician decision making and allow more sophisticated selection of ECT type according to the balance of efficacy, cognitive side effects and acceptability.Ethics This systematic review and NMA does not require research ethics approval as it will use published aggregate data and will not collect nor disclose individually identifiable participant data.PROSPERO registration number CRD42022357098.

Background: Electroconvulsive therapy (ECT) applies electric currents to the brain to induce seizures for therapeutic purposes. ECT increases gray matter (GM) volume, predominantly in the medial temporal lobe (MTL). The contribution of induced seizures to this volume change remains unclear. Methods: T1-weighted structural MRI was acquired from thirty patients with late-life depression (mean age 72.5 ± 7.9 years, 19 female), before and one week after one course of right unilateral ECT. Whole brain voxel-/deformation-/surface-based morphometry analyses were conducted to identify tissue-specific (GM, white matter: WM), and cerebrospinal fluid (CSF) and cerebral morphometry changes following ECT. Whole-brain voxel-wise electric field (EF) strength was estimated to investigate the association of EF distribution and regional brain volume change. The association between percentage volume change in the right MTL and ECT-related parameters (seizure duration, EF, and number of ECT sessions) was investigated using multiple regression. Results: ECT induced widespread GM volume expansion with corresponding contraction in adjacent CSF compartments, and limited WM change. The regional EF was strongly correlated with the distance from the electrodes, but not with regional volume change. The largest volume expansion was identified in the right MTL, and this was correlated with the total seizure duration. Conclusions: Right unilateral ECT induces widespread, bilateral regional volume expansion and contraction, with the largest change in the right MTL. This dynamic volume change cannot be explained by the effect of electrical stimulation alone and is related to the cumulative effect of ECT-induced seizures.

Major depression, currently the world's primary cause of disability, leads to profound personal suffering and increased risk of suicide. Unfortunately, the success of antidepressant treatment varies amongst individuals and can take weeks to months in those who respond. Electroconvulsive therapy (ECT), generally prescribed for the most severely depressed and when standard treatments fail, produces a more rapid response and remains the most effective intervention for severe depression. Exploring the neurobiological effects of ECT is thus an ideal approach to better understand the mechanisms of successful therapeutic response. Though several recent neuroimaging studies show structural and functional changes associated with ECT, not all brain changes associate with clinical outcome. Larger studies that can address individual differences in clinical and treatment parameters may better target biological factors relating to or predictive of ECT-related therapeutic response. We have thus formed the Global ECT-MRI Research Collaboration (GEMRIC) that aims to combine longitudinal neuroimaging as well as clinical, behavioral and other physiological data across multiple independent sites. Here, we summarize the ECT sample characteristics from currently participating sites, and the common data-repository and standardized image analysis pipeline developed for this initiative. This includes data harmonization across sites and MRI platforms, and a method for obtaining unbiased estimates of structural change based on longitudinal measurements with serial MRI scans. The optimized analysis pipeline, together with the large and heterogeneous combined GEMRIC dataset, will provide new opportunities to elucidate the mechanisms of ECT response and the factors mediating and predictive of clinical outcomes, which may ultimately lead to more effective personalized treatment approaches.

BackgroundCognitive side-effects are an important reason for the limited use of electroconvulsive therapy (ECT). Cognitive side-effects are heterogeneous and occur frequently in older persons. To date, insight into these side-effects is hampered due to inconsistencies in study designs and small sample sizes. Among all cognitive side-effects, confusion and delirious states are especially troublesome for patients, relatives and clinicians. In particular inter-ictal delirium-like states are worrisome, since they may lead to premature treatment discontinuation. Besides a need for further insight into determinants of cognitive side-effects of ECT, there is a great need for treatment options.Methods and designThe Rivastigmine for ECT-induced Cognitive Adverse effects in Late Life depression (RECALL) study combines a multicenter, prospective cohort study on older patients with depression, treated with ECT, with an embedded randomized, placebo-controlled cross-over trial to examine the effect of rivastigmine on inter-ictal delirium. Patients are recruited in four centers across the Netherlands and Belgium. We aim to include 150 patients into the cohort study, in order to be able to subsequently include 30 patients into the trial. Patients are included in the trial when inter-ictal delirium, assessed by the Confusion Assessment method (CAM), or a drop in Mini Mental State Examination (MMSE) score of ≥4 during ECT, develops. In the cohort study, comprehensive measurements of ECT-related cognitive side-effects—and their putative determinants—are done at baseline and during the ECT-course. The primary outcome of the clinical trial is the effectiveness of rivastigmine on inter-ictal delirium-severity, assessed with a change in the Delirium Rating Scale-Revised-98. Secondary outcomes of the clinical trial are several ECT-characteristics and side-effects of rivastigmine.DiscussionThis study is the first clinical trial with a focus on ECT-induced, inter-ictal delirium. The cohort provides the basis for recruitment of patients for the cross-over trial and additionally provides an excellent opportunity to unravel cognitive side-effects of ECT and identify putative determinants. This paper describes the rationale and study protocol.Clinical trial registrationEudraCT 2014-003385-24.

Introduction Introduction: Residual depressive symptoms are common after a successful acute treatment of late-life depression (LLD), and their presence predicts increased risk of relapse. While electroconvulsive therapy (ECT) is the most effective treatment for LLD, little is known about which particular symptoms remain and impact long-term outcome after a successful acute ECT course. Objectives Objectives: We aimed to assess the association between specific residual depressive symptoms after an effective acute ECT course for LLD and relapse at six-month follow-up. Methods Methods: In this prospective cohort study, including 110 patients aged 55 years and older with LLD, information about relapse was collected six months after the acute ECT course. Relapse was defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) score >15, hospital admission or restart of ECT. We used multivariable stepwise logistic regression models including the scores on the 10 individual MADRS items at the end of the acute ECT course to predict relapse. Results Results: Of the 80 responders with available six-month follow-up data, 29 patients (36.25%) had suffered relapse. Higher scores on the MADRS items ‘reduced sleep’ (odds ratio (OR)=2.03, 95% confidence interval (CI)=1.11-3.69, p=0.0214) and ‘lassitude’ (OR=1.62, 95% CI=1.00-2.62, p=0.0497) at the end of the acute ECT course were significantly associated with increased risk of relapse at six-month follow-up. Conclusions Conclusions: Some residual depressive symptoms, including sleep disturbance and fatigue, may help better identify patients vulnerable to relapse following a successful acute ECT course for LLD. Future studies assessing interventions that target specific residual symptoms may further reduce post-ECT depressive relapse. Disclosure No significant relationships.

Abstract Psychomotor dysfunction (PMD) is a core element and key contributor to disability in late life depression (LLD), which responds well to electroconvulsive therapy (ECT). The neurobiology of PMD and its response to ECT are not well understood. We hypothesized that PMD in LLD is associated with lower striatal volume, and that striatal volume increase following ECT explains PMD improvement. We analyzed data from a two-center prospective cohort study of 110 LLD subjects (>55 years) receiving ECT. Brain MRI and assessment of mood, cognition, and PMD was performed 1 week before, 1 week after, and 6 months after ECT. Volumetry of the caudate nucleus, putamen, globus pallidus, and nucleus accumbens was derived from automatically segmented brain MRIs using Freesurfer®. Linear multiple regression analyses were used to study associations between basal ganglia volume and PMD. Brain MRI was available for 66 patients 1 week post ECT and in 22 patients also six months post ECT. Baseline PMD was associated with a smaller left caudate nucleus. One week after ECT, PMD improved and volume increases were detected bilaterally in the caudate nucleus and putamen, and in the right nucleus accumbens. Improved PMD after ECT did not relate to the significant volume increases in these structures, but was predicted by a nonsignificant volume change in the right globus pallidus. No volume differences were detected 6 months after ECT, compared to baseline. Although PMD is related to lower striatal volume in LLD, ECT-induced increase of striatal volume does not explain PMD improvement.

Increased gray matter volume (GMV) following electroconvulsive therapy (ECT) has been well-documented, with limited studies reporting a subsequent decrease in GMV afterwards. This study characterized the reversion pattern of GMV after ECT and its association with clinical depression outcome, using multi-site triple time-point data from the Global ECT-MRI Research Collaboration (GEMRIC). 86 subjects from the GEMRIC database were included, and GMV in 84 regions-of-interest (ROI) was obtained from automatic segmentation of T1 MRI images at three timepoints: pre-ECT (T 0), within one-week post-ECT (T 1), and one to six months post-ECT (T 2). RM-ANOVAs were used to assess longitudinal changes and LMM analyses explored associations between GMV changes and demographical and clinical characteristics. 63 of the 84 ROIs showed a significant increase-and-decrease pattern (RM-ANOVA, Bonferroni corrected p < 0.00059). Post hoc tests indicated a consistent pattern in each of these 63 ROIs: significant increase from T 0 to T 1 in GMV , followed by significant decrease from T 1 to T 2 and no difference between T 0 and T 2 , except for both amygdalae, right hippocampus and pars triangularis, which showed the same increase and decrease but GMV at T 2 remained higher compared to T 0. No consistent relationship was found between GMV change pattern and clinical status. The GEMRIC cohort confirmed a rapid increase of GMV after ECT followed by reversion of GMV one to six months thereafter. The lack of association between the GMV change pattern and depression outcome scores implies a transient neurobiological effect of ECT unrelated to clinical improvement. • A mega-analysis of longitudinal T1-weighted MRI data of patients receiving ECT from eight different sites was performed. • A pattern of gray matter volume (GMV) increase during ECT and a subsequent decrease one to six months thereafter was observed. • Four regions – associated with cognition and emotions – showed sustained higher GMV at one to six months after the ECT-course. • The pattern of GMV change did not correspond with clinical improvement after ECT. [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) is the most effective treatment option for major depressive disorder, so understanding whether its clinical effect relates to structural brain changes is vital for current and future antidepressant research. Objective: To determine whether clinical response to ECT is related to structural volumetric changes in the brain as measured by structural magnetic resonance imaging (MRI) and, if so, which regions are related to this clinical effect. We also determine whether a similar model can be used to identify regions associated with electrode placement (unilateral versus bilateral ECT). Methods: Longitudinal MRI and clinical data (Hamilton Depression Rating Scale) was collected from 10 sites as part of the Global ECT-MRI research collaboration (GEMRIC). From 192 subjects, relative changes in 80 (sub)cortical areas were used as potential features for classifying treatment response. We used recursive feature elimination to extract relevant features, which were subsequently used to train a linear classifier. As a validation, the same was done for electrode placement. We report accuracy as well as the structural coefficients of regions included in the discriminative spatial patterns obtained. Results: A pattern of structural changes in cortical midline, striatal and lateral prefrontal areas discriminates responders from non-responders (75% accuracy, p

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe late-life depression (LLD), and several hypotheses on the precise working mechanism have been proposed. Preclinical evidence suggests that ECT induces changes in neurotrophin and inflammatory signaling and that these neurotrophic and inflammatory systems affect each other. We examine the relation, interaction, and ratio between the neurotrophic brain-derived neurotrophic factor (BDNF) and the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α), and depression severity during ECT. Methods: In this naturalistic longitudinal study, linear mixed models were used to analyze the relation between BDNF, IL-6, TNF-α, and depression severity (determined by the Montgomery-Åsberg Depression Rating Scale; MADRS) in 99 patients with severe LLD before ECT (T0), three weeks after the first ECT (T1), and one week after the last ECT (T2). Results: No significant association was found between BDNF, IL-6 and TNF-α, and MADRS scores at any time point. However, a significant interaction between TNF-α and BDNF in relation to MADRS was established (p ​= ​.020) at all time points. With higher levels of TNF-α, the relation between BDNF and MADRS becomes more negative. Furthermore, a higher ratio of TNF-α/BDNF was associated with a higher score on the MADRS (p ​= ​.007). Conclusion: A possible explanation for the absence of a significant coevolution between the proinflammatory cytokines and BDNF could be that the study design was unable to determine parameters shortly after ECT sessions. However, the TNF-α/BDNF ratio was positively associated with depression severity, and the association of BDNF-level and depression severity depended on the level of TNF-α. This suggests that the interaction and balance between neurotrophin and immune signaling, specifically BDNF and TNF-α, could be relevant in LLD. This could be a focus in future research regarding treatment and the working mechanism of ECT.

Abstract Background Major Depressive Disorder (MDD) is the leading cause of disability worldwide. The cardinal features of MDD are depressed mood and anhedonia. Anhedonia is defined as a “markedly diminished interest or pleasure in all, or almost all, activities of the day”, and has generally been investigated on group-level using retrospective data (e.g. via questionnaire/interview). However, inferences based on group-level findings not necessarily generalize to daily life experiences within individuals. Methods We repeatedly sampled pleasurable experiences within individuals’ daily lives by means of Experience Sampling Methods, and compared how positive affect unfolded in the daily life of healthy controls versus patients diagnosed with MDD and anhedonia. We sampled Positive Affect (PA) and reward experiences on 10 semi-random time points a day, for seven days in the daily lives of 47 MDD patients with anhedonia, and 40 controls. Results Multilevel models showed that anhedonia was associated with low PA, but not to differences in PA dynamics, nor reward frequency in daily life. In reaction to rewards, MDD patients with anhedonia showed no difference in their increase in PA (i.e., PA reactivity), and showed no signs of a faster return to baseline thereafter (i.e., PA recovery). Conclusions Our results suggest that the dynamical signature of anhedonia in MDD can be described best as a lower average level of PA, and “normal” in terms of PA dynamics, daily reward reactivity and reward recovery. Preregistration: https://osf.io/gmfsc/register/565fb3678c5e4a66b5582f67. Preprint: https://osf.io/cfkts

Introduction ECT is an effective treatment for depression. Beyond its therapeutic effect on mood it has a unique impact on psychomotor and cognitive symptoms.Its mechanism of action remains still unclear. To investigate this, we set out to study the brain’s response to ECT from a large-scale brain-network perspective. Objectives The aim of this study was to investigate changes in resting-state functional connectivity following ECT at the whole brain, between-network and within-network level, in patients with a depressive episode. Methods Resting-state FMRI data were collected from 17 patients with depression before and after an ECT course. Using a group independent component analysis approach, we focused on four networks that are known to be affected in depression: the salience network (SN), default mode network (DMN), cognitive executive network (CEN) and a subcortical network (SCN). Clinical measures including mood, cognition and psychomotor symptoms were assessed. Results ECT increased connectivity of the left CEN with the left angular gyrus and left middle frontal gyrus. An increase in left CEN within network connectivity was observed. Both the right CEN and the SCN showed increased connectivity with the precuneus. Furthermore, the anterior DMN showed increased connectivity with the left amygdala. Finally, improvement of psychomotor retardation was positively correlated with an increase of within-posterior DMN connectivity. Conclusions We demonstrate that ECT induces a significant increase of connectivity at both the whole brain and within-network level. Furthermore, we provide first evidence on the association between an increase of within posterior DMN connectivity and an improvement of psychomotor retardation, a core symptom of depression. Disclosure No significant relationships.

The discussion about whether or not to focus our attention on the ‘average’ ECT-treatment technique that suits the majority of our patients or tailor the treatment to the needs of individual patients is ongoing. The question is, however, whether the available evidence permits us to to offer treatment ‘à la tête du client’. The start of a treatment course can be personalized by choosing electrodeplacement (EP) (e.g. bilateral in case of a severe or life-threatening condition, when fast improvement prevails over cognitive impact), parameter selection (e.g. a shorter pulse-width in order to avoid cognitive side-effects), and a dosing strategy. A fixed-dose will lead to overdosing in some patients (causing side-effects) and under-dosing in others (delaying/decreasing response) (1) Adjusting an ongoing treatment-technique can be based on response, side-effects or on the quality of the elicited seizure (EEG). In case of inadequate response, the clinician can decide to switch EP or to increase dose. There is no consensus as to the number of sessions after which technique should be changed. In case of intolerable side-effects, parameter selection and/or EP can be adjusted. The evidence that is available to guide these steps is limited. There is some evidence for a relation between several EEG-characteristics and outcome. Thus, in the event of an inadequate seizure, changing the anesthetic regimen, optimizing ventilation, lengthening the anesthetic-ECT time-interval or increasing the stimulus dose, can be of help. 1. Sackeim et al. Treatment of the modal patient: does one size fit nearly all? J ECT 2001;17:219-222.

Introduction Vagus Nerve Stimulation (VNS) is a neuromodulatory intervention which involves attaching an electrode to the vagus nerve. Studies investigating VNS as an acute treatment method for treatment resistent depression have shown very limited results, however there are data suggesting that VNS might have a beneficial effect on a longer term. There are also studies that suggest that a history of response to ECT might indicate a higher response rate to VNS. VNS was suggested as treatment for a patient who received maintenance ECT for treatment resistant unipolar depression during 9 years. 3 months after VNS was implanted, ECT was stopped due to the Covid-19 pandemic. In this case study we will review the patient’s response to treatment with VNS and the sudden stop of long-term ECT treatment. Objectives To review the response to acute and maintenance ECT and VNS in this patient diagnosed with treatment resistant unipolar depression, and to compare this to the data suggesting VNS as an alternative treatment method for maintenance ECT in patients with treatment resistant depression. Methods Using the extensive data collected during the patient’s treatment, we will review the clinical response and side-effect burden of this patient to acute and maintenance ECT and to VNS. Results The patient showed a vast improvement in depressive symptoms a few months after start of VNS treatment, while long-term maintenance ECT was stopped. Conclusions This patient’s response to VNS supports the data suggesting VNS as an alternative treatment method for maintenance ECT in patients with treatment resistant depression. Conflict of interest This patient received VNS treatment as part of a study conducted in our centre (UPC KULeuven) with support of Livanova. Me nor my supervisor (prof. Sienaert Pascal) are directly involved in this study. I have received no financial or other compensation fr

Major depression, currently the world's primary cause of disability, leads to profound personal suffering and increased risk of suicide. Unfortunately, the success of antidepressant treatment varies amongst individuals and can take weeks to months in those who respond. Electroconvulsive therapy (ECT), generally prescribed for the most severely depressed and when standard treatments fail, produces a more rapid response and remains the most effective intervention for severe depression. Exploring the neurobiological effects of ECT is thus an ideal approach to better understand the mechanisms of successful therapeutic response. Though several recent neuroimaging studies show structural and functional changes associated with ECT, not all brain changes associate with clinical outcome. Larger studies that can address individual differences in clinical and treatment parameters may better target biological factors relating to or predictive of ECT-related therapeutic response. We have thus formed the Global ECT-MRI Research Collaboration (GEMRIC) that aims to combine longitudinal neuroimaging as well as clinical, behavioral and other physiological data across multiple independent sites. Here, we summarize the ECT sample characteristics from currently participating sites, and the common data-repository and standardized image analysis pipeline developed for this initiative. This includes data harmonization across sites and MRI platforms, and a method for obtaining unbiased estimates of structural change based on longitudinal measurements with serial MRI scans. The optimized analysis pipeline, together with the large and heterogeneous combined GEMRIC dataset, will provide new opportunities to elucidate the mechanisms of ECT response and the factors mediating and predictive of clinical outcomes, which may ultimately lead to more effective personalized treatment approaches.

Recent longitudinal neuroimaging studies in patients with electroconvulsive therapy (ECT) suggest local effects of electric stimulation (lateralized) occur in tandem with global seizure activity (generalized). We used electric field (EF) modeling in 151 ECT treated patients with depression to determine the regional relationships between EF, unbiased longitudinal volume change, and antidepressant response across 85 brain regions. The majority of regional volumes increased significantly, and volumetric changes correlated with regional electric field (t = 3.77, df = 83, r = 0.38, p=0.0003). After controlling for nuisance variables (age, treatment number, and study site), we identified two regions (left amygdala and left hippocampus) with a strong relationship between EF and volume change (FDR corrected p

BackgroundSevere depression is associated with high morbidity and mortality. Neural network dysfunction may contribute to disease mechanisms underlying different clinical subtypes. Here, we apply resting-state functional magnetic resonance imaging based measures of brain connectivity to investigate network dysfunction in severely depressed in-patients with and without psychotic symptoms.MethodsA cohort study was performed at two sites. Older patients with major depressive disorder with or without psychotic symptoms were included (n = 23 at site one, n = 26 at site two). Resting state 3-Tesla functional MRI scans, with eyes closed, were obtained and Montgomery-Åsberg Depression Rating Scales were completed. We denoised data and calculated resting state networks in the two groups separately. We selected five networks of interest (1. bilateral frontoparietal, 2.left lateralized frontoparietal, 3.right lateralized frontoparietal, 4.default mode network (DMN) and 5.bilateral basal ganglia and insula network) and performed regression analyses with severity of depression, as well as presence or absence of psychotic symptoms.ResultsThe functional connectivity (FC) patterns did not correlate with severity of depression. Depressed patients with psychotic symptoms (n = 14, 61%) compared with patients without psychotic symptoms (n = 9, 39%) from site one showed significantly decreased FC in the right part of the bilateral frontoparietal network (p = 0.002). This result was not replicated when comparing patients with (n = 9, 35%) and without (n = 17, 65%) psychotic symptoms from site two.ConclusionPsychotic depression may be associated with decreased FC of the frontoparietal network, which is involved in cognitive control processes, such as attention and emotion regulation. These findings suggest that FC in the frontoparietal network may be related to the subtype of depression, i.e. presence of psychotic symptoms, rather than severity of depression. Since the findings could not be replicated in the 2nd sample, replication is needed before drawing definite conclusions.

The recent network perspective of depression conceptualizes depression as a dynamic network of causally related symptoms, that contrasts with the traditional view of depression as a discrete latent entity that causes all symptoms. Electroconvulsive therapy (ECT) is an effective treatment for severe depression, but little is known about the temporal trajectories of symptom improvement during a course of ECT. To gain insight into the dynamics of depressive symptoms in individuals treated with ECT. The Quick Inventory of Depressive Symptomatology (QIDS) was used to assess symptoms twice a week in 68 participants with a unipolar or bipolar depression treated with ECT, with an average of 12 assessments per participant. Dynamic time warping (DTW) was used to analyze individual time series data, which were subsequently aggregated to calculate a directed symptom network and the in- and out-strength for each symptom. Participants had a mean age of 49.6 (SD = 12.8) and 60% were female. Somatic symptoms (e.g., decreased weight) and suicidal ideation showed the highest out-strength values, indicating that their improvement tended to precede improvements in mood symptoms, which showed high in-strength. Sad mood had the highest in-strength, and thus appeared to be the last symptom to improve during ECT treatment (p < 0.001). This study addresses a gap in the existing literature on ECT, by first analysing the temporal trajectories of symptoms within individual patients and subsequently aggregating them to the group level. The results show that somatic symptoms tend to improve before mood symptoms during ECT. • Somatic symptoms and suicidal ideation improve before mood symptoms during an acute course of electroconvulsive therapy. • DTW offers valuable insights into temporal dynamics of depressive symptoms, often lost in group-level analyses. • When we solely rely on sum-scores of depression questionnaires, interesting insights remain hidden. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? This study examined whether the Cortisol Awakening Response (CAR) could be a biomarker for cognitive change during electroconvulsive therapy (ECT). • What is the main finding of this study? We found no significant associations between the CAR and cognitive change during the ECT course in (un)adjusted models. • What is the meaning of the finding? Our results indicate that the CAR is not usable as a biomarker for ECT-induced cognitive change during the ECT course. To test whether the cortisol awakening response (CAR) could be a biomarker for cognitive decline during electroconvulsive therapy (ECT). We studied 50 older patients with depression who were treated with ECT from the MODECT cohort. We used linear regression analyses to examine the association between CAR and cognitive change, assessed by the change in Mini Mental State Examination scores between baseline and 1 week after ECT course. CAR was assessed by the area under the curve of cortisol levels, according to Pruessner's-formula. Associations were adjusted for putative confounders, based on previous literature and availability. We found no significant associations between the CAR and cognitive change during the ECT course in (un)adjusted models. Our results indicate that the CAR is not usable as a biomarker for ECT-induced cognitive decline during ECT course. Further research in cohorts with larger samples is needed. [ABSTRACT FROM AUTHOR]

Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depressive disorders. A recent multi-center study found no consistent changes in correlation-based (undirected) resting-state connectivity after ECT. Effective (directed) connectivity may provide more insight into the working mechanism of ECT. We investigated whether there are consistent changes in effective resting-state connectivity. This multi-center study included data from 189 patients suffering from severe unipolar depression and 59 healthy control participants. Longitudinal data were available for 81 patients and 24 healthy controls. We used dynamic causal modeling for resting-state functional magnetic resonance imaging to determine effective connectivity in the default mode, salience and central executive networks before and after a course of ECT. Bayesian general linear models were used to examine differences in baseline and longitudinal effective connectivity effects associated with ECT and its effectiveness. Compared to controls, depressed patients showed many differences in effective connectivity at baseline, which varied according to the presence of psychotic features and later treatment outcome. Additionally, effective connectivity changed after ECT, which was related to ECT effectiveness. Notably, treatment effectiveness was associated with decreasing and increasing effective connectivity from the posterior default mode network to the left and right insula, respectively. No effects were found using correlation-based (undirected) connectivity. A beneficial response to ECT may depend on how brain regions influence each other in networks important for emotion and cognition. These findings further elucidate the working mechanisms of ECT and may provide directions for future non-invasive brain stimulation research. • Previous mega-analyses did not show any associations between changes in brain structure or function and ECT outcome. • We used Dynamic causal modeling on multi-center resting-state fMRI data to infer effective connectivity before and after ECT. • The outcome of ECT was associated with effective connectivity from the posterior cingulate cortex to the bilateral insula. • This is the first study to show consistent changes in brain function related to ECT outcome. [ABSTRACT FROM AUTHOR]