Electroconvulsive therapy disrupts functional connectivity between hippocampus and posterior default mode network.

BACKGROUND: The mechanisms underlying memory deficits after electroconvulsive therapy (ECT) remain unclear but altered functional interactions between hippocampus and neocortex may play a role. OBJECTIVES: To test whether ECT reduces functional connectivity between hippocampus and posterior regions of the default mode network (DMN) and to examine whether altered hippocampal-neocortical functional connectivity correlates with memory impairment. A secondary aim was to explore if these connectivity changes are present 6 months after ECT. METHODS: In-patients with severe depression (n = 35) received bitemporal ECT. Functional connectivity of the hippocampus was probed with resting-state fMRI before the first ECT-session, after the end of ECT, and at a six-month follow-up. Memory was assessed with the Verbal Learning Test - Delayed Recall. Seed-based connectivity analyses established connectivity of four hippocampal seeds, covering the anterior and posterior parts of the right and left hippocampus. RESULTS: Compared to baseline, three of four hippocampal seeds became less connected to the core nodes of the posterior DMN in the week after ECT with Cohen's d ranging from -0.9 to -1.1. At the group level, patients showed post-ECT memory impairment, but individual changes in delayed recall were not correlated with the reduction in hippocampus-DMN connectivity. At six-month follow-up, no significant hippocampus-DMN reductions in connectivity were evident relative to pre-ECT, and memory scores had returned to baseline. CONCLUSION: ECT leads to a temporary disruption of functional hippocampus-DMN connectivity in patients with severe depression, but the change in connectivity strength is not related to the individual memory impairment.

Effect of erythropoietin on cognitive side-effects of electroconvulsive therapy in depression: A randomized, double-blind, placebo-controlled trial.

Electroconvulsive therapy (ECT) is one of the most effective and rapid-acting treatment for severe depression but is associated with cognitive side-effects. Identification of add-on treatments that counteract these side-effects would be very helpful. This randomized, double-blinded, placebo-controlled, parallel-group study investigated the effects of four add-on erythropoietin (EPO; 40,000 IU/ml) or saline (placebo) infusions over 2.5 weeks of ECT (eight ECT sessions) in severely depressed patients with unipolar or bipolar depression. Neuropsychological assessments were conducted pre-ECT, three days after the eighth ECT (week 4), and at a 3-month follow-up. Further, functional magnetic resonance imaging (fMRI) was conducted after the eighth ECT. The primary outcome was change from pre- to post-ECT in a 'speed of complex cognitive processing' composite. Secondary outcomes were verbal and autobiographical memory. Of sixty randomized patients, one dropped out before baseline. Data were thus analysed for 59 patients (EPO, n = 33; saline, n = 26), of whom 28 had fMRI data. No ECT-related decline occurred in the primary global cognition measure (ps≥0.1), and no effect of EPO versus saline was observed on this outcome (ps≥0.3). However post-ECT, EPO-treated patients exhibited faster autobiographical memory recall than saline-treated patients (p = 0.02), which was accompanied by lower memory-related parietal cortex activity. The absence of global cognition changes with ECT and EPO, coupled with the specific impact of EPO on autobiographical memory recall speed and memory-related parietal cortex activity, suggests that assessing autobiographical memory may provide increased sensitivity in evaluating and potentially preventing cognitive side-effects of ECT. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03339596, EudraCT no.: 2016-002326-36.

Blood-brain barrier permeability and electroconvulsive therapy: a systematic review.

OBJECTIVE: The cause of cognitive side effects after electroconvulsive therapy (ECT) is largely unknown. Alterations in the blood-brain barrier (BBB) have been considered in several recent ECT studies. We therefore found it worthwhile to perform a systematic review of the literature to examine if electrically induced seizures affect the permeability of the BBB. METHODS: PubMed/MEDLINE and Embase were searched 16 November 2022. Studies with a direct measurement of BBB permeability in animals treated with modified electroconvulsive stimulation (ECS) and in humans treated with ECT were included. Synthesis of results was narrative due to the low number of studies and differences in study designs. RESULTS: Four animal and two human (31 participants) studies were included. In animals, two studies found increased BBB permeability to some smaller molecules after modified ECS, while the two other studies found marginally increased or unchanged permeability to albumin after treatment. In contrast, the human studies did not find increased BBB permeability to smaller molecules or albumin after ECT. CONCLUSION: Animal but not human studies support increased BBB permeability to some smaller molecules after electrically induced seizures. However, this conclusion is confined by the low number of studies and the lack of studies applying state-of-the-art methods. More studies using modern approaches to measuring of BBB permeability are warranted. FUNDING AND REGISTRATION: The study was founded by Mental Health Services in the Capital Region of Denmark (grant number 61151-05) and was registered on PROSPERO before data extraction was initiated (CRD42022331385).

Cerebral perfusion is related to antidepressant effect and cognitive side effects of Electroconvulsive Therapy.

BACKGROUND: The mechanisms underlying the antidepressant effect and cognitive side effects of Electroconvulsive Therapy (ECT) remain elusive. The measurement of cerebral perfusion provides an insight into brain physiology. OBJECTIVE: We investigated ECT-related perfusion changes in depressed patients and tested whether these changes correlate with clinical effects. METHODS: A sample of 22 in-patients was examined at three time points: 1) within two days before, 2) within one week after, and 3) six months after an ECT series. Cerebral perfusion was quantified using arterial spin labeling magnetic resonance imaging. The primary regions of interest were the bilateral dorsolateral prefrontal cortices (DL-PFC) and hippocampi. The depression severity was assessed by the six-item Hamilton Depression Rating Scale, and cognitive performance by the Screen for Cognitive Impairment in Psychiatry. A linear mixed model and partial correlation were used for statistical analyses. RESULTS: Following an ECT series, perfusion decreased in the right (-6.0%, p = .01) and left DL-PFC (-5.6%, p = .001). Perfusion increased in the left hippocampus (4.8%, p = .03), while on the right side the increase was insignificant (2.3%, p = .23). A larger perfusion reduction in the right DL-PFC correlated with a better antidepressant effect, and a larger perfusion increase in the right hippocampus with worse cognitive impairment. CONCLUSION: ECT-induced attenuation of prefrontal activity may be related to clinical improvement, whereas a hippocampal process triggered by the treatment is likely associated with cognitive side effects.

[Electroconvulsive therapy remains the most effective treatment for depression].

This review summarises the current knowledge of electroconvulsive therapy (ECT) which is still the most potent and fast-acting antidepressant intervention. The modern procedure is safe when general precautions are taken. Cognitive side effects are transient in most patients, and concerns about side effects should not prevent relevant use. Due to the prognostic benefits of rapid remission, ECT should, in relevant patients, be considered early in the treatment course. Patients should be offered maintenance pharmacotherapy, and, in high-risk cases, tapering of the acute ECT course or maintenance ECT, in order to reduce the risk of relapse.

Serum S100B protein after electroconvulsive therapy in patients with depression.

OBJECTIVE: S100B is a glial cell protein with bimodal function. In low concentrations, it exerts neurotrophic effects, but higher levels reflect neuronal distress. Recent research suggests that this molecule may be a biomarker of response to electroconvulsive therapy (ECT). We examined the effect of ECT on serum S100B and its utility as 1) a biomarker of a depressive state and 2) a predictor of ECT response. We also wanted to ensure that ECT does not cause a marked serum S100B elevation, indicating neural distress. METHODS: We measured serum S100B in 22 in-patients treated with ECT due to depression. Depression severity was assessed using 17-item Hamilton Rating Scale for Depression (HAMD-17). The data were collected before an ECT series, within 1 week after the series (post-ECT), and at a 6-month follow-up. Changes in serum S100B and clinical outcomes were tested using a linear mixed model. A relationship between serum S100B and the clinical outcomes was examined using Spearman's and partial correlation. RESULTS: Serum S100B did not change significantly immediately after an ECT series or 6 months later. The post-ECT serum S100B change was not associated with the clinical effect (rho = 0.14, n = 22, p = 0.54). The baseline serum S100B did not predict the clinical effect when controlling for age (r = 0.02, n = 22, df = 19, p = 0.92). CONCLUSION: The study neither supports serum S100B as a state marker of depression nor a predictor of ECT response. No evidence for ECT-related neural distress was found.

Treatment of difficult-to-treat depression - clinical guideline for selected interventions.

BACKGROUND: Difficult-to-treat-depression (DTD) is a clinical challenge. The interventions that are well-established for DTD are not suitable or effective for all the patients. Therefore, more treatment options are highly warranted. We formulated an evidence-based guideline concerning six interventions not well-established for DTD in Denmark. METHODS: Selected review questions were formulated according to the PICO principle with specific definitions of the patient population (P), the intervention (I), the comparison (C), and the outcomes of interest (O), and systematic literature searches were performed stepwise for each review question to identify relevant systematic reviews/meta-analyses, and randomized controlled trials. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the methodological quality of the included studies. Clinical recommendations were formulated based on the evidence, the risk-benefit ratio, and perceived patient preferences. RESULTS: We found sufficient evidence for a weak recommendation of repetitive transcranial magnetic stimulation (rTMS) and cognitive behavioural analysis system of psychotherapy (CBASP). The use of bright light therapy in DTD was not sufficiently supported by the evidence, but should be considered as good clinical practice. The interventions should be considered in addition to ongoing antidepressant treatment. We did not find sufficient evidence to recommend intravenous ketamine/esketamine, rumination-focused psychotherapy, or cognitive remediation to patients with DTD. CONCLUSION: The evidence supported two of the six reviewed interventions, however it was generally weak which emphasizes the need for more good quality studies. This guideline does not cover all treatment options and should be regarded as a supplement to relevant DTD-guidelines.

[Continuation electroconvulsive therapy for depression].

Electroconvulsive therapy (ECT) is a highly effective treatment for depression. Continuation ECT (C-ECT) is indicated for patients suffering from severe, recurrent or treatment-resistant forms of depression who have responded to an index course of ECT. This review aims at giving an updated set of guidelines for the use of C-ECT for patients suffering from depression. The guidelines will describe which patients are likely to benefit from the treatment, what to consider before administering the treatments and potential adverse effects.

Hippocampal volume and memory impairment after electroconvulsive therapy in patients with depression.

OBJECTIVE: Patients hesitate to consent to electroconvulsive therapy (ECT) because of the fear of memory impairment. The mechanisms underlying this impairment are unclear, but several observations suggest hippocampal alterations may be involved. We investigated whether ECT-induced change in hippocampal volume correlates with memory impairment. METHODS: Using a 3 T MRI scanner, we acquired brain images and assessed cognitive performance in 22 severely depressed patients at three time points: (1) before ECT series, (2) within one week after the series, and (3) at six-month follow-up. The hippocampus was segmented into subregions using FreeSurfer. The dentate gyri (DG) were the primary regions of interest (ROIs) and major hippocampal subregions secondary ROIs. Cognitive performance was assessed using the Screen for Cognitive Impairment in Psychiatry and verbal memory using the Verbal Learning subtest. The linear mixed model and the repeated-measures correlation were used for statistical analyses. RESULTS: ECT induced an increase in the right and left DG volume with co-occurring worsening in verbal memory, and these changes were within-patients negatively correlated (right DG, rrm  = -0.85, df = 18, p = 0.0000002; left DG, rrm  = -0.58, df = 18, p = 0.008). At a six-month follow-up, the volume of both DG decreased with a co-occurring improvement in verbal memory, and these changes were negatively correlated in the right DG (rrm  = -0.64, df = 15, p = 0.005). Volume increases in 14 secondary ROIs were also negatively correlated with memory impairment. CONCLUSION: ECT-related transient increases in the volume of major hippocampal subregions within-patients are associated with memory impairment. Hippocampal alterations following ECT should be the focus in searching for causes of the cognitive side effects.

Volume of hippocampal subregions and clinical improvement following electroconvulsive therapy in patients with depression.

It is thought that the hippocampal neurogenesis is an important mediator of the antidepressant effect of electroconvulsive therapy (ECT). However, most previous studies failed to demonstrate the relationship between the increase in the hippocampal volume and the antidepressant effect. We reinvestigated this relationship by looking at distinct hippocampal subregions and applying repeated measures correlation. Using a 3 Tesla MRI-scanner, we scanned 22 severely depressed in-patients at three time points: before the ECT series, after the series, and at six-month follow-up. The depression severity was assessed by the 17-item Hamilton Rating Scale for Depression (HAMD-17). The hippocampus was segmented into subregions using Freesurfer software. The dentate gyrus (DG) was the primary region of interest (ROI), due to the role of this region in neurogenesis. The other major hippocampal subregions were the secondary ROIs (n = 20). The general linear mixed model and the repeated measures correlation were used for statistical analyses. Immediately after the ECT series, a significant volume increase was present in the right DG (Cohen's d = 1.7) and the left DG (Cohen's d = 1.5), as well as 15 out of 20 secondary ROIs. The clinical improvement, i.e., the decrease in HAMD-17 score, was correlated to the increase in the right DG volume (rrm = -0.77, df = 20, p < .001), and the left DG volume (rrm = -0.75, df = 20, p < .001). Similar correlations were observed in 14 out of 20 secondary ROIs. Thus, ECT induces an increase not only in the volume of the DG, but also in the volume of other major hippocampal subregions. The volumetric increases may reflect a neurobiological process that may be related to the ECT's antidepressant effect. Further investigation of the relationship between hippocampal subregions and the antidepressant effect is warranted. A statistical approach taking the repeated measurements into account should be preferred in the analyses.

A case of Capgras syndrome and folie à duex in monozygotic twins.

Both Capgras syndrome and folie à deux (insanity of two) are rare and fascinating psychopathological syndromes. Their etiology and the nosological position remain unclear. We present a case of substance-induced Capgras syndrome emerging as folie à deux (insanity of two) in monozygotic twins with strongly overlapping life histories. Then, we discuss the etiology and the nosological position of these two conditions as well as their significance for understanding the concept of psychosis.

Depressed Patients Hospitalized in Southeast-Facing Rooms Are Discharged Earlier than Patients in Northwest-Facing Rooms.

BACKGROUND AND AIM: Improvement in patients admitted to inpatient wards with severe depression is slow, and such patients are often discharged with residual symptoms which put them at risk for relapse. New treatments that can speed up recovery are highly desired. This naturalistic follow-up study in a specialized affective disorders unit investigated the impact of daylight on the length of hospital stay and improvement of depression. METHODS: For a period of 1 year, we collected data on sociodemographics, length of stay, vitamin D, and depression severity for patients in an inpatient affective disorders unit. The ward is located with one facade that faces southeast (SE); the opposite one faces northwest (NW) and receives far less light and no direct sunlight during winter. RESULTS: SE-facing rooms received far more daylight than NW-facing rooms. The length of stay was significantly lower in the SE rooms, i.e., 29.2 (±26.8) versus 58.8 (±42.0) days in the NW rooms (p = 0.01). There was a statistically nonsignificant greater reduction of 52.2% in depression severity for the patients staying in the SE rooms compared to 42.2% in the NW rooms, which may nevertheless be clinically relevant. CONCLUSION: Due to the study design, no causality for the observed difference in length of stay can be given, but the results support findings in previous studies of the importance of architectural orientation providing natural daylight as a factor for improvement.