No Effect of Serum Electrolyte Levels on Electroconvulsive Therapy Seizure Quality Parameters.

INTRODUCTION: Seizure quality is considered to be associated with treatment outcomes of electroconvulsive therapy (ECT). A wide range of treatment parameters and patient characteristics are known to influence seizure quality. However, conflicting results exist for the role of serum electrolyte levels and seizure quality. METHODS: We retrospectively analyzed a total of 454 patients and a total of 2119 individual acute ECT sessions irrespective of diagnosis where a clinical evaluation of serum levels of sodium, potassium, and calcium took place routinely up to 2 days before the ECT session. To assess the impact of serum electrolyte levels on seizure quality parameters, we used mixed-effects linear regression analysis with Bonferroni correction for multiple testing. RESULTS: Serum sodium, potassium, and calcium levels were not associated with seizure quality markers after correcting the significance level for multiple testing. Younger age was consistently associated with higher postictal suppression, interhemispheric coherence, midictal amplitude, and peak heart rate. Lower dose was consistently associated with longer electroencephalogram and motor seizure duration. CONCLUSIONS: Our results suggest that there is no clinically relevant effect of serum electrolyte levels on seizure quality, at least within clinically commonly observed ranges of serum electrolyte concentrations.

Cerebral and Aortic Aneurysms in Electroconvulsive Therapy Patients: A Systematic Review and Results From 12 Years of Screening.

INTRODUCTION: Theoretically, the procedural risk of electroconvulsive therapy (ECT) could be increased in the presence of undetected aneurysms due to the hemodynamic changes associated with ECT. However, empirical evidence is limited to few individual case reports and case series. METHODS: We performed a systematic review of available evidence on ECT treatment in patients with intracranial aneurysms and untreated aortic aneurysms and we retrospectively analyzed data from 252 consecutive patients referred for ECT at the Department of Psychiatry, Psychotherapy and Psychosomatics of Siegen Hospital, Germany, who received magnetic resonance angiographies and abdominal sonographies as part of their routine pre-ECT workup. RESULTS: Of 252 patients referred for ECT, 5 (2.0%) were found to have an intracerebral aneurysm and 1 (0.4%) was found to have an abdominal aortic aneurysm. These cases are reported in detail together with 2 additional cases of aortic aneurysms from the Central Institute of Mental Health, Mannheim, Germany. Electroconvulsive therapy was performed without complications in all 8 cases. CONCLUSIONS: Aneurysms might occur in ECT patients at a similar rate as in the general population. The number of ECTs performed annually in mostly unscreened patients suggests that there might be a significant number of patients with undetected aneurysms in whom ECT is performed without reported complications.

Catatonia and ECT across the lifespan.

Electroconvulsive therapy (ECT) is a safe and effective treatment for catatonia with high response rates. Although empirical data suggest that tolerability and efficacy are at least as good as in adults, ECT treatment of children, adolescents, and geriatric patients seems to pose a specific challenge for many practitioners. This article intends to explore and discuss reasons hindering the use of ECT in these patient groups, give an overview on the use of ECT to treat catatonia and provide practical advice on ECT in children, adolescents, and geriatric patients for the treatment of catatonia. Classification of catatonia as a subform of schizophrenia and a diagnostic overlap with other common conditions in children, adolescents, and geriatric patients might lead to underdiagnosis of catatonia. Concerns about the mechanism of action and about a lack of controlled studies as well as general concerns about the use of ECT in children and adolescents might lead to underutilization of ECT. However, studies of ECT to treat catatonia in children, adolescents, and geriatric patients consistently show its safety and effectiveness. Administration of ECT needs to consider some specific characteristics of children, adolescents, and geriatric patients. In conclusion, ECT is a safe and highly effective treatment for catatonia across the lifespan. Existing evidence does not warrant restrictions of its use in certain age groups.

Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this causal depression network (CDN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis Principal Component Analysis (PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CDN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CDN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes (t = -2.35, p = 0.019). This evidence further supports that treatment interventions converge on a CDN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

Baseline levels of miR-223-3p correlate with the effectiveness of electroconvulsive therapy in patients with major depression.

There is a strong medical need to develop suitable biomarkers to improve the diagnosis and treatment of depression, particularly in predicting response to certain therapeutic approaches such as electroconvulsive therapy (ECT). MicroRNAs are small non-coding RNAs that have the ability to influence the transcriptome as well as proteostasis at the systems level. Here, we investigate the role of circulating microRNAs in depression and response prediction towards ECT. Of the 64 patients with treatment-resistant major depression (MDD) who received ECT treatment, 62.5% showed a response, defined as a reduction of ≥50% in the MADRS total score from baseline. We performed smallRNA sequencing in blood samples that were taken before the first ECT, after the first and the last ECT. The microRNAome was compared between responders and non-responders. Co-expression network analysis identified three significant microRNA modules with reverse correlation between ECT- responders and non-responders, that were amongst other biological processes linked to inflammation. A candidate microRNA, namely miR-223-3p was down-regulated in ECT responders when compared to non-responders at baseline. In line with data suggesting a role of miR-223-3p in inflammatory processes we observed higher expression levels of proinflammatory factors Il-6, Il-1b, Nlrp3 and Tnf-α in ECT responders at baseline when compared to non-responders. ROC analysis of confirmed the diagnostic power of miR-223-3p demarcating ECT-responders from non-responder subjects (AUC = 0.76, p = 0.0031). Our data suggest that miR-223-3p expression and related cytokine levels could serve as predictors of response to ECT in individuals with treatment-resistant depressive disorders.

Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this common causal network (CCN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis (Principal Component Analysis, PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CCN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CCN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes. This evidence further supports that treatment interventions converge on a CCN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

[Electroconvulsive Therapy in the New National Guideline Depression: Effectiveness, Evidence, and Grade of Recommendation]. / Elektrokonvulsionstherapie in der neuen NVL Depression: vom Unterschied zwischen Effektivität, Evidenz und Empfehlungsgraden.

In comparison to the previous version, the new national guideline 'Unipolar Depression' comprises more differentiated statements and recommendations regarding the use of electroconvulsive therapy (ECT). In principle, this is most welcome, as it clarifies the particular significance of ECT in different clinical situations. In parallel, this differentiation of recommendations depending on the presence of specific features of depressive disorders (e. g., psychotic symptoms, suicidality) led to different grades of recommendations for ECT. This may be correct and rational under the strict methodology of a guideline process, but nevertheless may appear confusing and contradictory in clinical practice. This article describes the relationships and putative discrepancies between the effectiveness of ECT, scientific evidence, and grading of guideline recommendations with comments on these for clinical practice from experts' point of view.

Age-Dependent Dose Increase During an Acute Electroconvulsive Therapy Series.

INTRODUCTION: Electroconvulsive therapy (ECT) dose is highly relevant for ECT efficacy as well as adverse effects. It is often based on seizure threshold (ST). Studies have shown that ST increases over the course of an ECT series. Clinical observation suggests that this rise might be more pronounced in geriatric patients. METHODS: Retrospectively, we analyzed ECT dose during the first 20 ECT treatments in 472 patients undergoing ECT. Dose adjustments were assessed in relation to patients' age using generalized least squares regression analysis. Response was defined as Clinical Global Impression Improvement Scale < 4. RESULTS: Dose increased in all patients during the course of the ECT series (mean initial dose, 64.97 ± 68.04 mC; at 10th ECT, 385.46 ± 211.28 mC). Dose was significantly correlated with ECT treatment number, electrode placement, and the interaction between age and ECT treatment number. In other words, dose increase was significantly positively correlated with increasing age, that is dose increased more in older compared with younger patients during the course of an ECT series ( z = 9.47, P < 0.001). Response was not correlated with age-dependent dose increase; however, the length of the ECT series in responders was negatively associated with the dose increase from the first to the seventh ECT session ( F = 5.28, P = 0.0228). CONCLUSIONS: Our results indicate that ST increases more rapidly during the course of an ECT series in older compared with younger patients. To ensure high efficacy throughout the course of treatment, attention should be paid to decreasing seizure quality, especially in older patients, and dose should be adjusted accordingly.

[Current aspects on the antipsychotic treatment of older people with schizophrenia spectrum disorders]. / Aktuelle Aspekte zur antipsychotischen Behandlung älterer Menschen mit Erkrankungen des schizophrenen Spektrums.

BACKGROUND: From a geriatric perspective, the use of antipsychotic drugs (AP) is associated with significant risks in addition to their known effects. These include unfavorable interactions with geriatric syndromes, such as immobility and risk of falling, and potentially increased mortality, at least in certain patient groups. With reference to this the current state of knowledge on treatment with AP in older people with schizophrenia spectrum disorders is summarized with a focus on the typical multimorbidity of geriatric patients. METHODS: Narrative review with special consideration of guidelines and consensus papers from German speaking countries and a PubMed-supported literature search for current systematic reviews and meta-analyses. RESULTS: Antipsychotic agents are an essential part of a comprehensive treatment concept for schizophrenia with well-documented evidence. In geriatric patients adaptations under gerontopharmacological aspects are necessary. A sufficient data basis for evidence-based recommendations for the treatment of multimorbid and frail geriatric patients does not exist. CONCLUSION: An effective and as safe as possible treatment with AP requires a careful risk-benefit assessment, combined with an individual adaptation regarding the substance applied, dose and treatment duration in an interdisciplinary/multiprofessional context.

Electroconvulsive Stimulation in Rats Induces Alterations in the Hippocampal miRNome: Translational Implications for Depression.

MicroRNAs (miRNAs) may contribute to the development of depression and its treatment. Here, we used the hypothesis-neutral approach of next-generation sequencing (NGS) to gain comprehensive understanding of the effects of a course of electroconvulsive stimulation (ECS), the animal model equivalent of electroconvulsive therapy (ECT), on rat hippocampal miRNAs. Significant differential expression (p < 0.001) of six hippocampal miRNAs was noted following NGS, after correcting for multiple comparisons. Three of these miRNAs were upregulated (miR-132, miR-212, miR-331) and three downregulated (miR-204, miR-483, miR-301a). qRT-PCR confirmed significant changes in four of the six miRNAs (miR-132, miR-212, miR-204, miR-483). miR-483 was also significantly reduced in frontal cortex, though no other significant alterations were noted in frontal cortex, cerebellum, or whole blood. Assessing the translatability of the results, miR-132 and miR-483 were significantly reduced in whole blood samples from medicated patients with depression (n = 50) compared to healthy controls (n = 45), though ECT had no impact on miRNA levels. Notably, pre-ECT miR-204 levels moderately positively correlated with depression severity at baseline and moderately negatively correlated with mood score reduction post-ECT. miRNAs were also examined in cerebrospinal fluid and serum from a separate cohort of patients (n = 8) treated with ECT; no significant changes were noted post-treatment. However, there was a large positive correlation between changes in miR-212 and mood score post-ECT in serum. Though replication studies using larger sample sizes are required, alterations in miRNA expression may be informative about the mechanism of action of ECS/ECT and in turn might give insight into the neurobiology of depression.

[Acute catatonia]. / Akute katatone Zustände.

BACKGROUND: Catatonia is an underdiagnosed psychomotor syndrome that can occur in the context of various mental and somatic diseases. Malignant catatonia is particularly relevant in the context of intensive medical care. Clear recommendations in guidelines are missing. OBJECTIVE: To present the current state of the diagnosis and treatment of catatonia, especially malignant catatonia. MATERIAL AND METHODS: The literature was evaluated with respect to acute catatonic conditions, with a special focus on the differential diagnosis, relevance to intensive medical care and treatment of catatonia. RESULTS: In psychiatric inpatients, catatonic syndromes are relatively frequent with a prevalence between 9% and 17%, and in neurological patients somewhat less frequent with a prevalence of 3.3%. There is a clear recommendation for pharmacological treatment with lorazepam. Additional electroconvulsive therapy (ECT) should be considered as early as possible, especially in cases not responding to benzodiazepines. Response rates to ECT have been shown to be 80-100%. In malignant catatonia, ECT should be performed immediately as an emergency indication. CONCLUSION: Several factors lead to the underdiagnosis of catatonia. It is problematic that even life-threatening malignant catatonia is often not recognized as such, although there is a mortality of about 50% if untreated. The best treatment outcome is achieved with a combination of benzodiazepines and ECT. The treatment of severe malignant catatonia represents an emergency indication for ECT.

TRIAC Treatment Improves Impaired Brain Network Function and White Matter Loss in Thyroid Hormone Transporter Mct8/Oatp1c1 Deficient Mice.

Dysfunctions of the thyroid hormone (TH) transporting monocarboxylate transporter MCT8 lead to a complex X-linked syndrome with abnormal serum TH concentrations and prominent neuropsychiatric symptoms (Allan-Herndon-Dudley syndrome, AHDS). The key features of AHDS are replicated in double knockout mice lacking MCT8 and organic anion transporting protein OATP1C1 (Mct8/Oatp1c1 DKO). In this study, we characterize impairments of brain structure and function in Mct8/Oatp1c1 DKO mice using multimodal magnetic resonance imaging (MRI) and assess the potential of the TH analogue 3,3',5-triiodothyroacetic acid (TRIAC) to rescue this phenotype. Structural and functional MRI were performed in 11-weeks-old male Mct8/Oatp1c1 DKO mice (N = 10), wild type controls (N = 7) and Mct8/Oatp1c1 DKO mice (N = 13) that were injected with TRIAC (400 ng/g bw s.c.) daily during the first three postnatal weeks. Grey and white matter volume were broadly reduced in Mct8/Oatp1c1 DKO mice. TRIAC treatment could significantly improve white matter thinning but did not affect grey matter loss. Network-based statistic showed a wide-spread increase of functional connectivity, while graph analysis revealed an impairment of small-worldness and whole-brain segregation in Mct8/Oatp1c1 DKO mice. Both functional deficits could be substantially ameliorated by TRIAC treatment. Our study demonstrates prominent structural and functional brain alterations in Mct8/Oatp1c1 DKO mice that may underlie the psychomotor deficiencies in AHDS. Additionally, we provide preclinical evidence that early-life TRIAC treatment improves white matter loss and brain network dysfunctions associated with TH transporter deficiency.

Striatal hub of dynamic and stabilized prediction coding in forebrain networks for olfactory reinforcement learning.

Identifying the circuits responsible for cognition and understanding their embedded computations is a challenge for neuroscience. We establish here a hierarchical cross-scale approach, from behavioral modeling and fMRI in task-performing mice to cellular recordings, in order to disentangle local network contributions to olfactory reinforcement learning. At mesoscale, fMRI identifies a functional olfactory-striatal network interacting dynamically with higher-order cortices. While primary olfactory cortices respectively contribute only some value components, the downstream olfactory tubercle of the ventral striatum expresses comprehensively reward prediction, its dynamic updating, and prediction error components. In the tubercle, recordings reveal two underlying neuronal populations with non-redundant reward prediction coding schemes. One population collectively produces stabilized predictions as distributed activity across neurons; in the other, neurons encode value individually and dynamically integrate the recent history of uncertain outcomes. These findings validate a cross-scale approach to mechanistic investigations of higher cognitive functions in rodents.

Electroconvulsive Therapy in Children and Adolescents in Germany-A Case Series From 3 University Hospitals.

OBJECTIVE: Electroconvulsive therapy (ECT) is a well-established, safe, and efficacious treatment for severe psychiatric disorders. In children and adolescents, it is used much less frequently than in adults, likely because of a lack of knowledge. METHODS: We retrospectively analyzed all patients aged 12 to 17 years who completed a course of ECT at 3 psychiatric university hospitals in Germany between 2010 and 2020. Clinical Global Impression Severity (CGI-S) scores were assessed based on electronic medical records. Changes in CGI-S scores were assessed using a paired samples t test. Predictors for response and remission were assessed using binomial logistic regression. RESULTS: We included 32 patients. The CGI-S scores improved significantly from before to after ECT treatment (6.9 vs 3.9, t = 10.0, P < 0.01). A total of 40.6% of patients responded (CGI ≤ 3) and 21.9% remitted (CGI ≤ 2). The number of ineffective medication trials in the 6 months before ECT treatment was significantly associated with response (odds ratio, 0.54; P = 0.028) and remission (odds ratio, 0.31; P = 0.048). Five patients reported subjective cognitive adverse effects, 2 patients exhibited a prolonged seizure, 1 patient reported headaches, and 1 patient experienced a mild allergic reaction after anesthesia with etomidate. A total of 65.6% of patients experienced no adverse effects at all. CONCLUSIONS: This retrospective analysis found ECT to be effective and safe in children and adolescents irrespective of their main diagnosis. The reported data point to the importance of an early use of ECT for severe psychiatric diseases in child and adolescent psychiatry.