Intestinal metabolites predict treatment resistance of patients with depression and anxiety.

BACKGROUND: The impact of the gut microbiota on neuropsychiatric disorders has gained much attention in recent years; however, comprehensive data on the relationship between the gut microbiome and its metabolites and resistance to treatment for depression and anxiety is lacking. Here, we investigated intestinal metabolites in patients with depression and anxiety disorders, and their possible roles in treatment resistance. RESULTS: We analyzed fecal metabolites and microbiomes in 34 participants with depression and anxiety disorders. Fecal samples were obtained three times for each participant during the treatment. Propensity score matching led us to analyze data from nine treatment responders and nine non-responders, and the results were validated in the residual sample sets. Using elastic net regression analysis, we identified several metabolites, including N-ε-acetyllysine; baseline levels of the former were low in responders (AUC = 0.86; 95% confidence interval, 0.69-1). In addition, fecal levels of N-ε-acetyllysine were negatively associated with the abundance of Odoribacter. N-ε-acetyllysine levels increased as symptoms improved with treatment. CONCLUSION: Fecal N-ε-acetyllysine levels before treatment may be a predictive biomarker of treatment-refractory depression and anxiety. Odoribacter may play a role in the homeostasis of intestinal L-lysine levels. More attention should be paid to the importance of L-lysine metabolism in those with depression and anxiety.

Neurobiological mechanisms of electroconvulsive therapy for depression: Insights into hippocampal volumetric increases from clinical and preclinical studies.

Depression is a highly prevalent and disabling psychiatric disorder. The hippocampus, which plays a central role in mood regulation and memory, has received considerable attention in depression research. Electroconvulsive therapy (ECT) is the most effective treatment for severe pharmacotherapy-resistant depression. Although the working mechanism of ECT remains unclear, recent magnetic resonance imaging (MRI) studies have consistently reported increased hippocampal volumes following ECT. The clinical implications of these volumetric increases and the specific cellular and molecular significance are not yet fully understood. This narrative review brings together evidence from animal models and human studies to provide a detailed examination of hippocampal volumetric increases following ECT. In particular, our preclinical MRI research using a mouse model is consistent with human findings, demonstrating a marked increase in hippocampal volume following ECT. Notable changes were observed in the ventral hippocampal CA1 region, including dendritic growth and increased synaptic density at excitatory synapses. Interestingly, inhibition of neurogenesis did not affect the ECT-related hippocampal volumetric increases detected on MRI. However, it remains unclear whether these histological and volumetric changes would be correlated with the clinical effect of ECT. Hence, future research on the relationships between cellular changes, ECT-related brain volumetric changes, and antidepressant effect could benefit from a bidirectional translational approach that integrates human and animal models. Such translational research may provide important insights into the mechanisms and potential biomarkers associated with ECT-induced hippocampal volumetric changes, thereby advancing our understanding of ECT for the treatment of depression.

Neurogenesis-independent mechanisms of MRI-detectable hippocampal volume increase following electroconvulsive stimulation.

Electroconvulsive therapy (ECT) is one of the most effective psychiatric treatments but the underlying mechanisms are still unclear. In vivo human magnetic resonance imaging (MRI) studies have consistently reported ECT-induced transient hippocampal volume increases, and an animal model of ECT (electroconvulsive stimulation: ECS) was shown to increase neurogenesis. However, a causal relationship between neurogenesis and MRI-detectable hippocampal volume increases following ECT has not been verified. In this study, mice were randomly allocated into four groups, each undergoing a different number of ECS sessions (e.g., 0, 3, 6, 9). T2-weighted images were acquired using 11.7-tesla MRI. A whole brain voxel-based morphometry analysis was conducted to identify any ECS-induced brain volume changes. Additionally, a histological examination with super-resolution microscopy was conducted to investigate microstructural changes in the brain regions that showed volume changes following ECS. Furthermore, parallel experiments were performed on X-ray-irradiated mice to investigate the causal relationship between neurogenesis and ECS-related volume changes. As a result, we revealed for the first time that ECS induced MRI-detectable, dose-dependent hippocampal volume increase in mice. Furthermore, increased hippocampal volumes following ECS were seen even in mice lacking neurogenesis, suggesting that neurogenesis is not required for the increase. The comprehensive histological analyses identified an increase in excitatory synaptic density in the ventral CA1 as the major contributor to the observed hippocampal volume increase following ECS. Our findings demonstrate that modification of synaptic structures rather than neurogenesis may be the underlying biological mechanism of ECT/ECS-induced hippocampal volume increase.

A voxel- and source-based morphometry analysis of grey matter volume differences in very-late-onset schizophrenia-like psychosis.

BACKGROUND: Very-late-onset schizophrenia-like psychosis (VLOSLP) is associated with significant burden. Its clinical importance is increasing as the global population of older adults rises, yet owing to limited research in this population, the neurobiological underpinnings of VLOSP remain insufficiently clarified. Here we address this knowledge gap using novel morphometry techniques to investigate grey matter volume (GMV) differences between VLOSLP and healthy older adults, and their correlations with neuropsychological scores. METHODS: In this cross-sectional study, we investigated whole-brain GMV differences between 35 individuals with VLOSLP (mean age 76.7, 26 female) and 36 healthy controls (mean age 75.7, 27 female) using whole-brain voxel-based morphometry (VBM) and supplementary source-based morphometry (SBM) on high resolution 3D T1-weighted MRI images. Additionally, we investigated relationships between GMV differences and cognitive function assessed with an extensive neuropsychological battery. RESULTS: VBM showed lower GMV in the thalamus, left inferior frontal gyrus and left insula in patients with VLOSLP compared to healthy controls. SBM revealed lower thalamo-temporal GMV in patients with VLOSLP. Processing speed, selective attention, mental flexibility, working memory, verbal memory, semantic fluency and confrontation naming were impaired in patients with VLOSLP. Correlations between thalamic volumes and memory function were significant within the group of individuals with VLOSLP, whereas no significant associations remained in the healthy controls. CONCLUSIONS: Lower GMV in the thalamus and fronto-temporal regions may be part of the underlying neurobiology of VLOSLP, with lower thalamic GMV contributing to memory impairment in the disorder.

Live two-way video versus face-to-face treatment for depression, anxiety, and obsessive-compulsive disorder: A 24-week randomized controlled trial.

AIM: Live two-way video, easily accessible from home via smartphones and other devices, is becoming a new way of providing psychiatric treatment. However, lack of evidence for real-world clinical setting effectiveness hampers its approval by medical insurance in some countries. Here, we conducted the first large-scale pragmatic, randomized controlled trial to determine the effectiveness of long-term treatment for multiple psychiatric disorders via two-way video using smartphones and other devices, which are currently the primary means of telecommunication. METHODS: This randomized controlled trial compared two-way video versus face-to-face treatment for depressive disorder, anxiety disorder, and obsessive-compulsive disorder in the subacute/maintenance phase during a 24-week period. Adult patients with the above-mentioned disorders were allocated to either a two-way video group (≥50% video sessions) or a face-to-face group (100% in-person sessions) and received standard treatment covered by public medical insurance. The primary outcome was the 36-Item Short-Form Health Survey Mental Component Summary (SF-36 MCS) score. Secondary outcomes included all-cause discontinuation, working alliance, adverse events, and the severity rating scales for each disorder. RESULTS: A total of 199 patients participated in this study. After 24 weeks of treatment, two-way video treatment was found to be noninferior to face-to-face treatment regarding SF-36 MCS score (48.50 vs 46.68, respectively; p < 0.001). There were no significant differences between the groups regarding most secondary end points, including all-cause discontinuation, treatment efficacy, and satisfaction. CONCLUSION: Two-way video treatment using smartphones and other devices, was noninferior to face-to-face treatment in real-world clinical settings. Modern telemedicine, easily accessible from home, can be used as a form of health care.

Ketamine or ECT? What Have We Learned From the KetECT and ELEKT-D Trials?

1. Two recent clinical trials, KetECT and ELEKT-D, compared the effectiveness of ketamine and electroconvulsive therapy (ECT) for major depressive disorder. Notably, these trials reported marked differences in ECT's clinical outcomes of, with remission rates of 63% for KetECT and a strikingly lower rate of 22% for ELEKT-D, while the remission rates for ketamine were 46% and 38%, respectively. Considering that the primary objective of both trials was to compare the standard treatment (ECT) with an experimental intervention (ketamine), it is crucial to highlight the pronounced disparities in ECT's clinical outcomes. This article offers a comprehensive comparison of these trials while also exploring how patient characteristics, treatment protocols, and study designs may contribute to such pronounced outcome discrepancies. These differences highlight the heterogeneous nature of depression and underscore the need for personalized treatments. These studies also provide valuable insights into identifying the most suitable candidates for ketamine and ECT.

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.

Calcified deep somatic soft tissue leiomyoma of the leg: A case report.

Deep somatic soft tissue leiomyoma is a rare benign smooth muscle tumor, with around 60 cases reported thus far in the literature. Herein, we report a huge leiomyoma in deep somatic soft tissue with massive calcification in the peroneus longus muscle. A 29-year-old male patient presented with a hard, spindle-shaped, 15-cm-diameter mass of the left lower leg. Plain radiography showed marked calcification within the lesion, and magnetic resonance imaging revealed a well-circumscribed lesion with strong contrast enhancement within the peroneus longus. A core needle biopsy was performed to rule out a soft tissue sarcoma, and deep somatic soft tissue leiomyoma was preoperatively diagnosed. A marginal excision was performed, and the patient recovered without event and has been recurrence-free for 16 months. As far as we know, the present soft tissue leiomyoma was one of the largest to be documented, the previously reported cases being up to 14 cm in maximum diameter. Leiomyomas of deep somatic soft tissue should be included in the differential diagnosis of a huge, deep-seated tumor with marked calcification as well as sarcomas, especially in younger patients.

Telepsychiatry versus face-to-face treatment: systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The COVID-19 pandemic has transformed healthcare significantly and telepsychiatry is now the primary means of treatment in some countries. AIMS: To compare the efficacy of telepsychiatry and face-to-face treatment. METHOD: A comprehensive meta-analysis comparing telepsychiatry with face-to-face treatment for psychiatric disorders. The primary outcome was the mean change in the standard symptom scale scores used for each psychiatric disorder. Secondary outcomes included all meta-analysable outcomes, such as all-cause discontinuation and safety/tolerability. RESULTS: We identified 32 studies (n = 3592 participants) across 11 mental illnesses. Disease-specific analyses showed that telepsychiatry was superior to face-to-face treatment regarding symptom improvement for depressive disorders (k = 6 studies, n = 561; standardised mean difference s.m.d. = -0.325, 95% CI -0.640 to -0.011, P = 0.043), whereas face-to-face treatment was superior to telepsychiatry for eating disorder (k = 1, n = 128; s.m.d. = 0.368, 95% CI 0.018-0.717, P = 0.039). No significant difference was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined (k = 26, n = 2290; P = 0.248). Telepsychiatry had significantly fewer all-cause discontinuations than face-to-face treatment for mild cognitive impairment (k = 1, n = 61; risk ratio RR = 0.552, 95% CI 0.312-0.975, P = 0.040), whereas the opposite was seen for substance misuse (k = 1, n = 85; RR = 37.41, 95% CI 2.356-594.1, P = 0.010). No significant difference regarding all-cause discontinuation was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined (k = 27, n = 3341; P = 0.564). CONCLUSIONS: Telepsychiatry achieved a symptom improvement effect for various psychiatric disorders similar to that of face-to-face treatment. However, some superiorities/inferiorities were seen across a few specific psychiatric disorders, suggesting that its efficacy may vary according to disease type.

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.

Clinical characteristics and potential association to Parkinson's disease and dementia with Lewy bodies in patients with major depressive disorder who received maintenance electroconvulsive therapy: a retrospective chart review study.

BACKGROUND: Maintaining remission after electroconvulsive therapy (ECT) is clinically relevant in patients with depression, and maintenance ECT has been introduced in patients who fail to maintain remission after ECT. However, the clinical characteristics and biological background of patients who receive maintenance ECT are poorly understood. Thus, this study aimed to examine the clinical background of patients who underwent maintenance ECT. METHODS: Patients with major depressive disorder who underwent ECT followed by maintenance ECT (mECT group) and those who did not (acute ECT [aECT] group) were included. Clinical characteristics, including the results of neuroimaging examinations for Parkinson's disease (PD) and dementia with Levy body (DLB) such as myocardial 123I-metaiodobenzylguanidine (MIBG) scintigraphy and dopamine transporter imaging single-photon emission computerized tomography (DaT-SPECT), were compared between the groups. RESULTS: In total, 13 and 146 patients were included in the mECT and aECT groups, respectively. Compared to the aECT group, the mECT group showed a significantly higher prevalence of melancholic features (92.3% vs. 27.4%, p < 0.001) and catatonic features (46.2% vs. 9.6%, p = 0.002). Overall, 8 of the 13 patients in the mECT group and 22 of the 146 patients in the aECT group underwent neuroimaging examinations for PD/DLB. The rate of patients examined is significantly higher in the mECT group than in the aECT group (61.5% vs. 11.2%, p < 0.001). Among the groups examined, 7/8 patients in the mECT group and 16/22 patients in the aECT group showed relevant neuroimaging findings for PD/DLB; the positive rate was not significantly different between the two groups (87.5% vs. 72.7%, p = 0.638). CONCLUSIONS: Patients who receive acute and maintenance ECT may have underlying neurodegenerative diseases, including PD/DLB. Investigating the neurobiology of patients who receive maintenance ECT is important for developing appropriate treatments for depression.

Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults.

BACKGROUND: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology "P-score". METHODS: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. RESULTS: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex. CONCLUSIONS: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.

Language patterns in Japanese patients with Alzheimer disease: A machine learning approach.

AIM: The authors applied natural language processing and machine learning to explore the disease-related language patterns that warrant objective measures for assessing language ability in Japanese patients with Alzheimer disease (AD), while most previous studies have used large publicly available data sets in Euro-American languages. METHODS: The authors obtained 276 speech samples from 42 patients with AD and 52 healthy controls, aged 50 years or older. A natural language processing library for Python was used, spaCy, with an add-on library, GiNZA, which is a Japanese parser based on Universal Dependencies designed to facilitate multilingual parser development. The authors used eXtreme Gradient Boosting for our classification algorithm. Each unit of part-of-speech and dependency was tagged and counted to create features such as tag-frequency and tag-to-tag transition-frequency. Each feature's importance was computed during the 100-fold repeated random subsampling validation and averaged. RESULTS: The model resulted in an accuracy of 0.84 (SD = 0.06), and an area under the curve of 0.90 (SD = 0.03). Among the features that were important for such predictions, seven of the top 10 features were related to part-of-speech, while the remaining three were related to dependency. A box plot analysis demonstrated that the appearance rates of content words-related features were lower among the patients, whereas those with stagnation-related features were higher. CONCLUSION: The current study demonstrated a promising level of accuracy for predicting AD and found the language patterns corresponding to the type of lexical-semantic decline known as 'empty speech', which is regarded as a characteristic of AD.

What Can We Tell About the Effect of Electroconvulsive Therapy on the Human Hippocampus?

Electroconvulsive therapy (ECT) is the most effective antidepressant treatment, although its mechanisms of action remain unclear. Since 2010, several structural magnetic resonance imaging studies based on a neuroplastic hypothesis have consistently reported increases in the hippocampal volume following ECT. Moreover, volume increases in the human dentate gyrus, where neurogenesis occurs, have also been reported. These results are in line with the preclinical findings of ECT-induced neuroplastic changes, including neurogenesis, gliogenesis, synaptogenesis, and angiogenesis, in rodents and nonhuman primates. Despite this robust evidence of an effect of ECT on hippocampal plasticity, the clinical relevance of these human hippocampal changes continues to be questioned. This narrative review summarizes recent findings regarding ECT-induced hippocampal volume changes. Furthermore, this review also discusses methodological considerations and future directions in this field.

Understanding psychiatric illness through natural language processing (UNDERPIN): Rationale, design, and methodology.

Introduction: Psychiatric disorders are diagnosed through observations of psychiatrists according to diagnostic criteria such as the DSM-5. Such observations, however, are mainly based on each psychiatrist's level of experience and often lack objectivity, potentially leading to disagreements among psychiatrists. In contrast, specific linguistic features can be observed in some psychiatric disorders, such as a loosening of associations in schizophrenia. Some studies explored biomarkers, but biomarkers have yet to be used in clinical practice. Aim: The purposes of this study are to create a large dataset of Japanese speech data labeled with detailed information on psychiatric disorders and neurocognitive disorders to quantify the linguistic features of those disorders using natural language processing and, finally, to develop objective and easy-to-use biomarkers for diagnosing and assessing the severity of them. Methods: This study will have a multi-center prospective design. The DSM-5 or ICD-11 criteria for major depressive disorder, bipolar disorder, schizophrenia, and anxiety disorder and for major and minor neurocognitive disorders will be regarded as the inclusion criteria for the psychiatric disorder samples. For the healthy subjects, the absence of a history of psychiatric disorders will be confirmed using the Mini-International Neuropsychiatric Interview (M.I.N.I.). The absence of current cognitive decline will be confirmed using the Mini-Mental State Examination (MMSE). A psychiatrist or psychologist will conduct 30-to-60-min interviews with each participant; these interviews will include free conversation, picture-description task, and story-telling task, all of which will be recorded using a microphone headset. In addition, the severity of disorders will be assessed using clinical rating scales. Data will be collected from each participant at least twice during the study period and up to a maximum of five times at an interval of at least one month. Discussion: This study is unique in its large sample size and the novelty of its method, and has potential for applications in many fields. We have some challenges regarding inter-rater reliability and the linguistic peculiarities of Japanese. As of September 2022, we have collected a total of >1000 records from >400 participants. To the best of our knowledge, this data sample is one of the largest in this field. Clinical Trial Registration: Identifier: UMIN000032141.

Intergenerational concordance of brain structure between depressed mothers and their never-depressed daughters.

AIM: Parents have significant genetic and environmental influences, which are known as intergenerational effects, on the cognition, behavior, and brain of their offspring. These intergenerational effects are observed in patients with mood disorders, with a particularly strong association of depression between mothers and daughters. The main purpose of our study was to investigate female-specific intergenerational transmission patterns in the human brain among patients with depression and their never-depressed offspring. METHODS: We recruited 78 participants from 34 families, which included remitted parents with a history of depression and their never-depressed biological offspring. We used source-based and surface-based morphometry analyses of magnetic resonance imaging data to examine the degree of associations in brain structure between four types of parent-offspring dyads (i.e. mother-daughter, mother-son, father-daughter, and father-son). RESULTS: Using independent component analysis, we found a significant positive correlation of gray matter structure between exclusively the mother-daughter dyads within brain regions located in the default mode and central executive networks, such as the bilateral anterior cingulate cortex, posterior cingulate cortex, precuneus, middle frontal gyrus, middle temporal gyrus, superior parietal lobule, and left angular gyrus. These similar observations were not identified in other three parent-offspring dyads. CONCLUSIONS: The current study provides biological evidence for greater vulnerability of daughters, but not sons, in developing depression whose mothers have a history of depression. Our findings extend our knowledge on the pathophysiology of major psychiatric conditions that show sex biases and may contribute to the development of novel interventions targeting high-risk individuals.

Effectiveness of electroconvulsive therapy in patients lacking decision making capacity: A systematic review and meta-analysis.

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.