Search

Background: Traumatic physical injuries can lead to psychological distress and increased risk of psychiatric disorders, often reflected in dysregulated autonomic responses measurable through heart rate variability (HRV). Slow-paced breathing has shown potential in enhancing HRV, but its effectiveness in injured survivors remains unexplored. This study investigates the effect of slow-paced breathing on HRV among injured survivors compared to non-injured individuals and explores the influence of psychological distress and spontaneous respiratory rate on this effect., Methods: The study involved 120 injured individuals and 112 non-injured controls with similar age, sex, and education levels. Injured participants with minor-to-moderate injuries from traffic crashes were assessed 3-6 weeks post-injury. Psychological distress was defined as the risk of post-traumatic stress disorder and/or major depression. Physiological assessment (HRV) included a 2-min resting baseline and a 2-min slow-paced breathing session (6 breaths/min). Repeated measure MANCOVA assessed HRV changes between groups, while correlation analyses examined the relationship between these changes., Results: Injured survivors had significantly lower HRV than non-injured controls. Both groups showed notable HRV increases during slow-paced breathing. Among injured individuals, those with higher psychological distress exhibited greater HRV increases, particularly in parasympathetic activity and overall variability. Higher spontaneous respiratory rates were associated with greater HRV changes, especially in non-injured individuals., Conclusion: Slow-paced breathing demonstrated significant physiological effects for injured survivors, particularly those with higher psychological distress, and supports its potential in improving stress regulation post-injury. Future research should examine the long-term effects of sustained breathing practice and clinical applicability in reducing psychological distress and disability post-injury., Competing Interests: Declaration of competing interest The author(s) declare none., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Major depressive disorder (MDD) is a highly prevalent psychiatric condition whose pathophysiology has been linked to neuroinflammatory processes involving the NLRP3 inflammasome. To address this point, the study investigated the association of the NLRP3 rs10754558 polymorphism with MDD diagnosis in a young adults population based study and the effectiveness of brief psychotherapies in a randomized clinical trial. A cross-sectional, population-based study was conducted with 1100 individuals aged 18-35 years, including 615 controls and 485 patients with MDD. Diagnosis was determined using the Mini International Neuropsychiatric Interview (M.I.N.I.) based on DSM-IV criteria. Our clinical trial included 227 participants with MDD aged 18-60 years from a randomized clinical trial evaluating the effectiveness of two brief psychotherapies for MDD. Depressive and anxiety symptoms were assessed at baseline, post-treatment (16-18 weeks), and 6-month follow-up using the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory (BAI). Statistical analyses included logistic regression and generalized estimating equation (GEE) model adjusted for demographic and clinical variables. The results showed no significant association between rs10754558 genotypes and MDD diagnosis. However, when evaluating the efficacy of brief psychotherapies, the GG genotype was associated with poorer treatment outcomes for both depressive and anxiety symptoms compared to the GC/CC genotypes (p < 0.05). Longitudinal analysis revealed significant differences over time, with GG individuals demonstrating less symptom improvement (BDI-II: baseline 36.61 to follow-up 21.75; BAI: baseline 26.32 to follow-up 19.55) compared to GC/CC genotypes (BDI-II: baseline 32.05 to follow-up 20.29; BAI: baseline 22.05 to follow-up 17.96). These findings suggest that the GG genotype, previously characterized as a gain-of-function variant, may contribute to genetic heterogeneity influencing psychotherapy outcomes. This highlights the potential for genetic markers, such as rs10754558, to inform personalized psychiatric treatments and improve therapeutic strategies., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Objective: This study scrutinizes the meaning of deterioration in psychotherapy beyond the widely used statistical definition of reliable symptom increase pre-to-post treatment., Method: An explanatory sequential mixed-methods multiple case study was conducted, combining quantitative pre-post outcome evaluation of self-reported depression symptoms and qualitative analysis of patients' interviews. In a Randomized Controlled Study on the treatment of Major Depression, three patients showing reliable increase in symptom severity on the BDI-II pre-to-post therapy were selected. An interpretative phenomenological analysis (IPA) was performed on individual interviews conducted pre-, peri- and post-treatment., Results: Cross-case outcome experiences were: (1) uncontrollable complaints; (2) remaining questions and uninternalized insights and (3) persisting interpersonal difficulties. Within-case idiosyncratic differences revealed that the statistical classification of "deterioration" not necessarily corresponds to a "deteriorated experience," nor univocally indicates unwanted therapy effects. Our findings point at the influences of the patient's (lack of) agency in the process, a discrepancy between patients' expectations and the therapy offer, the therapeutic relationship, interpersonal difficulties, and contextual influences., Conclusion: The meaning of symptomatic deterioration should be interpreted within a patient's idiosyncratic context. The multi-faceted nature of deterioration requires further research to rely on multiple perspectives and mixed methods.

In response to restrictions on electroconvulsive therapy (ECT) access during COVID-19, we designed a trial to assess the clinical outcomes service impacts, employing an extended course of accelerated intermittent theta burst stimulation (aiTBS), in patients with moderate to severe depression in need of ECT. This open label clinical trial was comprised of 3 phases: (i) an acute phase, where iTBS treatments were administered 8 times daily, for up to 10 days; (ii) a tapering phase of 2 treatment days per week for 2 weeks, followed by 1 treatment day per week for 2 weeks; and (iii) a symptom-based relapse prevention phase, whereby treatments were scheduled based on symptom re-emergence, for up to 6 months. Of the 155 patients who completed the acute phase of the study, the remission rate was 16.1%. The mean reduction from baseline on the HRSD-24 was 29.4% (p < 0.001) and the response rate was 25.2%. Of the 110 patients who completed the tapering phase, the mean reduction from baseline was 42.6% (p < 0.001) and response and remission rates were 49.6% and 34.8%, respectively. Of the 61 patients who were eligible for the relapse prevention phase, 43 completed, with a mean reduction from baseline of 60.1% (p < 0.001); 7 patients relapsed during this phase. This study demonstrated that an extended aiTBS protocol safely led to meaningful clinical outcomes in patients with severe depression, who otherwise would have received ECT, and thus reduced pressure on ECT services during the pandemic. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04384965 ( https://clinicaltrials.gov/study/NCT04384965?term=NCT04384965&rank=1 )., Competing Interests: Competing interests: DV holds the Labatt Family Professorship in Depression Biology, a University Named Professorship at the University of Toronto. She receives research support from CIHR, NIMH, the Center for Addiction and Mental Health (CAMH), The Center for Mental Health at University Health Network and the Department of Psychiatry at the University of Toronto. DV declares no biomedical interests or conflicts. FVR receives research support from CIHR, Brain Canada, Michael Smith Foundation for Health Research, Vancouver Coastal Health Research Institute, and Weston Brain Institute for investigator-initiated research. Philanthropic support from Seedlings Foundation. In-kind equipment support for investigator-initiated research from MagVenture. He has received honoraria for participation in an advisory board for Allergan. FVR is a volunteer director on the board of directors of the British Columbia Schizophrenia Society. TSK receives research support from the Canadian Institutes of Health Research, Patient-Centered Outcomes Research Institute, and the AFP Innovation Fund In the last 10 years, ZJD has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc and Magventure Inc. He also currently serves on the scientific advisory board for Brainsway Inc. His work has been supported by the National Institutes of Mental Health (NIMH), the Canadian Institutes of Health Research (CIHR), Brain Canada and the Temerty Family, Grant and Kreutzkamp Family Foundations. DMB receives research support from CIHR, NIH, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Family Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. He was the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. He also received in-kind equipment support from Magventure for two investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior. He is a scientific advisor for Sooma Medical. He is the Co-Chair of the Clinical Standards Committee of the Clinical TMS Society (unpaid). The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Recent studies have provided promising evidence that neuroimaging data can predict treatment outcomes for patients with major depressive disorder (MDD). As most of these studies had small sample sizes, a meta-analysis is warranted to identify the most robust findings and imaging modalities, and to compare predictive outcomes obtained in magnetic resonance imaging (MRI) and studies using clinical and demographic features. We conducted a literature search from database inception to July 22, 2023, to identify studies using pretreatment clinical or brain MRI features to predict treatment outcomes in patients with MDD. Two meta-analyses were conducted on clinical and MRI studies, respectively. The meta-regression was employed to explore the effects of covariates and compare the predictive performance between clinical and MRI groups, as well as across MRI modalities and intervention subgroups. Meta-analysis of 13 clinical studies yielded an area under the curve (AUC) of 0.73, while in 44 MRI studies, the AUC was 0.89. MRI studies showed a higher sensitivity than clinical studies (0.78 vs. 0.62, Z = 3.42, P = 0.001). In MRI studies, resting-state functional MRI (rsfMRI) exhibited a higher specificity than task-based fMRI (tbfMRI) (0.79 vs. 0.69, Z = -2.86, P = 0.004). No significant differences in predictive performance were found between structural and functional MRI, nor between different interventions. Of note, predictive MRI features for treatment outcomes in studies using antidepressants were predominantly located in the limbic and default mode networks, while studies of electroconvulsive therapy (ECT) were restricted mainly to the limbic network. Our findings suggest a promise for pretreatment brain MRI features to predict MDD treatment outcomes, outperforming clinical features. While tasks in tbfMRI studies differed, those studies overall had less predictive utility than rsfMRI data. Overlapping but distinct network-level measures predicted antidepressants and ECT outcomes. Future studies are needed to predict outcomes using multiple MRI features, and to clarify whether imaging features predict outcomes generally or differ depending on treatments., Competing Interests: Competing interests: Melissa P. DelBello receives research support from national institutes of health (NIH), PCORI, Acadia, Allergan, Janssen, Johnson and Johnson, Lundbeck, Otsuka, Pfizer, and Sunovion. She is also a consultant, on the advisory board, or has received honoraria for speaking for Alkermes, Allergan, Assurex, CMEology, Janssen, Johnson and Johnson, Lundbeck, Myriad, Neuronetics, Otsuka, Pfizer, Sunovion, and Supernus. Robert K. McNamara has received research support from Martek Biosciences Inc, Royal DSM Nutritional Products, LLC, Inflammation Research Foundation, Ortho-McNeil Janssen, AstraZeneca, Eli Lilly, NARSAD, and NIH, and previously served on the scientific advisory board of the Inflammation Research Foundation. The remaining authors declare no potential conflicts of interest with regard to this manuscript., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This study aimed to analyze the transferability of non-invasive brain stimulation (NIBS) interventions in individuals with major depressive disorder (MDD) based on the FIELD model (Function, Implementation, Ecology, Level, and Duration), encompassing function, implement, ecology, level, and duration. A systematic search of electronic databases yielded a total of 21 eligible studies, comprising 12 transcranial direct current stimulation (tDCS) and 9 transcranial magnetic stimulation (TMS) trials, involving 1029 individuals with MDD. The meta-analysis of effect sizes revealed positive transfer effects across all domains of the FIELD model, suggesting that NIBS interventions have potential efficacy in improving various facets of MDD. The subgroup analysis highlighted that bilateral dlPFC stimulation exhibited the highest effect size for transferability, indicating greater transferability for rTMS, a higher dose of stimulation, and the integration of additional interventions. Additionally, the study discusses the implications of bilateral dorsolateral prefrontal cortex (dlPFC) stimulation and the integration of complementary therapies for optimizing treatment efficacy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Abstract: Electroconvulsive therapy (ECT) is an effective and safe treatment for severe major depressive disorder. However, status epilepticus is a rare yet serious complication that can occur following treatment. We present a case of a patient with severe major depression who experienced convulsive status epilepticus during the first treatment of her fourth ECT course. Electroconvulsive therapy treatment was then discontinued, and the patient underwent unsuccessful medication trials. Due to deterioration of depressive symptoms, ECT resumption was considered 3 months later after the patient had been maintained on an antiepileptic drug and no further seizures had occurred. Electroconvulsive therapy was resumed with a detailed safety protocol that included electroencephalographic monitoring before and after ECT treatment, remaining on an antiepileptic drug during the course of treatment, performing ECT in the operating room, and preparing seizure-terminating drugs before each treatment. The patient completed her ECT course with no tardive seizures or other neurological complications. We present the safety measures taken for resumption of ECT in our patient, and we offer preliminary clinical guidelines for resuming ECT after a complication of status epilepticus., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Major depressive disorder (MDD) disproportionately affects those living with autism spectrum disorder (ASD) and is associated with significant impairment and treatment recidivism., Methods: We studied the use of accelerated theta burst stimulation (ATBS) for the treatment of refractory MDD in ASD (3 treatments daily x 10 days). This prospective open-label 12-week trial included 10 subjects with a mean age of 21.5 years, randomized to receive unilateral or bilateral stimulation of the dorsolateral prefrontal cortex., Results: One participant dropped out of the study due to intolerability. In both treatment arms, depressive symptoms, scored on the Hamilton Depression Rating Scale scores, diminished substantially. At 12 weeks post-treatment, full remission was sustained in 5 subjects and partial remission in 3 subjects. Treatment with ATBS, regardless of the site of stimulation, was associated with a significant, substantial, and sustained improvement in depressive symptomatology via the primary outcome measure, the Hamilton Depression Rating Scale. Additional secondary measures, including self-report depression scales, fluid cognition, and sleep quality, also showed significant improvement. No serious adverse events occurred during the study. Mild transient headaches were infrequently reported, which are expected side effects of ATBS., Conclusion: Overall, ATBS treatment was highly effective and well-tolerated in individuals with ASD and co-occurring MDD. The findings support the need for a larger, sham-controlled randomized controlled trial to further evaluate efficacy of ATBS in this population., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interest (either financial or non-financial interest) with the present submitted manuscript described by the Journal of Autism and Developmental Disorders policy. The present study was federally funded by the Cincinnati Children’s Hospital Research Foundation. We have opted to provide full disclosures of all authors’ external commitments for the editor’s review for transparency. The basis of our disclosure was made after review of after review of these activities. The corresponding author, Dr. Pedapati reports no conflicts of interest and is supported by an NIH K23 Clinical Development Award (K23MH112936) and has received past research support from the American Academy of Child and Adolescent Psychiatry, and Cincinnati Children’s Hospital Research Foundation and textbook royalties from Springer. In the past he has consulted for Eccrine Systems, Forge Therapeutics, P&G, and Autism Speaks. The senior author Dr. Erickson is the principal investigator of the human portion of the NIH FXS Center. He has received compensation from Confluence Pharma, Novartis, F. Hoffmann-La Roche Ltd., Seaside Therapeutics, Riovant Sciences, Inc., Fulcrum Therapeutics, Forge Therapeutics, Neuren Pharmaceuticals Ltd., Alcobra Pharmaceuticals, Neurotrope, Zynerba Pharmaceuticals, Inc., and Ovid Therapeutics Inc. to consult on trial design or development strategies and/or conduct clinical trials in neurodevelopmental disorders. Dr. Erickson is additionally the inventor or co-inventor on several patents held by Cincinnati Children’s Hospital Medical Center and Indiana University School of Medicine describing methods of treatment of neurodevelopmental disorders. Dr. Wu receives research support from NIH, Quince Therapeutics, and Emalax Biosciences. Dr. Sweeney consults to VeraSci and has received support from NIH and Sichuan University. Dr. Horn has no conflicts of interest to disclose. Dr. Gilbert has received compensation for expert testimony for the U.S. National Vaccine Injury Compensation Program, through the Department of Health and Human Services. He has received payment for medical expert opinions through TeladocHealth International. He has served as a paid consultant for Emalex Biosciences. He has received research support from the United States National Institutes of Health (Tourette Syndrome, ADHD research) and the Department of Defense (Neurofibromatosis research). He has received salary compensation through Cincinnati Children’s for work as a clinical trial site investigator from Emalex (clinical trial, Tourette Syndrome), PTC Therapeutics (registry and clinical trial, Amino Acid Decarboxylase Deficiency). He has received book/publication royalties from Elsevier and Wolters Kluwer. Dr. Larsh has received research and travel support from the Tourette Association of America (TAA), as well as travel support and honoraria from the Child Neurology Society (CNS). Dr. Elmaghraby, Dr. Liu, and Dr. Smith have no disclosures of funding or external compensation. Finally, we acknowledge that Dr. Craig Erickson serves as an Associate Editor for the Journal of Autism and Developmental Disorders. Ethics Approval and Consent: This study was approved by the institutional review board at Cincinnati Children’s Hospital Medical Center (CCHMC) and registered with ClinicalTrials.gov (NCT01609374). Recruitment took place between November 2021 and November 2022 through clinician referrals, community flyers, emails, and clinics at a tertiary academic pediatric hospital. All participants provided written informed consent or assent for all study procedures., (© 2024. The Author(s).)

This is a review of the existing literature and guidelines for the screening, management, and follow-up of perinatal mood and anxiety disorders, with a focus on major depressive disorder and generalized anxiety disorder., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Self-criticism is a risk factor for depression and depressive symptom persistence, however higher degrees of self-criticism have been associated with greater antidepressant benefits from repetitive transcranial magnetic stimulation (rTMS), suggesting that self-criticism may act as a proxy for function of the targeted circuit. We test this hypothesis using secondary data from an rTMS treatment trial where an NMDA receptor agonist (D-Cycloserine) was used to enhance TMS synaptic plasticity to improve efficacy. We hypothesized that self-criticism would be more strongly associated with treatment outcome when stimulation was paired with D-Cycloserine than with a placebo., Methods: In a 4-week single-site double-blind randomized placebo-controlled trial, fifty adults with Major Depressive Disorder (MDD) (NCT03937596) were randomized to receive placebo or D-Cycloserine (100 mg) with daily intermittent theta-burst stimulation (iTBS) to the left dorsolateral prefrontal cortex (DLPFC). At baseline and after treatment, self-criticism was assessed using the Depressive Experiences Questionnaire as a secondary trial outcome and depressive symptoms were assessed using the clinician rated Montgomery Asberg Depression Rating scale (MADRS). Clinical response was defined as a ≥50 % decrease on the MADRS., Results: Self-criticism differentially predicted antidepressant effects when operationalized as both percent decrease on the MADRS and clinical response (≥50 % decrease), with a statistically significantly stronger association in the iTBS+D-Cycloserine group than the iTBS+Placebo condition. Self-criticism did not significantly change in either condition over the course of treatment., Conclusions: Our data suggests that iTBS to the left DLPFC engages a circuit related to self-criticism. Higher levels of self-criticism predicted better response to iTBS with an adjuvant that enhances synaptic plasticity. This suggests that personality traits may be used to tailor non-invasive neurostimulation treatments., Competing Interests: Declaration of competing interest AJ, MNS, MW and DKS have nothing to declare. AM is a founder of MCGRx Corp and is listed as an inventor on patent 63/193,643 pertaining to the use of D-Cycloserine as an adjunct to transcranial magnetic stimulation for the treatment of Major Depressive Disorder., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Deficits in working memory (WM) are common in patients with Major Depression Disorder (MDD). Previous research mainly in healthy adults indicated that physical exercise training may improve cognitive functions by stimulating neuronal plasticity particularly in hippocampal structures. Thus, the goal of this functional Magnetic Resonance Imaging (fMRI) study was to examine alterations in neuronal activity during a WM task and to investigate changes in brain volume and functioning following a physical exercise training in patients with MDD with a specific focus on hippocampal structures., Methods: 86 (39 female) MDD outpatients (average age 37.3), diagnosed by clinical psychologists, were randomly assigned to one of three groups for a 12-week intervention: High intensity exercise training (HEX), low intensity exercise training (LEX) or waiting list control group (WL). An n-back task (with WM loads of 0, 1, 2, and 3) during fMRI was conducted before and after interventions/waiting period., Results: Both exercise groups showed better performance and shorter reaction times at higher WM loads after 12-weeks of physical exercise training. Specifically in the HEX, we found an improvement in physical fitness and an increase in neural activation in the left hippocampus as compared to the WL following the exercise training. Training-related structural volume changes in gray matter or hippocampus were not detected., Conclusions: Our results partly support the hypothesis that physical exercise training positively affects WM functions by improving neuronal plasticity in hippocampal regions. Exercise training seems to be a promising intervention to improve deficient WM performance in patients with MDD., Clinical Trials Registration Name: Neurobiological correlates and mechanisms of the augmentation of psychotherapy with endurance exercise in mild to moderate depression - SPeED, http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00008869, DRKS00008869., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective Aspects of our emotional state are constantly being broadcast via our facial expressions. Psychotherapeutic theories highlight the importance of emotional dynamics between patients and therapists for an effective therapeutic relationship. Two emotional dynamics suggested by the literature are emotional reactivity (i.e., when one person is reacting to the other) and emotional stability (i.e., when a person has a tendency to remain in a given emotional state). Yet, little is known empirically about the association between these dynamics and the therapeutic alliance. This study investigates the association between the therapeutic alliance and the emotional dynamics of reactivity and stability, as manifested in the facial expressions of patients and therapists within the session. Methods: Ninety-four patients with major depressive disorder underwent short-term treatment for depression ( N  = 1256 sessions). Results: Both therapist reactivity and stability were associated with the alliance, across all time spans. Patient reactivity was associated with the alliance only in a short time span (1 s). Conclusions: These findings may potentially guide therapists in the field to attenuate not only their emotional reaction to their patients, but also their own unique presence in the therapy room.

Background: Repetitive Transcranial Magnetic Stimulation (rTMS) and intermittent Theta Burst Stimulation (iTBS) are non-invasive treatments for major depressive disorder (MDD). While effective, variability in outcomes necessitates identifying predictors of therapeutic response. This study examined whether motor threshold (MT), percentage of motor threshold (%MT), and treatment intensity could predict clinical outcomes in MDD patients undergoing rTMS and iTBS., Methods: Adult MDD patients treated with NeuroStar rTMS or iTBS at Mayo Clinic from February 2016 to April 2024 were included. MT, %MT, and treatment intensity were recorded. Clinical outcomes were assessed via Patient Health Questionnaire-9 (PHQ-9) score changes, response (PHQ-9 change ≥50 %), remission (PHQ-9 < 5), and a patient-reported outcome (PRO) on treatment helpfulness. Linear and logistic regression models were used to assess predictors of clinical outcomes., Results: Among 149 patients analyzed (mean age 45.7, 67.8 % female), response rate was 43.0 % and remission rate was 16.8 %. MT and %MT did not significantly correlate with clinical outcomes. Treatment intensity and TMS type did not predict PHQ-9 score changes. Higher treatment intensity was associated with decreased odds of positive PRO responses. Linear regression showed that age and gender significantly predicted PHQ-9 score changes, with older patients and females showing greater improvement. MT was significantly lower in men and with iTBS compared to rTMS., Conclusion: MT, %MT, and treatment intensity did not reliably predict outcomes. Higher intensity was linked to reduced patient-reported helpfulness, suggesting that patient comfort is crucial. iTBS's lower MT may benefit those needing less stimulation. Future research should identify better predictors to improve TMS outcomes., Competing Interests: Declaration of competing interest Simon Kung reports a relationship with Psychopharmacology Institute that includes: speaking and lecture fees. Paul Croarkin reports a relationship with Neuronetics that includes: funding grants and non-financial support. Paul Croarkin reports a relationship with MagVenture Inc. that includes: non-financial support. Paul Croarkin reports a relationship with Meta Platforms Inc. that includes: consulting or advisory. Paul Croarkin reports a relationship with Sumitomo Pharma America Inc. that includes: consulting or advisory. Dr. Croarkin has received research support from the National Institutes of Health (NIH), National Science Foundation (NSF), Brain and Behavior Research Foundation and the Mayo Clinic Foundation. Dr. Croarkin has received research support from Pfizer, Inc. He has received grant-in-kind equipment support from Neuronetics, Inc., and MagVenture, Inc. He received grant-in-kind supplies and genotyping from Assurex Health, Inc. for an investigator-initiated study. He served as the principal investigator for a multicenter study funded by Neuronetics, Inc. and a site principal investigator for a study funded by NeoSync, Inc. Dr. Croarkin served as a paid consultant for Engrail Therapeutics, Sunovion, Procter & Gamble Company, Meta Platforms, Inc., and Myriad Neuroscience. Dr. Croarkin is employed by Mayo Clinic. He receives compensation as the Editor-in-Chief for the Journal of Child and Adolescent Psychopharmacology. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Patients with major depressive disorder (MDD) hospitalized for psychiatric emergencies (PE) represent a high-risk population, requiring immediate intervention. Overall survival and healthcare resource utilization were evaluated among MDD patients with PE (MDD-PE) vs without PE (MDD-nonPE) using data from the Hungarian National Health Insurance Fund database (2009 to 2020)., Methods: Patients with MDD were selected if they had at least (i) 2 records of MDD diagnosis, or (ii) 1 record of MDD diagnosis and 1 prescription of antidepressant within 90 days of each other between 01 January 2010 and 31 December 2020. MDD-PE patients should have an inpatient hospitalization in a psychiatric ward dedicated for acute treatment, and/or a visit to an emergency department with ≥1 psychiatric and/or suicidal condition among the discharge diagnoses. Patients in the MDD-PE and MDD-nonPE cohorts were matched using a 1:1 propensity score matching algorithm based on age, gender, location of residence, and selected pre-index comorbidities., Results: 28,988 MDD-PE and 28,988 MDD-nonPE patients were included after propensity score matching. Overall survival was significantly shorter among MDD-PE vs matched MDD-nonPE patients (HR: 1.40, 95%CI: 1.33-1.48; p < 0.001). MDD-PE (vs matched MDD-nonPE) patients had significantly higher mean all-cause inpatient admissions (3.9 vs 1.4, p < 0.001) per patient per year (PPPY), and MDD-related inpatient admissions (2.3 vs 0.7, p < 0.001) PPPY with more days in hospital PPPY (all-cause: 65.4 vs 17.4 days; MDD-related: 25.9 vs 8.7 days)., Conclusions: Findings emphasize the need for comprehensive care prioritizing increased vigilance for suicide risk and appropriate follow-up post-discharge among MDD-PE patients., Competing Interests: Declaration of competing interest QC, AE, JG, LF are employees of Janssen and may hold company stocks. PK was an employee of Janssen during the time the study was carried out. IB received consulting fees from Gedeon Richter and Janssen/ Janssen-Cilag; speaker's honoraria from Gedeon Richter, Hikma Pharmaceuticals, Janssen/Janssen-Cilag, KRKA, Lundbeck and Medichem Pharmaceuticals Inc. by Unilab; received research grant from Gedeon Richter; royalties from Oxford University Press. ZR received consulting fees from Janssen/Janssen-Cilag, received speaker's honoraria from Janssen/Janssen-Cilag, Servier and Krka, and served as an advisory board member for Lundbeck, Janssen/Janssen- Cilag, Servier and Krka. PD received consulting fees from Janssen/Janssen-Cilag. GS received consulting fees from Janssen/Janssen-Cilag and KRKA; speaker's honoraria from Janssen/Janssen-Cilag, Lundbeck, KRKA, Gedeon Richter, Mylan and Egis/Servier., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study investigated spaced transcranial direct current stimulation for major depressive disorder, focusing on feasibility., Methods: In a prospective open-label study, 30 participants with major depressive disorder were enrolled to receive a 50-session transcranial direct current stimulation (tDCS) treatment over 2 weeks. The feasibility, safety, tolerability, and preliminary therapeutic effects of this tDCS protocol were assessed using the 17-item Hamilton Depression Rating Scale (HAM-D-17) and the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline and 1-week and 4-week follow-ups, as well as with the 6-item HAM-D (HAM-D-6) daily during treatment., Results: The protocol demonstrated good feasibility, with a retention rate of 93.3% and an adherence rate of 99.7%. There were no serious adverse events. The most common side effect was a mild tingling and itching sensation during stimulation (100%) and temporary skin redness following stimulation (100%). Additionally, 64.3% of participants presented with mild irritative contact dermatitis, which had disappeared by the 1-week follow-up for most participants and completely resolved by the 4-week follow-up for the remaining cases; this was not treatment limiting and did not require specific treatment. HAM-D-17 scores decreased from a mean of 21.3 (SD=3.0) at baseline to 15.3 (SD=6.3) at 1 week and 13.2 (SD=7.1) at 4 weeks. Depressive symptom severity, as measured by the HAM-D-17, showed significant reductions over time, with similar trends observed on the MADRS. HAM-D-6 scores highlighted important differences between response groups, particularly during the later stages of treatment, suggesting a potential for differential response patterns between the 1-week and 4-week follow-ups., Conclusions: The protocol was feasible, safe, and well-tolerated and led to significant reductions in depressive symptoms. These results will need to be validated in a sham-controlled randomized trial. The inclusion of neurophysiological measures in future trials for purposes of biological target engagement might also contribute to our understanding of underlying mechanisms and biomarker discovery., Competing Interests: Dr. Nitsche has served on scientific advisory boards for Neuroelectrics and Precisis, and he has received travel funds from NeuroDevice. Dr. Blumberger has received research support from Brain Canada, the Canadian Institutes of Health Research, NIMH, and the Temerty Family through the CAMH Foundation and the Campbell Family Research Institute; he has received research support and in-kind equipment support for an investigator-initiated study from BrainsWay, and he was the site principal investigator for three sponsor-initiated studies for BrainsWay; he has received in-kind equipment support from MagVenture for two investigator-initiated studies; he has received medication supplies for an investigator-initiated trial from Indivior; he has served as a scientific adviser for Sooma Medical; and he is co-chair of the Clinical Standards Committee of the Clinical TMS Society (unpaid). Dr. Weissman has served as a consultant for GoodCap Pharmaceuticals, and he has received support from the Brain and Behavior Research Foundation, NIMH, and Wellcome Leap. Dr. Daskalakis has received research and in-kind equipment support for an investigator-initiated study through BrainsWay and MagVenture, and he has served on the scientific advisory board for BrainsWay. The other authors report no financial relationships with commercial interests.

Background: Rumination is implicated in the onset and maintenance of major depressive disorder (MDD). Rumination-Focused Cognitive Behavioral Therapy (RF-CBT) effectively targets rumination and may change resting-state brain connectivity and change in activation during a rumination induction task (RIT) post-intervention predicts depressive symptoms two years later. We examined brain activation changes during an RIT in adolescents with remitted MDD following RF-CBT and evaluated RIT reliability (or stability) during treatment as usual (TAU)., Method: Fifty-five adolescents ages 14-17 completed an RIT at baseline, were randomized to 10-14 sessions of RF-CBT (n = 30) or treatment as usual (n = 25) and completed an RIT at post-treatment or equivalent time delay. The RIT includes recalling negative memories (Rumination Instruction), dwelling on their meaning/consequences (Rumination Prompt), and imagining unrelated scenes and objects (Distraction). We assessed activation change in the RF-CBT group using paired-samples t-tests. We assessed reliability (or stability) via intraclass correlation coefficients (ICCs) of five rumination-related ROIs for TAU and RF-CBT separately across task blocks., Results: Following treatment, participants receiving RF-CBT demonstrated increased activation of left precuneus during Rumination Instruction and of left angular and superior temporal gyri during Rumination Prompt blocks (p < .01). From baseline to post-treatment, across most ROIs and task blocks, the RF-CBT group demonstrated poor stability (M = 0.21, range = -0.19-0.69), while the TAU group demonstrated fair-to-excellent stability (M = 0.52, range = 0.27-0.86)., Conclusion: RF-CBT changes activation of rumination-related circuitry during state-induced rumination, offering exciting avenues for future interventions. The RIT has fair-to-excellent stability among individuals not explicitly treated for rumination, and as expected, RIT stability is disrupted by RF-CBT., Competing Interests: Declaration of competing interest This research was funded by the National Institutes of Mental Health (NIMH; R61MH118060/R33MH118060) awarded to Drs. Scott Langenecker and Edward Watkins. The authors have no financial conflicts of interest. This study was approved by the Institutional Review Board at the University of Utah., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cognitive dysfunction is common in late life depression (LLD) and is a major risk factor for dementia. Recent studies show limited improvement in cognition with commonly employed treatments for LLD, contradicting the notion that cognition "returns to normal" with treatment. However, findings differ with the treatments used. The aim of this study is to perform a systematic review of studies of antidepressants and psychotherapies commonly employed in LLD to determine their effects on cognition, particularly processing speed, memory, and executive function. We searched for trials of acute phase treatment, in nondemented individuals 60 years and older with unipolar nonpsychotic Major Depressive Disorder, that assessed cognitive performance with neuropsychological tests before and after treatment. We compared the magnitude of change in cognition by examining within group effect sizes. Six antidepressant trials and two psychotherapy trials (both using Problem Solving Therapy)(PST) provided relatively comparable data that allowed for quantitative comparison. Nine other antidepressant trials provided descriptive findings. Sertraline and vortioxetine had significant positive effects on processing speed and memory. Duloxetine had significant effects on memory. The most selective SRIs-citalopram and escitalopram-had minimal effects on cognition and citalopram had adverse effects in depression nonresponders. PST had modest effects on processing speed and no effect on memory. Effects of practice and improvement in depression on cognition are examined. In all but one study, cognition was a secondary outcome and various quality indicators (e.g. blinding cognitive assessment to treatment) were often not reported. As a consequence, these findings must be considered preliminary., Competing Interests: DISCLOSURES During the past 2 years JCN has received research support from National Institute of Mental Health; consultation fees from Biohaven, Clexio, Johnson and Johnson, Novartis, and Otsuka; and royalties from UpToDate. JG reports no conflicts with any product mentioned or concept discussed in this article. RSM has received research support from the National Institute of Mental Health, National Institute of Aging, Johnson and Johnson, and Janssen Research and Development LLC., (Copyright © 2024 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Abstract: Electroconvulsive therapy (ECT) is considered an effective therapy for patients suffering from severe, life-threatening, intractable depression. This treatment modality delivers controlled electrical currents (typically no more than 100 J) under general anesthesia to induce seizure. Although generally considered to have a high safety profile, physiological changes induced during the ictal phase of ECT, such as elevation in blood pressure and intracranial pressure, impose additional risks to patients with concomitant cardiovascular or cerebrovascular conditions. We describe the successful use of ECT in a unique case complicated by a combination of acute vertebral artery dissection, traumatic intracerebral hemorrhage, and cervical spine injury sustained from a suicide attempt by intentional motor vehicle collision. Although ECT can be safely administered in the presence of recent vertebral artery dissection and traumatic intraparenchymal hemorrhage, an emphasis on multispecialty coordination is crucial to monitor and reduce the risk of elevated blood pressure and further cervical spine injury., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Intermittent Theta Burst Stimulation (iTBS), a specific form of repetitive transcranial magnetic stimulation (rTMS) is increasingly used for treating affective disorders. Accelerated iTBS protocols (aiTBS) with shorter treatment duration may lead to equal but faster response rates compared to standard protocols., Methods: Here, we retrospectively analyzed the records of 66 rTMS in- and out-patients with major depressive disorder in a tertiary care hospital between April 2023 and September 2023. All patients received left prefrontal iTBS with 1200 pulses, either one session/workday over 4 weeks (n = 34) or left prefrontal aiTBS on five sessions/workday for one week (n = 32). Depressive symptoms were assessed with the 21-item Hamilton Depression Rating Scale (HAMD-21) and the Major Depression Inventory (MDI) before and at the end of the respective treatment., Results: With both treatments, iTBS and aiTBS, the severity of depression improved significantly according to HAMD-21 and MDI. Response rates for iTBS were 38 % (HAMD-21) and 35 % (MDI), for aiTBS 19 % (HAMD-21) and 16 % (MDI), respectively. Remission rates showed a similar pattern. Effect sizes for group differences were small to medium. No serious adverse events occurred in any group. Tolerability was lower in aiTBS. Overall satisfaction was low for aiTBS on a qualitative and subjective level., Conclusion: aiTBS with 1200 pulses and five daily sessions lead to amelioration of symptoms within one week. But benefit, satisfaction, tolerability was slightly lower in contrast to four weeks of iTBS. For everyday clinical practice, aiTBS protocols can be considered after weighing up the logistical disadvantages, such as possible longer waiting time for new patients that want to start a therapy with TMS. Future studies should explore the optimal dosage regime (number of sessions per day, number of pulses per session) for fast and effective symptom reduction., Competing Interests: Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Major depressive disorder (MDD) is considered a psychiatric disorder and have a relationship with stressful events. Although the common therapeutic approaches against MDD are diverse, a large number of patients do not present an adequate response to antidepressant treatments. On the other hand, effective non-pharmacological treatments for MDD and their tolerability are addressed. Several affective treatments for MDD are used but non-pharmacological strategies for decreasing the common depression-related drugs side effects have been focused recently. However, the potential of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs), microRNAs (miRNAs) as cell-based therapeutic paradigms, besides other non-pharmacological strategies including mitochondrial transfer, plasma, transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), and exercise therapy needs to further study. This review explores the therapeutic potential of cell-based therapeutic non-pharmacological paradigms for MDD treatment. In addition, plasma therapy, mitotherapy, and exercise therapy in several in vitro and in vivo conditions in experimental disease models along with tDCS and TMS will be discussed as novel non-pharmacological promising therapeutic approaches.

Background: Unguided internet-based cognitive behavioral therapy (ICBT) has been proven effective for major depressive disorder (MDD). However, few studies have examined its cost-effectiveness in low-resource countries and under nonspecialist routine care., Objective: This study aimed to evaluate the short- and long-term cost utility of unguided ICBT compared to a waitlist control for persons with MDD from the perspectives of society and the health care system., Methods: This analysis was implemented alongside an 8-week 2-arm randomized controlled trial with a 12-month follow-up period conducted in Shenzhen, China. Outcomes including cost and health utility were collected at the pretreatment and posttreatment time points and 3, 6, and 12 months after the intervention. Direct medical costs and indirect costs were prospectively collected using the hospital information system and the Sheehan Disability Scale. Health outcomes were measured using the Chinese version of the Short-Form Six-Dimension health index. The primary outcome was incremental cost utility ratio (ICUR) expressed as the difference in costs between 2 therapies by the difference in quality-adjusted life years (QALYs). The seemingly unrelated regression model and the bootstrap method were performed to estimate adjusted ICURs. Cost-effectiveness planes and cost-effectiveness acceptability curves were used to demonstrate uncertainty. A series of scenario analyses were conducted to verify the robustness of base-case results., Results: In total, 244 participants with MDD were randomly allocated to the ICBT (n=122, 50%) or waitlist control (n=122, 50%) groups. At the pretreatment time point, no statistically significant difference was observed in direct medical cost (P=.41), indirect cost (P=.10), or health utility (P=.11) between the 2 groups. In the base-case analysis, the ICBT group reported higher direct medical costs and better quality of life but lower total costs at the posttreatment time point. The adjusted ICURs at the posttreatment time point were CN ¥-194,720.38 (US $-26,551.50; 95% CI CN ¥-198,766.78 to CN ¥-190,673.98 [US $-27,103.20 to US $-25,999.70]) and CN ¥49,700.33 (US $6776.99; 95% CI CN ¥46,626.34-CN ¥52,774.31 [US $6357.83-$7196.15]) per QALY from the societal and health care system perspectives, respectively, with a probability of unguided ICBT being cost-effective of 75.93% and 54.4%, respectively, if the willingness to pay was set at 1 time the per-capita gross domestic product. In the scenario analyses, the probabilities increased to 76.85% and 77.61%, respectively, indicating the potential of ICBT to be cost-effective over the long term., Conclusions: Unguided ICBT is a cost-effective treatment for MDD. This intervention not only helps patients with MDD improve clinically but also generates societal savings. These findings provide health economic evidence for a potential scalable MDD treatment method in low- and middle-income countries., Trial Registration: Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100046425; https://tinyurl.com/bdcrj4zv., (©Wenjing Zhou, Yan Chen, Herui Wu, Hao Zhao, Yanzhi Li, Guangduoji Shi, Wanxin Wang, Yifeng Liu, Yuhua Liao, Huimin Zhang, Caihong Gao, Jiejing Hao, Gia Han Le, Roger S McIntyre, Xue Han, Ciyong Lu. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 19.02.2025.)

Partial remission after major depressive disorder (MDD) is common and a robust predictor of relapse. However, it remains unclear to which extent preventive psychological interventions reduce depressive symptomatology and relapse risk after partial remission. We aimed to identify variables predicting relapse and to determine whether, and for whom, psychological interventions are effective in preventing relapse, reducing (residual) depressive symptoms, and increasing quality of life among individuals in partial remission. This preregistered (CRD42023463468) systematic review and individual participant data meta-analysis (IPD-MA) pooled data from 16 randomized controlled trials ( n  = 705 partial remitters) comparing psychological interventions to control conditions, using 1- and 2-stage IPD-MA. Among partial remitters, baseline clinician-rated depressive symptoms ( p  = .005) and prior episodes ( p  = .012) predicted relapse. Psychological interventions were associated with reduced relapse risk over 12 months (hazard ratio [HR] = 0.60, 95% confidence interval [CI] 0.43-0.84), and significantly lowered posttreatment depressive symptoms (Hedges' g  = 0.29, 95% CI 0.04-0.54), with sustained effects at 60 weeks (Hedges' g  = 0.33, 95% CI 0.06-0.59), compared to nonpsychological interventions. However, interventions did not significantly improve quality of life at 60 weeks (Hedges' g  = 0.26, 95% CI -0.06 to 0.58). No moderators of relapse prevention efficacy were found. Men, older individuals, and those with higher baseline symptom severity experienced greater reductions in symptomatology at 60 weeks. Psychological interventions for individuals with partially remitted depression reduce relapse risk and residual symptomatology, with efficacy generalizing across patient characteristics and treatment types. This suggests that psychological interventions are a recommended treatment option for this patient population.

Background: Depression is one of the most widespread diseases worldwide, with the highest rates of disability. Considering its chronic course, over the years several treatment options have been developed and validated, however still with high relapse rates. Therefore, in recent years, the so-called third wave psychotherapies have been developed for the treatment of psychiatric disorders. Among these, the Metacognitive therapy (MCT) has proven to be effective in treating depression. The aim of this review is to evaluate the efficacy of MCT as monotherapy or adjunctive treatment in reducing depressive symptoms in patients suffering from major depression or dysthymia., Methods: From bibliographic research in PubMed until December 2023, we retrieved 12 original studies meeting our research criteria., Results: The total sample of patients undergoing metacognitive therapy (MCT) included 376 individuals, while the control groups comprised 300 subjects, with a gender ratio of the participants of 0.48 %. The results show that metacognitive therapy is an effective approach in reducing depressive symptoms in patients with a diagnosis of depression or dysthymia when used as add-on therapy, with an efficacy comparable to CBT and superior to pharmacotherapy and as monotherapy, with an efficacy comparable to therapy with antidepressants compared to the control group and compared to cognitive-behavioral therapy with higher rates of reduction of depressive symptoms after treatment and at six months. Preliminary data also indicate its efficacy in terms of reduction of depressive symptoms in elderly people, suggesting its possible use in this population., Limitations: The methodological heterogeneity in terms of treatment protocols of MCT and treatment control as well as the clinical heterogeneity of the sample employed may have limited the generalizability of the results., Conclusions: The results suggest that the use of MCT, both as monotherapy and as an add-on treatment, is a valid therapeutic option for major depression, even at the later stages. However, further studies are needed for deeper our comprehension of the efficacy of MCT in depression., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Given both the large volume and manifold preferences of patients with depression, the availability of various effective treatments is important. Psychodynamic psychotherapy (PDT) has received less research in comparison to cognitive behavioural therapy (CBT) for major depressive disorder (MDD). This study aimed to establish whether short-term psychodynamic supportive psychotherapy (SPSP) is non-inferior to CBT in the treatment of MDD., Methods: A non-inferiority trial was conducted in a Dutch mental health setting, with 290 patients randomised to receive 16 sessions of either CBT or SPSP, over eight weeks. Primary outcome was depressive symptom severity assessed using the self-rated Inventory of Depressive Symptomatology (IDS-SR). The non-inferiority margin was prespecified as a - 5 post-treatment difference on the IDS-SR. Secondary outcome measures were functional impairment caused by symptoms assessed using the Sheehan disability scale (SDS), and wellbeing measured by the Mental Health Continuum-Short Form (MHC-SF)., Results: Both intention-to-treat (baseline-adjusted mean difference 1.62, 95 % CI -1.82 to 5.05) and per-protocol analyses (mean difference 2.54; 95 % CI -0.63 to 5.72) showed SPSP to be non-inferior to CBT in reducing depressive symptoms. SPSP showed slightly but significantly higher remission rates and wellbeing scores., Limitations: Patients opting for other therapies or medication did not take part in the trial. Follow-up measures or clinician-rated questionnaires were not included., Conclusions: The findings support SPSP as a viable treatment option for MDD, expanding the available choices for patients and broadening treatment options., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Intravenous (IV) ketamine has been evaluated alongside electroconvulsive therapy (ECT) in addressing major depressive disorder (MDD) or bipolar depression (BD), though the comparative outcomes remain inconclusive. This meta-analysis aimed to provide a systematic assessment of the efficacy, safety, and tolerability of IV ketamine relative to ECT for treating MDD or BD., Methods: Randomized controlled trials (RCTs) comparing IV ketamine and ECT in terms of efficacy, safety, and tolerability for MDD or BD were identified and reviewed. Three independent investigators extracted relevant data, which was synthesized using RevMan 5.3 software under a random effects model., Results: Five RCTs encompassing 664 patients diagnosed with MDD or BD were analyzed. At 24 h post-initial treatment, IV ketamine demonstrated a statistically greater reduction in depressive symptoms compared to ECT (standardized mean difference (SMD) = -0.49, 95 % CI = -0.96 to -0.03, I 2 = 77 %; P = 0.04). However, no significant differences were observed between groups in terms of the study-defined response (risk ratio (RR) = 1.49, 95 % CI = 0.08 to 28.42, I 2 = 0 %; P = 0.79) at 24 h. Similarly, no notable differences were found for depressive symptom improvement (SMD = -0.48, 95 % CI = -2.41 to 1.45, I 2 = 99 %; P = 0.63), the study-defined response (RR = 0.96, 95 % CI: 0.70 to 1.31, I 2 = 75 %; P = 0.79) or remission (RR = 0.91, 95 % CI: 0.45 to 1.82, I 2 = 90 %; P = 0.78) at the end-of-treatment visit. Among the three RCTs (60 %) comparing the neurocognitive outcomes of IV ketamine and ECT through varying test batteries, results were inconsistent. IV ketamine was associated with marked increases in dissociation, blurred vision, dizziness, and diplopia, while ECT led to a significant rise in muscle pain (all Ps < 0.05). Discontinuation rates due to any cause were comparable between both groups (P > 0.05)., Conclusion: IV ketamine demonstrates a faster onset of antidepressant effects compared to ECT, despite both treatments yielding comparable outcomes at the end-of-treatment visit for patients with MDD or BD. However, large-scale RCTs are required to thoroughly evaluate the long-term efficacy and safety of IV ketamine relative to ECT in these populations., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in conducting this study or preparing the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To explore the short-term and long-term effects of electroconvulsive therapy (ECT) on depression among adolescents and to determine the relationship between the effects of ECT and family functioning. Sixty-five adolescent inpatients with major depressive disorder (MDD) who received ECT were recruited. We assessed the severity of MDD with the Hamilton Depression Rating Scale-24 (HDRS-24) before (T0), 1-2 days after the end of ECT treatment (T1), and 3 months after the end of ECT treatment (T2). We calculated the reduction in HDRS scores at T1 (short-term effect) and T2 (long-term effect). Additionally, we examined the relationship between family functioning and the effects of ECT. The short-term response rate to ECT was 64.6%, but the long-term response rate decreased to 22.2%. HDRS scores were significantly lower at T1 and T2 than at T0 (P < .01). Independent sample t tests showed that the mean scores for the communication, roles, affective responsiveness, affective involvement, and overall functionality dimensions of the Family Assessment Device were significantly lower in the responder group than in the nonresponder group at T2 (P < .05). Forward entry binary logistic regression showed that the short-term effects of ECT were stronger among patients who were hospitalized in a psychiatric ward for the first time, and the affective involvement dimension of the Family Assessment Device was significantly negatively correlated with the long-term effects of ECT (P < .05). ECT may be an effective intervention for MDD among adolescents; however, its short-term effects are more prominent than its long-term effects. In addition, family functioning may be related to long-term responses to ECT., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Suicide is a complex behavior strongly associated with depression. Despite extensive research, an objective biomarker for evaluating suicide risk precisely and timely is still lacking. Using the precision resting-state fMRI method, we studied 61 depressive patients with suicide ideation (SI) or suicide attempt (SA), and 35 patients without SI to explore functional biomarkers of suicide risk. Among them, 21 participants also completed electroconvulsive therapy (ECT) treatment, allowing the examination of functional changes across different risk states within the same individual. Functional networks were localized in each subject using resting-state fMRI and then an individualized connectome was constructed to represent the subject's functional brain organization. We identified a set of connections that track suicide risk (r = 0.41, p = 0.001) and found that these risk-associated connections were hyper-connected in the frontoparietal network (FPN, p = 0.008, Cohen's d = 0.58) in patients with suicide risk compared to those without. Moreover, ECT treatment significantly reduced (p = 0.001, Cohen's d = 0.56) and normalized these FPN hyper-connections. These findings suggest that connections involving FPN may constitute an important biomarker for evaluating suicide risk and may provide potential targets for interventions such as non-invasive brain stimulation., Competing Interests: Competing interests: HL is the chief scientist of the Neural Galaxy. Neural Galaxy is not a sponsor of this study and did not provide any other support. The remaining authors declare no competing interests. Ethics approval and consent to participate: The current study was conducted in accordance with the Declaration of Helsinki, approved by the Ethics Committee of Anding Hospital, Capital Medical University (No.202194FS-2). All participants gave written informed consent., (© 2025. The Author(s).)

Background: More studies with low risk of bias on the effectiveness of cognitive behavioral therapy (CBT) and short-term psychodynamic psychotherapy (STPP) for major depressive disorder (MDD) are needed. This study compares the outcome of CBT and STPP and examines the improvements in each treatment, focusing on effect sizes, reliable change, dropout rates, and remission rates, using broad inclusion criteria (e.g. participants using antidepressants or with strong suicidal ideation)., Methods: One hundred patients were randomly allocated to CBT or STPP. All patients were offered either 16 weekly sessions followed by 3 monthly booster sessions in CBT, or 28 weekly sessions in STPP. Primary outcome measures were Hamilton Depression Rating Scale (HDRS) and Beck's Depression Inventory-II (BDI-II). Secondary outcome measures were Work and Social Adjustment Scale (WSAS), Generalized Anxiety Disorder-7 (GAD-7), Global Assessment of Functioning (GAF) and Short Form Health Survey-12 (SF-12)., Results: No significant differences in outcomes were found between the two treatment groups on any of the measures. The within-group effects were large (> 0.8) for the primary outcome measures and moderate to large for the secondary outcome measures. According to the reliable change index (RCI), 79% of patients reliably improved on HDRS and 76% improved on BDI-II, whereas respectively 6% and 10% reliably deteriorated., Conclusions: These findings support the assumption that CBT and STPP are equally effective treatments for patients with depressive disorders in psychiatric outpatient clinics. Additionally, they strengthen the evidence for the effectiveness of both CBT and STPP in these settings, while also highlighting that not all depressed patients respond to short-term treatment., Clinical Trial Registration: Clinical Trial gov. Identifier: NCT03022071. Date of registration: 2016-11-14., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki. The Regional Committee for Medical and Health Research Ethics, Southeast Norway (REK 2016/340) approved the study (Clinical Trial gov. Identifier: NCT03022071). Patients received both written and oral information about the study before they were asked to give their written informed consent to participate. All methods were performed in accordance with the relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objectives: Mindfulness-Based (non-contact) Boxing Therapy (MBBT) is a novel intervention designed to empower and promote self-agency through behavioral interventions, while reducing barriers to exercise for individuals with mental disorders. MBBT is an instructor-led, manualized, non-contact boxing group-exercise program (delivered in 90 min sessions, twice a week, over 10 weeks) that blends principles of mindfulness, meditation and group therapy. The current study tested the acceptability and feasibility of delivering MBBT to adults with major depressive disorder (MDD) or generalized anxiety disorder (GAD)., Methods: Nine adult outpatients with MDD or GAD were recruited from a psychiatric outpatient clinic in Toronto, Canada in a 10-week feasibility trial of MBBT using a pre-post design. Feasibility was assessed through recruitment and retention rates, while acceptability was assessed through the CSQ-8, and self-questionnaires. Secondary clinical outcomes included the PHQ-9, GAD-7, K10, CGI, and MAAS. Trial registry: ISRCTN23023309., Results: Eight participants (5 female, 3 male) were included in the final analysis. Results indicated a high user retention (89%), attendance (84%), and satisfaction (98%). The study observed a statistically significant mean percent reduction in depression (54%), anxiety (51%) and distress (36%), alongside a mean percent increase in mindfulness (79%). Post intervention qualitative feedback from participants revealed themes of inclusivity and accessibility, cathartic release and control of emotions, improved self-esteem and confidence, self-agency, community, and trust in leadership., Conclusions: Given the limitation of the study, MBBT appeared to be feasible and acceptable as an exercise/behavioural intervention. Further well-designed randomized clinical trials are warranted to confirm the clinical benefits of MBBT., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Bozdarov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: A patient with major depressive disorder (MDD) was receiving transcranial magnetic stimulation (TMS). A little over halfway through the course the patient was bereaved and experienced normal sadness. Our objective is to describe the tracking and outcome of this common emotionally distressing event., Method: Routine assessments conducted at the centre include the six-item Hamiton depression rating (HAMD6) scale, the Clinical Global Impression-Severity (CGI-S) scale, and the Subjective Depression Scale (SDS6). In addition, the Daily Sadness Scale (DSS) is applied at each treatment day; this is a single question asking how much sadness/depression is being experienced., Results: On the 19th treatment day, the patient was bereaved and experienced appropriate sadness. The pathological state (MDD) resolved, as reflected by changes in the psychometric tools. Following the death, normal sadness emerged and lessened over a few weeks., Conclusion: This case illustrates that while TMS can effectively treat MDD, it does not prevent the emergence of sadness in uncomplicated bereavement., (Copyright © 1964–2025 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Modern psychiatry aims to adopt precision models and promote personalized treatment within mental health care. However, the complexity of factors underpinning mental disorders and the variety of expressions of clinical conditions make this task arduous for clinicians. Globally, major depression is a common mental disorder and encompasses a constellation of clinical manifestations and a variety of etiological factors. In this context, the use of Artificial Intelligence might help clinicians in the screening and diagnosis of depression on a wider scale and could also facilitate their task in predicting disease outcomes by considering complex interactions between prodromal and clinical symptoms, neuroimaging data, genetics, or biomarkers. In this narrative review, we report on the most significant evidence from current international literature regarding the use of Artificial Intelligence in the diagnosis and treatment of major depression, specifically focusing on the use of Natural Language Processing, Chatbots, Machine Learning, and Deep Learning.

Background: Ventral capsule/ventral striatum deep brain stimulation (VC/VS-DBS) for treatment-resistant depression (TRD) has shown promising results. Despite its efficacy, DBS is costly and less accessible, while anterior capsulotomy (ACAPS), though permanent and non-adjustable, offers clinical advantages., Methods: A systematic review and data analysis were conducted to evaluate articles reporting on clinical outcomes and adverse effects of VC/VS-DBS and ACAPS for TRD. A quality assessment of the included studies was performed to determine homogeneity across reports. To assess the intervention's efficacy, changes in pre- and post-intervention scores on the Hamilton Depression Rating Scale (HRSD-17) were analyzed., Results: Seven studies with 138 TRD patients were analyzed. Among 75 ACAPS patients, mean pre-operative HRSD-17 scores decreased by 46 %, from 26.97 ± 3.12-14.53 ± 1.15, with an improvement of 11.87 points (95 % CI: 8.83-14.91). For 63 VC/VS-DBS patients, scores declined by 42 %, from 27.5 ± 4.13-15.93 ± 5.13, corresponding to an improvement of 9.68 points (95 % CI: 5.08-14.27). Adverse effects included suicidal ideation (7 %) and hypomania (3.6 %) with DBS, while ACAPS was associated with headaches and long-term effects like reduced motivation and weight gain in 15-20 % of patients., Conclusion: Both VC/VS-DBS and ACAPS show efficacy in treating TRD, with ACAPS showing slightly better outcomes and no significant adverse effects reported. However, given study heterogeneity, a robust, well-powered randomized controlled trial is essential to more precisely compare these techniques and clarify their clinical impact on TRD., Competing Interests: Declaration of Competing Interest The authors have declared no conflicts of interest with respect to the research of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Determining anesthetic depth has been used to assess the optimal timing of electrical stimulus application in electroconvulsive therapy (ECT). This has improved the quality and effectiveness of seizures, as some anesthetics used can decrease efficacy. This study evaluated the influence of the Patient State Index (PSi) on the course of ECT in patients with major depressive disorder (MDD)., Methods: this was an experimental prospective study with a control group involving 47 patients (22 assessed with the PSi, 25 controls) admitted and diagnosed with MDD. Clinical evolution variables, procedural characteristics, cognitive variables, and seizure adequacy were analyzed using mixed-effects linear models and Kaplan-Meier survival curves., Results: the PSi group had fewer restimulations during treatment, higher values of seizure concordance, and higher "time to peak coherence" as parameters of seizure quality. No significant differences were observed between the two groups regarding improvement in depression, intra-ECT awareness, or adverse cognitive effects., Conclusion: the use of the PSi for measuring anesthetic depth in modified ECT with propofol appeared to improve procedure effectiveness without increasing the incidence of intra-ECT awareness or cognitive side effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: A few sham-controlled studies have examined the efficacy, safety, and tolerability of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in adolescents with first-episode major depressive disorder (FE-MDD)., Methods: Forty adolescents (aged 13-17 years) with FE-MDD were randomly assigned to receive active rTMS (n = 20) or sham rTMS (n = 20) for 10 sessions over two weeks. The severity of baseline depressive symptoms and their improvement on the day immediately after the second, fourth, sixth, eighth, and tenth sessions were assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17)., Results: After completing 10 rTMS treatment sessions, there was no significant difference in antidepressant response (70.0 % vs. 60.0 %, p > 0.05) and antidepressant remission (55.0 % vs. 35.0 %, p > 0.05) between rTMS groups. The linear mixed model analysis did not show a significant group-by-time interaction (F = 1.26; p > 0.05) in the HAMD-17 scores. There was a significant time main effect on the speed of processing (F = 13.61; p < 0.05), but this did not differ significantly between groups (p > 0.05). There were no other main effects and group-by-time interactions in the other MATRICS Consensus Cognitive Battery domains (all p > 0.05). All adverse event categories, such as fatigue and headache, were similar in the two groups (all p > 0.05)., Conclusions: In this study that compared a combination of LF-rTMS + medication with sham + medication, LF-rTMS had higher response and remission rates than a sham procedure in adolescents with FE-MDD, but the change was not statistically significant. LF-rTMS is generally safe, with mild adverse effects and no negative impact on neurocognitive performance for adolescents with FE-MDD., Registration Number: ChiCTR2000037878., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in conducting this study or preparing the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Electroconvulsive therapy (ECT) is a widely recognized treatment for severe depressive disorders, particularly in cases of inadequate response to pharmacological interventions or when rapid symptom relief is essential. Although ECT demonstrates high efficacy, a notable proportion of patients relapse after a successful ECT course., Methods: This study investigated clinical baseline characteristics and residual depressive symptoms associated with relapse - defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) score >15, restart of ECT, or suicide attempt - within six months after successful ECT. Data were obtained from the PROTECT study, a single-site, prospective cohort study conducted at the University Psychiatric Center Duffel, Belgium., Results: - Among the 65 patients who completed the ECT course, 40 patients (62%) achieved remission. At six months, 32 patients were reassessed, and 18 (56%) of them experienced relapse. No significant associations were identified between relapse and baseline factors, including age, social circumstances, baseline depression severity, psychomotor symptoms, cognitive functioning, treatment resistance, lithium use, or the presence of psychotic or melancholic features. Residual depressive symptoms at the end of the ECT course also did not predict relapse., Discussion: - The observed high relapse rate underscores the critical need for robust continuation and maintenance strategies following ECT. Future research should prioritize larger cohorts to better identify predictors of relapse and optimize post-ECT treatment protocols., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Despite effective psychotherapy options for posttraumatic stress disorder (PTSD), some patients do not fully respond, and even among those reporting substantial improvement, residual symptoms following treatment are common. Psychiatric conditions frequently co-occur with PTSD, yet research on residual symptoms among comorbid samples is lacking. This study examined residual symptoms of PTSD and depression among 71 active duty service members with PTSD and comorbid major depressive disorder (MDD). As part of a clinical trial, participants were randomized to cognitive processing therapy (CPT) or a novel treatment designed to address PTSD and comorbid MDD, behavioral activation-enhanced CPT (BA + CPT). Analyses compared individual residual symptoms between treatments and groups based on PTSD and MDD diagnostic status at posttreatment. For both PTSD and MDD, the conditional probabilities for each residual symptom did not differ between CPT and BA + CPT, suggesting treatment type did not influence which symptoms persisted. For the 36 service members who lost their PTSD diagnosis at posttreatment, conditional probabilities of residual PTSD symptoms were highest for sleep problems, concentration difficulties, and hypervigilance; for MDD symptoms, conditional probabilities were highest for sleep problems, concentration difficulties, and low energy. These most common residual symptoms were identical for the 31 service members who lost their MDD diagnosis at posttreatment. Residual symptoms observed among service members with PTSD and comorbid MDD mirrored those commonly identified among single disorder PTSD or MDD samples. Identifying and addressing residual symptoms most meaningful to patients will maximize benefit from PTSD treatment., Competing Interests: Declaration of competing interest None., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Repetitive transcranial magnetic stimulation (TMS) has gained interest as a treatment for major depressive disorder (MDD). However, the literature on its efficacy and safety for pregnant patients with MDD is limited. This article reviews and appraises available studies on TMS in pregnant women with MDD., Methods: We reviewed randomized controlled trials and open-label studies on TMS in pregnant women with MDD., Results: Studies indicate that TMS is a safe and effective treatment for MDD during pregnancy, showing significant reductions in depression scores and increased response and remission rates compared to sham TMS. TMS was well tolerated with minimal side effects., Conclusion: Larger, multicenter trials are needed to develop evidence-based protocols for TMS use in pregnancy., (© 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Objective: To compare the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) under facial feature point (FFP) localization versus neuro-navigated localization for depression., Methods: 42 depressed patients were randomly assigned to two groups, received 10 Hz rTMS twice daily for 10 consecutive days. Relevant symptom scale assessments were conducted by professionals at baseline, after 10 sessions, and at the end of treatment. The confidence interval was calculated at a 95 % confidence level. The significant level was set at p < 0.05., Results: The absolute change in Hamilton Rating Scale for Depression (HAMD) total score from baseline to the end of therapy did not differ significantly between the groups. The generalized estimating equation showed the main effect of time was significant, which showed improvement of depressive symptoms in patients throughout treatment. Upon completion of the treatment, FFP group showed a response rate of 64.7 % and a remission rate of 29.4 %, whereas the navigated group exhibited a response rate of 61.1 % and a remission rate of 44.4 %. There was no serious adverse events occurred during the treatment process. Throughout the study, no intervention was made on the normal medication treatment, and some patients had concomitant antidepressants and benzodiazepines., Conclusion: There was no significant difference in clinical efficacy between FFP localization and navigated localization in the small-sample study. However, due to the limited sample size and lack of rigorous non-inferiority testing, the superiority of one over the other remains uncertain, necessitating rigorous experimental design to validate the efficacy difference between the two localization methods., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Major depressive disorder (MDD) is prevalent among older patients and is frequently associated with cognitive decline and a reduced quality of life. Non-invasive brain stimulation (NIBS) techniques show promise for treating MDD, but their comparative efficacy and safety older populations remain unclear. This study aimed to compare the efficacy and cognitive effects of various NIBS techniques in treating MDD in older patients., Methods: We searched the PubMed, EMBASE, Cochrane Library, and Web of Science core databases from inception to March 2024. Seventeen randomized controlled trials (RCTs) were included., Results: Surfaces under the cumulative ranking curve (SUCRA) values were used to rank the interventions. The SUCRA rankings for the Hamilton Depression Rating Scale (HDRS) outcomes indicated that repetitive transcranial magnetic stimulation (rTMS) (89.0 %) had the highest efficacy, followed by transcranial direct current stimulation (tDCS) (68.7 %). rTMS demonstrated significantly superior efficacy compared with bilateral electroconvulsive therapy (BL ECT) and right unilateral electroconvulsive therapy (RUL ECT). Theta burst stimulation (TBS) had the highest response rate (69.6 %), followed by rTMS (61.8 %). Based on the Mini-Mental State Examination, rTMS (86.4 %) ranked the highest, with RUL ECT showing significantly better outcomes than BL ECT., Conclusion: NIBS, particularly rTMS and TBS, may offer effective treatment options for older patients with MDD. Further research with larger sample sizes and longer follow-up periods is required to validate these findings and inform clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests or financial conflicts that could have influenced the work reported in this study. All affiliations and funding sources relevant to the research have been disclosed., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Postpartum mood disorders are heterogenous disorders and comprise postpartum psychosis and postpartum depression. Evidence is accumulating that systemic monocyte/macrophage activation, low-grade inflammation and (premature senescence related) T cell defects increase the risk for mood disorders outside pregnancy by affecting the function of microglia and T cells in the emotional brain (the cortico-limbic system) leading to inadequate mood regulation upon stress., Areas Covered: The evidence in the literature that similar immune dysregulations are present in postpartum mood disorders., Results: The physiological postpartum period is characterized by a rapid T cell surge and a mild activation of the monocyte/macrophage system. Postpartum mood disorder patients show a diminished T cell surge (including that of T regulatory cells) and an increase in low grade inflammation, that is, an increased inflammatory state of monocytes/macrophages and higher levels of serum pro-inflammatory cytokines., Expert Opinion: Anti-inflammatory agents (e.g. COX-2 inhibitors) and T cell boosting agents (e.g. low-dose IL-2 therapy) should be further investigated as treatment. The hypothesis should be investigated that postpartum mood disorders are active episodes (triggered by changes in the postpartum immuno-endocrine milieu) in ongoing, dynamically fluctuating aberrant neuro-immune-endocrine trajectories leading to mood disorders in women (inheritably) vulnerable to these disorders.

Background: The insula has a significant impact on interoception and depression. This study aims to explore the role of the insula in mediating treatment responses to high-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC)., Methods: Twenty-five patients with either bipolar disorder (BD, n = 15) or major depressive disorder (MDD, n = 10) were recruited. All subjects were aged between 20 and 70, with a minimum score of 18 on the 24-item Hamilton Rating Scale for Depression (HDRS-24). Each patient received 12 sessions of rTMS treatment using a figure-eight-shaped coil at 10 Hz high-frequency stimulation intensity, targeted to the left DLPFC. Resting-state functional magnetic resonance imaging was conducted before and after the rTMS treatment to assess changes in insula-seeded functional connectivity., Results: Both BD and MDD patients experienced significant reductions in depressive symptoms following rTMS therapy. The respective response rates at weeks 4, 8 and 12 were 64.0 %, 64.0 % and 68.0 % and remission rates were 40.0 %, 36.0 % and 44.0 %. Decreases in functional connectivity between the right anterior insula and right calcarine were significantly larger in the remitters than in the non-remitters (p = 0.013). Additionally, a higher baseline functional connectivity between the right anterior insula and right superior temporal gyrus correlated with better treatment outcome., Limitations: The small sample size of 25 participants is small., Conclusion: Our findings highlight the potential role of the insula in depression and suggest that insula-seeded functional connectivity could serve as a predictive biomarker for rTMS efficacy., Competing Interests: Declaration of competing interest The funding agencies for this study did not have any involvement in the study's design, data collection, data analysis, data interpretation, manuscript preparation, or the decision to submit the paper for publication. The authors declare that they have no financial ties to commercial entities., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To describe the quality of life and clinical characteristics of treatment-resistant depression (TRD) patients in an Australian patient cohort recruited cross-sectionally during admission., Method: Inpatients admitted for TRD treatment completed a quality of life questionnaire (AQoL-8D) and a depression severity assessment (HAM-D). A chart review and patient interview occurred for demographic and patient characteristics. Comparisons between the mean AQoL-8D scores of the study population and Australian population norms occurred., Results: 79 TRD inpatients (70.9% female), mean age of 44.8 ± 14.9 years, were recruited, with 78.5% having an anxiety disorder, 48.1% post-traumatic stress disorder, and 30.4% a personality disorder. Adjunctive to antidepressants, 92.4% were taking antipsychotics and 55.7% were taking mood stabilisers. Approximately 42% of patients received transcranial magnetic stimulation, and 35.4% received electroconvulsive therapy. Mean HAM-D score was 20.3 ± 5.2, and AQoL-8D score (120.1 ± 16.5) was significantly higher than Australian population norms ( p < .001) indicating reduced quality of life., Conclusions: Personal and clinical characteristics of patients hospitalised for TRD were similar to TRD globally with impaired quality of life relative to the general Australian population. TRD patients on average presented with moderate/severe depression, highlighting the need for greater support for these individuals., Competing Interests: DisclosureThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A reliable physiological biomarker for major depressive disorder is essential for developing and optimizing neuromodulatory treatment paradigms. In this study, we investigated a passive electrophysiologic biomarker that tracks changes in depressive symptom severity on the order of minutes to hours., Methods: We analyzed brief recordings from intracranial electrodes implanted deep in the brain during a clinical trial of deep brain stimulation for treatment-resistant depression in 5 human participants (n female  = 3, n male  = 2). This surgical setting allowed for precise temporal and spatial sensitivity in the ventromedial prefrontal cortex, a challenging area to measure. We focused on the aperiodic slope of the power spectral density, a metric that reflects the balance of activity across all frequency bands and may serve as a proxy for excitatory/inhibitory balance in the brain., Results: Our findings demonstrated that shifts in aperiodic slope correlated with depression severity, with flatter (less negative) slopes indicating reduced depression severity. This significant correlation was observed in all 5 participants, particularly in the ventromedial prefrontal cortex., Conclusions: This biomarker offers a new way to track patient responses to major depressive disorder treatment, thus paving the way for individualized therapies in both intracranial and noninvasive monitoring contexts., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Major depressive disorder (MDD) is one of the most prevalent and disabling mental disorders with high recurrence rate. There is often a gap between scientific evidence related to the effective and cost-effective treatment of depression and clinical practice. Implementation science is a field of inquiry that aims to advance the process of applying evidence-based interventions to real-world problems. Implementation research consists of two broad phases. The first phase seeks to identify the gaps that exist between evidence and practice and their impact on outcomes. The second phase, building on the first, evaluates the effectiveness of implementation strategies by examining various implementation indicators to support the adoption and scale up of interventions. Although implementation research can facilitate the uptake and adoption of evidence-based interventions, it is underused in depression research. In this narrative review, the authors will introduce the definition of implementation science and the state of implementation science in MDD in order to support more widespread use of implementation science for scaling up evidence-based interventions., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Electroconvulsive therapy (ECT) is highly efficacious for the treatment of major depressive disorder (MDD), but its mechanisms still require clarification. Even though depression is associated with alterations in functional connectivity (FC), EEG studies investigating effects of ECT on FC have not been systematically reviewed. Understanding these effects may help to identify the role of functional brain circuits in depression and its remission. This systematic review aimed to synthesize EEG studies investigating FC changes in ECT-treated patients with depression. A systematic literature search was conducted following PRISMA guidelines. Peer-reviewed studies on pre-to post-ECT resting-state EEG FC changes in adult patients with MDD were included. Three of 143 studies were included, of which two reported reduced FC in the alpha and beta frequency bands and increased theta band FC in patients with ECT-treated MDD. Changes in alpha band FC were associated with treatment outcomes. Patients with MDD exhibit increased electrophysiological resting-state alpha band FC, particularly frontally, compared with healthy subjects. Thus, ECT-induced decrease might indicate a trend toward normalization of oscillatory brain rhythms. As brain oscillations have been proposed to be involved in neuronal synchronization, which is important for communication between networks, the potential restoration in patients with depression and the association of FC changes with clinical improvement may indicate a potential mechanism of action of ECT. Understanding ECT's underlying mechanisms might ultimately enable treatment optimization, thus enhancing patient care. However, the number of studies is limited, with low-to-moderate EEG study quality, small sample sizes, and different electrophysiological FC measures., Competing Interests: Declaration of Competing Interest All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Magnetic seizure therapy (MST) is under investigation as a treatment for adults with major depression. Previous research has suggested that MST has antidepressant efficacy comparable to that of electroconvulsive therapy (ECT), but with greater cognitive safety. The objective of the study was to compare the neurocognitive outcomes of patients receiving an acute course of MST with the outcomes of those receiving ECT for the treatment of major depressive episode., Methods: This was a between-subjects, double-masked, randomized, multicenter clinical trial. Seventy-three participants with a severe major depressive episode were enrolled and randomly assigned to treatment with MST (n = 35) or ultra-brief pulse right unilateral ECT (n = 38). The main outcome was change in performance from baseline to the end of acute treatment on multiple neurocognitive measures., Results: Compared with patients who received ECT, patients who received MST had superior cognitive outcomes up to 72 hours posttreatment. Specifically, following MST treatment, there was significant improvement in fine motor dexterity (p = .017) and no significant change in cognitive domains of attention, verbal fluency, executive function, or verbal learning and memory. In contrast, following treatment with ECT, patients demonstrated significantly worse performance on measures of verbal fluency (p < .001), executive function (p = .038), and verbal memory retention (p < .001). Autobiographical memory consistency decreased significantly following treatment with both ECT (p < .001) and MST, although the magnitude of change was greater for ECT., Conclusions: The study findings confirm previous work and provide new evidence supporting the enhanced cognitive safety of MST relative to ECT. Future research on MST is warranted to optimize its application to individuals with neuropsychiatric illnesses across the life span., (Copyright © 2024 Society of Biological Psychiatry. All rights reserved.)

Objective. The transient autonomic nervous system responses induced by electroconvulsive therapy (ECT) may serve as critical indicators of treatment efficacy and potential side effects; however, their precise characteristics remains unclear. Considering that the intense stimulation of ECT may disrupt the typical antagonistic relationship between the sympathetic and parasympathetic branches, this study aims to conduct a meticulous analysis of the rapid changes in heart rate variability (HRV) and HR during ECT, with a particular focus on their synchronized interplay. Methods. Pulse interval sequences were collected from 50 sessions of bitemporal ECT administered to 27 patients diagnosed with major depressive disorder. The average HR and ultra-short term HRV indices RMSSD and SDNN, as well as the Poincaré indices SD1, SD2 and SD2/SD1, were calculated using a 10 s sliding window with a step size of 1 s. In particular, the synchronous changes between SD1, SD2, SD2/SD1 and HR were analyzed. Results. The synchronous changes of the indices showed different characteristics over time. In particular, SD1, SD2 and HR increased significantly by 41.50 ± 11.45 ms, 33.97 ± 10.98 ms and 9.68 ± 2.00 bpm respectively between 8 and 20 s, whereas they decreased significantly by 19.89 ± 9.07 ms, 17.54 ± 8.54 ms and 3.80 ± 1.33 bpm respectively between 45 and 53 s after ECT stimulus onset. SD1 and SD2 both had highly significant positive correlations with HR in the above phases. Conclusion. The results suggest that bitemporal ECT induces the sympathetic and parasympathetic co-activation during the early ictal period and brief co-inhibition approximately 45 s after stimulus. Our findings may provide new insights comprehending the mechanisms of ECT and its associated cardiovascular risks., (© 2025 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Individuals experiencing major depression with psychotic features (MD-P) may respond better and have fewer cognitive effects with electroconvulsive therapy (ECT) than those without psychotic features (MD-NP). However, this may be due to differences in patient characteristics aside from psychotic symptoms. The objectives of this study were to (1a) compare ECT treatment response and (1b) adverse cognitive effects between patients with MD-P and MD-NP and (2a) explore factors associated with treatment response or (2b) adverse cognitive effects., Methods: This was a retrospective cohort study of adult inpatients with MD-P or MD-NP treated with an acute course of ECT at an academic psychiatric hospital June 2010-September 2021 in Toronto, Canada. Logistic regression was used to account for differences in patient characteristics between groups. Outcomes were identified using the clinical global impression improvement and cognitive function scales., Results: 542 patients were included, 115 (21%) with MD-P and 427 (79%) with MD-NP. MD-P patients were more likely to be rated "very much improved" with ECT (41% vs 27%, P = .003) while adverse cognitive effects were similar (21% MD-NP vs 24% MD-P; P > .05). However, after accounting for confounders, psychotic symptoms were not associated with response (adjusted odds ratio [AOR]: 1.04; 95% confidence interval [CI], 0.95-1.14) or adverse cognitive effects (AOR: 1.30; 95% CI, 0.78-2.18)., Conclusions: Individuals with MD-P had a higher rate of response and similar rates of adverse cognitive effects compared to patients with MD-NP with ECT treatment. However, after accounting for differences in patient characteristics, we no longer identified an association between psychotic symptoms and treatment response., (© Copyright 2025 Physicians Postgraduate Press, Inc.)

Background: Increasing evidence suggests that insomnia plays an important role in the development of depression, supporting insomnia intervention as a promising approach to prevent depression in youth. This randomized controlled trial evaluated the effectiveness of app-based cognitive behavioral therapy for insomnia (CBT-I) in preventing future onset of major depressive disorder (MDD) in youth., Methods and Findings: This was a randomized, assessor-blind, parallel group-controlled trial in Chinese youth (aged 15-25 years) with insomnia disorder and subclinical depressive symptoms. Participants were randomly assigned (1:1) to 6-week app-based CBT-I or 6-week app-based health education (HE) delivered through smartphones. Online assessments and telephone clinical interviews were conducted at baseline, post-intervention, 6- and 12-month follow-ups. The primary outcome was time to onset of MDD. The secondary outcomes included depressive symptoms and insomnia at both symptom and disorder levels. Between September 9, 2019, and November 25, 2022, 708 participants (407 females [57%]; mean age, 22.1 years [SD = 1.9]) were randomly allocated to app-based CBT-I group (n = 354) or app-based HE group (n = 354). Thirty-seven participants (10%) in the intervention group and 62 participants (18%) in the control group developed new-onset MDD throughout the 12-month follow-up, with a hazard ratio of 0.58 (95% confidence interval 0.38-0.87; p = 0.008). The number needed to treat to prevent MDD at 1 year was 10.9 (6.8-26.6). The app-based CBT-I group has higher remission rates of insomnia disorder than the controls at post-intervention (52% versus 28%; relative risk 1.83 [1.49-2.24]; p < 0.001) and throughout 12-month follow-up. In addition, the CBT-I group reported a greater decrease in depressive (adjusted difference -1.0 [-1.6 to -0.5]; Cohen's d = 0.53; p < 0.001) and insomnia symptoms (-2.0 [-2.7 to -1.3], d = 0.78; p < 0.001) than the controls at post-intervention and throughout 6-month follow-up. Insomnia was a mediator of intervention effects on depression. No adverse events related to the interventions were reported., Conclusions: App-based CBT-I is effective in preventing future onset of major depression and improving insomnia outcomes among youth with insomnia and subclinical depression. These findings highlight the importance of targeting insomnia to prevent the onset of MDD and emphasize the need for wider dissemination of digital CBT-I to promote sleep and mental health in the youth population., Trial Registration: ClinicalTrials.Gov (NCT04069247)., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: YKW received personal fees from Eisai Co, Ltd, for delivering a lecture and Consultation, and sponsorship from Lundbeck HK Ltd and Aculys Pharma, Inc outside the submitted work. CMM received research support from Idorsia, Eisai and Lallemand Health Solutions, personal fees from Idorsia, Eisai and Haleon, and received royalties from Mapi Research Trust outside the submitted work. JHZ provided consultancy for BestCare & SuMian BioTech Co, Ltd. JWYC received personal fee from Eisai Co., Ltd and travel support from Lundbeck HK limited for overseas conference outside the submitted work. The other authors have declared that no competing interests exist (SJC, QJY, NYC, LS, SXL, WZH, CXC, CCT, YLH, and LL)., (Copyright: © 2025 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The varying sizes of effects in published meta-analyses on digital interventions for depression prompt questions about their efficacy., Methods: A systematic search in Embase, PsycINFO, and PubMed identified 125 randomised controlled trials up to February 2023, comparing digital interventions for depression against inactive controls. The stability of results was evaluated with a multiverse meta-analysis, thousands of meta-analyses were conducted based on different combinations of analytical choices, like target populations, intervention characteristics, and study designs., Results: A total of 3638 meta-analyses were performed based on 125 randomised controlled trials and 263 effect sizes, with a total of 32,733 participants. The average effect size was Hedges' g = 0.43, remaining positive at both the 10th (g = 0.16) and 90th percentiles (g = 0.74). Most meta-analyses indicated a statistically significant benefit of digital interventions. Larger effects were observed in meta-analyses focusing on adults, low- and middle-income countries, guided interventions, comparing interventions with waitlist controls, and patients with major depressive or unipolar mood disorders. Smaller effects appeared when adjusting for publication bias and in assessments after 24 weeks., Limitations: While multiverse meta-analysis aims to exhaustively investigate various analytical decisions, some subjectivity remains due to the necessity of making choices that affect the methodology. Additionally, the quality of the included primary studies was low., Conclusions: The analytical decisions made during performing pairwise meta-analyses result in vibrations from small to medium effect sizes. Our study provides robust evidence for the effectiveness of digital interventions for depression while highlighting important factors associated with treatment outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)