Neural response during prefrontal theta burst stimulation: Interleaved TMS-fMRI of full iTBS protocols.

BACKGROUND: Left prefrontal intermittent theta-burst stimulation (iTBS) has emerged as a safe and effective transcranial magnetic stimulation (TMS) treatment protocol in depression. Though network effects after iTBS have been widely studied, the deeper mechanistic understanding of target engagement is still at its beginning. Here, we investigate the feasibility of a novel integrated TMS-fMRI setup and accelerated echo planar imaging protocol to directly observe the immediate effects of full iTBS treatment sessions. OBJECTIVE/HYPOTHESIS: In our effort to explore interleaved iTBS-fMRI feasibility, we hypothesize that TMS will induce acute BOLD signal changes in both the stimulated area and interconnected neural regions. METHODS: Concurrent TMS-fMRI with full sessions of neuronavigated iTBS (i.e. 600 pulses) of the left dorsolateral prefrontal cortex (DLPFC) was investigated in 18 healthy participants. In addition, we conducted four TMS-fMRI sessions in a single patient on long-term maintenance iTBS for bipolar depression to test the transfer to clinical cases. RESULTS: Concurrent TMS-fMRI was feasible for iTBS sequences with 600 pulses. During interleaved iTBS-fMRI, an increase of the BOLD signal was observed in a network including bilateral DLPFC regions. In the clinical case, a reduced BOLD response was found in the left DLPFC and the subgenual anterior cingulate cortex, with high variability across individual sessions. CONCLUSIONS: Full iTBS sessions as applied for the treatment of depressive disorders can be established in the interleaved iTBS-fMRI paradigm. In the future, this experimental approach could be valuable in clinical samples, for demonstrating target engagement by iTBS protocols and investigating their mechanisms of therapeutic action.

Transcranial direct current stimulation as an additional treatment to selective serotonin reuptake inhibitors in adults with major depressive disorder in Germany (DepressionDC): a triple-blind, randomised, sham-controlled, multicentre trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been proposed as a feasible treatment for major depressive disorder (MDD). However, meta-analytic evidence is heterogenous and data from multicentre trials are scarce. We aimed to assess the efficacy of tDCS versus sham stimulation as an additional treatment to a stable dose of selective serotonin reuptake inhibitors (SSRIs) in adults with MDD. METHODS: The DepressionDC trial was triple-blind, randomised, and sham-controlled and conducted at eight hospitals in Germany. Patients being treated at a participating hospital aged 18-65 years were eligible if they had a diagnosis of MDD, a score of at least 15 on the Hamilton Depression Rating Scale (21-item version), no response to at least one antidepressant trial in their current depressive episode, and treatment with an SSRI at a stable dose for at least 4 weeks before inclusion; the SSRI was continued at the same dose during stimulation. Patients were allocated (1:1) by fixed-blocked randomisation to receive either 30 min of 2 mA bifrontal tDCS every weekday for 4 weeks, then two tDCS sessions per week for 2 weeks, or sham stimulation at the same intervals. Randomisation was stratified by site and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score (ie, <31 or ≥31). Participants, raters, and operators were masked to treatment assignment. The primary outcome was change on the MADRS at week 6, analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one treatment session. The trial was registered with ClinicalTrials.gov (NCT02530164). FINDINGS: Between Jan 19, 2016, and June 15, 2020, 3601 individuals were assessed for eligibility. 160 patients were included and randomly assigned to receive either active tDCS (n=83) or sham tDCS (n=77). Six patients withdrew consent and four patients were found to have been wrongly included, so data from 150 patients were analysed (89 [59%] were female and 61 [41%] were male). No intergroup difference was found in mean improvement on the MADRS at week 6 between the active tDCS group (n=77; -8·2, SD 7·2) and the sham tDCS group (n=73; -8·0, 9·3; difference 0·3 [95% CI -2·4 to 2·9]). Significantly more participants had one or more mild adverse events in the active tDCS group (50 [60%] of 83) than in the sham tDCS group (33 [43%] of 77; p=0·028). INTERPRETATION: Active tDCS was not superior to sham stimulation during a 6-week period. Our trial does not support the efficacy of tDCS as an additional treatment to SSRIs in adults with MDD. FUNDING: German Federal Ministry of Education and Research.

Neurocognitive function as outcome and predictor for prefrontal transcranial direct current stimulation in major depressive disorder: an analysis from the DepressionDC trial.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex might beneficially influence neurocognitive dysfunctions associated with major depressive disorder (MDD). However, previous studies of neurocognitive effects of tDCS have been inconclusive. In the current study, we analyzed longitudinal, neurocognitive data from 101 participants of a randomized controlled multicenter trial (DepressionDC), investigating the efficacy of bifrontal tDCS (2 mA, 30 min/d, for 6 weeks) in patients with MDD and insufficient response to selective serotonin reuptake inhibitors (SSRI). We assessed whether active tDCS compared to sham tDCS elicited beneficial effects across the domains of memory span, working memory, selective attention, sustained attention, executive process, and processing speed, assessed with a validated, digital test battery. Additionally, we explored whether baseline cognitive performance, as a proxy of fronto-parietal-network functioning, predicts the antidepressant effects of active tDCS versus sham tDCS. We found no statistically significant group differences in the change of neurocognitive performance between active and sham tDCS. Furthermore, baseline cognitive performance did not predict the clinical response to tDCS. Our findings indicate no advantage in neurocognition due to active tDCS in MDD. Additional research is required to systematically investigate the effects of tDCS protocols on neurocognitive performance in patients with MDD.

Intermittent theta burst stimulation in adolescents and young adults with depressive disorders: protocol of a randomized, sham-controlled study with a sequential Bayesian design for adaptive trials.

Intermittent theta burst stimulation (iTBS), a variant of repetitive transcranial magnetic stimulation (rTMS), is an established treatment for adults with major depressive disorder (MDD). Due to its favorable safety profile, iTBS is also a promising early intervention in the transition phase from adolescence to early adulthood, but this has not been systematically investigated to date. Thus, the EARLY-BURST trial investigates the efficacy and safety of iTBS over the left dorsolateral prefrontal cortex (lDLPFC) in treatment-seeking young patients (age 16-26 years) with depressive disorders (i.e. major depressive disorder, persistent depressive disorder, bipolar depression), allowing for relevant co-morbidities. Participants have not received antidepressant or antipsychotic medication during the last 12 months except for short-term (< 2 weeks) on-demand medication. The trial will employ a novel sequential Bayesian, randomized, double-blind, parallel-group, sham-controlled design. Up to 90 patients at two clinical sites (Munich, Augsburg) will be randomized 1:1 to the treatment groups, with sequential analyses starting after 26 patients in each group completed the treatment. The primary outcome will be the difference in depression severity at week 6 (post-treatment visit) between active iTBS and sham iTBS, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). The trial is planned to be expanded towards a three-arm leapfrog design, contingent on securing additional funding. Thus, in addition to potentially providing evidence of iTBS's efficacy in adolescents and young adults with depressive disorders, the EARLY-BURST trial aims at setting the stage for subsequent platform trials in this dynamic research field, where novel adaptive study designs are required to meet the need for rapidly testing promising new vs established rTMS protocols.Trial registration: DRKS00033313.

Preemptive treatment of type II endoleak for abdominal aortic aneurysm with renal fusion (horseshoe kidney).

OBJECTIVE: To assess viability and safety of preemptive treatment of type II endoleak for abdominal aortic aneurysm (AAA) repairs. METHODS: A 69-year-old man with renal fusion (horseshoe kidney) was referred for treatment of a 5.5 cm AAA. His anatomy was suitable for endovascular repair. The risk for type II endoleak was increased because of multiple infrarenal arterial orifices originating within the aneurysm sac. These included an accessory renal artery that supplied the renal isthmus, a patent inferior mesenteric artery, and a pair of large lumbar arteries originating from a single orifice (8 mm) at L3 spinal level. The lumbar orifice was selectively cannulated and occluded with thrombogenic coils 1 week prior to his endovascular aneurysm repair. RESULTS: Aneurysm repair was uneventful with no signs of early or delayed endoleak and long-term follow-up of 5 years. CONCLUSIONS: Preemptive coil embolization of perianeurysmal arteries may be considered as a safe and effective strategy for management of potential type II endoleak.

Culturally sensitive stepped care for adolescent refugees: efficacy and cost-utility of a multicentric randomized controlled trial.

Adolescent refugees and asylum seekers (ARAS) are highly vulnerable to mental health problems. Stepped care models (SCM) and culturally sensitive therapies offer promising treatment approaches to effectively provide necessary medical and psychological support. To our knowledge, we were the first to investigate whether a culturally sensitive SCM will reduce symptoms of depression and PTSD in ARAS more effectively and efficiently than treatment as usual (TAU). We conducted a multicentric, randomized, controlled and rater-blinded trial across Germany with ARAS between the ages of 14 to 21 years. Participants (N = 158) were stratified by their level of depressive symptom severity and then equally randomized to either SCM or TAU. Depending on their severity level, SCM participants were allocated to tailored interventions. Symptom changes were assessed for depression (PHQ) and PTSD (CATS) at four time points, with the primary end point at post-intervention after 12 weeks. Based on an intention-to-treat sample, we used a linear mixed model approach for the main statistical analyses. Further evaluations included cost-utility analyses, sensitivity analyses, follow-up-analyses, response and remission rates and subgroup analysis. We found a significant reduction of PHQ (d = 0.52) and CATS (d = 0.27) scores in both groups. However, there was no significant difference between SCM and TAU. Cost-utility analyses indicated that SCM generated greater cost-utility when measured as quality-adjusted life years compared to TAU. Subgroup analysis revealed different effects for the SCM interventions depending on the outcome measure. Although culturally sensitive, SCMs did not prove to be more effective in symptom change and represent a more cost-effective treatment alternative for mentally burdened ARAS. Our research contributes to the optimization of clinical productivity and the improvement of therapeutic care for ARAS. Disorder-specific interventions should be further investigated.

[Video-Assisted Psychotherapy For Refugees: A Pilot Study]. / Videogestützte Psychotherapie für Geflüchtete: Eine Pilotstudie.

OBJECTIVE: Global conflicts and humanitarian crises led to an increase in forced migration to Germany in recent years. To improve the mental health care system for refugees and asylum seekers in Germany perspectively, we aim to examine the feasibility of implementing the culturally sensitive group psychotherapy Empowerment for refugees with affective disorders in a video-assisted setting. METHODS: Empowerment is a culturally sensitive, interpreter-assisted intervention for the treatment of depressive and stress-related symptoms in refugees. Four male refugees from Afghanistan participated in a pilot study. The intervention included 16 modules delivered via video over a 12-week period. RESULTS: The internet connection was frequently unstable and led to organizational challenges. The therapy was feasible in terms of linguistic and interactional aspects. DISCUSSION: The stability of the internet connection represents the major criterion for a successful implementation of the therapy. Implications for future studies are discussed. CONCLUSION: Regarding the potential opportunities to improve the mental health care provision to refugees and asylum seekers in the future, the video-assisted therapy concept could be investigated in a randomized controlled trial.

[On the Admission of Patients with Borderline Personality Disorder to Outpatient Psychotherapy]. / Zur Aufnahme von Patient*innen mit Borderline Persönlichkeitsstörung in die ambulante Psychotherapie.

BACKGROUND: Patients with borderline personality disorder (BPD) present difficulties in self-regulation and interaction, which is a challenge for psychotherapists that is also addressed in BPD-specific interventions. Against this background, outpatient psychotherapists were surveyed about the factors playing a decisive role in their treatment offer for patients with BPD. METHODS: Psychotherapists for adults were contacted via their email address published on the website of the Kassenärztliche Vereinigung (Association of Statutory Health Insurance Physicians), 231 of whom answered an online questionnaire. The results were analysed descriptively and examined inferentially with regard to the psychotherapists' admission behaviour. RESULTS: Almost 90% reported that they would generally accept patients with BPD in therapy. However, of those, 85% did not have a therapy slot available. The psychotherapists' learned approach of treatment was not a decisive factor in determining whether they were willing to provide treatment. Most of the psychotherapists (85%) recommended a BPD disorder-specific therapy such as Dialectical Behavior Therapy (DBT), Mentalization-Based Treatment (MBT), Transference-Focused Psychotherapy (TFP) or Schema Therapy (ST). However, only just under 7% were certified in such a disorder-specific approach. Significant individual stress factors described by the psychotherapists were suicidal risk (70%) and potential other-directed aggression (59%). In addition, it was shown that it played a role whether the psychotherapists were trained in an additional therapy approach (with at least 16 teaching units) or not. CONCLUSION: The care situation for people with BPD seeking an outpatient psychotherapy place is clearly in need of improvement. This is mainly due to a general lack of available therapy places as well as various fears and anxieties, such as increased suicidality, which in turn can have a negative impact on the provision of outpatient therapy. Psychotherapists who have undergone disorder-specific further training feel less burdened by suicidal behaviour. However, since only a small number of them are able to offer BPD-specific therapies, it is essential to expand and (financially) support specific training programmes. In order to meet the demand for care, professional changes are urgently needed.

Altered amygdalar emotion space in borderline personality disorder normalizes following dialectical behaviour therapy.

BACKGROUND: Borderline personality disorder (BPD) is a mental health condition characterized by an inability to regulate emotions or accurately process the emotional states of others. Previous neuroimaging studies using classical univariate analyses have tied such emotion dysregulation to aberrant activity levels in the amygdala of patients with BPD. However, multivariate analyses have not yet been used to investigate how representational spaces of emotion information may be systematically altered in patients with BPD. METHODS: Patients with BPD performed an emotional face matching task while undergoing MRI before and after a 10-week inpatient program of dialectical behavioural therapy. Representational similarity analysis (RSA) was applied to activity patterns (evoked by angry, fearful, neutral and surprised faces) in the amygdala and temporo-occipital fusiform gyrus of patients with BPD and in the amygdala of healthy controls. RESULTS: We recruited 15 patients with BPD (8 females, 6 males, 1 transgender male) to participate in the study, and we obtained a neuroimaging data set for 25 healthy controls for a comparative analysis. The RSA of the amygdala revealed a negative bias in the underlying affective space (in that activity patterns evoked by angry, fearful and neutral faces were more similar to each other than to patterns evoked by surprised faces), which normalized after therapy. This bias-to-normalization effect was present neither in activity patterns of the temporo-occipital fusiform gyrus of patients nor in amygdalar activity patterns of healthy controls. LIMITATIONS: Larger samples and additional questionnaires would help to better characterize the association between specific aspects of therapy and changes in the neural representational space. CONCLUSION: Our findings suggest a more refined role for the amygdala in the pathological processing of perceived emotions and may provide new diagnostic and prognostic imaging-based markers of emotion dysregulation and personality disorders.Clinical trial registration: DRKS00019821, German Clinical Trials Register (Deutsches Register Klinischer Studien).

Targeting metacognitive change mechanisms in acute inpatients with psychotic symptoms: feasibility and acceptability of a modularized group intervention.

Emerging evidence suggests the usefulness of psychological interventions targeting metacognitive change mechanisms in patients experiencing psychosis. Although many of these patients are treated in acute psychiatric contexts, only few studies have adapted such interventions for acute inpatient settings. The present study aimed to assess the feasibility, acceptability, and preliminary clinical outcomes of a novel modularized group intervention focusing on different aspects of metacognitive change mechanisms. In particular, the intervention aims to reduce patients' acute symptoms by enhancing cognitive insight and to relieve distress via cognitive defusion (i.e. coping). A sample of 37 participants with acute psychosis received up to nine sessions of the intervention. Baseline and post-intervention assessments were conducted for general psychopathology, psychotic symptoms, global functioning, and symptom distress. Measures of change mechanisms were assessed before and after the respective treatment module. Participants' experiences were explored in feedback questionnaires and interviews. Recruitment, retention, and attendance rate met the pre-set feasibility benchmark of 80%. The intervention was well received by participants, who emphasised the group's clear structure, positive atmosphere, and helpful contents. Response rates were high and linear mixed models revealed significant medium-to-large time effects on all clinical outcomes. As expected, increase in hypothesised change mechanisms cognitive insight and decrease in cognitive fusion was found. However, the uncontrolled design limits interpreting clinical effects. The study provides evidence that an intervention based on a metacognitive model is feasible and acceptable for acute inpatients with psychosis. Positive results on clinical outcomes and change mechanisms warrant further exploration in a randomized controlled trial.

Transcranial direct current stimulation combined with a brief intervention for smoking cessation: a randomized double-blind clinical trial.

Non-invasive brain stimulation methods are currently being evaluated for treatment of addictive disorders. Some evidence indicates that modulating left and right prefrontal brain activity by transcranial direct current stimulation (tDCS) can reduce craving and relapse rates in tobacco addiction. Therefore, this study investigated the effects of active and sham tDCS as an add-on treatment to a standardized brief intervention for smoking cessation. This randomized, double-blind study included 36 participants (22 women and 14 men) with nicotine dependence according to ICD-10 criteria. At five visits on alternate days, participants underwent a 20-min active or sham tDCS over the left dorsolateral prefrontal cortex and subsequently participated in a 10-min brief intervention for smoking cessation. Patients were followed up after 3 months. On each treatment day and at follow-up, abstinence was assessed as the smoking status nonsmoker and craving was assessed with the German version of the Questionnaire on Smoking Urges. At each visit, the number of cigarettes smoked per day was recorded and carbon monoxide in expired air and cotinine in saliva were measured. At follow-up, a study-specific questionnaire was used to assess tobacco use. All 36 participants completed the treatment sessions, but one participant in each group was lost to follow-up. Abstinence rates were not significantly different between the groups at any of the study visits, but craving was significantly lower in the active group at tDCS session 5 compared with session 1. tDCS combined with a brief intervention may support smoking cessation, but studies need to evaluate whether longer and more intensive treatment can achieve significant, sustainable effects.

TDCS at home for depressive disorders: an updated systematic review and lessons learned from a prematurely terminated randomized controlled pilot study.

The application of transcranial direct current stimulation (tDCS) at home for the treatment of major depressive disorder (MDD) is the subject of current clinical trials. This is due to its positive safety profile, cost-effectiveness, and potential scalability for a wide outreach in clinical practice. Here, we provide a systematic review of the available studies and also a report on the results of a randomized controlled trial (RCT) on tDCS at home for the treatment of MDD. This trial had to be prematurely terminated due to safety concerns. The HomeDC trial is a double-blinded, placebo-controlled, parallel-group study. Patients with MDD (DSM-5) were randomized to active or sham tDCS. Patients conducted tDCS at home for 6 weeks with 5 sessions/week (30 min at 2 mA) anode over F3, cathode over F4. Sham tDCS resembled active tDCS, with ramp-in and ramp-out periods, but without intermittent stimulation. The study was prematurely terminated due to an accumulation of adverse events (AEs, skin lesions), so that only 11 patients were included. Feasibility was good. Safety monitoring was not sufficient enough to detect or prevent AEs within an appropriate timeframe. Regarding antidepressant effects, the reduction in depression scales over time was significant. However, active tDCS was not superior to sham tDCS in this regard. Both the conclusions from this review and the HomeDC trial show that there are several critical issues with the use of tDCS at home that need to be addressed. Nevertheless the array of transcranial electric simulation (TES) methods that this mode of application offers, including tDCS, is highly interesting and warrants further investigation in high quality RCTs. TRIAL REGISTRATION: www. CLINICALTRIALS: gov . TRIAL REGISTRATION NUMBER: NCT05172505. Registration date: 12/13/2021, https://clinicaltrials.gov/ct2/show/NCT05172505 . *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers) **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. https://doi.org/10.1136/bmj.n71 . For more information, visit: http://www.prisma-statement.org/.

Mental health problems during the COVID-19 pandemic among residents of Jimma town: a cross-sectional study.

The COVID-19 pandemic presents an unprecedented challenge to community wellbeing and mental health. However, quantifiable information on the extent of mental health problems and associated factors due to the pandemic is still lacking in low-income countries. Thus, this study aimed to investigate the levels of depression, anxiety, and stress and their association with risk and resilience factors among residents of Jimma town in Southwestern Ethiopia. A community-based cross-sectional study was conducted between October 2021 and November 2021. Data were collected from 1196 adult Jimma town residents selected through multi-stage sampling. The following scales were used for the cross-sectional assessment of depressions, anxiety and stress and their associations: depression, anxiety, and stress-21(DASS-21), World Health Organization (WHO) wellbeing, University of California, Los Angeles Loneliness Scale (UCLA), Childhood trauma questionnaire, and brief resilience scales. A pre-tested, interviewer-completed questionnaire was used for data collection. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated with depression, anxiety, and stress. Odds ratios consistent with 95% CI were used to report the presence of an association between risk and resilience factors and the outcome variable at a P-value < 0.05. Overall, 963 (80.53%) respondents had divergent DASS-21 score findings. Specifically, 27.68%, 31.52% and 21.32% experienced depression, anxiety, and stress respectively. Higher DASS-21 scores were associated with the presence of one or more COVID-19 risk factors for anyone close to the participants (AOR = 1.53, 95% CI 1.03-2.27), feelings of stress/burden (ß = 1.09, 95% CI 1.07-1.12), positive coping (ß = 1.044, 95% CI 1.01-1.07), loneliness (ß = 1.063, 95% CI 1.04-1.08), and childhood trauma (ß = 1.03, 95% CI 1.01-1.04). In contrast, lower DASS-21 scores were associated with beliefs about the necessity of solidarity-based behavior (ß = 0.94, 95% CI 0.90-0.98), resilience (ß = 0.92, 95% CI 0.87-0.97) and wellbeing (ß = 0.90, 95% CI 0.87-0.94). In the course of the COVID-19 pandemic in 2021, symptoms of depression, anxiety, and stress in the study community were prevalent, and associated with numerous risk and resilience factors. Although causality cannot be inferred, these findings underscore the importance of strengthening mental health services and may guide COVID-19 prevention and treatment strategies.

Mapping Research Domain Criteria using a transdiagnostic mini-RDoC assessment in mental disorders: a confirmatory factor analysis.

This study aimed to build on the relationship of well-established self-report and behavioral assessments to the latent constructs positive (PVS) and negative valence systems (NVS), cognitive systems (CS), and social processes (SP) of the Research Domain Criteria (RDoC) framework in a large transnosological population which cuts across DSM/ICD-10 disorder criteria categories. One thousand four hundred and thirty one participants (42.1% suffering from anxiety/fear-related, 18.2% from depressive, 7.9% from schizophrenia spectrum, 7.5% from bipolar, 3.4% from autism spectrum, 2.2% from other disorders, 18.4% healthy controls, and 0.2% with no diagnosis specified) recruited in studies within the German research network for mental disorders for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) were examined with a Mini-RDoC-Assessment including behavioral and self-report measures. The respective data was analyzed with confirmatory factor analysis (CFA) to delineate the underlying latent RDoC-structure. A revised four-factor model reflecting the core domains positive and negative valence systems as well as cognitive systems and social processes showed a good fit across this sample and showed significantly better fit compared to a one factor solution. The connections between the domains PVS, NVS and SP could be substantiated, indicating a universal latent structure spanning across known nosological entities. This study is the first to give an impression on the latent structure and intercorrelations between four core Research Domain Criteria in a transnosological sample. We emphasize the possibility of using already existing and well validated self-report and behavioral measurements to capture aspects of the latent structure informed by the RDoC matrix.

Examining the synergistic effects of a cognitive control video game and a home-based, self-administered non-invasive brain stimulation on alleviating depression: the DiSCoVeR trial protocol.

Enhanced behavioral interventions are gaining increasing interest as innovative treatment strategies for major depressive disorder (MDD). In this study protocol, we propose to examine the synergistic effects of a self-administered home-treatment, encompassing transcranial direct current stimulation (tDCS) along with a video game based training of attentional control. The study is designed as a two-arm, double-blind, randomized and placebo-controlled multi-center trial (ClinicalTrials.gov: NCT04953208). At three study sites (Israel, Latvia, and Germany), 114 patients with a primary diagnosis of MDD undergo 6 weeks of intervention (30 × 30 min sessions). Patients assigned to the intervention group receive active tDCS (anode F3 and cathode F4; 2 mA intensity) and an action-like video game, while those assigned to the control group receive sham tDCS along with a control video game. An electrode-positioning algorithm is used to standardize tDCS electrode positioning. Participants perform their designated treatment at the clinical center (sessions 1-5) and continue treatment at home under remote supervision (sessions 6-30). The endpoints are feasibility (primary) and safety, treatment efficacy (secondary, i.e., change of Montgomery-Åsberg Depression Rating Scale (MADRS) scores at week six from baseline, clinical response and remission, measures of social, occupational, and psychological functioning, quality of life, and cognitive control (tertiary). Demonstrating the feasibility, safety, and efficacy of this novel combined intervention could expand the range of available treatments for MDD to neuromodulation enhanced interventions providing cost-effective, easily accessible, and low-risk treatment options.ClinicalTrials.gov: NCT04953208.

[Inpatient psychotherapy of depressive disorders: options and challenges]. / Stationäre Psychotherapie depressiver Störungen: Möglichkeiten und Herausforderungen.

BACKGROUND: The psychotherapy of depressive disorders has become established as a central component of inpatient treatment in psychiatric and psychosomatic hospitals and furthermore constitutes an important component of the residency training in Germany; however, the number of studies examining the effectiveness and efficacy is limited. METHODS: This narrative review summarizes the current state of research on inpatient psychotherapy for depressive disorders. The results of meta-analyses as well as practice-based observational studies from routine treatment in Germany, disorder-specific special programs, and side effects of inpatient psychotherapy are summarized. RESULTS: The number of studies on the efficacy of inpatient psychotherapy of depressive disorders is overall low. The main finding of the largest recent meta-analysis indicates that psychotherapy in clinics and other facilities has a significant effect on depressive symptoms, with small to moderate effect sizes in randomized controlled studies. The effects are mostly maintained even after 9-15 months follow-up. An observational study from routine treatment with a very large sample size reported large pre-post and pre-follow-up effect sizes. It additionally revealed factors that appear to be difficult to change during inpatient psychotherapy, negatively affect treatment success and could be specifically addressed in future trials. Special programs, such as inpatient Interpersonal Psychotherapy (IPT) and the inpatient Cognitive Behavioral Analysis System of Psychotherapy (CBASP) indicate acceptance and efficacy/effectiveness in an initial randomized controlled (IPT) study and in observational (CBASP) studies. Side effects of inpatient psychotherapy were reported by 60-94% of patients with depressive disorders, whereby a perceived dependence on the therapist or the therapeutic setting was identified as a frequent side effect. CONCLUSION: Overall, the results of the narrative review reveal that inpatient psychotherapy appears to be meaningful and effective for many patients with depressive disorders. Specific side effects, cost-effectiveness, and the question of differential indications (what works for whom?) should be further investigated.

Open versus Endovascular Repair of Abdominal Aortic Aneurysm.

BACKGROUND: Elective endovascular repair of an abdominal aortic aneurysm results in lower perioperative mortality than traditional open repair, but after 4 years this survival advantage is not seen; in addition, results of two European trials have shown worse long-term outcomes with endovascular repair than with open repair. Long-term results of a study we conducted more than a decade ago to compare endovascular repair with open repair are unknown. METHODS: We randomly assigned patients with asymptomatic abdominal aortic aneurysms to either endovascular repair or open repair of the aneurysm. All the patients were candidates for either procedure. Patients were followed for up to 14 years. RESULTS: A total of 881 patients underwent randomization: 444 were assigned to endovascular repair and 437 to open repair. The primary outcome was all-cause mortality. A total of 302 patients (68.0%) in the endovascular-repair group and 306 (70.0%) in the open-repair group died (hazard ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.13). During the first 4 years of follow-up, overall survival appeared to be higher with endovascular repair than with open repair; from year 4 through year 8, overall survival was higher in the open-repair group; and after 8 years, overall survival was once again higher in the endovascular-repair group (hazard ratio for death, 0.94; 95% CI, 0.74 to 1.18). None of these trends were significant. There were 12 aneurysm-related deaths (2.7%) in the endovascular-repair group and 16 (3.7%) in the open-repair group (between-group difference, -1.0 percentage point; 95% CI, -3.3 to 1.4); most deaths occurred during the perioperative period. Aneurysm rupture occurred in 7 patients (1.6%) in the endovascular-repair group, and rupture of a thoracic aneurysm occurred in 1 patient (0.2%) in the open-repair group (between-group difference, 1.3 percentage points; 95% CI, 0.1 to 2.6). Death from chronic obstructive lung disease was just over 50% more common with open repair (5.4% of patients in the endovascular-repair group and 8.2% in the open-repair group died from chronic obstructive lung disease; between-group difference, -2.8 percentage points; 95% CI, -6.2 to 0.5). More patients in the endovascular-repair group underwent secondary procedures. CONCLUSIONS: Long-term overall survival was similar among patients who underwent endovascular repair and those who underwent open repair. A difference between groups was noted in the number of patients who underwent secondary therapeutic procedures. Our results were not consistent with the findings of worse performance of endovascular repair with respect to long-term survival that was seen in the two European trials. (Funded by the Department of Veteran Affairs Office of Research and Development; OVER ClinicalTrials.gov number, NCT00094575.).

Loneliness in Personality Disorders.

PURPOSE OF REVIEW: Loneliness is a common experience in patients with personality disorders (PDs) that are characterized by impairment in self (identity, self-direction) and interpersonal functioning (empathy, intimacy). Here, we review studies assessing the association of loneliness with PD or PD traits including DSM-5's Alternative Model of PD (AMPD). RECENT FINDINGS: The number of loneliness studies varied greatly among different PDs with most studies conducted in borderline PD. Across PDs, loneliness was associated with the severity of psychopathological symptoms and with several AMPD trait domains. Consequently, loneliness may contribute to PD severity and further impair personality functioning. Loneliness and PD share intra- and interpersonal factors (i.e., increased rejection sensitivity, information processing biases, social withdrawal) and common origins in childhood maltreatment that may explain their close association. Future research needs to investigate mechanisms on how loneliness and core characteristics of PD mutually reinforce each other in order to therapeutically address loneliness in PD.

Differential psychological response to the COVID-19 pandemic in psychiatric inpatients compared to a non-clinical population from Germany.

The COVID-19 pandemic is an inherently stressful situation, which may lead to adverse psychosocial outcomes in various populations. Yet, individuals may not be affected equally by stressors posed by the pandemic and those with pre-existing mental disorders could be particularly vulnerable. To test this hypothesis, we assessed the psychological response to the pandemic in a case-control design. We used an age-, sex- and employment status-matched case-control sample (n = 216) of psychiatric inpatients, recruited from the LMU Psychiatry Biobank Munich study and non-clinical individuals from the general population. Participants completed validated self-report measures on stress, anxiety, depression, paranoia, rumination, loneliness, well-being, resilience, and a newly developed index of stressors associated with the COVID-19 pandemic. Multiple linear regression analyses were conducted to assess the effects of group, COVID-19-specific stressors, and their interaction on the different psychosocial outcomes. While psychiatric inpatients reported larger mental health difficulties overall, the impact of COVID-19-specific stressors was lower in patients and not associated with worse psychological functioning compared to non-clinical individuals. In contrast, depressive symptoms, rumination, loneliness, and well-being were more strongly associated with COVID-19-specific stressors in non-clinical individuals and similar to the severity of inpatients for those who experienced the greatest COVID-19-specific stressor impact Contrary to expectations, the psychological response to the pandemic may not be worse in psychiatric inpatients compared to non-clinical individuals. Yet, individuals from the general population, who were hit hardest by the pandemic, should be monitored and may be in need of mental health prevention and treatment efforts.

[Transcranial electrical brain stimulation methods for treatment of negative symptoms in schizophrenia]. / Transkranielle elektrische Hirnstimulationsverfahren zur Behandlung der Negativsymptomatik bei Schizophrenie.

In recent years noninvasive brain stimulation (NIBS) applications have emerged as a third and novel treatment option alongside psychopharmacology and psychotherapy in the treatment of mental diseases. It is assumed that NIBS could represent a supplement or (in some indications) even replacement to established therapeutic strategies, e.g. in disorders with high resistance to current treatment regimens, such as negative symptoms or cognitive impairments in schizophrenia. Although positive symptoms in schizophrenia can be treated sufficiently with antipsychotic drugs, patients with negative symptoms frequently suffer from persistent lack of impetus, cognitive decline, social withdrawal and loss of global functioning in the activities of daily life; however, in these cases, current treatment strategies exert only moderate effects, and new treatment options are urgently needed. This review article provides a summary of the clinical effects of new electrical NIBS methods, e.g. transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS) for the treatment of negative symptoms in schizophrenia. These new NIBS methods could help restore the disrupted neuronal networks and improve disturbed connectivity, especially of the left dorsolateral prefrontal cortex and left temporoparietal junction. Promising results are reported for the treatment of negative symptoms with tDCS, tACS and tRNS and could thus represent new therapeutic options in the treatment of schizophrenia.