Dose-dependent target engagement of a clinical iTBS protocol: An interleaved TMS-fMRI study in healthy subjects.

BACKGROUND: Intermittent theta burst stimulation (iTBS) of the dorsolateral prefrontal cortex (DLPFC) is widely applied as therapeutic intervention in mental health, however understanding of its mechanisms is still incomplete. Prior MRI studies have mainly used offline iTBS or short sequences in concurrent TMS-fMRI. This study investigated a full 600 stimuli iTBS protocol using interleaved TMS-fMRI in comparison with two control conditions in healthy subjects. METHODS: In a crossover design, 18 participants underwent three sessions of interleaved iTBS-fMRI: 1) left DLPFC at 40% resting motor threshold (rMT) intensity, 2) left DLPFC at 80% rMT intensity, and 3) left primary motor cortex (M1) at 80% rMT intensity. We compared immediate blood-oxygen-level-dependent (BOLD) responses during interleaved iTBS-fMRI across these conditions including correlations between individual fMRI BOLD activation and iTBS induced electric field (E-field) strength at the target sites. RESULTS: Whole-brain analysis showed increased activation in several regions following iTBS. Specifically, left DLPFC, as well as bilateral M1, anterior cingulate cortex, and insula showed increased activation during 80% rMT left DLPFC stimulation. Increased BOLD activity in the left DLPFC was not observed with 40% rMT left DLPFC stimulation nor left M1 80% rMT iTBS, whereas activation in other regions was found to overlap between conditions. Of note, BOLD activation and E-field intensities were only correlated for M1 stimulation, but not for the DLPFC conditions. CONCLUSIONS: The study showed dosage and target specific BOLD activation during interleaved TMS-fMRI with 600 stimuli iTBS in healthy subjects. Future studies may use our approach for demonstrating target engagement.

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.

Childhood Trauma Questionnaire-based child maltreatment profiles to predict efficacy of the Cognitive Behavioral Analysis System of Psychotherapy versus non-specific psychotherapy in adults with early-onset chronic depression: cluster analysis of data from a randomised controlled trial.

BACKGROUND: Child maltreatment is a broadly confirmed risk factor for mental and physical illness. Some psychological treatments specifically target mental health conditions associated with child maltreatment. For example, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) focuses on maladaptive interpersonal behaviours in chronic depression. However, how the assessment of child maltreatment could inform personalised treatment is unclear. We used data from a previously published clinical trial to investigate whether a pre-established child maltreatment clustering approach predicts differential outcomes after CBASP versus non-specific supportive psychotherapy in patients with early-onset chronic depression. METHODS: We did a cluster analysis of data from a previous randomised controlled trial of unmedicated adult outpatients with early-onset chronic depression who were treated at eight university clinics and psychological institutes in Germany with 32 sessions of CBASP or non-specific supportive psychotherapy. Participants were eligible for the original trial if they were aged 18-65 years; had major depressive disorder (MDD) with an early onset and duration of at least 2 years, current MDD superimposed on a pre-existing dysthymic disorder, or recurrent MDD with incomplete remission between episodes as defined by DSM-IV; and had a score of at least 20 points on the 24-item Hamilton Rating Scale for Depression (HRSD-24). Participants were included in the current study if they had completed the short form of the Childhood Trauma Questionnaire (CTQ) at trial baseline. We used an agglomerative hierarchical clustering approach to derive child maltreatment clusters from individual patterns across the five domains of the CTQ. We used linear mixed models to investigate whether clustering could predict differential clinical outcomes (change in symptom severity on the HRSD-24) up to 2 years after treatment onset. People with lived experience were involved in the current study. FINDINGS: 253 patients (129 [51%] treated with CBASP and 124 [49%] with supportive psychotherapy) had complete CTQ records and were included in the analysis. 169 (67%) participants were women, 84 (33%) were men, and the mean age was 45·9 years (SD 11·7). We identified seven child maltreatment clusters and found significant differences in treatment effects of CBASP and supportive psychotherapy between the clusters (F(6,948·76)=2·47; p=0·023); differences were maintained over the 2-year follow-up. CBASP was superior in distinct clusters of co-occurring child maltreatment: predominant emotional neglect (change in ß -6·02 [95% CI -11·9 to -0·13]; Cohen's d=-0·98 [95% CI -1·94 to -0·02]; p=0·045), predominant emotional neglect and abuse (-6·39 [-10·22 to -2·56]; -1·04 [-1·67 to -0·42]; p=0·0011), and emotional neglect and emotional and physical abuse (-9·41 [-15·91 to -2·91]; -1·54 [-2·6 to -0·47]; p=0·0046). INTERPRETATION: CTQ-based cluster analysis can facilitate identification of patients with early-onset chronic depression who would specifically benefit from CBASP. Child maltreatment clusters could be implemented in clinical assessments and serve to develop and personalise trauma-informed care in mental health. FUNDING: The German Research Foundation and the German Federal Ministry of Education and Research.

Non-invasive brain stimulation for treatment-resistant schizophrenia: protocol of a systematic review and network meta-analysis.

BACKGROUND: Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia. METHODS: We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach. DISCUSSION: Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO-ID CRD42023410645.

Female sex and age-based advantage of simulated electric field in TMS to the prefrontal cortex in schizophrenia and mood disorders.

This study investigates computational models of electric field strength for transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex (DLPFC) based on individual MRI data of patients with schizophrenia (SZ), major depressive disorder (MDD), bipolar disorder (BP), and healthy controls (HC). In addition, it explores the association of electric field intensities with age, gender and intracranial volume. The subjects were 23 SZ (12 male, mean age = 45.30), 24 MDD (16 male, mean age = 43.57), 23 BP (16 male, mean age = 39.29), 23 HC (13 male, mean age = 40.91). Based on individual MRI sequences, electric fields were computationally modeled by two independent investigators using SimNIBS ver. 2.1.1. There was no significant difference in electric field strength between the groups (HC vs SZ, HC vs MDD, HC vs BP, SZ vs MDD, SZ vs BP, MDD vs BP). Female subjects showed higher electric field intensities in widespread areas than males, and age was positively significantly associated with electric field strength in the left parahippocampal area as observed. Our results suggest differences in electric field strength of left DLPFC TMS for gender and age. It may open future avenues for individually modeling TMS based on structural MRI data.

Longitudinal assessment of health-related quality of life and clinical outcomes with at home advanced pneumatic compression treatment of lower extremity lymphedema.

OBJECTIVE: This prospective, longitudinal, pragmatic study describes at home treatment with a proprietary advanced pneumatic compression device (APCD) for patients with lower extremity lymphedema (LED). METHODS: Following institutiona review board approval, four participating Veterans Affairs centers enrolled LED patients from 2016 to 2022. The primary outcome measures were health-related quality of life (HR-QoL) questionnaires (lymphedema quality of life-leg and the generic SF-36v2) obtained at baseline and 12, 24, and 52 weeks. The secondary outcome measures were limb circumference, cellulitis events, skin quality, and compliance with APCD and other compression therapies. RESULTS: Because a portion of the trial was conducted during the coronavirus disease 2019 pandemic, 179 patients had 52 weeks of follow-up, and 143 had complete measurements at all time points. The baseline characteristics were a mean age of 66.9 ± 10.8 years, 91% were men, and the mean body mass index was 33.8 ± 6.9 kg/m2. LED was bilateral in 92.2% of the patients. Chronic venous insufficiency or phlebolymphedema was the most common etiology of LED (112 patients; 62.6%), followed by trauma or surgery (20 patients; 11.2%). Cancer treatment as a cause was low (4 patients; 2.3%). Patients were classified as having International Society for Lymphology (ISL) stage I (68.4%), II (27.6%), or III (4.1%). Of the primary outcome measures, significant improvements were observed in all lymphedema quality of life-leg domains of function, appearance, symptoms, and emotion and the overall score after 12 weeks of treatment (P < .0001) and through 52 weeks of follow-up. The SF-36v2 demonstrated significant improvement in three domains at 12 weeks and in the six domains of physical function, bodily pain, physical component (P < .0001), social functioning (P = .0181), role-physical (P < .0005), and mental health (P < .0334) at 52 weeks. An SF-36v2 score <40 indicates a substantial reduction in HR-QoL in LED patients compared with U.S. norms. Regarding the secondary outcome measures at 52 weeks, compared with baseline, the mean limb girth decreased by 1.4 cm (P < .0001). The maximal reduction in mean limb girth was 1.9 cm (6.0%) at 12 weeks in ISL stage II and III limbs. New episodes of cellulitis in patients with previous episodes (21.4% vs 6.1%, P = .001) were reduced. The 75% of patients with skin hyperpigmentation at baseline decreased to 40% (P < .01) at 52 weeks. At 52 weeks, compliance, defined as use for 5 to 7 days per week, was reported for the APCD by 72% and for elastic stockings by 74%. CONCLUSIONS: This longitudinal study of Veterans Affairs patients with LED demonstrated improved generic and disease-specific HR-QoL through 52 weeks with at home use of an APCD. Limb girth, cellulitis episodes, and skin discoloration were reduced, with excellent compliance.

Impact of adult-onset multiple sclerosis on MRI-based intracranial volume: A study in clinically discordant monozygotic twins.

OBJECTIVE: Intracranial volume (ICV) represents the maximal brain volume for an individual, attained prior to late adolescence and remaining constant throughout life after. Thus, ICV serves as a surrogate marker for brain growth integrity. To assess the potential impact of adult-onset multiple sclerosis (MS) and its preceding prodromal subclinical changes on ICV in a large cohort of monozygotic twins clinically discordant for MS. METHODS: FSL software was used to derive ICV estimates from 3D-T1-weighted-3 T-MRI images by using an atlas scaling factor method. ICV were compared between clinically affected and healthy co-twins. All twins were compared to a large healthy reference cohort using standardized ICV z-scores. Mixed models assessed the impact of age at MS diagnosis on ICV. RESULTS: 54 twin-pairs (108 individuals/80female/42.45 ± 11.98 years), 731 individuals (375 non-twins, 109/69 monozygotic/dizygotic twin-pairs; 398female/29.18 ± 0.13 years) and 35 healthy local individuals (20male/31.34 ± 1.53 years). In 45/54 (83 %) twin-pairs, both clinically affected and healthy co-twins showed negative ICV z-scores, i.e., ICVs lower than the average of the healthy reference cohort (M = -1.53 ± 0.11, P<10-5). Younger age at MS diagnosis was strongly associated with lower ICVs (t = 3.76, P = 0.0003). Stratification of twin-pairs by age at MS diagnosis of the affected co-twin (≤30 versus > 30 years) yielded lower ICVs in those twin pairs with younger age at diagnosis (P = 0.01). Comparison within individual twin-pairs identified lower ICVs in the MS-affected co-twins with younger age at diagnosis compared to their corresponding healthy co-twins (P = 0.003). CONCLUSION: We offer for the first-time evidence for strong associations between adult-onset MS and lower ICV, which is more pronounced with younger age at diagnosis. This suggests pre-clinical alterations in early neurodevelopment associated with susceptibility to MS both in individuals with and without clinical manifestation of the disease.

Clinician treatment choices for post-traumatic stress disorder: ambassadors survey of psychiatrists in 39 European countries.

BACKGROUND: Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians' treatment choices for post-traumatic stress disorder (PTSD). METHODS: The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148). RESULTS: About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct "profiles" of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines. CONCLUSIONS: Clinicians' decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

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.

[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.

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.

Home-Use Transcranial Direct Current Stimulation for the Treatment of a Major Depressive Episode: A Randomized Clinical Trial.

Importance: Transcranial direct current stimulation (tDCS) is moderately effective for depression when applied by trained staff. It is not known whether self-applied tDCS, combined or not with a digital psychological intervention, is also effective. Objective: To determine whether fully unsupervised home-use tDCS, combined with a digital psychological intervention or digital placebo, is effective for a major depressive episode. Design, Setting, and Participants: This was a double-blinded, sham-controlled, randomized clinical trial with 3 arms: (1) home-use tDCS plus a digital psychological intervention (double active); (2) home-use tDCS plus digital placebo (tDCS only), and (3) sham home-use tDCS plus digital placebo (double sham). The study was conducted between April 2021 and October 2022 at participants' homes and at Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. Included participants were aged 18 to 59 years with major depression and a Hamilton Depression Rating Scale, 17-item version (HDRS-17), score above 16, a minimum of 8 years of education, and access to a smartphone and internet at home. Exclusion criteria were other psychiatric disorders, except for anxiety; neurologic or clinical disorders; and tDCS contraindications. Interventions: tDCS was administered in 2-mA, 30-minute prefrontal sessions for 15 consecutive weekdays (1-mA, 90-second duration for sham) and twice-weekly sessions for 3 weeks. The digital intervention consisted of 46 sessions based on behavioral therapy. Digital placebo was internet browsing. Main Outcomes and Measures: Change in HDRS-17 score at week 6. Results: Of 837 volunteers screened, 210 participants were enrolled (180 [86%] female; mean [SD] age, 38.9 [9.3] years) and allocated to double active (n = 64), tDCS only (n = 73), or double sham (n = 73). Of the 210 participants enrolled, 199 finished the trial. Linear mixed-effects models did not reveal statistically significant group differences in treatment by time interactions for HDRS-17 scores, and the estimated effect sizes between groups were as follows: double active vs tDCS only (Cohen d, 0.05; 95% CI, -0.48 to 0.58; P = .86), double active vs double sham (Cohen d, -0.20; 95% CI, -0.73 to 0.34; P = .47), and tDCS only vs double sham (Cohen d, -0.25; 95% CI, -0.76 to 0.27; P = .35). Skin redness and heat or burning sensations were more frequent in the double active and tDCS only groups. One nonfatal suicide attempt occurred in the tDCS only group. Conclusions and Relevance: Unsupervised home-use tDCS combined with a digital psychological intervention or digital placebo was not found to be superior to sham for treatment of a major depressive episode in this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04889976.

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.

Loneliness Is Associated With Lower Self- and Clinician-Rated Levels of Personality Functioning.

Personality disorders (PDs) are associated with interpersonal dysfunction, loneliness, and reduced social embeddedness. This study investigates loneliness and social network size in association with self- and clinician-rated personality functioning regarding the DSM-5's Alternative Model for Personality Disorders (AMPD). Eighty psychiatric inpatients including participants with and without PDs completed the Semi-structured Interview for Personality Functioning, the Level of Personality Functioning Scale - Brief Form, the UCLA Loneliness Scale, and the Social Network Index. Patients with PDs reported more loneliness and personality dysfunctioning than patients without PDs. Social network size did not differ between patient groups and showed lower correlations with personality functioning compared to loneliness. Loneliness was further associated with deficits in personality functioning. Deficits in distinct AMPD domains and loneliness may constitute transdiagnostically relevant factors that are related and mutually reinforcing. This could be important for identifying patients beyond PD diagnoses who are at risk of poor psychosocial functioning and require tailored psychotherapy.

EMDR therapy vs. supportive therapy as adjunctive treatment in trauma-exposed bipolar patients: A randomised controlled trial.

INTRODUCTION: Patients with bipolar disorder (BD) are frequently exposed to traumatic events which worsen disease course, but this study is the first multicentre randomised controlled trial to test the efficacy of a trauma-focused adjunctive psychotherapy in reducing BD affective relapse rates. MATERIALS AND METHODS: This multicentre randomised controlled trial included 77 patients with BD and current trauma-related symptoms. Participants were randomised to either 20 sessions of trauma-focused Eye Movement Desensitization and Reprocessing (EMDR) therapy for BD, or 20 sessions of supportive therapy (ST). The primary outcome was relapse rates over 24-months, and secondary outcomes were improvements in affective and trauma symptoms, general functioning, and cognitive impairment, assessed at baseline, post-treatment, and at 12- and 24-month follow-up. The trial was registered prior to starting enrolment in clinical trials (NCT02634372) and carried out in accordance with CONSORT guidelines. RESULTS: There was no significant difference between treatment conditions in terms of relapse rates either with or without hospitalisation. EMDR was significantly superior to ST at the 12-month follow up in terms of reducing depressive symptoms (p=0.0006, d=0.969), manic symptoms (p=0.027, d=0.513), and improving functioning (p=0.038, d=0.486). There was no significant difference in dropout between treatment arms. CONCLUSIONS: Although the primary efficacy criterion was not met in the current study, trauma-focused EMDR was superior to ST in reducing of affective symptoms and improvement of functioning, with benefits maintained at six months following the end of treatment. Both EMDR and ST reduced trauma symptoms as compared to baseline, possibly due to a shared benefit of psychotherapy. Importantly, focusing on traumatic events did not increase relapses or dropouts, suggesting psychological trauma can safely be addressed in a BD population using this protocol.

Transcranial direct current stimulation as treatment for major depression in a home treatment setting (HomeDC trial): study protocol and methodology of a double-blind, placebo-controlled pilot study.

INTRODUCTION: Transcranial direct current stimulation (tDCS) of prefrontal cortex regions has been reported to exert therapeutic effects in patients with major depressive disorder (MDD). Due to its beneficial safety profile, its easy mode of application, and its cost-effectiveness, tDCS has recently been proposed for treatment at home. This would offer new chances for regionally widespread and long-term application. However, tDCS at home must meet the new methodological challenges of handling and adherence. At the same time, data from randomized controlled trials (RCT) investigating this mode of application are still lacking. In this pilot RCT, we therefore investigate the feasibility, safety, and effectiveness of a new antidepressant tDCS application set-up. METHODS AND ANALYSIS: The HomeDC trial will be conducted as a double-blind, placebo-controlled, parallel-group design trial. Thirty-two study participants with MDD will be randomly assigned to active or sham tDCS groups. Participants will self-administer prefrontal tDCS for 6 weeks. Active tDCS will be conducted with anode over F3, cathode over F4, for 5 sessions/week, with a duration of 30 min/day, and 2 mA stimulation intensity. Sham tDCS, conversely, follows an identical protocol in regard to electrode montage and timing, but with no electric stimulation between the ramp-in and ramp-out periods. Both conditions will be administered either as a monotherapy or an adjunctive treatment to a stable dose of antidepressant medication. Adjunctive magnetic resonance imaging (MRI) and electric field (E-field) modelling will be conducted at baseline. Primary outcome is feasibility based on successfully completed stimulations and drop-out rates. The intervention is considered feasible when 20 out of 30 sessions have been fully conducted by at least 75% of the participants. Effectiveness and safety will be assessed as secondary outcomes. DISCUSSION: In the HomeDC trial, the technical requirements for a placebo-controlled tDCS study in a home-based treatment setting have been established. The trial addresses the crucial points of the home-based tDCS treatment approach: uniform electrode positioning, frequent monitoring of stimulation parameters, adherence, and ensuring an appropriate home treatment environment. This study will further identify constraints and drawbacks of this novel mode of treatment. TRIAL REGISTRATION: www. CLINICALTRIALS: gov . TRIAL REGISTRATION NUMBER: NCT05172505. Registration date: 12/13/2021.

Driving-related cognitive skills during antidepressant transcranial direct current stimulation: results in a subsample from the DepressionDC trial.

Therapeutic transcranial direct current stimulation (tDCS) is a well-tolerated neuromodulatory intervention. However, there are currently no data on its impact on driving skills. Therefore, we conducted a validated assessment of driving-related cognitive skills in participants of the DepressionDC trial, a multicenter, randomized-controlled trial investigating the antidepressant effects of 6-week prefrontal tDCS in patients with major depressive disorder (MDD). Twenty-one patients (12 women, active tDCS, n = 11, sham, n = 10) underwent an assessment of driving-related cognitive skills before and after the intervention. Using a Bayesian analysis approach, we found no group differences between active tDCS and sham tDCS in the pre-post treatment changes for visual perception (estimated median difference: 3.41 [-3.17, 10.55 89%-CI], BF01: 2.1), stress tolerance (estimated median difference: 0.77 [-2.40, 4.15 89%-CI], BF01: 1.6), and reaction time (estimated median difference: 2.06 [-12.33, 16.83 89%-CI], BF01: 6.5). Our results indicate that repeated sessions of a conventional bifrontal tDCS protocol do not negatively impact driving-related cognitive skills in patients with MDD.