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 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 = .0186), role-physical (P < .0006), and mental health (P < .0333) 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.

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.

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.

[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.

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.

[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.

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.

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.

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.

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.

Transcranial magnetic stimulation as a feasible, non-invasive, neuromodulatory intervention in fetal alcohol spectrum disorders. A very first proof of concept.

INTRODUCTION: A neurobiological feature of Fetal Alcohol Spectrum Disorder (FASD) is a global decrease in neuronal connectivity, which leads to significant impairments in everyday functionality. Non-invasive repetitive transcranial magnetic stimulation (rTMS) could potentially positively influence neuronal plasticity but has not yet been studied in FASD. The present trial addresses this gap, making it the first-ever study of rTMS in FASD. MATERIALS AND METHODS: The prospective clinical trial was conducted at the LMU University Hospital Munich and enrolled eight FASD participants aged 6-16. Six sessions of 1 Hz-rTMS over the left dorsolateral prefrontal cortex were administered two times a week for three weeks consisting of 1500 pulses at 90 % of resting motor threshold in four trains of 375s. Outcome measures investigated feasibility and treatment response of rTMS on executive functions, attention/impulsivity, social-emotional regulation and quality of life (QoL) via standardized tests and the FASD parents' app. RESULTS: Adherence and retention rate were 100 %. Adverse events (AEs) were mild and self-limiting, resulting in a per-session risk of 53.3 %, with local paraesthesia accounting for 54.2 % of the AEs. There were individual relevant but no significant group-level improvements in the investigated functional cerebral domains or participants' QoL. The FASD parents' app showed no significant change in participants' daily functioning or caregivers' QoL. Caregivers' parental stress decreased significantly. CONCLUSION: FASD is a very complex disorder that is difficult to treat. In addition, comorbidities as atypical responses to pharmacotherapies are frequent. For this reason, non-invasive, innovative therapies for children with FASD have to be developed. For the first time, rTMS was shown to be safe, tolerable, and acceptable and thus well feasible in paediatric patients with FASD. Further clinical studies with larger samples are needed to identify effective stimulation protocols and to evaluate treatment response.

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.

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).

Suicidal behaviors and adverse childhood experiences: A cross-diagnostic study in persistent depressive disorder and borderline personality disorder.

Adverse childhood experiences (ACE) constitute a known risk factor for suicidality. There is a research gap regarding differential patterns of associations between variants of suicidal ideations and behaviors (SIB) and characteristics of ACE in severe mental disorders. This cross-diagnostic study investigates whether SIB are related to ACE subtypes in two high-risk conditions, i.e., persistent depressive disorder (PDD) and borderline personality disorder (BPD). Inpatients with PDD (n = 117; age 40.2 years ± 12.3) and BPD (n = 74; age 26.2 ± 7.9) were assessed with the Columbia-Suicide Severity Rating Scale for suicidal ideations (SI), suicidal behaviors (SB) and actual suicide attempts (SA); ACE were recorded with the Childhood Trauma Questionnaire. In PDD, SI and SA were associated with childhood physical abuse (ORs 7.2 and 2.3, respectively). In BPD, SA were associated with severe experiences of physical abuse (OR 6.5). Weaker yet significant associations were found for childhood emotional abuse in PDD with SB (including SA), and in BPD with SA. Recall of childhood physical abuse may be clinically relevant information for identifying particular risks of SIB. Future studies should investigate these differential patterns in more depth and in terms of causality.

Effects of resilience and timing of adverse and adaptive experiences on interpersonal behavior: a transdiagnostic study in a clinical sample.

Adverse childhood experiences (ACE) have been linked to less prosocial behavior during social exclusion in vulnerable groups. However, little is known about the impact of the timing of ACE and the roles of protective factors. Therefore, this study investigated the association of the behavioral response to experimental partial social exclusion with adverse and adaptive experiences across age groups and resilience in clinical groups with persistent depressive disorder and borderline personality disorder, i.e., groups with high ACE, and in healthy controls (HC) (N = 140). Adverse and adaptive experiences during childhood, youth, and adulthood were assessed with the Traumatic Antecedents Questionnaire, and resilience was measured with the Connor Davidson Resilience Scale. A modified version of the Cyberball paradigm was used to assess the direct behavioral response to partial social exclusion. In patients, adverse events during youth (B = - 0.12, p = 0.016) and adulthood (B = - 0.14, p = 0.013) were negatively associated with prosocial behavior, whereas in the HC sample, adaptive experiences during youth were positively associated with prosocial behavior (B = 0.25, p = 0.041). Resilience did not mediate these effects. The findings indicate that critical events during youth may be particularly relevant for interpersonal dysfunction in adulthood.