The impact of aerobic endurance training on cognitive performance in schizophrenic inpatients in a clinical routine setting.

The primary aim of this study was to investigate the impact of aerobic endurance training in schizophrenic inpatients on cognitive performance in a clinical routine setting. Of secondary interest was the influence on psychopathological symptoms. A total of 31 schizophrenic inpatients were randomly assigned to receive either controlled endurance training or occupational therapy. The experimental group underwent endurance training of 20-30 min each, 3 times per week for a total of up to 22 training sessions. The control group received about 90 min of occupational therapy, 2-3 times per week for up to 22 sessions. Cognitive performance was assessed via an extensive neuropsychological examination before randomization and prior to discharge. Significant improvements in cognitive functions and psychopathology could be shown in both groups. For verbal memory functions (short-term memory, working memory, and learning performance), there was a significant advantage for the aerobic endurance training group. Physical exercise is a feasible, easy-to-implement add-on therapy for schizophrenic patients in a clinical routine setting with positive effects on verbal memory functions. Besides, it seems important to fill the gap between inpatient and outpatient health care, providing physical training supply for this patient group.

[Treatment resistance in anxiety disorders-Definition and treatment options]. / Therapieresistenz bei Angsterkrankungen ­ Definition und Behandlungsoptionen.

Treatment resistance in anxiety disorders represents a clinical challenge, contributes to the chronicity of the diseases as well as sequential comorbidities, and is associated with a significant individual and socioeconomic burden. This narrative review presents the operational definition of treatment resistance in anxiety disorders according to international consensus criteria (< 50% reduction in the Hamilton Anxiety Scale, HAM­A, score or < 50% reduction in the Beck Anxiety Inventory, BAI, score or a clinical global impression-improvement, CGI­I, score > 2). At least two unsuccessful guideline-based treatment attempts with pharmacological monotherapy or at least one unsuccessful treatment attempt with adequately delivered cognitive behavioral therapy are required. Pharmacotherapeutically, after excluding pseudo-resistance, switching the medication within one class or to another class and augmentation strategies with other antidepressants (mirtazapine, agomelatine), antipsychotics (quetiapine) or anticonvulsants (valproate) are recommended. Psychotherapeutically, third-wave therapies, psychodynamic therapy, systemic therapy and physical exercise can be considered for therapy resistance. In cases of no response to psychotherapy or pharmacotherapy, the respective other form of therapy or a combination of both should be offered. Compounds targeting the glutamatergic and endocannabinoid systems as well as neuropeptides are being tested as potential innovative pharmaceuticals for treatment-resistant anxiety disorders. There is an urgent need for further research to identify predictive markers and mechanisms as well as to develop innovative pharmacological and psychotherapeutic interventions for treatment-resistant anxiety disorders.

Mental health improvement after the COVID-19 pandemic in individuals with psychological distress.

The COVID-19 pandemic and associated countermeasures had an immensely disruptive impact on people's lives. Due to the lack of systematic pre-pandemic data, however, it is still unclear how individuals' psychological health has been affected across this incisive event. In this study, we analyze longitudinal data from two healthy samples (N = 307) to provide quasi-longitudinal insight into the full trajectory of psychological burden before (baseline), during the first peak, and at a relative downturn of the COVID-19 pandemic. Our data indicated a medium rise in psychological strain from baseline to the first peak of the pandemic (d = 0.40). Surprisingly, this was overcompensated by a large decrease of perceived burden until downturn (d = - 0.93), resulting in a positive overall effect of the COVID-19 pandemic on mental health (d = 0.44). Accounting for this paradoxical positive effect, our results reveal that the post-pandemic increase in mental health is driven by individuals that were already facing psychological challenges before the pandemic. These findings suggest that coping with acute challenges such as the COVID-19 pandemic can stabilize previously impaired mental health through reframing processes.

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.

The definition of treatment resistance in anxiety disorders: a Delphi method-based consensus guideline.

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment-resistant anxiety disorders (TR-AD) informing such trials is currently lacking. We used a Delphi method-based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR-AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free-text responses to a 29-item questionnaire on relevant aspects of TR-AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR-AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR-AD vs. "difficult-to-treat" anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method-based consensus on operational criteria for TR-AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence-based stepped-care treatment algorithms for patients with anxiety disorders.

[VR-supported therapy for anxiety and posttraumatic stress disorder: current possibilities and limitations]. / VR-gestützte Therapie bei Angst und posttraumatischer Belastungsstörung: aktuelle Möglichkeiten und Grenzen.

BACKGROUND: Virtual reality (VR) is increasingly used in psychotherapy, and the speed of development of therapeutic VR tools is continuously increasing. OBJECTIVE: This narrative review provides an overview of the state of the art regarding VR applications for psychotherapy. MATERIAL AND METHODS: The current state of VR therapy research for anxiety disorders and posttraumatic stress disorder (PTSD) is summarized. The focus lies on VR exposure therapy. Current developments in the field are outlined. RESULTS: For anxiety disorders, especially phobic disorders, there are already positive recommendations in the current German S3 guidelines. For PTSD, the development of VR therapy tools is still in a relatively early stage. CONCLUSION: The development of mobile cost-effective VR solutions in recent years has enabled entirely new applications for VR. The empirical challenges of these new developments are considerable. Nevertheless, the chances for an improvement of psychotherapeutic routine care are good.

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.

Systematic analysis of nonfatal suicide attempts and further diagnostic of secondary injury in strangulation survivors: A retrospective cross-sectional study.

Background and Aims: Data on nonfatal suicide attempts in Germany are sparse. The study aimed to analyze data on nonfatal suicide attempts and consecutive diagnostic steps to identify secondary injuries after strangulation. Methods: All admissions after nonfatal suicide attempt in a large Bavarian psychiatric hospital between 2014 and 2018 were reviewed and the methods were analyzed. Results: A total of 2125 verified cases out of 2801 registered cases of nonfatal suicide attempts were included in further analysis. The most common methods were intoxication (n = 1101, 51.8%), cutting (n = 461, 21.7%), and strangulation (n = 183, 8.6%). Among survivors of strangulation with external neck compression (n = 99, 54.1%), no diagnostic steps were performed in 36 (36.4%) patients and insufficient imaging in 13 (20.6%) patients. Carotid artery dissection was detected in two (4.0%) of 50 patients with adequate neuroimaging. Conclusions: This study provides details on nonfatal suicide attempts in Germany. Slightly more than half of the patients with strangulation underwent adequate diagnostic work-up, with 4.0% being diagnosed with dissection. Further studies with systematic screening for dissection after strangulation in psychiatric hospitals are recommended to reduce possible under-reporting.

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.

Distraction versus focusing during VR exposure therapy for acrophobia: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: The therapeutic mechanisms of exposure therapy are not well understood. Research suggests that focusing on the most feared aspect might not be necessary, and that distraction with a low cognitive load (e.g., conversation) might enhance exposure. We aimed at systematically testing the efficacy of exposure therapy with focusing vs. conversational distraction, hypothesizing that distracted exposure would yield superior effects. METHODS: Thirty-eight patients with acrophobia (specific phobia of heights; clinician-determined) (free from relevant somatic or other mental disorders) were randomly assigned (1:1) to one virtual reality (VR) session of either focused (n = 20) or distracted exposure (n = 18). This monocentric trial took place at a psychiatric university hospital. RESULTS: Both conditions resulted in a significant reduction of acrophobic fear and avoidance, and a significant increase of self-efficacy (primary outcome variables). However, condition did not have a significant effect on any of these variables. Effects were stable at four-week follow-up. Heart rate and skin conductance level indicated significant arousal, but did not differ between conditions. LIMITATIONS: Eye-tracking was unavailable, nor did we assess emotions other than fear. Power was limited due to sample size. CONCLUSIONS: A balanced exposure protocol combining attention to fear cues with conversational distraction, while not being superior, might be as effective as focused exposure for acrophobia, at least during the initial stages of exposure therapy. These results support previous findings. This study demonstrates how VR can be exploited for therapy process research, as VR supports dismantling designs and the incorporation of online process measures.

[Anxiety, agitation, suicidality - Psychiatric emergencies in the general hospital]. / Angst, Erregung, Suizidalität ­ Psychiatrische Notfälle im Allgemeinkrankenhaus.

Psychiatric emergencies are encountered by every physician - regardless of specialty. Nevertheless, psychiatric emergencies in general hospitals are often a very significant challenge. In this article, the most important psychiatric emergency situations, diagnostic aspects as well as corresponding therapy options are presented.

Facing Your Fear in Immersive Virtual Reality: Avoidance Behavior in Specific Phobia.

Specific phobias are the most common anxiety disorder and are characterized by avoidance behavior. Avoidance behavior impacts daily function and is proposed to impair extinction learning. However, despite its prevalence, its objective assessment remains a challenge. To this end, we developed a fully automated experimental procedure using immersive virtual reality. The procedure contained a behavioral search, forced-choice, and an approach task with varying degrees of freedom and task relevance of the stimuli. In this study, we examined the sensitivity and feasibility of these tasks to assess avoidance behavior in patients with specific phobia. We adapted the tasks by replacing the originally conditioned stimuli with a spider and a neutral animal and investigated 31 female participants composed of 15 spider-phobic and 16 non-phobic participants. As the non-phobics were quite heterogeneous in terms of their Fear of Spiders Questionnaire (FSQ) scores, we subdivided them into six "fearfuls" that had elevated FSQ scores, and 10 "non-fearfuls" that had no fear of spiders. The phobics successfully managed to complete the procedure and showed consistent avoidance behavior across all behavioral tasks. Compared to the non-fearfuls, which did not show any avoidance behavior at all, the phobics looked at the spider much more often and clearly directed their body toward it in the search task. In the approach task, they hesitated most when they were close to the spider, and their difficulty to touch the spider was reflected in a strong increase in right hand acceleration changes. The fearfuls showed avoidance behavior depending on the tasks: strongest in the search task and weakest in the approach task. Additionally, we identified subjective valence ratings of the spider as the main influence on both objective avoidance behavior and subjective well-being after exposure, mediating the effect of the FSQ. In summary, the behavioral tasks are well suited to assess avoidance behavior in phobic participants and provide detailed insights into the process of avoidance.

Evidence and expert consensus based German guidelines for the use of repetitive transcranial magnetic stimulation in depression.

INTRODUCTION: Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) offer a promising alternative to psychotherapeutic and pharmacological treatments for depression. This paper aims to present a practical guide for its clinical implementation based on evidence from the literature as well as on the experience of a group of leading German experts in the field. METHODS: The current evidence base for the use of rTMS in depression was examined via review of the literature. From the evidence and from clinical experience, recommendations for the use of rTMS in clinical practice were derived. All members of the of the German Society for Brain Stimulation in Psychiatry and all members of the sections Clinical Brain Stimulation and Experimental Brain Stimulation of the German Society for Psychiatry, Psychotherapy, Psychosomatics and Mental Health were invited to participate in a poll on whether they consent with the recommendations. FINDINGS: Among rTMS experts, a high consensus rate could be identified for clinical practice concerning the setting and the technical parameters of rTMS treatment in depression, indications and contra-indications, the relation of rTMS to other antidepressive treatment modalities and the frequency and management of side effects.

A Common CDH13 Variant Is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD.

The cell-cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.

Protocol for the conceptualization and evaluation of a screening-tool for fitness-to-drive assessment in older people with cognitive impairment.

INTRODUCTION: Due to aging and health status people may be subjected to a decrease of cognitive ability and subsequently also a decline of driving safety. On the other hand there is a lack of valid and economically applicable instruments to assess driving performance. OBJECTIVE: The study is designed to develop a valid screening-tool for fitness-to-drive assessment in older people with cognitive impairment externally validated on the basis of on-road driving performance. METHODS: In a single-centre, non-randomized cross-sectional trial cognitive functioning and on-road-driving-behavior of older drivers will be assessed. Forty participants with cognitive impairment of different etiology and 40 healthy controls will undergo an extensive neuropsychological assessment. Additionally, an on-road driving assessment for external validation of fitness to drive will be carried out. Primary outcome measures will be performance in attention, executive functions and visuospatial tasks that will be validated with respect to performance on the on-road-driving-test. Secondary outcome measures will be sociodemographic, clinical- and driving characteristics to systematically examine their influence on the prediction of driving behavior. DISCUSSION: In clinical practice counselling patients with respect to driving safety is of great relevance. Thus, having valid, reliable, time economical and easily interpretable screening-tools on hand to counsel patients is of great relevance for practitioners. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee at the Ludwig-Maximilians-University Munich. The trial results will be disseminated through peer-reviewed publications and various conferences. TRIAL REGISTRATION: 18-640. Trial registration: German Clinical Trials Register. Registration number: DRKS00023549.

Virtuelle Realität bei Angsterkrankungen ­ vom experimentellen Tool zur klinischen Praxis.

Anxiety disorders are among the most frequent psychiatric disorders. According to national and international guidelines, psychopharmacological as well as psychotherapeutic approaches are recommended as first-choice treatments, depending on diagnosis and severity. Among psychotherapeutic approaches, cognitive-behavioral therapy (CBT) has been investigated most. Here, exposure is of special relevance as the core element of treatment. The technology of virtual reality (VR) has been increasingly investigated as a possible add-on strategy or alternative to conventional exposure therapy. Numerous studies of VR exposure for anxiety disorders have been published. Further, the comparison of exposure treatment in vivo vs. in VR has been investigated in meta-analyses. The results are promising overall, however they do not yet justify a general recommendation of this treatment. There is still the need for more research, especially regarding treatment efficacy in large-scale studies with larger patient samples.