Lack of evidence for predictive utility from resting state fMRI data for individual exposure-based cognitive behavioral therapy outcomes: A machine learning study in two large multi-site samples in anxiety disorders.

Data-based predictions of individual Cognitive Behavioral Therapy (CBT) treatment response are a fundamental step towards precision medicine. Past studies demonstrated only moderate prediction accuracy (i.e. ability to discriminate between responders and non-responders of a given treatment) when using clinical routine data such as demographic and questionnaire data, while neuroimaging data achieved superior prediction accuracy. However, these studies may be considerably biased due to very limited sample sizes and bias-prone methodology. Adequately powered and cross-validated samples are a prerequisite to evaluate predictive performance and to identify the most promising predictors. We therefore analyzed resting state functional magnet resonance imaging (rs-fMRI) data from two large clinical trials to test whether functional neuroimaging data continues to provide good prediction accuracy in much larger samples. Data came from two distinct German multicenter studies on exposure-based CBT for anxiety disorders, the Protect-AD and SpiderVR studies. We separately and independently preprocessed baseline rs-fMRI data from n = 220 patients (Protect-AD) and n = 190 patients (SpiderVR) and extracted a variety of features, including ROI-to-ROI and edge-functional connectivity, sliding-windows, and graph measures. Including these features in sophisticated machine learning pipelines, we found that predictions of individual outcomes never significantly differed from chance level, even when conducting a range of exploratory post-hoc analyses. Moreover, resting state data never provided prediction accuracy beyond the sociodemographic and clinical data. The analyses were independent of each other in terms of selecting methods to process resting state data for prediction input as well as in the used parameters of the machine learning pipelines, corroborating the external validity of the results. These similar findings in two independent studies, analyzed separately, urge caution regarding the interpretation of promising prediction results based on neuroimaging data from small samples and emphasizes that some of the prediction accuracies from previous studies may result from overestimation due to homogeneous data and weak cross-validation schemes. The promise of resting-state neuroimaging data to play an important role in the prediction of CBT treatment outcomes in patients with anxiety disorders remains yet to be delivered.

Advising activity-knowledge, attitudes, beliefs, and behaviors regarding the recommendation of physical activity in clinical psychologists.

BACKGROUND: Regular physical activity comes with multiple benefits for physical but also mental health and can be a pivotal element in the prevention and treatment of mental disorders. Clinical psychologists play an important role in supporting their patients in increasing physical activity levels. Up to date, there is only little research on recommendation of physical activity in psychologists worldwide and no such research for psychologists in Germany. Aim of this study was to assess knowledge, attitudes, beliefs and behaviors regarding physical activity in psychologists in Germany. METHODS: We assessed knowledge, attitudes, beliefs and behaviors regarding physical activity among a sample of clinical psychologists in Germany using the "Exercise in Mental Illness Questionnaire-German" (EMIQ-G) in a cross-sectional online survey. RESULTS: 454 participants were included in the analysis. Participants reported moderate levels of knowledge and self-confidence in recommending physical activity. Only 14% of the participants received formal training regarding physical activity recommendation. Most participants recommended physical activity to their patients, primarily through personal discussions and referrals to exercise professionals. About one third did not give any recommendations regarding intensity. Strength training was only recommended by a minority. CONCLUSION: There is a need for greater integration of information and instructions regarding the recommendation of physical activity in the treatment of people with mental disorders in the training and further education of psychologists.

Step away from depression-results from a multicenter randomized clinical trial with a pedometer intervention during and after inpatient treatment of depression.

Evidence for the effectiveness of physical activity (PA) in the treatment of depression prevails for outpatients with mild and moderate symptom levels. For inpatient treatment of severe depression, evidence-based effectiveness exists only for structured and supervised group PA interventions. The Step Away from Depression (SAD) study investigated the effectiveness of an individual pedometer intervention (PI) combined with an activity diary added to inpatient treatment as usual (TAU). In this multicenter randomized controlled trial, 192 patients were randomized to TAU or TAU plus PI. The two primary outcomes at discharge were depression-blindly rated with the Montgomery-Åsberg Depression Rating Scale (MADRS)-and average number of daily steps measured by accelerometers. Secondary outcomes were self-rated depression and PA, anxiety, remission and response rates. Multivariate analysis of variance (MANOVA) revealed no significant difference between both groups for depression and daily steps. Mean MADRS scores at baseline were 29.5 (SD = 8.3) for PI + TAU and 28.8 (SD = 8.1) for TAU and 16.4 (SD = 10.3) and 17.2 (SD = 9.9) at discharge, respectively. Daily steps rose from 6285 (SD = 2321) for PI + TAU and 6182 (SD = 2290) for TAU to 7248 (SD = 2939) and 7325 (SD = 3357). No differences emerged between groups in secondary outcomes. For severely depressed inpatients, a PI without supervision or further psychological interventions is not effective. Monitoring, social reinforcement and motivational strategies should be incorporated in PA interventions for this population to reach effectiveness.

Viral Transmission? A Longitudinal Study of Media Use and Its Relation to Mental Strain During the First 2 Years of the COVID-19 Pandemic.

BACKGROUND: In light of the dynamic COVID-19 pandemic, the exposure to pandemic-related media coverage may change over time and may be particularly relevant due to associations with psychopathological symptoms. The aims of the present study were to examine changes in media consumption over time and to analyze its prospective associations with psychological strain. METHOD: The study uses a longitudinal observational design with ten periods of online data collection from March 2020 to April 2022 in an adult convenience sample (N = 8337) of the general population in Germany. RESULTS: Our data revealed that the frequency and duration of pandemic-related media exposure as well as their subjective critical evaluation showed the highest levels at the beginning of the pandemic and peaked again in autumn 2020 and spring 2021. The primarily used media formats changed only slightly over time. The amount of media exposure at baseline was associated with more impairing pandemic-related anxiety 1 month, 1 year, and 2 years later. CONCLUSION: Our results hint to potentially problematical and long-lasting associations of pandemic-related media consumption with mental strain. Our findings could serve as an orientation for recommendations, further research, and adequate interventions for a responsible dealing with media coverage. TRIAL REGISTRATION: The authors have pre-registered this research at clinicaltrials.gov without an analysis plan; retrievable at: https://clinicaltrials.gov/ct2/show/NCT04331106 .

[Non-response to psychotherapy: concepts, problems and referral options]. / Nichtansprechen auf Psychotherapie: Konzepte, Problemstellungen, Zuweisungsoptionen.

AIM: In this paper we review the current literature on the clinical problem that some patients do not achieve response after adequately conducted psychotherapy. We explicate our understanding of nonresponse and treatment resistance including the operational definitions, summarize the theoretical explanations and empirical studies and put forward possible study designs and treatment options. METHODS: Literature search using PubMed and Web of Science. RESULTS: For the domain of psychotherapy, the term treatment resistance does not seem appropriate; instead, we use the more descriptive terms nonresponse and recurrent nonresponse. Generally, this topic is far less represented in psychotherapy than in pharmacotherapy. Controlled switching studies with a switch from pharmacotherapy to psychotherapy are rare and those switching from one psychotherapeutic approach to another are nearly nonexistent. Building on clinical considerations, we propose a flow-chart for clinical decision making after nonresponse in psychotherapy. DISCUSSION: Learning from errors is highly beneficial. This principle should be more consistently followed up in psychotherapy research as well as in supervision and training. Guidelines should include consensual and evidence-based advice on how to deal with nonresponse and recurring nonresponse.

Tracking changes in physical activity during inpatient treatment in a psychiatric clinic in Germany by asking two simple questions.

Increasing physical activity is essential to improve psychiatric patients' physical and mental health. This study aimed to characterise the physical activity levels of inpatients in a general psychiatric clinic and to determine the feasibility of using a simple tool in everyday practice to assess physical activity levels in standard patient documentation. We assessed the level of physical activity undertaken by patients treated on an inpatient basis in a psychiatric hospital over 20 months. A total of 328 patients were included in the analysis. Physical activity was measured using a slightly altered version of the Exercise as a vital sign (EVS) questionnaire. All information was extracted from letters of discharge. During inpatient treatment, moderate to vigorous activity levels increased, and more patients engaged in physical activity. Patients with mood or anxiety disorders displayed the most considerable increase in physical activity. Patients with other diagnoses, such as schizophrenia, benefitted less or not at all. Factors associated with physical activity included-among others-history of substance use, education and month of admission. Investigating the feasibility of standardised documentation of physical activity showed fluctuation in documentation rates throughout the study. The level of physical activity performed by psychiatric patients can be increased during inpatient treatment. Implementing physical activity level as part of standard patient documentation is a first step in gathering data to assess the need for interventions to achieve an optimal physical activity in psychiatric patients throughout inpatient treatment.

Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression.

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

[Sports psychiatry and psychotherapy]. / Sportpsychiatrie und -psychotherapie.

Sports psychiatry and psychotherapy is a relatively young field and is comprised of two key segments: the special features of the diagnostics and therapy of mental disorders in elite athletes and the use of exercise and sports in the development and treatment of mental disorders. Although all mental disorders can in principle also occur in (elite) athletes, there are additionally sport-specific mental disorders, such as anorexia athletica and other eating disorders, chronic traumatic encephalopathy, misuse of and dependency on performance-enhancing substances (doping) and muscle dysmorphia. Many high-quality clinical trials over the past two decades have been able to demonstrate a therapeutic efficacy of physical activity and sport in the treatment of various mental disorders. All clinicians active in psychiatry and psychotherapy should possess a basic knowledge of sports psychiatry.

[Social Anxiety Disorder - an Update]. / Die soziale Angststörung ­ ein Update.

It can happen that one behaves in a supposedly embarrassing or insufficient manner; however, short-term feelings such as shame or self-doubt usually remain without significance. However, if there is excessive and persistent fear or significant avoidance behaviour, it may be a case of social anxiety disorder (SAS). This article provides an overview of the current status of the aetiology, diagnosis and therapy of SAS.

Efficacy of temporally intensified exposure for anxiety disorders: A multicenter randomized clinical trial.

BACKGROUND: The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions. METHODS: This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression. RESULTS: Both treatments resulted in substantial improvements at post (PeEx-I: dwithin = 1.50, PeEx-S: dwithin = 1.78) and follow-up (PeEx-I: dwithin = 2.34; PeEx-S: dwithin = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TRPeEx-I = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse. CONCLUSIONS: Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.

Associations between COVID-19 related media consumption and symptoms of anxiety, depression and COVID-19 related fear in the general population in Germany.

In context of the current COVID-19 pandemic the consumption of pandemic-related media coverage may be an important factor that is associated with anxiety and psychological distress. Aim of the study was to examine those associations in the general population in Germany. 6233 participants took part in an online-survey (March 27th-April 6th, 2020), which included demographic information and media exploitation in terms of duration, frequency and types of media. Symptoms of depression, unspecific anxiety and COVID-19 related anxiety were ascertained with standardized questionnaires. Frequency, duration and diversity of media exposure were positively associated with more symptoms of depression and unspecific and COVID-19 specific anxiety. We obtained the critical threshold of seven times per day and 2.5 h of media exposure to mark the difference between mild and moderate symptoms of (un)specific anxiety and depression. Particularly the usage of social media was associated with more pronounced psychological strain. Participants with pre-existing fears seem to be particularly vulnerable for mental distress related to more immoderate media consumption. Our findings provide some evidence for problematical associations of COVID-19 related media exposure with psychological strain and could serve as an orientation for recommendations-especially with regard to the thresholds of critical media usage.

An investigation of genetic variability of DNA methyltransferases DNMT3A and 3B does not provide evidence for a major role in the pathogenesis of panic disorder and dimensional anxiety phenotypes.

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation-DNA methyltransferases (DNMTs)-has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.

[Dealing with psychological distress by healthcare professionals during the COVID-19 pandemia]. / Umgang mit psychischer Belastung bei Gesundheitsfachkräften im Rahmen der Covid-19-Pandemie.

BACKGROUND: In the current COVID-19 pandemia, health workers from all professions are facing great challenges in coping with the crisis. In this situation health professionals are confronted with specific stressors and risks not only for the physical but also for the mental health. OBJECTIVE: This article summarizes the first recommendations for the reduction of stress and psychological burden in health professionals during the current COVID-19 pandemia. METHODS: The recommendations of the World Health Organization, the United Nations and the International Red Cross Society are summarized. Recommendations for the reduction of stress and psychological distress in health professionals as well as important factors that team leaders can consider in order to reduce psychological distress in employees are presented. RESULTS: The normalization of strong emotions and stress, the fulfillment of basic needs, social support, clear communication and distribution of tasks, flexible working hours and the utilization of psychosocial and psychological help without stigmatization seem to be particularly important measures. CONCLUSION: This article presents guidelines for health professionals and team leaders in healthcare that help to maintain mental health during the COVID-19 pandemia.

Reduced Sensitivity to Non-Fear-Related Stimulus Changes in Panic Disorder.

Panic disorder (PD) is associated with increased body vigilance and reduced cognitive resources directed at non-fear-related stimuli, particularly in the absence of stimulus-rich environments. To date, only few studies have investigated whether this deficit in PD is reflected in reduced mismatch negativity (MMN), an event-related potential indexing preattentive sensitivity to unexpected stimulus changes. We tested 35 patients affected by PD and 42 matched healthy controls in an oddball paradigm, using frequency and duration deviant stimuli to measure auditory MMN. PD patients displayed reduced duration MMN amplitudes in comparison to healthy controls. No group differences were detected for duration MMN latency, as well as frequency MMN indices. Results support the notion of reduced processing of non-fear-related stimuli in PD patients, particularly with regard to the preattentive processing of sound duration deviants. Additionally, our findings are in line with clinical studies reporting divergent deficits in preattentive processing of frequency and duration deviants.

Increasing physical activity and healthy diet in outpatients with mental disorders: a randomized-controlled evaluation of two psychological interventions.

INTRODUCTION: While physical activity (PA) can play an important role in the treatment of mental disorders (MD), large proportions of patients with MD do not meet PA recommendations. The aim of this trial was to evaluate whether structured psychological intervention (MoVo-LISA) is effective in helping outpatients with MD to increase their level of PA. As active control group (CG) we modified MoVo-LISA to target healthy diet behavior. METHODS: N = 83 outpatients with MD (F1-F4) were randomized to the two conditions. PA (self-report and accelerometry), dietary behavior, social-cognitive determinants of health behavior change, psychiatric symptoms and health-related quality of life were assessed at baseline, 1 and 12 weeks after the intervention. RESULTS: Significant time*group interaction effects for objectively measured PA, dietary behavior and fruit and vegetable consumption indicated differential effects of the interventions on these outcomes. PA increased in the MoVo-LISA group (IG) from baseline to follow-up while it decreased in CG. IG showed a significant higher level of objectively measured PA at follow-up compared to CG. Dietary behavior and fruit and vegetable consumption significantly increased from baseline to follow-up in CG, but not IG. IG showed a significant increase in some, but not all social cognitive determinants of health behavior change. CONCLUSIONS: MoVo-LISA is effective in helping outpatients with MD to increase their level of PA in short- and mid-term. The used intervention strategies are effective for the promotion of healthy diet in patients with MD as well.

High-Intensity Interval Training in Panic Disorder Patients: A Pilot Study.

High-intensity interval training (HIIT) may produce strong physiological but also psychological effects within a short period. However, it is questionable if this type of training is applicable and effective in patients with panic disorder (PD) because they are more vulnerable to the adverse effects of exercise. Twelve PD patients performed a 12-day HIIT trial. Every second day, patients performed 10 high-intensive 1-minute intervals at 77% to 95% of their maximum heart rate separated by 1-minute intervals with moderate to low intensity. All patients completed the 12-day training period. PD severity, agoraphobia, depression, general disorder severity, and endurance performance improved substantially with moderate to large effects sizes. Moreover, the increase in endurance performance was correlated with the reduction of depression and agoraphobia. HIIT was well tolerated by patients with PD and may induce rapid and strong therapeutic effects. A randomized controlled clinical trial is needed to verify our findings.

Patients' characteristics and their influence on course of fear during agoraphobic symptom provocation: may SS(N)RI treatment compensate unfavorable individual preconditions?

BACKGROUND: Patients' characteristics and antidepressants are discussed to be relevant in the context of phobic exposure. AIMS: To identify patients characteristics associated with a differential course of fear during disorder-specific symptom provocation as well as to elucidate the effect of selective serotonin-(noradrenalin-) reuptake inhibitors [SS(N)RI] on development of fear in the context of re-exposure to the phobic stimuli. METHODS: Twenty-eight clinically well-characterized patients with panic disorder and agoraphobia (PD/AG) were classified into subjects who show a reduction of fear ('Fear-') during a symptom provocation via a picture-based paradigm (T1) and those who did not ('Fear+'). Subsequently, SS(N)RI treatment was administered to all patients and subjects were re-exposed to the feared stimuli after 8 weeks of treatment (T2). Moreover, brain activity within the 'fear network' was measured via functional magnetic resonance imaging (fMRI) at T1 and T2. RESULTS: Fear - were significantly younger and demonstrated increased exposure-related fear as well as stronger activity in several fear-related brain areas than Fear+. We found significant improvements in all clinical parameters after pharmacological intervention for the whole sample (T1-T2; all measures p < .02). However, reduction of fear as well as activation in (para)limbic structures during symptom provocation were now attenuated in Fear - but increased in Fear+. CONCLUSIONS: Advanced age may predict a therapeutically unfavorable course of fear during agoraphobic symptom provocation. Since we found no negative impact of medication on fear development at all, there was some evidence that SS(N)RI treatment might improve the individual ability to get involved with the agoraphobic stimuli while conducting disorder-specific exposure.

Clinical and neurobiological effects of aerobic exercise in dental phobia: A randomized controlled trial.

BACKGROUND: Physical activity has shown to be effective in anxiety disorders. For specific phobia, no studies are available that systematically examined the effects of an aerobic exercise intervention on phobic fear within a randomized-controlled design. Therefore, we investigated the acute effect of a standardized aerobic training on clinical symptoms of dental phobia as well as on stress-related neurobiological markers. METHODS: Within a crossover design, 30 patients with dental phobia (mean age: 34.1 years; mean score of the Dental Anxiety Scale: 18.8) underwent two minor dental interventions separated by 7 days. Dental treatment was performed after 30 min of physical activity at either 20% VO2 max (control) or 70% VO2 max (intervention), respectively. To control for habituation, patients were randomly assigned to one of the two conditions prior to the first intervention. Moreover, saliva samples were collected at five times in order to determine changes in salivary cortisol (sC) and alpha-amylase (sAA) due to treatment. RESULTS: In comparison to baseline, aerobic exercise within 70% VO2 max significantly reduced clinical anxiety and sC concentrations before, during, and after the dental treatment. In contrast, the control condition led to decreased sAA levels at different time points of measurement. Habituation occurred at the second study day, independent of the order. CONCLUSIONS: Our study provides evidence for an effect of moderate-intense exercise on clinical symptoms and sC in patients with dental phobia. Therefore, acute aerobic exercise might be a simple and low-cost intervention to reduce disorder-specific phobic fear.

Physical activity in outpatients with mental disorders: status, measurement and social cognitive determinants of health behavior change.

INTRODUCTION: Physical activity (PA) can play an important role in improving the mental and physical health in patients with mental disorders but is not well studied in this population. The aim of this study was to assess the status of PA in outpatients with mental disorders, compare the convergence of self-rating and accelerometer measurement and examine the influence of social cognitive variables from the Motivation-Volition (MoVo) model and clinical measures on PA. METHODS: Eighty-four patients were recruited from three psychiatric outpatient clinics and local psychiatrists (Distribution of ICD-10-Diagnoses: F3.x = 59.5%, F4.x = 20.2%, F2.x = 17.9%, F1.x = 2.4%). PA, Self-efficacy, Outcome-expectancies, Intention, Self-concordance, Action- and Coping-planning, Health-related Quality of Life (SF-12) and Psychiatric Symptoms (SCL-27) were assessed through questionnaires. PA was assessed objectively by accelerometers. RESULTS: Most of the participants did not reach PA recommendations. Subjective and objective measurement of PA showed good accordance for total PA on group level but lower accordance on individual level. Motivational and volitional determinants of health behavior change showed a similar pattern of correlations with PA as in populations without mental disorders. CONCLUSION: Outpatients with mental disorders have the ability and are willing to perform PA but a large proportion of our sample did not meet PA recommendations. To assess group levels of PA, subjective and objective measurement seem equally apt, for individual diagnostics, a combination of both should be considered. Social cognitive determinants of health behavior change seem to be as helpful for the design of PA interventions for patients with mental disorders as they are in other populations.