Andreas Ströhle’s research while affiliated with Charité Universitätsmedizin Berlin and other places

Epigenetic mechanisms such as DNA methylation are hypothesized to play a pivotal role in the pathogenesis of anxiety disorders and to predict as well as relate to treatment response. An epigenome-wide association study (EWAS) (Illumina MethylationEPIC BeadChip) was performed at baseline (BL), post-treatment (POST) and 6-month follow-up (FU) in the so far largest longitudinal sample of patients with anxiety disorders (N = 415) treated with exposure-based cognitive behavioral therapy (CBT), and in 315 healthy controls. Independent of comorbidity with depression, anxiety disorders were significantly (p ≤ 6.409E–08) associated with altered DNA methylation at 148 CpGs partly mapping to genes previously implicated in processes related to anxiety, brain disorders, learning or plasticity (e.g., GABBR2, GABRD, GAST, IL12RB2, LINC00293, LOC101928626, MFGE8, NOTCH4, PTPRN2, RIMBP2, SPTBN1) or in a recent cross-anxiety disorders EWAS (TAOK1) after pre-processing and quality control (N = 378 vs. N = 295). Furthermore, BL DNA methylation at seven and three CpGs, respectively, was suggestively (p < 1E–5) associated with treatment response at POST (ABCA7, ADRA2C, LTBR, RPSAP52, SH3RF3, SLC47A2, ZNF251) and FU (ADGRD1, PRSS58, USP47). Finally, suggestive evidence for dynamic epigenome-wide DNA methylation changes along with CBT response emerged at four CpGs from BL to FU (ADIPOR2, EIF3B, OCA2, TMCC1). The identification of epigenetic biomarkers may eventually aid in developing environment-based preventive strategies aimed at increasing resilience by providing deeper molecular insights into the mechanisms underlying anxiety disorders. Defining epigenetic signatures as predictors or key mechanisms in exposure-based interventions could pave the way for more targeted and personalized treatments for anxiety disorders.

Introduction Specific phobia (SPH) is a prevalent anxiety disorder and may involve advanced biological aging. However, brain age research in psychiatry has primarily examined mood and psychotic disorders. This mega-analysis investigated brain aging in SPH participants within the ENIGMA-Anxiety Working Group. Methods 3D brain structural MRI scans from 17 international samples (600 SPH individuals, of whom 504 formally diagnosed and 96 questionnaire-based cases; 1,134 controls; age range: 22-75 years) were processed with FreeSurfer. Brain age was estimated from 77 subcortical and cortical regions with a publicly available ENIGMA brain age model. The brain-predicted age difference (brain-PAD) was calculated as brain age minus chronological age. Linear mixed-effect models examined group differences in brain-PAD and moderation by age. Results No significant group difference in brain-PAD manifested (βdiagnosis (SE)=0.37 years (0.43), p=0.39). A negative diagnosis-by-age interaction was identified, which was most pronounced in formally diagnosed SPH (βdiagnosis-by-age=-0.08 (0.03), pFDR=0.02). This interaction remained significant when excluding participants with anxiety comorbidities, depressive comorbidities, and medication use. Post-hoc analyses revealed a group difference for formal SPH diagnosis in younger participants (22-35 years; βdiagnosis=1.20 (0.60), p<0.05, mixed-effects d (95% confidence interval)=0.14 (0.00-0.28)), but not older participants (36-75 years; βdiagnosis=0.07 (0.65), p=0.91). Conclusions Brain aging did not relate to SPH in the full sample. However, a diagnosis-by-age interaction was observed across analyses, and was strongest in formally diagnosed SPH. Post-hoc analyses showed a subtle advanced brain aging in young adults with formally diagnosed SPH. Taken together, these findings indicate the importance of clinical severity, impairment and persistence, and may suggest a slightly earlier end to maturational processes or subtle decline of brain structure in SPH.

Professional musicians are often confronted with multiple profession-related stressors, which may be associated with an increased risk of mental strain, but empirical evidence focusing on clinical samples of musicians is limited. The aim of this study was to examine clinically confirmed mental disorders and personality accentuations in musicians attending a musician-specific outpatient service, to better understand how occupational and person-related stressors may impact their mental health. We performed a cross-sectional secondary data analysis of diagnoses and sociodemographic data of 678 professional musicians (including music students) that were routinely collected in the outpatient clinic. Of the 678 patients, 110 (16.2%) received a tentative psychiatric diagnosis, and 46 presented themselves to the psychiatric outpatient clinic for extensive diagnostics (using ICD-10 and SKID-II). In these 46 musicians, depression (39%) and music performance anxiety (26%) were the most frequent diagnoses, followed by adjustment disorders (13%) and somatoform disorders (11%). Twenty-eight percent of the sample fulfilled the criteria of either a personality disorder or accentuation. The frequency rates emphasize the importance of targeting the mental health of professional musicians with preventive and therapeutic measures. Further research with larger sample sizes is needed to validate and extend our findings and develop individual preventive measures.

Zusammenfassung Hintergrund Psychotherapie bei Menschen mit Psychosen galt lange als kontraindiziert. In der heutigen Zeit empfehlen Leitlinien und die Psychotherapierichtlinie die Psychotherapie in allen Behandlungsphasen. Studien zeigen, dass diese neuen Erkenntnisse nur langsam in die Praxis gelangen und eine große Versorgungslücke in diesem Bereich besteht. Ziel der Arbeit Die vorliegende Studie untersucht, was Psychologische Psychotherapeut:innen in Ausbildung über Psychotherapie bei Psychosen wissen, wie viel Lehre sie dazu erhalten, wie gut sie sich auf die Behandlung von Menschen mit einer Psychose vorbereitet fühlen, und welche Stereotype bestehen. Material und Methoden Es handelt sich um eine querschnittliche Studie mit einer Gelegenheitsstichprobe von 235 Psychotherapeut:innen in Ausbildung, die mittels Online-Fragebogen untersucht wurden. Ergebnisse Nur etwa 40 % der Befragten gaben an, in ihrer Ausbildung konkrete Inhalte einer Psychotherapie bei Menschen mit Psychose vermittelt bekommen zu haben. Im Vergleich zu anderen Störungsbildern fühlten sie sich weniger gut auf die Behandlung von Menschen mit einer Psychosen vorbereitet. Über 70 % der Teilnehmenden äußerten den Wunsch, in der Ausbildung mehr Inhalte vermittelt zu bekommen. Selbstberichtete Stereotype bezüglich Psychosen waren in der Stichprobe sehr niedrig ausgeprägt. Diskussion Wenngleich alte Stereotype bezüglich Psychosen bei Psychotherapeut:innen in Ausbildung kaum vorhanden scheinen und ein großes Interesse an Psychosenpsychotherapie besteht, zeigt sich ein deutlicher Verbesserungsbedarf bei der Vermittlung von Wissen und Kompetenzen für die Behandlung von Menschen mit Psychosen in der psychotherapeutischen Ausbildung.

At present there is no comprehensive overview of the long-term development of the clinical picture, disease-associated impairments and neurobiological correlates of anxiety disorders as well as what influence certain risk factors and treatment have on the prognosis. This article presents findings regarding disorder-specific symptoms and disorder-associated changes in the areas of functional level, quality of life, neurocognitive performance and structural brain anatomy over the lifespan. It also reports on how patient-related and environment-related aspects as well as guideline-oriented therapy influence the course of the disorder. A literature search was conducted in PubMed on the aspects of individual components. Meta-analyses, longitudinal and cohort studies were included. To illustrate changes over time, the findings were predominantly presented separately for children and adolescents as well as for early and late adulthood. Anxiety disorders primarily exhibit age-associated differences in the symptom profile but also in the areas of functional level and quality of life. Risk factors for an unfavorable course of the disorder were identified particularly for young and middle-aged people; however, the findings indicate that evidence-based psychotherapy or pharmacotherapy also has a lasting effect even after termination. For long-term therapeutic success, age-dependent characteristics and limitations as well as prognostically relevant aspects in the diagnostics and treatment of anxiety disorders should be taken into consideration and treatment should be started as soon as possible.

Background The Personalized Advantage Index (PAI) shows promise as a method for identifying the most effective treatment for individual patients. Previous studies have demonstrated its utility in retrospective evaluations across various settings. In this study, we explored the effect of different methodological choices in predictive modelling underlying the PAI. Methods Our approach involved a two-step procedure. First, we conducted a review of prior studies utilizing the PAI, evaluating each study using the Prediction model study Risk Of Bias Assessment Tool (PROBAST). We specifically assessed whether the studies adhered to two standards of predictive modeling: refraining from using leave-one-out cross-validation (LOO CV) and preventing data leakage. Second, we examined the impact of deviating from these methodological standards in real data. We employed both a traditional approach violating these standards and an advanced approach implementing them in two large-scale datasets, PANIC-net ( n = 261) and Protect-AD ( n = 614). Results The PROBAST-rating revealed a substantial risk of bias across studies, primarily due to inappropriate methodological choices. Most studies did not adhere to the examined prediction modeling standards, employing LOO CV and allowing data leakage. The comparison between the traditional and advanced approach revealed that ignoring these standards could systematically overestimate the utility of the PAI. Conclusion Our study cautions that violating standards in predictive modeling may strongly influence the evaluation of the PAI's utility, possibly leading to false positive results. To support an unbiased evaluation, crucial for potential clinical application, we provide a low-bias, openly accessible, and meticulously annotated script implementing the PAI.