Nina Romanczuk-Seiferth

Introduction: Interpersonal problems are a transdiagnostic risk factor for the development and maintenance of various psychiatric disorders, including anxiety and depression. Interventions that address these interpersonal challenges could therefore play a crucial role in enhancing mental health. This study aims to evaluate the efficacy and feasibility of a transdiagnostic group intervention, the Kiesler Circle Training (KCT), in improving interpersonal skills. Methods and analysis: In a prospective randomised controlled trial (RCT), 156 outpatients with a primary diagnosis of either depression or anxiety disorder according to DSM-5, and significant interpersonal problems, will be investigated. All patients will receive individual, state-of-the-art cognitive behavioural therapy (CBT) during the study. They will be randomly assigned to one of two conditions: the experimental group will receive the KCT in group sessions, in addition to individual CBT, while the control group will receive only individual CBT. The KCT intervention consists of 1 introductory individual session and 12 weekly group sessions, each lasting 100 min, with groups of up to 10 patients. KCT includes five sequential modules: the interpersonal circle, nonverbal communication, verbal communication, conflict resolution and empathy training. It is hypothesised that the experimental group will show (a) greater reduction in interpersonal problems from pre-assessment to post-assessment and (b) greater symptomatic improvement regarding the primary diagnosis. Child maltreatment is expected to moderate the trajectory of interpersonal problems. This study aims to provide evidence for the feasibility of KCT as a modular transdiagnostic add-on approach for patients with interpersonal difficulties. Ethics and dissemination: This study obtained approval from the ethics committees at the Charité Berlin, the Medical School of Berlin and the University of Greifswald. All results will be disseminated through peer-reviewed articles in scientific journals and contributions to national and international conferences. Trial registration number: DRKS00032467, NCT06170801 (see Supplementary Material).

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson’s disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.

Objective Assessing the effects of Mindfulness-Based Stress Reduction (MBSR) and Acceptance and Commitment Therapy (ACT) on symptoms of OSA, especially on the main outcome, excessive daytime sleepiness (EDS). Methods Parallel randomized controlled trial. 16 OSA patients with residual EDS (rEDS) were randomized and assigned to the two programs via a central computer system using REDCap. Participants completed a standardized 8-week MBSR program or a time-matched program on Acceptance and Commitment Therapy (ACT). Both programs were conducted online. Participants answered questionnaires online at baseline (pre), post-intervention (post), three months after the intervention (follow-up) and were blinded to whether their group was the treatment or control group but not to group allocation. Three participants dropped out early. Most analyses are based on the remaining 13 patients. Results There was a significant difference between the MBSR (n=7) and ACT group (n=6) in changes of EDS between pre and post (p=.043) and a significant reduction of EDS for patients in the ACT group at post (p=.034). This EDS reduction averaging 2.17 points on the Epworth Sleepiness Scale reached the prespecified bar for clinical significance of two points on that scale. Insomnia symptoms reduced significantly following ACT (p=.017). In MBSR, both participants and the MBSR-trainer judged movement-based exercises to be most efficacious. Conclusion ACT shows potential as adjunctive therapy for OSA with rEDS, although further studies are needed. It seems promising to develop therapeutic approaches for OSA with rEDS using ACT, especially if they are tailored to patients’ needs. Trial registration drks.de; Identifier: DRKS00026812

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability.

Substance-related disorders are complex psychiatric disorders that are characterized by continued consumption in spite of harmful consequences. Addiction affects various brain networks critically involved in learning, reward, and motivation, as well as inhibitory control. Currently applied therapeutic approaches aim at modification of behavior that ultimately leads to decrease of consumption or abstinence in individuals with substance use disorders. However, traditional treatment methods might benefit from recent neurobiological and cognitive neuroscientific research findings. Novel cognitive-behavioral approaches in the treatment of addictive behavior aim at enhancement of strategies to cope with stressful conditions as well as craving-inducing cues and target erroneous learning mechanisms, including cognitive bias modification, reconsolidation-based interventions, mindfulness-based interventions, virtual-reality-based cue exposure therapy as well as pharmacological augmentation strategies. This review discusses therapeutic strategies that target dysregulated neurocognitive processes associated with the development and maintenance of disordered substance use and may hold promise as effective treatments for substance-related disorders.

Ziel: Diese Arbeit gibt einen Überblick über bisherige wissenschaftliche Empfehlungen zur Implementierung der blended therapy, d.h. der Kombination von Therapien in Präsenz und via digitaler Medien. Die Empfehlungen um­fassen die Themen: (1) wahrgenommene Barrieren von Psychotherapeut*innen, (2) Format der blended therapy und (3) Indikationen für Patient*innen. In diesem Rahmen werden Faktoren aufgezeigt, die Akteur*innen im Gesundheitssystem als Orientierung dienen können, welche Determinanten bei der Implementierung in die Routineversorgung zu berücksichtigen sind. Methodik: Die systematische Suche erfolgte in den Datenbanken PsycArticles, PsycInfo, PSYNDEX und PubMed. Ergebnisse: Die Publikationen umfassen vier quantitative, neun qualitative sowie drei Mixed-Methods-Studien. Die bisherigen Arbeiten kommen zu dem Ergebnis, dass Psychotherapeut*innen frühzeitig in den Implementierungsprozess einbezogen und langfristige supportive Maßnahmen für die Umstrukturierung der bisherigen Arbeitsroutine geschaffen werden sollten. Das Format der blended therapy sollte nicht standardisiert angewandt, sondern vielmehr individuell an die Patient*innen angepasst werden. Hinsichtlich möglicher Indikationen werden verschiedene Einflussfaktoren der Patient*innen diskutiert, die bisher jedoch nur unzureichend untersucht wurden. Diskussion: Bisherige Studien weisen größtenteils homogene Charakteristika und Ergebnisse auf. Forschungslücken bestehen hinsichtlich der Frage, inwieweit sich die Ergebnisse auf andere Therapieschulen, Berufsgruppen und Störungsbilder übertragen lassen. Schlussfolgerung: Das Review veranschaulicht, dass es wichtiger Vorarbeit hinsichtlich der Anwendungsunterstützung für Psychotherapeut*innen sowie weiterer Forschungsaktivität bedarf, um die Implementierung von blended therapy im Sinne einer möglichen Verbesserung der psychotherapeutischen Versorgung voranzutreiben.

Purpose of Review: While the treatment of addictive disorders proves to be challenging, new treatment approaches that evolved around the concepts of mindfulness and acceptance have been utilized and investigated in recent years. Our goal is to summarize the efficacy and possible underlying mechanisms of mindfulness-based interventions (MBI) in addictive disorders. Recent Findings: Various meta-analyses have suggested that MBIs show clinical efficacy in the treatment of addictive disorders. Considering the factors that impact addictive disorders, MBIs have been indicated to augment responsiveness to natural rewards in contrast to addiction-related cues as well as to increase top-down cognitive control, decrease subjective and physiological stress perception, and enhance positive affect. Summary: In summary, MBIs hold promise in treating addictive disorders while larger randomized controlled trials with longitudinal study designs are needed to confirm their utility. Newest clinical endeavors strive to enhance the clinical utility of MBIs by augmentation or personalization.