Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

Accumulating clinical evidence shows that psychedelic therapy, by synergistically combining psychopharmacology and psychological support, offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and/or maladaptive habitual patterns of emotion, cognition and behavior, notably, depression (MDD), treatment resistant depression (TRD) and addiction disorders, but perhaps also anxiety disorders, obsessive-compulsive disorder (OCD), Post-Traumatic Stress Disorder (PTSD) and eating disorders. Despite the emergent transdiagnostic evidence, the specific clinical dimensions that psychedelics are efficacious for, and associated underlying neurobiological pathways, remain to be well-characterized. To this end, this review focuses on pre-clinical and clinical evidence of the acute and sustained therapeutic potential of psychedelic therapy in the context of a transdiagnostic dimensional systems framework. Focusing on the Research Domain Criteria (RDoC) as a template, we will describe the multimodal mechanisms underlying the transdiagnostic therapeutic effects of psychedelic therapy, traversing molecular, cellular and network levels. These levels will be mapped to the RDoC constructs of negative and positive valence systems, arousal regulation, social processing, cognitive and sensorimotor systems. In summarizing this literature and framing it transdiagnostically, we hope we can assist the field in moving toward a mechanistic understanding of how psychedelics work for patients and eventually toward a precise-personalized psychedelic therapy paradigm.

Implementation, efficacy and cost effectiveness of the unified protocol in a blended format for the transdiagnostic treatment of emotional disorders: a study protocol for a multicentre, randomised, superiority controlled trial in the Spanish National Health System

IntroductionEmotional disorders (EDs) have become the most prevalent psychological disorders in the general population, which has boosted the economic burden associated with their management. Approximately half of the individuals do not receive adequate treatment. Consequently, finding solutions to deliver cost-effective treatments for EDs has become a key goal of today’s clinical psychology. Blended treatments, a combination of face-to-face and online interventions, have emerged as a potential solution to the previous. The Unified Protocol for the Transdiagnostic Treatment of EDs (UP) might serve this purpose, as it can be applied to a variety of disorders simultaneously and its manualised format makes it suitable for blended interventions.Methods and analysisThe study is a multicentre, randomised, superiority, clinical trial. Participants will be 310 individuals with a diagnosis of an ED. They will be randomised to a treatment as usual (individual cognitive behavioural therapy) or a UP condition in a blended format (face-to-face individual UP +online, app-based UP). Primary outcomes will be ED diagnostic criteria and depression and anxiety symptoms. Cost efficiency of the intervention, app usability, as well as opinion and confidence in the treatment will also be evaluated. Assessment points will include baseline and 3 months, 6 months and 12 months after UP treatment.Ethics and disseminationThe study has received approvals by the Ethics Research Committee of Navarra, Castellón, Euskadi, Castilla y León, Extremadura, Lleida and Aragón. The study is currently under an approval process by the Ethics Research Committees of all the remaining collaborating centres. Outcomes will be disseminated through publication in peer-reviewed journals and presentations at international conference meetings.Trial registration numberNCT04304911.

The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders Among Japanese Children: A Pilot Study

At present, there is no established cognitive behavioral therapy (CBT) for treating emotional disorders in Japanese children. Therefore, we introduced the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Children (UP-C) in Japan and adapted it to the Japanese context. We then examined its feasibility and preliminary efficacy using a single-arm pretest, posttest, follow-up design. Seventeen Japanese children aged between 8 and 12 years (female n = 11; male n = 6; M = 10.06 ± 0.97 years) with a principal diagnosis of anxiety, obsessive-compulsive, or depressive disorders, and their parents were enrolled in the study. The primary outcome was the overall severity of emotional disorders as assessed by psychiatrists using the Clinical Global Impression-Severity Scale. Secondary outcomes included child- and parent-reported anxiety symptoms, depressive symptoms, and functional status. No severe adverse events were observed. The feasibility was confirmed by the low dropout proportion (11.76%), high attendance proportion (children: 95.6%; parents: 94.6%), and sufficient participant satisfaction. Linear mixed models (LMMs) showed that the overall severity of emotional disorders and child- and parent-reported anxiety symptoms improved from pre-treatment to post-treatment, and that these treatment effects were maintained during the 3-month follow-up period. Additionally, child- and parent-reported functional status improved from pre-treatment to the 3-month follow-up. In contrast, child-reported depressive symptoms improved from pre-treatment to follow-up, but there was no significant change in parent-reported depressive symptoms between pre-treatment and other time points. These findings demonstrate the feasibility and preliminary efficacy of the Japanese version of the UP-C, suggesting that future randomized controlled trials (RCTs) are warranted (Clinical trial registration: UMIN000026911).

Categories or dimensions? Towards a transdiagnostic treatment of eating psychopathology / ¿Categorías o dimensiones? Hacia un tratamiento transdiagnóstico de la psicopatología alimentaria

The purpose of this research was to contrast the categorial and dimensional approaches within the eating disorders area. Research on the eating problems categorical model reveals vast evidence against its validity: excessive comorbidity, inadequate coverage, diagnostic migration, residual categories, false positives and negatives, etc. The dimensional conceptualization of the eating psychopathology study would achieve more accurate findings by considering eating problems according to the degree in which they manifest, avoiding diagnostics based on arbitrary cut-off points and facilitating the analysis of eating psychopathology at early age, as well as following symptom evolution throughout development. Based on the dimensional model, transdiagnostic perspective has received empirical support, which endorses the use of the transdiagnostic treatment aimed to underlying psychological mechanisms, such as negative affect and emotional dysregulation.ResumenEl propósito de la presente investigación fue contrastar los enfoques categorial y dimensional dentro del área de los trastornos alimentarios. La investigación sobre el modelo categorial de los problemas alimentarios revela un amplio cúmulo de pruebas en contra de su validez, como comorbilidad excesiva, cobertura inadecuada, migración diagnóstica, categorías residuales, falsos positivos y negativos, etc. El estudio de la psicopatología alimentaria desde una conceptuación dimensional permitiría obtener hallazgos más precisos, al considerar a los problemas alimentarios según el grado en el que se presentan, evitar diagnósticos basados en puntos de corte arbitrarios, facilitar su análisis a edad temprana, así como seguir la evolución de los síntomas a lo largo del desarrollo. Apoyada en el modelo dimensional, la perspectiva transdiagnóstica ha recibido respaldo empírico que fundamenta su uso en el tratamiento de los mecanismos psicológicos subyacentes a las problemáticas alimentarias, como el afecto negativo y la desregulación emocional.

Enhancing Cognitive Restructuring with Concurrent fMRI-guided Neurostimulation for Emotional Dysregulation: A Randomized Controlled Trial

Background: Transdiagnostic clinical emotional dysregulation is a key component of psychopathology and offers an avenue to address multiple disorders with one transdiagnostic treatment. In the current study, we pilot a one-time intervention that combines cognitive restructuring (CR) with repetitive transcranial magnetic stimulation (rTMS), targeted using functional magnetic resonance imaging (fMRI). Methods: Thirty-seven clinical adults with high emotional dysregulation were enrolled in this randomized, double-blind, placebo-controlled trial. fMRI was collected as participants were reminded of lifetime stressors and asked to downregulate their distress using CR tactics. fMRI BOLD data were analyzed to identify the cluster of voxels within the left dorsolateral prefrontal cortex (dlPFC) with the highest activation when participants attempted to downregulate, versus passively remember, distressing memories. Participants underwent active or sham rTMS (10 Hz) over the target while practicing CR following autobiographical emotional induction. Results: Receiving active versus sham rTMS led to significantly higher high frequency heart rate variability during regulation, lower regulation duration, and higher likelihood to use CR during the week following the intervention. There were no differences between conditions when administering neurostimulation without CR compared to sham. Participants in the sham versus active condition experienced less distress the week after the intervention. There were no differences between conditions at the one-month follow up. Conclusion: This study demonstrated that combining active rTMS with emotion regulation training significantly enhances emotion regulation and augments the impact of training for as long as a week. These findings are a promising step towards a combined intervention for transdiagnostic emotion dysregulation.

Transdiagnostic Processes as Mediators of Change in an Internet-Delivered Intervention Based on the Unified Protocol

Background Transdiagnostic treatments target shared mechanisms between disorders to facilitate change across diagnoses. The Unified Protocol (UP) aims at changing dysfunctional reactions towards emotions by increasing mindful emotion awareness and cognitive flexibility, as well as decreasing anxiety sensitivity and emotion avoidance. Method We investigated whether these transdiagnostic processes were malleable by treatment and mediated the relationship between treatment and outcome in an internet-delivered adaptation of the UP. N = 129 participants with mixed anxiety, depressive, and somatic symptom disorders were randomized to treatment or waitlist. Results The treatment yielded significant changes in all transdiagnostic processes over time in comparison to a waitlist condition. In separate mediator models, significant mediating effects were found for mindfulness, cognitive flexibility, behavioral activation, and experiential avoidance. When all mediators were combined in a multiple mediator model, the indirect effects through mindfulness and cognitive flexibility emerged as significant. Conclusion These findings add to the growing body of research on transdiagnostic processes as mediators of change and emphasize mindfulness and cognitive flexibility as a transdiagnostic treatment target. However, these results should be interpreted cautiously, as temporal precedence could not be established.

Culturally and Linguistically Sensitive Applications in Other Countries

Cultural adaptation can help maintain a balance between scientifically rigorous interventions and culturally sensitive, effective practice. When introducing the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Children and Adolescents (UP-C/A) into a new cultural context, translating the treatment may be sufficient in some countries and regions, while others may require more systematic modification. This chapter discusses specific steps that were taken for adapting the UP-C/A in the context of Japanese culture and presents a case study in Japan. When introducing the UP-C/A into the Japanese context, modifications were made to increase the treatment’s acceptability and comprehension, but there were no significant modifications in the content of the intervention protocol. In the future, as the UP-C/A is introduced into other cultures, its effectiveness will be further evaluated and the cultural adaptations needed to accommodate new cultural groups will become increasingly apparent.