An app-based training for adolescents with problematic digital-media use and their parents (Res@t digital): protocol for a cluster-randomized clinical trial

BackgroundDigital media-use disorders (DMUD) in adolescents are a rising phenomenon associated with psychological distress, comorbid mental disorders, and high burden on affected families. Since the ICD-11 introduced criteria for gaming disorder, these can now be transferred to describe additional DMUD associated with social media platforms and streaming services. Most evidence for effective treatments comes from cognitive-behavioral therapy (CBT). However, interventions based on theoretical models for adolescents and their parents are widely missing, leading to a significant clinical gap.MethodsRes@t digital (Resource-Strengthening Training for Adolescents with Problematic Digital-Media Use and their Parents) is the app-based translation of the first model-based digital intervention for adolescents with DMUD and their parents based on CBT. It comprises separate but content-related modules for adolescents (Res@t–A) and parents (Res@t–P), applying multimodal techniques. The effectiveness of Res@t will be evaluated within a multicenter cluster-randomized controlled evaluator-blinded pre–post follow-up trial with the waitlist control group (CG). In addition to the Res@t program in the intervention group, both groups will receive treatment as usual within primary child and adolescent psychiatric/psychotherapeutic healthcare. The primary outcome addresses DMUD symptom reduction after 10 weeks. Secondary outcomes are related to a reduction in psychological and family-related problems and an increase in parental self-efficacy. All outcomes will be assessed using standardized self-report measures. A total of 1,334 participating adolescent–parent dyads from a large clinical network throughout Germany are planned to be included in the primary analyses based on an intention-to-treat approach, applying linear mixed models.DiscussionAssuming superiority of Res@t over the control condition, the intervention has the potential to provide evidence-based treatment for a significant number of help-seeking families, supporting local healthcare structures and resources. It is a promising program for practicable implementation and flexible use in different settings.Clinical trial registrationhttps://drks.de, DRKS00031043

A genotype-first approach identifies an intellectual disability-overweight syndrome caused by PHIP haploinsufficiency

Genotype-first combined with reverse phenotyping has shown to be a powerful tool in human genetics, especially in the era of next generation sequencing. This combines the identification of individuals with mutations in the same gene and linking these to consistent (endo) phenotypes to establish disease causality. We have performed a MIP (molecular inversion probe)based targeted re-sequencing study in 3,275 individuals with intellectual disability (ID) to facilitate a genotype-first approach for 24 genes previously implicated in ID. Combining our data with data from a publicly available database, we confirmed 11 of these 24 genes to be relevant for ID. Amongst these, PHIP was shown to have an enrichment of disruptive mutations in the individuals with ID (5 out of 3,275). Through international collaboration, we identified a total of 23 individuals with PHIP mutations and elucidated the associated phenotype. Remarkably, all 23 individuals had developmental delay/ID and the majority were overweight or obese. Other features comprised behavioral problems (hyperactivity, aggression, features of autism and/or mood disorder) and dysmorphisms (full eyebrows and/or synophrys, upturned nose, large ears and tapering fingers). Interestingly, PHIP encodes two protein-isoforms, PHIP/DCAF14 and NDRP, each involved in neurodevelopmental processes, including E3 ubiquitination and neuronal differentiation. Detailed genotype-phenotype analysis points towards haploinsufficiency of PHIP/DCAF14, and not NDRP, as the underlying cause of the phenotype. Thus, we demonstrated the use of large scale re-sequencing by MIPs, followed by reverse phenotyping, as a constructive approach to verify candidate disease genes and identify novel syndromes, highlighted by PHIP haploinsufficiency causing an ID-overweight syndrome