Langversion der interdisziplinären evidenz- und konsensbasierten S3-Leitlinie für Diagnostik und Therapie von Zwangsstörungen im Kindes- und Jugendalter

Zwangsstörungen gehören mit einer Langzeitprävalenz von 1-3% auch im Kindes- und Jugendalter zu den häufigsten psychischen Störungen. Es liegen zwei Erkrankungsgipfel im Altersbereich von 11-14 Jahren und im jungen Erwachsenenalter mit 20 Jahren vor. 20% der Zwangsstörungen beginnen vor dem Alter von 10 Jahren und 60% vor dem Alter von 25 Jahren. Die Erkrankung wird oftmals sehr spät erkannt. Es dauert im Durchschnitt über 10 Jahre bis die Patienten professionelle Hilfe aufsuchen. Es gibt einige behandlungsrelevante Unterschiede von Zwangsstörungen im Kindes- und Jugendalter im Vergleich zum Erwachsenenalter. In der Diagnostik und Behandlung müssen das Alter und der Entwicklungsstand der Betroffenen sowie die Bedingungen um familiären und sozialen Umfeld berücksichtigt werden. Die Fehl- und Unterdiagnosen sind im Kindes- und Jugendalter wie im Erwachsenenalter sehr hoch. Verlaufsstudien zeigen, dass die Erkrankung oft chronisch verläuft und zu einer erheblichen psychosozialen Beeinträchtigung führt. Auch ist das Risiko für die Entwicklung von weiteren psychischen, aber auch somatischen Störungen und Folgeerkrankungen hoch. Aus der Studienlage wird deutlich, dass der frühe Behandlungsbeginn einer der wichtigsten positiven prognostischen Faktoren ist (Walitza et al., 2020, Fineberg et al., 2019). Wegen der hohen Bedeutung der Früherkennung und frühen Interventionen wurde 2019 ein internationales Consensus-Statement verfasst (Fineberg et al., 2019) in welchem auch die Aspekte, die Kinder und Jugendliche betreffen, berücksichtigt werden. Zudem besteht eine Unterversorgung, diese kommt unter anderem zustande durch mangelnde Verfügbarkeit von einer anwendergerechten Zusammenfassung der Evidenz von Behandlungsansätzen im Rahmen einer Leitlinie für Diagnostik und Therapie im Kindes- und Jugendalter. Diese Gründe, aber auch das Ziel der breiten Disseminierung der Leitlinie zu allen Versorgern, die Kinder und Jugendliche sehen, ist Anlass und Grund für diese Leitlinie. Neben der Praxis und Anwendung selbst, ist eine Leitlinie auch relevant für die Aus- und Weiterbildung. Zum aktuellen Zeitpunkt werden die evidenzbasierten Therapien national und international nicht flächendeckend eingesetzt. Bislang gibt es für Zwangsstörungen im Kindes- und Jugendalter keine S3-Leitlinie. Ziel ist es die Diagnostik und Behandlung von Zwangsstörungen zu verbessern und den Therapeuten eine Leitlinie auf S3 Niveau an die Hand zu geben. Die Langversion der Leitlinie gibt zusätzlich eine Zusammenfassung des Hintergrundwissens zu Zwangsstörungen im Kindes- und Jugendalter und einen Teil der Diskussion im Konsentierungsprozess wieder, die neben der Evidenz und der Konsentierung ebenfalls hinter den Empfehlungen steht

Pilot study on HTR2A promoter polymorphism, −1438G/A (rs6311) and a nearby copy number variation showed association with onset and severity in early onset obsessive-compulsive disorder

A previous study showed that a single nucleotide polymorphism (SNP), −1438G/A (rs6311), found in the transcriptional control region of the gene that encodes the serotonin-receptor 2A (HTR2A) was associated with obsessive-compulsive disorder (OCD) in a sample of children and adolescents. In this study, we reanalyzed the association of this SNP with OCD in an enlarged population of 136 cases (55 previous+81 new cases) and compared them to 106 newly recruited, healthy, age-matched controls. We also investigated whether this SNP or its copy number variations (CNV) was associated with OCD severity and age of onset. The CNV was analyzed in a DNA region located near rs6311. The results confirmed the association between the A-allele and early onset OCD in children and adolescents, with an odds ratio (OR) of 1.69 [95% CI (1.17, 2.46); p=0.005]. Strikingly, we found that carriers of one copy (deletion) of the CNV were associated with a very early onset OCD (2.5years earlier than the typical onset), and they had increased CY-BOCS scores (8.7 points higher compared to "normal” CNV and duplications); which is related to increased severity of OCD symptoms (p=0.031; p=0.004, respectively). Compared to the normal CNV and duplications, the association between the deletion and OCD showed an OR of 7.56 [95% CI (1.32, 142.84); p=0.020]. These results pointed to the functional importance of this promoter region of HTR2A; it influenced the occurrence, the onset, and the severity of OC

Internet-based psychotherapy in children with obsessive-compulsive disorder (OCD): protocol of a randomized controlled trial

Background: Obsessive-compulsive disorder (OCD) in children can lead to a huge burden on the concerned patients and their family members. While successful state-of-the art cognitive behavioral interventions exist, there is still a lack of available experts for treatment at home, where most symptoms manifest. Internet-based cognitive behavioral therapy (iCBT) could overcome these restrictions; however, studies about iCBT in children with OCD are rare and mostly target computerized self-help resources and only email contact with the therapist. Therefore, we intended to build up and to evaluate an iCBT approach for children with OCD, replacing successful elements of traditional in-office face-to-face CBT, with face-to-face teleconferences, online materials, and apps. Methods: With the help of a pilot feasibility study, we developed the iCBT consisting of 14 teleconference sessions with the child and parents. The sessions are supported by an app assessing daily and weekly symptoms and treatment course completed by children and parents. Additionally, we obtain heart rate and activity scores from the child via wristbands during several days and exposure sessions. Using a waiting list randomized control trial design, we aim to treat and analyze 20 children with OCD immediately after a diagnostic session whereas the control group of another set of 20 OCD patients will be treated after waiting period of 16 weeks. We will recruit 30 patients in each group to take account for potential dropouts. Outcomes for the treatment group are evaluated before randomization (baseline, t0), 16 weeks (end of treatment, t1), 32 weeks (follow-up 1, t2), and 48 weeks after randomization (follow-up 2, t3). For the waiting list group, outcomes are measured before the first randomization (baseline), at 16 weeks (waiting list period), 32 weeks (end of treatment), 48 weeks after the first randomization (follow-up I), and 64 weeks after the first randomization (follow-up II). Discussion: Based on our experience of feasibility during the pilot study, we were able to develop the iCBT approach and the current study will investigate treatment effectiveness. Building up an iCBT approach, resembling traditional in-office face-to-face therapy, may ensure the achievement of well-known therapy effect factors, the acceptance in both patients and clinicians, and the wide distribution within the health system. Trial registration: ClinicalTrials.gov NCT05037344 . Registered May 2019, last release August 13th, 2021

Therapeutic drug monitoring in adolescents with anorexia nervosa for safe treatment with adjunct olanzapine

Objective: Medication is commonly used in anorexia nervosa (AN) despite largely missing high grade evidence. Olanzapine (OLZ) is the best-evidenced substance used off-label in this group, with conflicting outcome regarding BMI, clinical and safety parameters. Therefore, it is important to strictly assure quality of treatment with OLZ in AN by using 'Therapeutic Drug Monitoring' according to AGNP-guidelines, including serum levels and adverse drug reactions (ADRs) to support safety for adolescents with AN and attempt to generate an initial age- and disorder-specific therapeutic reference range. Method: Sixty-five adolescents with AN (aged 10-18) treated with OLZ (98% female; 97.5% AN-restricting-type) were prospectively observed, ADRs reported, and correlations between dosage and serum levels measured at trough level were calculated, a preliminary therapeutic range defined. Results: Mean dosage of OLZ was 8.15 (SD: 2.91) mg and 0.19 (SD: 0.07) mg/kg respectively, average concentration was 26.57 (SD: 13.46) ng/mL. Correlation between daily dosage/dosage per kg and serum level was 0.72 (**p < 0.001)/0.65 (**p < 0.001), respectively. ADRs with impairment were rare (6.3%). 75% improved clinically (CGI). BMI increased significantly by 1.5 kg/m2 (t = 10.6, p < 0.001). A preliminary therapeutic reference range is 11.9 and 39.9 ng/mL. Conclusions: OLZ in the hands of specialists is a well-tolerated and safe treatment adjunct for adolescents with AN

No Association of Variants of the NPY-System With Obsessive-Compulsive Disorder in Children and Adolescents

Obsessive-compulsive disorder (OCD) causes severe distress and is therefore counted by the World Health Organisation (WHO) as one of the 10 most impairing illnesses. There is evidence for a strong genetic underpinning especially in early onset OCD (eoOCD). Though several genes involved in neurotransmission have been reported as candidates, there is still a need to identify new pathways. In this study, we focussed on genetic variants of the Neuropeptide Y (NPY) system. NPY is one of the most abundant neuropeptides in the human brain with emerging evidence of capacity to modulate stress response, which is of high relevance in OCD. We focussed on tag-SNPs of NPY and its receptor gene NPY1R in a family-based approach. The sample comprised 86 patients (children and adolescents) with eoOCD with both their biological parents. However, this first study on genetic variants of the NPY-system could not confirm the association between the investigated SNPs and eoOCD. Based on the small sample size results have to be interpreted as preliminary and should be replicated in larger samples. However, also in an additional GWAS analysis in a large sample, we could not observe an associations between NPY and OCD. Overall, these preliminary results point to a minor role of NPY on the stress response of OCD