TY - JOUR A1 - Hebestreit, Helge A1 - Zeidler, Cornelia A1 - Schippers, Christopher A1 - de Zwaan, Martina A1 - Deckert, Jürgen A1 - Heuschmann, Peter A1 - Krauth, Christian A1 - Bullinger, Monika A1 - Berger, Alexandra A1 - Berneburg, Mark A1 - Brandstetter, Lilly A1 - Deibele, Anna A1 - Dieris-Hirche, Jan A1 - Graessner, Holm A1 - Gündel, Harald A1 - Herpertz, Stephan A1 - Heuft, Gereon A1 - Lapstich, Anne-Marie A1 - Lücke, Thomas A1 - Maisch, Tim A1 - Mundlos, Christine A1 - Petermann-Meyer, Andrea A1 - Müller, Susanne A1 - Ott, Stephan A1 - Pfister, Lisa A1 - Quitmann, Julia A1 - Romanos, Marcel A1 - Rutsch, Frank A1 - Schaubert, Kristina A1 - Schubert, Katharina A1 - Schulz, Jörg B. A1 - Schweiger, Susann A1 - Tüscher, Oliver A1 - Ungethüm, Kathrin A1 - Wagner, Thomas O. F. A1 - Haas, Kirsten T1 - Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study JF - Orphanet Journal of Rare Diseases N2 - Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. Study design This multi-center, prospective controlled study has a two-phase cohort design. Methods Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD’s outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). Outcomes Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients’ quality of life and evaluation of care; and f) physicians’ satisfaction with the innovative care approach. Conclusions This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease. KW - rare diseases KW - multi‑center cohort study KW - dual guidance Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300440 VL - 17 IS - 1 ER - TY - JOUR A1 - Egberts, Karin A1 - Fekete, Stefanie A1 - Häge, Alexander A1 - Hiemke, Christoph A1 - Scherf-Clavel, Maike A1 - Taurines, Regina A1 - Unterecker, Stefan A1 - Gerlach, Manfred A1 - Romanos, Marcel T1 - Therapeutisches Drug Monitoring zur Optimierung der Psychopharmakotherapie von Kindern und Jugendlichen: Update und Leitfaden für die Praxis JF - Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie N2 - Trotz verbesserter Evidenzbasis bestehen in der kinder- und jugendpsychiatrischen Pharmakotherapie viele Unsicherheiten über die Wirkung und Verträglichkeit der häufig off-label oder in Kombinationstherapie verordneten Medikamente. Gerade auch vor dem Hintergrund der in vielen Fällen notwendigen mittel- bis langfristigen Einnahme sollen unerwünschte Arzneimittelwirkungen in dieser Altersstufe möglichst minimiert und eine auf die individuellen Charakteristika der Patientin oder des Patienten zugeschnittene, effektive Dosierung gefunden werden. Kinder und Jugendliche scheinen nicht nur besonders anfällig für bestimmte unerwünschte Arzneimittelwirkungen, sondern sind auch iatrogenen Risiken durch Dosierungs- oder Applikationsfehler ausgesetzt, die zu Unter- oder Überdosierungen führen können mit entsprechend negativen Auswirkungen auf den Therapieerfolg. Neben einer strengen Indikationsstellung sind daher eine präzise Dosisfindung sowie systematische Überwachung der Sicherheit der Psychopharmakotherapie unverzichtbar. In diesem Artikel wird Therapeutisches Drug Monitoring als hilfreiches klinisches Instrument vorgestellt und beschrieben, wie dessen richtige Anwendung sowohl die Wirksamkeit als auch die Sicherheit und Verträglichkeit einer Psychopharmakotherapie im Kindes- und Jugendalter zum unmittelbaren Nutzen für die Patientinnen und Patienten verbessern kann. N2 - Despite the improved evidence base, many uncertainties remain in child and adolescent psychiatric pharmacotherapy about the efficacy and tolerability of drugs, which are often prescribed off-label or in combination therapy in this age group. Because medium- to long-term use is unavoidable in many cases, clinicians should minimize adverse drug reactions as far as possible and tailor an effective dosage to the individual characteristics of the patient. Not only are children and adolescents particularly vulnerable to certain adverse drug effects, they are also exposed to iatrogenic risks from dosing or application errors, which can lead to under- or overdosing with correspondingly negative effects on the success of the therapy. In addition to determining a strict indication, it is therefore essential to establish precise dosage and systematic monitoring of the safety of the psychopharmacotherapy. This article introduces therapeutic drug monitoring as a useful clinical tool and describes how its correct application in practice can improve the efficacy as well as the safety and tolerability of psychotropic therapy in children and adolescents for the immediate benefit of patients. T2 - Therapeutic drug monitoring to optimize psychopharmacotherapy in children and adolescents - Update and guidelines for practice KW - Psychopharmakotherapie KW - unerwünschte Arzneimittelwirkungen KW - Pharmakovigilanz KW - Therapeutisches Drug Monitoring KW - Qualitätssicherung KW - psychopharmacotherapy KW - adverse drug reactions KW - pharmacovigilance KW - therapeutic drug monitoring KW - quality assurance Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262038 SN - 1422-4917 SN - 1664-2880 VL - 50 IS - 2 ER - TY - JOUR A1 - Buerger, Arne A1 - Emser, Theresa A1 - Seidel, Alexandra A1 - Scheiner, Christin A1 - von Schoenfeld, Cornelia A1 - Ruecker, Viktoria A1 - Heuschmann, Peter U. A1 - Romanos, Marcel T1 - DUDE - a universal prevention program for non-suicidal self-injurious behavior in adolescence based on effective emotion regulation: study protocol of a cluster-randomized controlled trial JF - Trials N2 - Background Non-suicidal self-injury (NSSI) has become a substantial public health problem. NSSI is a high-risk marker for the development and persistence of mental health problems, shows high rates of morbidity and mortality, and causes substantial health care costs. Thus, there is an urgent need for action to develop universal prevention programs for NSSI before adolescents begin to show this dangerous behavior. Currently, however, universal prevention programs are lacking. Methods The main objective of the present study is to evaluate a newly developed universal prevention program (“DUDE – Du und deine Emotionen / You and your emotions”), based on a skills-based approach in schools, in 3200 young adolescents (age 11–14 years). The effectiveness of DUDE will be investigated in a cluster-randomized controlled trial (RCT) in schools (N = 16). All groups will receive a minimal intervention called “Stress-free through the school day” as a mental health literacy program to prevent burnout in school. The treatment group (N = 1600; 8 schools) will additionally undergo the universal prevention program DUDE and will be divided into treatment group 1 (DUDE conducted by trained clinical psychologists; N = 800; 4 schools) and treatment group 2 (DUDE conducted by trained teachers; N = 800; 4 schools). The active control group (N = 1600; 8 schools) will only receive the mental health literacy prevention. Besides baseline assessment (T0), measurements will occur at the end of the treatment (T1) and at 6- (T2) and 12-month (T3) follow-up evaluations. The main outcome is the occurrence of NSSI within the last 6 months assessed by a short version of the Deliberate Self-Harm Inventory (DSHI-9) at the 1-year follow-up (primary endpoint; T3). Secondary outcomes are emotion regulation, suicidality, health-related quality of life, self-esteem, and comorbid psychopathology and willingness to change. Discussion DUDE is tailored to diminish the incidence of NSSI and to prevent its possible long-term consequences (e.g., suicidality) in adolescents. It is easy to access in the school environment. Furthermore, DUDE is a comprehensive approach to improve mental health via improved emotion regulation. KW - universal prevention KW - NSSI KW - self-injury KW - emotion regulation KW - RCT KW - school-based prevention KW - adolescence Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265874 VL - 23 ER - TY - JOUR A1 - Aster, Hans-Christoph A1 - Romanos, Marcel A1 - Walitza, Susanne A1 - Gerlach, Manfred A1 - Mühlberger, Andreas A1 - Rizzo, Albert A1 - Andreatta, Marta A1 - Hasenauer, Natalie A1 - Hartrampf, Philipp E. A1 - Nerlich, Kai A1 - Reiners, Christoph A1 - Lorenz, Reinhard A1 - Buck, Andreas K. A1 - Deserno, Lorenz T1 - Responsivity of the striatal dopamine system to methylphenidate — A within-subject I-123-β-CIT-SPECT study in male children and adolescents with attention-deficit/hyperactivity disorder JF - Frontiers in Psychiatry N2 - Background: Methylphenidate (MPH) is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). MPH binds to the dopamine (DA) transporter (DAT), which has high density in the striatum. Assessments of the striatal dopamine transporter by single positron emission computed tomography (SPECT) in childhood and adolescent patients are rare but can provide insight on how the effects of MPH affect DAT availability. The aim of our within-subject study was to investigate the effect of MPH on DAT availability and how responsivity to MPH in DAT availability is linked to clinical symptoms and cognitive functioning. Methods Thirteen adolescent male patients (9–16 years) with a diagnosis of ADHD according to the DSM-IV and long-term stimulant medication (for at least 6 months) with MPH were assessed twice within 7 days using SPECT after application of I-123-β-CIT to examine DAT binding potential (DAT BP). SPECT measures took place in an on- and off-MPH status balanced for order across participants. A virtual reality continuous performance test was performed at each time point. Further clinical symptoms were assessed for baseline off-MPH. Results On-MPH status was associated with a highly significant change (−29.9%) of striatal DAT BP as compared to off-MPH (t = −4.12, p = 0.002). A more pronounced change in striatal DAT BP was associated with higher off-MPH attentional and externalizing symptom ratings (Pearson r = 0.68, p = 0.01). Striatal DAT BP off-MPH, but not on-MPH, was associated with higher symptom ratings (Pearson r = 0.56, p = 0.04). Conclusion Our findings corroborate previous reports from mainly adult samples that MPH changes striatal DAT BP availability and suggest higher off-MPH DAT BP, likely reflecting low baseline DA levels, as a marker of symptom severity. KW - methylphenidate KW - attention deficit/hyperactivity disorder (ADHD) KW - striatum KW - single photon emission computed tomography (SPECT) KW - responsivity KW - caudate nucleus KW - dopamine transporter (DAT) Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270862 SN - 1664-0640 VL - 13 ER - TY - JOUR A1 - Vloet, Timo D. A1 - Feteke, Stefanie A1 - Gerlach, Manfred A1 - Romanos, Marcel T1 - Das pharmakologische Management kinder- und jugendpsychiatrischer Notfälle : Evidenz und Qualitätssicherung JF - Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie N2 - Kinder- und jugendpsychiatrische Notfälle sind häufig und stellen die beteiligten Ärztinnen und Ärzte vor besondere Herausforderungen, da eine erhebliche Gefahr für die Patient_innen oder Dritte unter Anwendung möglichst wenig invasiver Mittel abzuwenden ist. In diesem Kontext werden neben haltgebenden, deeskalierenden und psychotherapeutischen Optionen häufig auch pharmakologische Interventionen eingesetzt. Da ein Mangel an systematisch erhobenen Daten besteht, findet die pharmakologische Notfallbehandlung in der Kinder- und Jugendpsychiatrie regelhaft im off-label-Bereich statt. Vor dem Hintergrund der komplexen klinischen und rechtlichen Anforderungen an die Ärztinnen und Ärzte werden im vorliegenden Artikel praxisrelevante Hinweise insbesondere zum pharmakologischen Management von in der Praxis häufig auftretenden kinder- und jugendpsychiatrischen Notfällen wie akuter Suizidalität, akut psychotischem Erleben, Delir und Bewusstseinsstörungen sowie akuter Intoxikation und Alkoholentzugssyndrom gegeben. Weiterhin werden Maßnahmen zur Qualitätssicherung und Arzneimittelsicherheit diskutiert. N2 - Emergencies in child and adolescent psychiatry are highly prevalent and often pose significant challenges to physicians, since substantial danger to the patient or others must be avoided through the application of largely moderate interventions. Besides using de-escalating strategies and exploiting psychotherapeutic options, the physician frequently employs psychopharmacological interventions. because of a lack of systematically assessed data, however, in emergencies in child and adolescent psychiatry most administrations of psychotropic drugs occur “off label.“ This review deduces practice-relevant recommendations for the pharmacological management of occurring child and adolescent emergencies such as acute suicidality, acute psychotic episodes, delirium, disorders of consciousness, acute intoxication, and alcohol withdrawal syndrome. We discuss the issue of quality and safety in pharmacological emergency strategies. T2 - The pharmacological management of emergencies in child and adolescent psychiatry KW - Psychiatrischer Notfall KW - Qualitätssicherung KW - Pharmakotherapie KW - Kinder und Jugendliche KW - TDM KW - psychiatric emergencies KW - quality assurance KW - pharmacotherapy KW - child and adolescent KW - TDM Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-280982 SN - 1422-4917 SN - 1664-2880 VL - 50 IS - 4 SP - 262-274 ER - TY - JOUR A1 - Lüffe, Teresa M. A1 - Bauer, Moritz A1 - Gioga, Zoi A1 - Özbay, Duru A1 - Romanos, Marcel A1 - Lillesaar, Christina A1 - Drepper, Carsten T1 - Loss-of-Function Models of the Metabotropic Glutamate Receptor Genes Grm8a and Grm8b Display Distinct Behavioral Phenotypes in Zebrafish Larvae (Danio rerio) JF - Frontiers in Molecular Neuroscience N2 - Members of the family of metabotropic glutamate receptors are involved in the pathomechanism of several disorders of the nervous system. Besides the well-investigated function of dysfunctional glutamate receptor signaling in neurodegenerative diseases, neurodevelopmental disorders (NDD), like autism spectrum disorders (ASD) and attention-deficit and hyperactivity disorder (ADHD) might also be partly caused by disturbed glutamate signaling during development. However, the underlying mechanism of the type III metabotropic glutamate receptor 8 (mGluR8 or GRM8) involvement in neurodevelopment and disease mechanism is largely unknown. Here we show that the expression pattern of the two orthologs of human GRM8, grm8a and grm8b, have evolved partially distinct expression patterns in the brain of zebrafish (Danio rerio), especially at adult stages, suggesting sub-functionalization of these two genes during evolution. Using double in situ hybridization staining in the developing brain we demonstrate that grm8a is expressed in a subset of gad1a-positive cells, pointing towards glutamatergic modulation of GABAergic signaling. Building on this result we generated loss-of-function models of both genes using CRISPR/Cas9. Both mutant lines are viable and display no obvious gross morphological phenotypes making them suitable for further analysis. Initial behavioral characterization revealed distinct phenotypes in larvae. Whereas grm8a mutant animals display reduced swimming velocity, grm8b mutant animals show increased thigmotaxis behavior, suggesting an anxiety-like phenotype. We anticipate that our two novel metabotropic glutamate receptor 8 zebrafish models may contribute to a deeper understanding of its function in normal development and its role in the pathomechanism of disorders of the central nervous system. KW - nervous system KW - brain disorders KW - psychiatric disorders KW - brain development KW - excitatory/inhibitory imbalance KW - metabotropic glutamate (mGlu) receptor Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-277429 SN - 1662-5099 VL - 15 ER - TY - JOUR A1 - Melfsen, Siebke A1 - Jans, Thomas A1 - Romanos, Marcel A1 - Walitza, Susanne T1 - Family relationships in selective mutism — a comparison group study of children and adolescents JF - Children N2 - Selective mutism (SM) mostly develops early in childhood and this has led to interest into whether there could be differences in relationships in families with SM compared to a control group without SM. Currently, there are merely few empirical studies examining family relationships in SM. A sample of 28 children and adolescents with SM was compared to 33 controls without SM. The groups were investigated using self-report questionnaires (Selective Mutism Questionnaire, Child-Parent Relationship Test—Child Version) for the assessment of SM and family relationships. Children with SM did not report a significantly different relationship to their mothers compared with the control group without SM. However, the scores in respect to the relationship to their fathers were significantly lower in cohesion, identification and autonomy compared with children without SM. Relationships in families with SM should be considered more in therapy. KW - selective mutism KW - family relations KW - parents KW - schoolchildren Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290386 SN - 2227-9067 VL - 9 IS - 11 ER -