@article{MittermeierSeidelScheineretal.2024, author = {Mittermeier, Sabrina and Seidel, Alexandra and Scheiner, Christin and Kleindienst, Nikolaus and Romanos, Marcel and Buerger, Arne}, title = {Emotional dysregulation and its pathways to suicidality in a community-based sample of adolescents}, series = {Child and Adolescent Psychiatry and Mental Health}, volume = {18}, journal = {Child and Adolescent Psychiatry and Mental Health}, issn = {1753-2000}, doi = {10.1186/s13034-023-00699-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357501}, year = {2024}, abstract = {Objective Effective suicide prevention for adolescents is urgently needed but difficult, as suicide models lack a focus on age-specific influencing factors such as emotional dysregulation. Moreover, examined predictors often do not specifically consider the contribution to the severity of suicidality. To determine which adolescents are at high risk of more severe suicidality, we examined the association between emotional dysregulation and severity of suicidality directly as well as indirectly via depressiveness and nonsuicidal self-injury. Method Adolescents from 18 high schools in Bavaria were included in this cross-sectional and questionnaire-based study as part of a larger prevention study. Data were collected between November 2021 and March 2022 and were analyzed from January 2023 to April 2023. Students in the 6th or 7th grade of high school (11-14 years) were eligible to participate. A total of 2350 adolescents were surveyed and data from 2117 students were used for the analyses after excluding incomplete data sets. Our main outcome variable was severity of suicidality (Paykel Suicide Scale, PSS). Additionally, we assessed emotional dysregulation (Difficulties in Emotion Regulation Scale, DERS-SF), depressiveness (Patient Health Questionnaire, PHQ-9) and nonsuicidal self-injury (Deliberate Self-Harm Inventory, DSHI). Results In total, 2117 adolescents (51.6\% female; mean age, 12.31 years [standard deviation: 0.67]) were included in the structural equation model (SEM). Due to a clear gender-specific influence, the model was calculated separately for male and female adolescents. For male adolescents, there was a significant indirect association between emotional dysregulation and severity of suicidality, mediated by depressiveness (β = 0.15, SE = .03, p = .008). For female adolescents, there was a significant direct path from emotional dysregulation to severity of suicidality and also indirect paths via depressiveness (β = 0.12, SE = .05, p = 0.02) and NSSI (β = 0.18, SE = .04, p < .001). Conclusions Our results suggest that gender-related risk markers in 11-14-year-olds need to be included in future suicide models to increase their predictive power. According to our findings, early detection and prevention interventions based on emotion regulation skills might be enhanced by including gender-specific adjustments for the co-occurrence of emotional dysregulation, depressiveness, and nonsuicidal self-injury in girls and the co-occurrence of emotional dysregulation and depressiveness in boys.}, language = {en} } @article{FeketeKulpokTaurinesetal.2023, author = {Fekete, Stefanie and Kulpok, Christine and Taurines, Regina and Egberts, Karin and Geissler, Julia and Gerlach, Manfred and Malonga Makosi, Doroth{\´e}e and K{\"o}nig, Jochem and Urschitz, Michael S. and Toni, Irmgard and Neubert, Antje and Romanos, Marcel}, title = {Value of a web-based pediatric drug information system to prevent serious adverse drug reactions in child and adolescent psychiatry}, series = {Journal of Neural Transmission}, volume = {130}, journal = {Journal of Neural Transmission}, number = {1}, doi = {10.1007/s00702-022-02563-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324817}, pages = {53-63}, year = {2023}, abstract = {Psychotropic drugs are frequently prescribed 'off-label' to children and adolescents and carry the risk of serious adverse drug reactions (sADR). We examined the frequency of sADRs of psychotropic drugs in pediatric inpatients and explored their potential preventability through following the recommendations of a web-based pediatric drug information system (PDIS). The potential socio-economic impacts of using this online system is also addressed. Routine clinical data from all inpatients treated in a child and adolescent psychiatry department between January 2017 and December 2018 were retrospectively examined for the occurrence of sADRs as defined by the European Medicines Agency. The preventability of the sADRs was assessed based on the information of the PDIS. Furthermore, the expected prolongation of the hospital stay due to sADRs was calculated as well as the associated treatment costs. The study was supported by the Innovation Fund of the Joint Federal Committee, grant number 01NVF16021. In total, 1036 patients were screened of whom 658 (63.5\%) received psychopharmacological treatment. In 53 (8.1\%) of these patients 54 sADRs were documented, of which 37 sADRs were identified as potentially preventable through PDIS. Mitigating sADR through PDIS would likely have prevented prolonged hospital stays and conferred considerable savings for health insurance companies. PDIS provides systematic and evidence-based information about pediatric psychopharmacotherapy and helps to prevent prescribing errors. Therefore, PDIS is a useful tool to increase drug therapy safety in child and adolescent psychiatry. Further prospective studies are needed to confirm the results.}, language = {en} } @article{MelfsenJansRomanosetal.2022, author = {Melfsen, Siebke and Jans, Thomas and Romanos, Marcel and Walitza, Susanne}, title = {Family relationships in selective mutism — a comparison group study of children and adolescents}, series = {Children}, volume = {9}, journal = {Children}, number = {11}, issn = {2227-9067}, doi = {10.3390/children9111634}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290386}, year = {2022}, abstract = {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.}, language = {en} } @article{LueffeBauerGiogaetal.2022, author = {L{\"u}ffe, Teresa M. and Bauer, Moritz and Gioga, Zoi and {\"O}zbay, Duru and Romanos, Marcel and Lillesaar, Christina and Drepper, Carsten}, title = {Loss-of-Function Models of the Metabotropic Glutamate Receptor Genes Grm8a and Grm8b Display Distinct Behavioral Phenotypes in Zebrafish Larvae (Danio rerio)}, series = {Frontiers in Molecular Neuroscience}, volume = {15}, journal = {Frontiers in Molecular Neuroscience}, issn = {1662-5099}, doi = {10.3389/fnmol.2022.901309}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-277429}, year = {2022}, abstract = {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.}, language = {en} } @article{ScheinerDaunkeSeideletal.2023, author = {Scheiner, Christin and Daunke, Andrea and Seidel, Alexandra and Mittermeier, Sabrina and Romanos, Marcel and K{\"o}lch, Michael and Buerger, Arne}, title = {LessStress - how to reduce stress in school: evaluation of a universal stress prevention in schools: study protocol of a cluster-randomised controlled trial}, series = {Trials}, volume = {24}, journal = {Trials}, number = {1}, doi = {10.1186/s13063-022-06970-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300393}, year = {2023}, abstract = {Background Chronic stress is detrimental to health, and children and young people have had to cope with significantly more stress since the start of the COVID-19 pandemic. In particular, stress at school and in relation to learning is a major problem in this age group. Studies in Germany have indicated that the pandemic has led to a reduced quality of life (QoL) and an increased risk for psychiatric disorders in children and adolescents. Schools are an ideal setting for interventions against stress, which is one of the strongest predictors for the development of psychosocial problems. The present study seeks to address stress by means of a short prevention training programme in schools, including emotion regulation, mindfulness, and self-compassion. In addition to information material for self-study, students should have the opportunity to actively deal with the topic of stress and develop coping strategies within a short space of time. In contrast to very long stress reduction programmes that often last several weeks, the programme is delivered in just 90 min. Methods The effectiveness of the short and economical prevention programme LessStress will be examined in a cluster-randomised controlled trial (RCT) encompassing 1894 students. At several measurement time points, students from two groups (intervention and control) will be asked about their subjectively perceived stress levels, among other aspects. Due to the clustered nature of the data, mainly multilevel analyses will be performed. Discussion In Germany, there are no nationwide universal prevention programmes for students against stress in schools, and this gap has become more evident since the outbreak of the pandemic. Universal stress prevention in schools may be a starting point to promote resilience. By dealing with stress in a healthy way, mental health can be strengthened and maintained. Moreover, to reach at-risk students at an early stage, we advocate for a stronger networking between child psychiatry and schools.}, language = {en} } @article{HebestreitZeidlerSchippersetal.2022, author = {Hebestreit, Helge and Zeidler, Cornelia and Schippers, Christopher and de Zwaan, Martina and Deckert, J{\"u}rgen and Heuschmann, Peter and Krauth, Christian and Bullinger, Monika and Berger, Alexandra and Berneburg, Mark and Brandstetter, Lilly and Deibele, Anna and Dieris-Hirche, Jan and Graessner, Holm and G{\"u}ndel, Harald and Herpertz, Stephan and Heuft, Gereon and Lapstich, Anne-Marie and L{\"u}cke, Thomas and Maisch, Tim and Mundlos, Christine and Petermann-Meyer, Andrea and M{\"u}ller, Susanne and Ott, Stephan and Pfister, Lisa and Quitmann, Julia and Romanos, Marcel and Rutsch, Frank and Schaubert, Kristina and Schubert, Katharina and Schulz, J{\"o}rg B. and Schweiger, Susann and T{\"u}scher, Oliver and Ungeth{\"u}m, Kathrin and Wagner, Thomas O. F. and Haas, Kirsten}, title = {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}, series = {Orphanet Journal of Rare Diseases}, volume = {17}, journal = {Orphanet Journal of Rare Diseases}, number = {1}, doi = {10.1186/s13023-022-02176-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300440}, year = {2022}, abstract = {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.}, language = {en} } @article{AsterRomanosWalitzaetal.2022, author = {Aster, Hans-Christoph and Romanos, Marcel and Walitza, Susanne and Gerlach, Manfred and M{\"u}hlberger, Andreas and Rizzo, Albert and Andreatta, Marta and Hasenauer, Natalie and Hartrampf, Philipp E. and Nerlich, Kai and Reiners, Christoph and Lorenz, Reinhard and Buck, Andreas K. and Deserno, Lorenz}, title = {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}, series = {Frontiers in Psychiatry}, volume = {13}, journal = {Frontiers in Psychiatry}, issn = {1664-0640}, doi = {10.3389/fpsyt.2022.804730}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270862}, year = {2022}, abstract = {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.}, language = {en} } @article{ZieglerKaiserIgeletal.2021, author = {Ziegler, Mirjam and Kaiser, Anna and Igel, Christine and Geissler, Julia and Mechler, Konstantin and Holz, Nathalie E. and Becker, Katja and D{\"o}pfner, Manfred and Romanos, Marcel and Brandeis, Daniel and Hohmann, Sarah and Millenet, Sabina and Banaschewski, Tobias}, title = {Actigraphy-derived sleep profiles of children with and without attention-deficit/hyperactivity disorder (ADHD) over two weeks — comparison, precursor symptoms, and the chronotype}, series = {Brain Sciences}, volume = {11}, journal = {Brain Sciences}, number = {12}, issn = {2076-3425}, doi = {10.3390/brainsci11121564}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250084}, year = {2021}, abstract = {Although sleep problems are common in children with ADHD, their extent, preceding risk factors, and the association between neurocognitive performance and neurobiological processes in sleep and ADHD, are still largely unknown. We examined sleep variables in school-aged children with ADHD, addressing their intra-individual variability (IIV) and considering potential precursor symptoms as well as the chronotype. Additionally, in a subgroup of our sample, we investigated associations with neurobehavioral functioning (n = 44). A total of 57 children (6-12 years) with (n = 24) and without ADHD (n = 33) were recruited in one center of the large ESCAlife study to wear actigraphs for two weeks. Actigraphy-derived dependent variables, including IIV, were analyzed using linear mixed models in order to find differences between the groups. A stepwise regression model was used to investigate neuropsychological function. Overall, children with ADHD showed longer sleep onset latency (SOL), higher IIV in SOL, more movements during sleep, lower sleep efficiency, and a slightly larger sleep deficit on school days compared with free days. No group differences were observed for chronotype or sleep onset time. Sleep problems in infancy predicted later SOL and the total number of movements during sleep in children with and without ADHD. No additional effect of sleep problems, beyond ADHD symptom severity, on neuropsychological functioning was found. This study highlights the importance of screening children with ADHD for current and early childhood sleep disturbances in order to prevent long-term sleep problems and offer individualized treatments. Future studies with larger sample sizes should examine possible biological markers to improve our understanding of the underlying mechanisms.}, language = {en} } @article{EgbertsFeketeHaegeetal.2022, author = {Egberts, Karin and Fekete, Stefanie and H{\"a}ge, Alexander and Hiemke, Christoph and Scherf-Clavel, Maike and Taurines, Regina and Unterecker, Stefan and Gerlach, Manfred and Romanos, Marcel}, title = {Therapeutisches Drug Monitoring zur Optimierung der Psychopharmakotherapie von Kindern und Jugendlichen: Update und Leitfaden f{\"u}r die Praxis}, series = {Zeitschrift f{\"u}r Kinder- und Jugendpsychiatrie und Psychotherapie}, volume = {50}, journal = {Zeitschrift f{\"u}r Kinder- und Jugendpsychiatrie und Psychotherapie}, number = {2}, issn = {1422-4917}, doi = {10.1024/1422-4917/a000845}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262038}, pages = {133-152}, year = {2022}, abstract = {Trotz verbesserter Evidenzbasis bestehen in der kinder- und jugendpsychiatrischen Pharmakotherapie viele Unsicherheiten {\"u}ber die Wirkung und Vertr{\"a}glichkeit der h{\"a}ufig off-label oder in Kombinationstherapie verordneten Medikamente. Gerade auch vor dem Hintergrund der in vielen F{\"a}llen notwendigen mittel- bis langfristigen Einnahme sollen unerw{\"u}nschte Arzneimittelwirkungen in dieser Altersstufe m{\"o}glichst minimiert und eine auf die individuellen Charakteristika der Patientin oder des Patienten zugeschnittene, effektive Dosierung gefunden werden. Kinder und Jugendliche scheinen nicht nur besonders anf{\"a}llig f{\"u}r bestimmte unerw{\"u}nschte Arzneimittelwirkungen, sondern sind auch iatrogenen Risiken durch Dosierungs- oder Applikationsfehler ausgesetzt, die zu Unter- oder {\"U}berdosierungen f{\"u}hren k{\"o}nnen mit entsprechend negativen Auswirkungen auf den Therapieerfolg. Neben einer strengen Indikationsstellung sind daher eine pr{\"a}zise Dosisfindung sowie systematische {\"U}berwachung 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 Vertr{\"a}glichkeit einer Psychopharmakotherapie im Kindes- und Jugendalter zum unmittelbaren Nutzen f{\"u}r die Patientinnen und Patienten verbessern kann.}, language = {de} } @article{VloetFetekeGerlachetal.2022, author = {Vloet, Timo D. and Feteke, Stefanie and Gerlach, Manfred and Romanos, Marcel}, title = {Das pharmakologische Management kinder- und jugendpsychiatrischer Notf{\"a}lle : Evidenz und Qualit{\"a}tssicherung}, series = {Zeitschrift f{\"u}r Kinder- und Jugendpsychiatrie und Psychotherapie}, volume = {50}, journal = {Zeitschrift f{\"u}r Kinder- und Jugendpsychiatrie und Psychotherapie}, number = {4}, issn = {1422-4917}, doi = {10.1024/1422-4917/a000833}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280982}, pages = {262-274}, year = {2022}, abstract = {Kinder- und jugendpsychiatrische Notf{\"a}lle sind h{\"a}ufig und stellen die beteiligten {\"A}rztinnen und {\"A}rzte vor besondere Herausforderungen, da eine erhebliche Gefahr f{\"u}r die Patient_innen oder Dritte unter Anwendung m{\"o}glichst wenig invasiver Mittel abzuwenden ist. In diesem Kontext werden neben haltgebenden, deeskalierenden und psychotherapeutischen Optionen h{\"a}ufig 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 {\"A}rztinnen und {\"A}rzte werden im vorliegenden Artikel praxisrelevante Hinweise insbesondere zum pharmakologischen Management von in der Praxis h{\"a}ufig auftretenden kinder- und jugendpsychiatrischen Notf{\"a}llen wie akuter Suizidalit{\"a}t, akut psychotischem Erleben, Delir und Bewusstseinsst{\"o}rungen sowie akuter Intoxikation und Alkoholentzugssyndrom gegeben. Weiterhin werden Maßnahmen zur Qualit{\"a}tssicherung und Arzneimittelsicherheit diskutiert.}, language = {de} }