@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{BuergerSchoenfeldScheineretal.2023, author = {B{\"u}rger, Arne and Schoenfeld, Cornelia von and Scheiner, Christin and Seidel, Alexandra and Wasserscheid, Antonia and Gad, Doreya and Kittel-Schneider, Sarah and Romanos, Marcel and Reiter, Andrea M. F.}, title = {Universal prevention for non-suicidal self-injury in adolescents is scarce - A systematic review}, series = {Frontiers in Psychiatry}, volume = {14}, journal = {Frontiers in Psychiatry}, doi = {10.3389/fpsyt.2023.1130610}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357490}, year = {2023}, abstract = {Non-suicidal self-injury (NSSI) during adolescence is a high-risk marker for the development and persistence of mental health problems and has been recognized as a significant public health problem. Whereas targeted prevention has indeed shown to be effective in reducing NSSI and improve mental health problems, access to such programs is limited. By face validity, universal prevention of NSSI seems an ideal starting point for a stepped-care model to circumvent a lack of resources in the medical care system. However, it is yet unclear how effective such approaches are. Here, we provide a summary of existing work on universal prevention of NSSI in adolescents younger than 21 years based on a systematic literature search. We found that only seven studies are available. None of the programs evaluated was found to be effective in reducing the incidence or frequency of NSSI. After providing a comprehensive summary of the existing work, we evaluate the fact that existing work primarily focusses on selected/targeted prevention and on psychoeducational methods. We derive implications for future directions in the field of universal prevention of NSSI.}, language = {en} } @article{LechermeierZimmerLueffeetal.2019, author = {Lechermeier, Carina G. and Zimmer, Frederic and L{\"u}ffe, Teresa M. and Lesch, Klaus-Peter and Romanos, Marcel and Lillesaar, Christina and Drepper, Carsten}, title = {Transcript analysis of zebrafish GLUT3 genes, slc2a3a and slc2a3b, define overlapping as well as distinct expression domains in the zebrafish (Danio rerio) central nervous system}, series = {Frontiers in Molecular Neuroscience}, volume = {12}, journal = {Frontiers in Molecular Neuroscience}, number = {199}, doi = {10.3389/fnmol.2019.00199}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201797}, year = {2019}, abstract = {The transport of glucose across the cell plasma membrane is vital to most mammalian cells. The glucose transporter (GLUT; also called SLC2A) family of transmembrane solute carriers is responsible for this function in vivo. GLUT proteins encompass 14 different isoforms in humans with different cell type-specific expression patterns and activities. Central to glucose utilization and delivery in the brain is the neuronally expressed GLUT3. Recent research has shown an involvement of GLUT3 genetic variation or altered expression in several different brain disorders, including Huntington's and Alzheimer's diseases. Furthermore, GLUT3 was identified as a potential risk gene for multiple psychiatric disorders. To study the role of GLUT3 in brain function and disease a more detailed knowledge of its expression in model organisms is needed. Zebrafish (Danio rerio) has in recent years gained popularity as a model organism for brain research and is now well-established for modeling psychiatric disorders. Here, we have analyzed the sequence of GLUT3 orthologs and identified two paralogous genes in the zebrafish, slc2a3a and slc2a3b. Interestingly, the Glut3b protein sequence contains a unique stretch of amino acids, which may be important for functional regulation. The slc2a3a transcript is detectable in the central nervous system including distinct cellular populations in telencephalon, diencephalon, mesencephalon and rhombencephalon at embryonic and larval stages. Conversely, the slc2a3b transcript shows a rather diffuse expression pattern at different embryonic stages and brain regions. Expression of slc2a3a is maintained in the adult brain and is found in the telencephalon, diencephalon, mesencephalon, cerebellum and medulla oblongata. The slc2a3b transcripts are present in overlapping as well as distinct regions compared to slc2a3a. Double in situ hybridizations were used to demonstrate that slc2a3a is expressed by some GABAergic neurons at embryonic stages. This detailed description of zebrafish slc2a3a and slc2a3b expression at developmental and adult stages paves the way for further investigations of normal GLUT3 function and its role in brain disorders.}, 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{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{HerzogAndreattaSchneideretal.2021, author = {Herzog, Katharina and Andreatta, Marta and Schneider, Kristina and Schiele, Miriam A. and Domschke, Katharina and Romanos, Marcel and Deckert, J{\"u}rgen and Pauli, Paul}, title = {Reducing Generalization of Conditioned Fear: Beneficial Impact of Fear Relevance and Feedback in Discrimination Training}, series = {Frontiers in Psychology}, volume = {12}, journal = {Frontiers in Psychology}, issn = {1664-1078}, doi = {10.3389/fpsyg.2021.665711}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239970}, year = {2021}, abstract = {Anxiety patients over-generalize fear, possibly because of an incapacity to discriminate threat and safety signals. Discrimination trainings are promising approaches for reducing such fear over-generalization. Here we investigated the efficacy of a fear-relevant vs. a fear-irrelevant discrimination training on fear generalization and whether the effects are increased with feedback during training. Eighty participants underwent two fear acquisition blocks, during which one face (conditioned stimulus, CS+), but not another face (CS-), was associated with a female scream (unconditioned stimulus, US). During two generalization blocks, both CSs plus four morphs (generalization stimuli, GS1-GS4) were presented. Between these generalization blocks, half of the participants underwent a fear-relevant discrimination training (discrimination between CS+ and the other faces) with or without feedback and the other half a fear-irrelevant discrimination training (discrimination between the width of lines) with or without feedback. US expectancy, arousal, valence ratings, and skin conductance responses (SCR) indicated successful fear acquisition. Importantly, fear-relevant vs. fear-irrelevant discrimination trainings and feedback vs. no feedback reduced generalization as reflected in US expectancy ratings independently from one another. No effects of training condition were found for arousal and valence ratings or SCR. In summary, this is a first indication that fear-relevant discrimination training and feedback can improve the discrimination between threat and safety signals in healthy individuals, at least for learning-related evaluations, but not evaluations of valence or (physiological) arousal.}, language = {en} } @article{KuhnScharfenortSchuemannetal.2016, author = {Kuhn, Manuel and Scharfenort, Robert and Sch{\"u}mann, Dirk and Schiele, Miriam A. and M{\"u}nsterk{\"o}tter, Anna L. and Deckert, J{\"u}rgen and Domschke, Katharina and Haaker, Jan and Kalisch, Raffael and Pauli, Paul and Reif, Andreas and Romanos, Marcel and Zwanzger, Peter and Lonsdorf, Tina B.}, title = {Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament}, series = {Social Cognitive and Affective Neuroscience}, volume = {11}, journal = {Social Cognitive and Affective Neuroscience}, number = {4}, doi = {10.1093/scan/nsv137}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189645}, pages = {537-547}, year = {2016}, abstract = {Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences.}, 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{BenderReschKleinetal.2012, author = {Bender, Stephan and Resch, Franz and Klein, Christoph and Renner, Tobias and Fallgatter, Andreas J. and Weisbrod, Matthias and Romanos, Marcel}, title = {Influence of Stimulant Medication and Response Speed on Lateralization of Movement-Related Potentials in Attention-Deficit/Hyperactivity Disorder}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {6}, doi = {10.1371/journal.pone.0039012}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135262}, pages = {e39012}, year = {2012}, abstract = {Background: Hyperactivity is one of the core symptoms in attention deficit hyperactivity disorder (ADHD). However, it remains unclear in which way the motor system itself and its development are affected by the disorder. Movement-related potentials (MRP) can separate different stages of movement execution, from the programming of a movement to motor post-processing and memory traces. Pre-movement MRP are absent or positive during early childhood and display a developmental increase of negativity. Methods: We examined the influences of response-speed, an indicator of the level of attention, and stimulant medication on lateralized MRP in 16 children with combined type ADHD compared to 20 matched healthy controls. Results: We detected a significantly diminished lateralisation of MRP over the pre-motor and primary motor cortex during movement execution (initial motor potential peak, iMP) in patients with ADHD. Fast reactions (indicating increased visuo-motor attention) led to increased lateralized negativity during movement execution only in healthy controls, while in children with ADHD faster reaction times were associated with more positive amplitudes. Even though stimulant medication had some effect on attenuating group differences in lateralized MRP, this effect was insufficient to normalize lateralized iMP amplitudes. Conclusions: A reduced focal (lateralized) motor cortex activation during the command to muscle contraction points towards an immature motor system and a maturation delay of the (pre-) motor cortex in children with ADHD. A delayed maturation of the neuronal circuitry, which involves primary motor cortex, may contribute to ADHD pathophysiology.}, language = {en} }