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Institute
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie (129) (remove)
Sonstige beteiligte Institutionen
Psychopathology, protective factors, and COVID-19 among adolescents: a structural equation model
(2023)
Since the outbreak of the COVID-19 pandemic in December 2019 and the associated restrictions, mental health in children and adolescents has been increasingly discussed in the media. Negative impacts of the pandemic, including a sharp increase in psychopathology and, consequently, reduced quality of life, appear to have particularly affected children and young people, who may be especially vulnerable to the adverse effects of isolation. Nevertheless, many children and adolescents have managed to cope well with the restrictions, without deterioration of their mental health. The present study therefore explored the links between COVID-19 infection (in oneself or a family member, as well as the death of a family member due to the virus), protective factors such as self-efficacy, resilience, self-esteem, and health-related quality of life, and measures of psychopathology such as depression scores, internalizing/externalizing problems, emotion dysregulation, and victimization. For this purpose, we examined data from 2129 adolescents (mean age = 12.31, SD = 0.67; 51% male; 6% born outside of Germany) using a structural equation model. We found medium to high loadings of the manifest variables with the latent variables (COVID-19, protective factors, and psychopathology). Protective factors showed a significant negative correlation with psychopathology. However, COVID-19 had a weak connection with psychopathology in our sample. External pandemic-related factors (e.g., restrictions) and their interaction with existing psychopathology or individual protective factors appear to have a greater influence on young people’s mental health than the impact of the virus per se. Sociopolitical efforts should be undertaken to foster prevention and promote individual resilience, especially in adolescence.
Task-based measures that capture neurocognitive processes can help bridge the gap between brain and behavior. To transfer tasks to clinical application, reliability is a crucial benchmark because it imposes an upper bound to potential correlations with other variables (e.g., symptom or brain data). However, the reliability of many task readouts is low. In this study, we scrutinized the retest reliability of a probabilistic reversal learning task (PRLT) that is frequently used to characterize cognitive flexibility in psychiatric populations. We analyzed data from N = 40 healthy subjects, who completed the PRLT twice. We focused on how individual metrics are derived, i.e., whether data were partially pooled across participants and whether priors were used to inform estimates. We compared the reliability of the resulting indices across sessions, as well as the internal consistency of a selection of indices. We found good to excellent reliability for behavioral indices as derived from mixed-effects models that included data from both sessions. The internal consistency was good to excellent. For indices derived from computational modeling, we found excellent reliability when using hierarchical estimation with empirical priors and including data from both sessions. Our results indicate that the PRLT is well equipped to measure individual differences in cognitive flexibility in reinforcement learning. However, this depends heavily on hierarchical modeling of the longitudinal data (whether sessions are modeled separately or jointly), on estimation methods, and on the combination of parameters included in computational models. We discuss implications for the applicability of PRLT indices in psychiatric research and as diagnostic tools.
Ziele: Das Ziel der vorliegenden Arbeit ist eine standardisierte Analyse der Patientenzufriedenheit mit dem Aufklärungsgespräch und die mögliche Einflussfaktoren, die hier eine Rolle spielen können, zu bieten.
Methodik: Es wurden 189 Fragebögen bzw. Aufklärungsgespräche in den Kliniken für Anästhesie und Innere Medizin im St. Josef Krankenhaus und Chirurgie und Kinder- und Jugendpsychiatrie im Leopoldina Krankenhaus in Schweinfurt untersucht.
Ergebnisse: Der Fragebogen, der verwendet wurde, war reliabel. Es zeigte sich eine schlechte Item-Selektivität. Die Kriteriumsvalidität konnte bestätigt werden jedoch nicht die diskriminante Validität. Die Patienten waren zufriedener mit Ärzten, die Deutsch als Muttersprache angaben, mit längeren Aufklärungsgesprächen und mit Fachärzten im Vergleich zu Assistenzärzten. Eine höhere allgemeine Lebenszufriedenheit war mit höherer Patientenzufriedenheit mit dem Aufklärungsgespräch assoziiert. Der moralistische Bias kann einen Störfaktor der Validität der Messungen darstellen.
Zusammenfassung: Eine angemessene Gesprächdauer, die deutsche Muttersprache und der Facharztstatus des aufklärenden Arztes haben einen positiven Einfluss auf die Patientenzufriedenheit mit dem Aufklärungsgespräch. Um sicher zu stellen, welche von diesen drei Faktoren besondere Wichtigkeit besitzt, werden weitere Untersuchungen benötigt.
Family relationships in selective mutism — a comparison group study of children and adolescents
(2022)
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.
Neuromelanin granules (NMGs) are organelle-like structures present in the human substantia nigra pars compacta. In addition to neuromelanin, NMGs contain proteins, lipids and metals. As NMG-containing dopaminergic neurons are preferentially lost in Parkinson’s disease and dementia with Lewy bodies (DLB), it is assumed that NMGs may play a role in neurodegenerative processes. Until now, this role is not completely understood and needs further investigation. We therefore set up an exploratory proteomic study to identify differences in the proteomic profile of NMGs from DLB patients (n = 5) compared to healthy controls (CTRL, n = 5). We applied a laser microdissection and mass-spectrometry-based approach, in which we used targeted mass spectrometric experiments for validation. In NMG-surrounding (SN\(_{Surr.}\)) tissue of DLB patients, we found evidence for ongoing oxidative damage and an impairment of protein degradation. As a potentially disease-related mechanism, we found α-synuclein and protein S100A9 to be enriched in NMGs of DLB cases, while the abundance of several ribosomal proteins was significantly decreased. As S100A9 is known to be able to enhance the formation of toxic α-synuclein fibrils, this finding points towards an involvement of NMGs in pathogenesis, however the exact role of NMGs as either neuroprotective or neurotoxic needs to be further investigated. Nevertheless, our study provides evidence for an impairment of protein degradation, ongoing oxidative damage and accumulation of potentially neurotoxic protein aggregates to be central mechanisms of neurodegeneration in DLB.
Biological Substrates of Waiting Impulsivity in Children and Adolescents with and without ADHD
(2023)
Focus of the present work were the questions whether and how the concept of waiting impulsivity (WI), defined as the ability to regulate a response in anticipation of reward and measured by the 4-choice serial reaction time task (4-CSRTT), may contribute to our understanding of Attention-Deficit/Hyperactivity Disorder (ADHD) and its neurobiological underpinnings.
To address this topic, two studies were conducted: in a first study, the relationship be-tween 4-CSRTT behavioral measures, neural correlates and ADHD symptom domains, i.e. inattention (IA) and hyperactivity/impulsivity (H/I) was explored in a pooled sample of 90 children and adolescents with (n=44) and without (n=46) ADHD diagnosis. As ex-pected, IA was associated with dorsolateral prefrontal brain regions linked with executive functions and attentional control, which was evident on the structural and the functional level. Higher levels of both IA and H/I covaried with decreased activity in the right ven-trolateral prefrontal cortex (PFC), a central structure for response inhibition. Moderation analyses revealed that H/I-related decreased activation in this region did not map linearly on difficulties on the behavioral level: brain activation was a significant predictor of task accuracy only, when H/I symptoms were low/absent but not for clinically relevant ADHD symptoms. Further, H/I was implicated in dysfunctional top-down control of reward eval-uation. Both symptom domains correlated positively with hippocampus (HC) activity in anticipation of reward. In addition, for high H/I symptoms, greater activation in the HC was found to correlate with higher motivation on the behavioral level, indicating that rein-forcement-learning and/or contingency awareness may contribute to altered reward pro-cessing in ADHD patients.
In a second study, the possible serotonergic modulation of WI and the ADHD-WI relation-ship was addressed in a sub-sample comprising 86 children and adolescents of study I. The effects of a functional variant in the gene coding for the rate-limiting enzyme in the synthesis of brain serotonin on behavior and structure or function of the WI-network was investigated. Moderation analyses revealed that on the behavioral level, a negative corre-lation between accuracy and IA was found only in GG-homozygotes, whereas no signifi-cant relationship emerged for carriers of the T-allele. This is in line with previous reports of differential effects of serotonergic modulation on attentional performance depending on the presence of ADHD symptoms. A trend-wise interaction effect of genotype and IA for regional volume of the right middle frontal gyrus was interpreted as a hint towards an involvement of the PFC in this relationship, although a more complex mechanism includ-ing developmental effects can be assumed. In addition, interaction effects of genotype and IA were found for brain activation in the amygdala (AMY) und HC during perfor-mance of the 4-CSRTT, while another interaction was found for H/I symptoms and geno-type for right AMY volume. These findings indicate a serotonergic modulation of coding of the emotional value of reward during performance of the 4-CSRTT that varies de-pending on the extent of psychopathology-associated traits.
Taken together, it was shown that the 4-CSRTT taps distinct domains of impulsivity with relevance to ADHD symptomatology: (proactive) response inhibition difficulties in relation with anticipation of reward. Furthermore, the two symptom domains, IA and H/I, contrib-ute differently to WI, which emphasizes the need to distinguish both in the research of ADHD. The results of study II emphasized the relevance of serotonergic transmission especially for attentional control and emotional processing. Although the present findings need replication and further refinement in more homogenous age groups, the use of the 4-CSRTT with a dimensional approach is a very promising strategy, which will hopefully extend our understanding of impulsivity-related mental disorders in the future.
Durch die vorliegende Arbeit konnte störungsübergreifend ein Zusammenhang zwischen dem Tag der Motorik-Testung und dem IQ einerseits und den Testbefunden zur Motorik andererseits gezeigt werden. Es gelang nicht, den vermuteten negativen Einfluss von psychosozialen Faktoren auf motorische Fähigkeiten zu demonstrieren.
Bezüglich der ADHS-Medikation konnte aufgrund des Studiendesigns als Querschnittstudie keine klare Aussage getroffen werden, ob ein positiver Einfluss auf motorische Fähigkeiten vorliegt. Bei den Patient-/innen mit Hyperkinetischer Störung des Sozialverhaltens (F90.1) fanden sich zwar bei bestehender ADHS-Medikation signifikant bessere Testbefunde der Balance, es konnte jedoch nicht geklärt werden, warum der positive Effekt der ADHS-Medikation nur auf diese Störungsgruppe und den Balance-Untertest der M-ABC II begrenzt war.
Im Gruppenvergleich konnten signifikant bessere motorische Fähigkeiten der Patient-/innen mit internalisierender Störung als jener mit externalisierender Störung festgestellt werden. Damit kongruent kam die Diagnose einer UEMF (F82) in der Gruppe der externalisierenden Störungen häufiger vor. Da ein Großteil der Patient-/innen der externalisierenden Störungsgruppe an Defiziten der Aufmerksamkeit, Impulskontrolle und der Motivation litt, ist davon auszugehen, dass diese Symptome zu schwerwiegenden Beeinträchtigungen der motorischen Fähigkeiten und damit auch zu weiteren Problemen im Alltag oder bei der Schullaufbahn führen. Innerhalb der Gruppe der externalisierenden Störungen konnte hinsichtlich der motorischen Fähigkeiten kein Unterschied zwischen Patient-/innen mit Hyperkinetischen Störungen (F90.-) und solchen mit Störung des Sozialverhaltens (F91) gefunden werden. Ein solcher Unterschied hätte einen Hinweis geben können, ob eher Defizite der Aufmerksamkeit und Impulskontrolle oder ein Motivationsdefizit mit motorischen Einschränkungen verbunden sind. Hierbei ist anzumerken, dass die Gruppengrößen für einen validen Vergleich dieser Störungsgruppen nicht ausreichend waren.
Der Vergleich motorischer Fähigkeiten sowie der Häufigkeit einer UEMF (F82) zwischen Patient-/innen mit umschriebener Entwicklungsstörung des Sprechens und der Sprache (F80) einerseits und Patient-/innen mit umschriebener Entwicklungsstörung der schulischen Fertigkeiten (F81) andererseits bestätigte die Vermutung, dass bei Patient-/innen der Störungsgruppe F80 schlechtere motorische Fähigkeiten und signifikant mehr motorische Defizite vorlagen. Ein Teil dieses Unterschieds lässt sich jedoch durch den signifikant niedrigeren IQ der Störungsgruppe F80 erklären. Es muss darüber hinaus berücksichtigt werden, dass bei den umschriebenen Entwicklungsstörungen F80 und F81 eine häufige Komorbidität mit externalisierenden Störungen bestand, sodass motorische Defizite auch durch ein ursächliches Defizit der Aufmerksamkeit und Impulskontrolle erklärt werden könnten.
In vorgegangenen Studien wurde bei erwachsenen Patienten mit Angststörungen eine verstärkte Furchtgeneralisierung, eine eingeschränkte Fähigkeit zur Reizdiskrimination sowie eine veränderte Aufmerksamkeitsverteilung nachgewiesen. In einer gesunden Studienpopulation konnte bei Kindern eine stärkere Furchtgeneralisierung nachgewiesen werden als bei Erwachsenen. Ihre Generalisierungsgradienten gleichen denen von Erwachsenen mit Angststörung. Möglicherweise haben gestörte Lernprozesse in der Kindheit somit langfristige Effekte auf die Entwicklung von Angststörungen. Obwohl die Vorgänge des Furchtlernens im Kindesalter entscheidend für das Verständnis von Angststörungen sind, gibt es kaum Studien in dieser Altersgruppe. Die vorliegende Studie untersucht die Zusammenhänge von Furchtgeneralisierung und Aufmerksamkeitsprozessen in einer klinischen Population mit internalisierender Störung im Kindes- und Jugendalter.
Hierzu durchliefen Kinder und Jugendliche mit internalisierender Störung (n= 49) sowie gesunde Kontrollen (n=48) im Alter von 9 bis 17 Jahre ein Furcht-generalisierungsparadigma mit Diskriminationstraining sowie einen modifizierten Dotprobe mit integriertem Eyetracking. Die Ängstlichkeit wurde mittels verschiedener Angstfragebögen gemessen. Im Generalisierungsparadigma wurden zwei weibliche Gesichter mit neutralem Gesichtsausdruck als Stimuli verwendet, die entweder mit (CS+) oder ohne (CS-) einem 95dB lauten Schrei sowie einem angsterfüllten Gesichtsausdruck gezeigt wurden. Zur Messung der Furchtreaktion wurden subjektive Ratings für Arousal, Valenz und Kontingenz erfasst, zudem wurde die Hautleitfähigkeit gemessen. Zur Auswertung des Dotprobes wurden die Reaktionszeiten und die Initialsakkade erfasst. Die statistische Analyse des Furchtgeneralisierungsparadigmas sowie des Dotprobe-Paradigmas wurde mittels Multivarianzanalysen mit Messwiederholung durchgeführt, gefolgt von t-Tests zur weiterführenden Analyse. Desweiteren wurden die Aufmerksamkeitsreaktionen von nicht-ängstlichen und ängstlichen Teilnehmern in Kategorien eingeteilt und mittels Chi-Quadrat Analysen verglichen. Zur Analyse des Zusammenhangs zwischen Furchtgeneralisierung und Aufmerksamkeitsprozessen erfolgte eine Regressionsanalyse mit einem GS Mittelwert als abhängiger Variable und der Ängstlichkeit und den Aufmerk-samkeitsprozessen als Prädiktoren.
Die Ergebnisse bestätigten eine solide Furchtkonditionierung anhand des „Screaming Lady“-Paradigmas in einer klinischen Population, dies war erkennbar an höheren Ratings für den aversiven Stimulus im Vergleich zum sicheren Stimulus in beiden Gruppen. Grundsätzlich höhere Furchtratings sowie höhere Ratings der Generalisierungsstimuli im Vergleich zum sicheren Stimulus wiesen auf eine stärkere Generalisierung in der Untergruppe mit höherem Angst-Trait innerhalb der internalisierenden Probandengruppe hin. Die Analyse der Dotprobe Daten ergab schnellere Reaktionszeiten sowie häufigere Initialsakkaden gegenüber furchteinflößenden Stimuli bei Patienten mit internalisierender Störung. Des Weiteren zeigten sehr ängstliche Probanden häufiger einen Attentional bias im Chi Quadrat Test als nicht-ängstliche Probanden. Dies wies daraufhin, dass sowohl bei Patienten mit internalisierender Störung als auch bei sehr ängstlichen Probanden ein Attentional bias gegenüber furchtrelevanten Stimuli vorliegt. Vor allem bei Kindern mit internalisierender Störung sagten die Ängstlichkeit und veränderte Aufmerksamkeitsprozesse die Ausprägung der Furchtgeneralisierung voraus. Somit kann ein Zusammenhang von veränderten Aufmerksamkeitsprozessen und Furchtgeneralisierung vermutet werden.
(1) Background: Evidence has accumulated that patients with anorexia nervosa (AN) are at higher risk for vitamin D deficiency than healthy controls. In epidemiologic studies, low 25(OH) vitamin D (25(OH)D) levels were associated with depression. This study analyzed the relationship between 25(OH)D serum levels in adolescent patients and AN and depressive symptoms over the course of treatment. (2) Methods: 25(OH)D levels and depressive symptoms were analyzed in 93 adolescent (in-)patients with AN from the Anorexia Nervosa Day patient versus Inpatient (ANDI) multicenter trial at clinic admission, discharge, and 1 year follow up. Mixed regression models were used to analyze the relationship between 25(OH)D levels and depressive symptoms assessed by the Beck Depression Inventory (BDI-II). (3) Results: Although mean 25(OH)D levels constantly remained in recommended ranges (≥50 nmol/L) during AN treatment, levels decreased from (in)patient admission to 1 year follow up. Levels of 25(OH)D were neither cross-sectionally, prospectively, nor longitudinally associated with the BDI-II score. (4) Conclusions: This study did not confirm that 25(OH)D levels are associated with depressive symptoms in patients with AN. However, increasing risks of vitamin D deficiency over the course of AN treatment indicate that clinicians should monitor 25(OH)D levels.
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.