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Background: Approximately 10% of children, adolescents and young adults with an intellectual and developmental disability (IDD) in Bavaria live in residential institutions. 2015 saw media reports raising suspicions about excessive use of coercive measures (cM) in those institutions. Until a law reform at the end of 2017 made permission from family courts mandatory for cM, their use was governed by parental consent. The REDUGIA project conducted a representative survey comparing cM and their relation to challenging behaviour (cB) and employee stress in Bavaria pre and post reform.
Methods: We sent questionnaires to 65 residential institutions for children, adolescents and young adults with IDD in 2017 (pre reform, T1) and 2019 (post reform, T2). To assess changes, we analysed data from all available questionnaire pairs (T1 and T2, N = 43). We calculated paired t-test and correlative analyses concerning the relationship between cB, cM, and employee stress.
Results: The number of residents overall (T1: N = 1,661; T2: N = 1,673) and per institution (T1: m = 38.6 ± 32.0; T2: m = 38.9 ± 34.5, p = 0.920) remained stable. We did not see any changes in the Index cB (p = 0.508) or the proportion of residents per institution displaying various types of challenging behaviour (all ps>0.220). There was no change in the Index cM (p = 0.089) or any indicator of employee stress, all ps > 0.323. At follow-up, the Index cB correlated positively with the Index cM (r = 0.519 p < 0.001). Regarding employee stress, the Index cB correlated positively with the frequency of sick leave (r = 0.322, p = 0.037) and physical attacks on employees (r = 0.552, p < 0.001). The Index cM also correlated positively with the frequency of sick leave (r = 0.340, p = 0.028) and physical attacks on employees (r = 0.492, p = 0.001).
Discussion: Coercive measures are not a general phenomenon, but are focused on specialised institutions. The law reform did not lead to changes in the number of children, adolescents and young adults with IDD affected by coercive measures in residential institutions in Bavaria. There were still large discrepancies between institutions in the prevalence of challenging behaviour and coercive measures. Coercive measures were associated with challenging behaviour and employee stress. Taken together, findings from REDUGIA emphasise the need to prevent challenging behaviour and thus coercive measures.
Fragestellung: In Bayern leben etwa 10 % aller jungen Menschen mit Intelligenzminderung in Heimeinrichtungen. 2016 wurde in Presseberichten der Vorwurf unzulässiger freiheitsentziehender Maßnahmen formuliert. Im Rahmen des Projekts REDUGIA wurde in bayerischen Heimeinrichtungen eine repräsentative Erhebung zu freiheitsentziehenden Maßnahmen (FeM), herausforderndem Verhalten (hfV) und der Mitarbeiterbelastung (MaB) durchgeführt. Methodik: 65 Einrichtungen für junge Menschen mit Intelligenzminderung in Bayern wurde ein Fragebogen zu strukturellen Gegebenheiten sowie MaB, hfV und FeM zugesendet. Neben deskriptiven Auswertungen wurden korrelative Analysen bzw. Regressionsanalysen zum Zusammenhang zwischen hfV, FeM und MaB durchgeführt. Ergebnisse: Es wurden Daten zu 1839 Personen in 61 Einrichtungen erhoben. 84.3 % der Einrichtungen berichteten geringe Raten an hfV und FeM, während 15.7 % ein gehäuftes Vorkommen von hfV und FeM angaben. Auf n = 1809 Vollzeitäquivalente kam es innerhalb von 14 Tagen zu 639 körperlichen Angriffen durch Bewohner_innen. In 12 Monaten wurden problemverhaltensassoziiert 85 Krankmeldungen sowie 33 Versetzungsanträge/Kündigungen berichtet. Es zeigte sich ein signifikant positiver Zusammenhang zwischen hfV und FeM (R² = .307, F = 21.719, p < .001). Die Mitarbeiterbelastung korrelierte positiv mit hfV (r = .507, p < .001). Schlussfolgerungen: Die Studienbefunde weisen darauf hin, dass hfV sowie FeM bei jungen Menschen mit Intelligenzminderung kein flächendeckendes Phänomen darstellen, sondern sich auf wenige spezialisierte Einrichtungen fokussieren. Mögliche Maßnahmen zur Prävention von Problemverhalten und Freiheitsentzug werden diskutiert.
Background
Obsessive-Compulsive Disorder (OCD) is a common and chronic disorder in which a person has uncontrollable, reoccurring thoughts and behaviours. It is a complex genetic condition and, in case of early onset (EO), the patients manifest a more severe phenotype, and an increased heritability. Large (>500 kb) copy number variations (CNVs) previously associated with autism and schizophrenia have been reported in OCD. Recently, rare CNVs smaller than 500 kb overlapping risk loci for other neurodevelopmental conditions have also been reported in OCD, stressing the importance of examining CNVs of any size range. The aim of this study was to further investigate the role of rare and small CNVs in the aetiology of EO-OCD.
Methods
We performed high-resolution chromosomal microarray analysis in 121 paediatric OCD patients and in 124 random controls to identify rare CNVs (>50 kb) which might contribute to EO-OCD.
Results
The frequencies and the size of the observed rare CNVs in the patients did not differ from the controls. However, we observed a significantly higher frequency of rare CNVs affecting brain related genes, especially deletions, in the patients (OR = 1.98, 95% CI 1.02–3.84; OR = 3.61, 95% CI 1.14–11.41, respectively). Similarly, enrichment-analysis of CNVs gene content, performed with three independent methods, confirmed significant clustering of predefined genes involved in synaptic/brain related functional pathways in the patients but not in the controls. In two patients we detected \(de-novo\) CNVs encompassing genes previously associated with different neurodevelopmental disorders \(\textit{NRXN1, ANKS1B, UHRF1BP1}\)).
Conclusions
Our results further strengthen the role of small rare CNVs, particularly deletions, as susceptibility factors for paediatric OCD.
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.
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.
(1) Background: We aimed to evaluate the effect of proposed “microbiome-stabilising interventions”, i.e., breastfeeding for ≥3 months and prophylactic use of Lactobacillus acidophilus/ Bifidobacterium infantis probiotics on neurocognitive and behavioral outcomes of very-low-birthweight (VLBW) children aged 5–6 years. (2) Methods: We performed a 5-year-follow-up assessment including a strength and difficulties questionnaire (SDQ) and an intelligence quotient (IQ) assessment using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI)-III test in preterm children previously enrolled in the German Neonatal Network (GNN). The analysis was restricted to children exposed to antenatal corticosteroids and postnatal antibiotics. (3) Results: 2467 primary school-aged children fulfilled the inclusion criteria. In multivariable linear regression models breastfeeding ≥3 months was associated with lower conduct disorders (B (95% confidence intervals (CI)): −0.25 (−0.47 to −0.03)) and inattention/hyperactivity (−0.46 (−0.81 to −0.10)) as measured by SDQ. Probiotic treatment during the neonatal period had no effect on SDQ scores or intelligence. (4) Conclusions: Prolonged breastfeeding of highly vulnerable infants may promote their mental health later in childhood, particularly by reducing risk for inattention/hyperactivity and conduct disorders. Future studies need to disentangle the underlying mechanisms during a critical time frame of development.
Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (n\(_{total}\) = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.
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.
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.
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.