[COVID-19 and Psychiatric Disorders in Minors: Changes in Inpatient Treatment According to Hospital Statistics]. / COVID-19 und psychische Störungen bei Minderjährigen: Veränderungen der Behandlungen nach der Krankenhausstatistik.

COVID-19 and Psychiatric Disorders in Minors: Changes in Inpatient Treatment According to Hospital Statistics Abstract: Increased rates of psychiatric disorders and psychiatric emergencies in children and adolescents stemming from the COVID-19 pandemic have been reported, with more children and adolescents suffering from internalizing disorders. This study analyzes whether the increased rates led to increased rates of inpatient treatment in child and adolescent psychiatric and pediatric hospitals in Germany as well as a change in diagnoses of the treated patients. We analyzed routine hospital data ("InEK" data, § 21 KHG data files) from a prepandemic (2019) and a pandemic (2021) half-year regarding changes in the number of cases, diagnoses, and length of stay (LoS) in child and adolescent psychiatry and pediatrics. We also investigated the development of psychiatric emergencies in minors. We found an increase in internalizing problems (depression, anorexia nervosa, trauma-related disorders) and a decrease in externalizing problems among the admitted psychiatric inpatients. Further, we observed a halving of cases treated for alcohol intoxication. However, we discovered no change for the frequency of psychiatric emergency treatments nationwide. A more detailed analysis revealed that, in areas with a low number of child and adolescent psychiatry inpatient beds, emergency care was prioritized and LoS decreased, whereas in areas with a fair bed-to-inhabitant ratio among minors, there was a trend toward increased LoS, also in pediatric departments. We recommend continued monitoring of inpatient care after the pandemic, with special attention paid to underprivileged children and adolescents such as those with externalizing problems.

Attitudes toward innovative mental health treatment approaches in Germany: E-mental health and home treatment.

E-mental health and home treatment are treatment approaches that have proven to be effective, but are only slowly implemented in the German health care system. This paper explores the attitudes toward these innovative treatment approaches. Data was collected in two large, non-clinical samples representative of the German population in spring 2020 (N = 2,503) and winter 2020/2021 (N = 2,519). Statistical associations between variables were examined using two-tailed tests. Binary and multinomial logistic regressions were performed to predict attitudes toward online-based treatment concepts and home treatment approaches. Only few (<20%) people preferred online-based treatment approaches, while a larger proportion (~50%) could imagine being treated at home. Overall, younger subjects were more open to online-therapy approaches, while people with lower education preferred more often a traditional therapy setting. Acceptance of online-therapy did not raise significantly during the first months of the COVID-19 pandemic. When different online-based treatment options were available, the probability of accepting home treatment significantly increased with increasing levels of therapeutic support. Further promotion of acceptance for online-therapy and home treatment seems to be necessary. In the future, more information on innovative treatment approaches should be actively provided.

The Hypertension Paradox: Survival Benefit After ST-Elevation Myocardial Infarction in Patients With History of Hypertension. A Prospective Cohort- and Risk-Analysis.

Background: Mortality after ST-elevation myocardial infarction (STEMI) is dependent from best-medical treatment after initial event. Objectives: Determining the impact of prescription of guideline-recommended therapy after STEMI in two cohorts, patients with and without history of arterial hypertension, on survival. Methods: 1,025 patients of the Cologne Infarction Model registry with invasively adjudicated STEMI were dichotomized according to their history of arterial hypertension. We recorded prescription rates and dosing of RAS-inhibitors, ß-blockers and statins in all patients. The primary outcome was all-cause death. Mean follow-up was 2.5 years. Results: Mean age was 64 ± 13 years, 246 (25%) were women. 749 (76%) patients had a history of hypertension. All-cause mortality was 24.2%, 30-day and 1-year mortality was 11.3% and 16.6%, respectively. History of hypertension correlated with lower mortality (hazard ratio [HR], @30 days: 0.41 [0.27-0.62], @1 year: 0.37 [0.26-0.53]). After adjusting for age, sex, Killip-class, diabetes mellitus, body-mass index, kidney function and statin prescription at discharge 1-year mortality HR was 0.24 (0.12-0.48). At discharge, prescription rates for RAS-inhibitors, ß-blockers and statins, as well as individual dosing and long-term persistence of RAS-inhibitors were higher in patients with history of hypertension. On the same lines, prescription rates for RAS-inhibitors, ß-blockers and statins at discharge correlated significantly with lower mortality regardless of history of hypertension. Conclusion: Patients with history of hypertension show higher penetration of guideline recommended drug therapy after STEMI, which may contribute to better survival. Better tolerance of ß-blockers and RAS-inhibitors in patients with history of hypertension, not hypertension itself, likely explains these differences in prescription and dosing.

The nonlinear association between grandiose and vulnerable narcissism: An individual data meta-analysis.

OBJECTIVE: Narcissism can manifest in grandiose and vulnerable patterns of experience and behavior. While largely unrelated in the general population, individuals with clinically relevant narcissism are thought to display both. Our previous studies showed that trait measures of grandiosity and vulnerability were unrelated at low-to-moderate levels of grandiose narcissism, but related at high levels. METHOD: We replicate and extend these findings in a preregistered individual data meta-analysis ("mega-analysis") using data from the Narcissistic Personality Inventory (NPI)/Hypersensitive Narcissism Scale (HSNS; N = 10,519, k = 28) and the Five-Factor Narcissism Inventory (FFNI; N = 7,738, k = 17). RESULTS: There was strong evidence for the hypothesis in the FFNI (ßGrandiose < 1 SD  = .08, ßGrandiose > 1 SD  = .36, ßGrandiose > 2 SD  = .53), and weaker evidence in the NPI/HSNS (ßGrandiose < 1 SD  = .00, ßGrandiose > 1 SD  = .12, ßGrandiose > 2 SD  = .32). Nonlinearity increased with age but was invariant across other moderators. Higher vulnerability was predicted by elevated antagonistic and low agentic narcissism at subfactor level. CONCLUSION: Narcissistic vulnerability increases at high levels of grandiosity. Interpreted along Whole Trait Theory, the effects are thought to reflect state changes echoing in trait measures and can help to link personality and clinical models.

Autism-associated R451C mutation in neuroligin3 leads to activation of the unfolded protein response in a PC12 Tet-On inducible system.

Several forms of monogenic heritable autism spectrum disorders are associated with mutations in the neuroligin genes. The autism-linked substitution R451C in neuroligin3 induces local misfolding of its extracellular domain, causing partial retention in the ER (endoplasmic reticulum) of expressing cells. We have generated a PC12 Tet-On cell model system with inducible expression of wild-type or R451C neuroligin3 to investigate whether there is activation of the UPR (unfolded protein response) as a result of misfolded protein retention. As a positive control for protein misfolding, we also expressed the mutant G221R neuroligin3, which is known to be completely retained within the ER. Our data show that overexpression of either R451C or G221R mutant proteins leads to the activation of all three signalling branches of the UPR downstream of the stress sensors ATF6 (activating transcription factor 6), IRE1 (inositol-requiring enzyme 1) and PERK [PKR (dsRNA-dependent protein kinase)-like endoplasmic reticulum kinase]. Each branch displayed different activation profiles that partially correlated with the degree of misfolding caused by each mutation. We also show that up-regulation of BiP (immunoglobulin heavy-chain-binding protein) and CHOP [C/EBP (CCAAT/enhancer-binding protein)-homologous protein] was induced by both mutant proteins but not by wild-type neuroligin3, both in proliferative cells and cells differentiated to a neuron-like phenotype. Collectively, our data show that mutant R451C neuroligin3 activates the UPR in a novel cell model system, suggesting that this cellular response may have a role in monogenic forms of autism characterized by misfolding mutations.

Multidimensional response to vaccination pain in very preterm, moderate- to-late preterm and full-term infants at age three months.

BACKGROUND: Very early life pain exposure and stress induces alterations in the developing brain and leads to altered pain sensitivity. In premature infants with a history of numerous early postnatal adverse events, behavioral responsiveness and hypothalamic-pituitary-adrenal (HPA) axis reactivity may show alterations as well. AIMS: We compared a multidimensional response to a painful situation (vaccination) in three month old infants. The study involved very preterm, moderate to late preterm infants and full-term infants with varying exposure to pain and stress within the first weeks of life. STUDY DESIGN: At the age of three months, we evaluated the infants' reactivity to intramuscular injections for immunization. SUBJECTS: The study included 61 very preterm infants, 30 moderate to late preterm infants and 30 full-term infants. OUTCOME MEASURES: We assessed heart rate recovery, Bernese pain Score and increase of salivary cortisol following vaccination. We also evaluated the flexor withdrawal reflex threshold as well as Prechtl's General Movements. Secondly, we assessed factors potentially influencing pain reactivity such as exposure to pain/stress, gender, use of steroids or opioids and mechanical ventilation. RESULTS: Very preterm, moderate to late preterm and full-term infants showed different reactivity to pain in all analyzed aspects. Very preterm infants showed a lower level of behavioral and physiologic reactivity and exposure to pain/stress predicted lower cortisol increase. CONCLUSION: At three months of age, very preterm infants show an altered level of HPA axis reactivity. Efforts aiming at minimizing pain and stress in premature infants should be taken.

Cystatin B and SOD1: protein­protein interaction and possible relation to neurodegeneration.

Cystatin B (CSTB), an inhibitor of the cysteine proteases, belongs to the cathepsin family and it is known to interact with a number of proteins involved in cytoskeletal organization. CSTB has an intrinsic tendency to form aggregates depending on the redox environment. The gene encoding for CSTB is frequently mutated in association with the rare neurodegenerative condition progressive myoclonus epilepsy. Increased levels of CSTB have been observed in the spinal cord of transgenic mice modeling SOD1-linked familial amyotrophic lateral sclerosis, a fatal neurodegenerative disease affecting motoneurons. In the present study, we have investigated the relationship occurring between the expression of SOD1 and CSTB either wild-type or double-cysteine substitution mutant (Cys 3 and Cys 64). Whether or not there is a physical interaction between the two proteins was also investigated in overexpression experiments using a human neuroblastoma cell line and mouse-immortalized motoneurons. Here we report evidences for a reciprocal influence of CSTB and SOD1 at the gene expression level and for a direct interaction of the two proteins.

Nicotine exposure during adolescence: cognitive performance and brain gene expression in adult heterozygous reeler mice.

RATIONALE: We have recently reported nicotine-induced stimulation of reelin and glutamic acid decarboxylase 67 (GAD67) mRNA expression levels in the brain of heterozygous reeler mice (HRM), a putative animal model for the study of symptoms relevant to major behavioral disorders. OBJECTIVES: We aimed to evaluate long-term behavioral effects and brain molecular changes as a result of adaptations to nicotine exposure in the developing HRM males. METHODS: Adolescent mice (pnd 37-42) were exposed to oral nicotine (10 mg/l) in a 6-day free-choice drinking schedule. As expected, no differences in total nicotine intake between WT (wild-type) mice and HRM were found. RESULTS: Long-term behavioral effects and brain molecular changes, as a consequence of nicotine exposure during adolescence, were only evidenced in HRM. Indeed, HRM perseverative exploratory behavior and poor cognitive performance were modulated to WT levels by subchronic exposure to nicotine during development. Furthermore, the expected reduction in the expression of mRNA of reelin and GAD67 in behaviorally relevant brain areas of HRM appeared persistently restored by nicotine. For brain-derived neurotrophic factor (BDNF) mRNA expression, no genotype-dependent changes appeared. However, expression levels were increased by previous nicotine in brains from both genotypes. The mRNA encoding for nicotine receptor subunits (α7, ß2 and α4) did not differ between genotypes and as a result of previous nicotine exposure. CONCLUSION: These findings support the hypothesis of pre-existing vulnerability (based on haploinsufficiency of reelin) to brain and behavioral disorders and regulative short- and long-term effects associated with nicotine modulation.