Premorbid body weight predicts weight loss in both anorexia nervosa and atypical anorexia nervosa: Further support for a single underlying disorder.

OBJECTIVE: For adolescents, DSM-5 differentiates anorexia nervosa (AN) and atypical AN with the 5th BMI-centile-for-age. We hypothesized that the diagnostic weight cut-off yields (i) lower weight loss in atypical AN and (ii) discrepant premorbid BMI distributions between the two disorders. Prior studies demonstrate that premorbid BMI predicts admission BMI and weight loss in patients with AN. We explore these relationships in atypical AN. METHOD: Based on admission BMI-centile < or ≥5th, participants included 411 female adolescent inpatients with AN and 49 with atypical AN from our registry study. Regression analysis and t-tests statistically addressed our hypotheses and exploratory correlation analyses compared interrelationships between weight loss, admission BMI, and premorbid BMI in both disorders. RESULTS: Weight loss in atypical AN was 5.6 kg lower than in AN upon adjustment for admission age, admission height, premorbid weight and duration of illness. Premorbid BMI-standard deviation scores differed by almost one between both disorders. Premorbid BMI and weight loss were strongly correlated in both AN and atypical AN. DISCUSSION: Whereas the weight cut-off induces discrepancies in premorbid weight and adjusted weight loss, AN and atypical AN overall share strong weight-specific interrelationships that merit etiological consideration. Epidemiological and genetic associations between AN and low body weight may reflect a skewed premorbid BMI distribution. In combination with prior findings for similar psychological and medical characteristics in AN and atypical AN, our findings support a homogenous illness conceptualization. We propose that diagnostic subcategorization based on premorbid BMI, rather than admission BMI, may improve clinical validity. PUBLIC SIGNIFICANCE: Because body weights of patients with AN must drop below the 5th BMI-centile per DSM-5, they will inherently require greater weight loss than their counterparts with atypical AN of the same sex, age, height and premorbid weight. Indeed, patients with atypical AN had a 5.6 kg lower weight loss after controlling for these variables. In comparison to the reference population, we found a lower and higher mean premorbid weight in patients with AN and atypical AN, respectively. Considering previous psychological and medical comparisons showing little differences between AN and atypical AN, we view a single disorder as the most parsimonious explanation. Etiological models need to particularly account for the strong relationship between weight loss and premorbid body weight.

[Legal, clinical and structural aspects of modern intensive care for children and adolescents with mental disorders]. / Rechtliche, fachliche und strukturelle Aspekte einer modernen akutstationären Versorgung von Kindern und Jugendlichen mit psychischen Störungen.

Recent years have seen a continuous rise in the proportion of emergency contacts across all mental health-related care structures for children and adolescents. Treatment in a protective intensive care unit constitutes an essential element of care and primarily serves the immediate protection of children and adolescents during mental health crises. Protective intensive care is subject to strict legal requirements. Those requirements were amended in 2017 via changes to § 1631b BGB (German Civil Code), leading to a clear separation of the stay in protective intensive care per se and the use of coercive measures. Using the restructuring of the intensive care unit of the Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy at the University Hospital Würzburg as an example, the article illustrates the requirements for modern acute care of children and adolescents with mental disorders.Following the modernisation at the university hospital Würzburg we could drastically reduce the duration of stays in the intensive care unit to a mean of 1.5 days across around 500 admissions per year. Consequently, the risk of hospitalism especially for patients with chronic suicidality is practically non-existent anymore. Since 2017, our cooperation with other clinics in the region has made it possible to care for all underage patients requiring treatment in a protective intensive care unit in child and adolescent psychiatric settings. Long-term treatment over many months in a protective intensive care unit no longer occurs in cases of chronic suicidality.

[How can we ensure the future care for children and adolescents with mental disorders?] / Wie sichern wir in Zukunft die Versorgung von Kindern und Jugendlichen mit psychischen Erkrankungen?

The interdisciplinary care of children and adolescents with mental disorders requires services from various German codes of social law and-within the medical care system-enclosing inpatient and outpatient services. The increasing demand, the increase in severity of disorders, and the general shortage of staff in social services put pressure on the structures of the interdisciplinary service networks resulting in long waiting periods, long distances, and regionally insufficient care. The medical field of child and adolescent psychiatry and psychotherapy (CAPP) plays the central and coordinating role within the cooperative care for children and adolescents with mental disorders. The CAPP is in clear need of reforms; however, these are markedly different from the reform needs of the German somatic medical care system and differ substantially from those of the (adult) psychiatry, psychotherapy, and psychosomatics disciplines. This discussion paper describes the reform requirements, the specifics of the CAPP structures, and suggestions to overcome sectors of service provision, enhance networking, intensify telemedicine, and develop evidence-based prevention and early recognition of child mental disorders.

[Ethical Considerations of Including Minors in Clinical Trials Using the Example of the Indicated Prevention of Psychotic Disorders]. / Minderjährige in klinischen Prüfungen: Ethische Abwägungen ihres Einbezugs am Beispiel der indizierten Prävention psychotischer Erkrankungen.

Ethical Considerations of Including Minors in Clinical Trials Using the Example of the Indicated Prevention of Psychotic Disorders Abstract: As a vulnerable group, minors require special protection in studies. For this reason, researchers are often reluctant to initiate studies, and ethics committees are reluctant to authorize such studies. This often excludes minors from participating in clinical studies. This exclusion can lead to researchers and clinicians receiving only incomplete data or having to rely on adult-based findings in the treatment of minors. Using the example of the study "Computer-Assisted Risk Evaluation in the Early Detection of Psychotic Disorders" (CARE), which was conducted as an 'other clinical investigation' according to the Medical Device Regulation, we present a line of argumentation for the inclusion of minors which weighs the ethical principles of nonmaleficence (especially regarding possible stigmatization), beneficence, autonomy, and fairness. We show the necessity of including minors based on the development-specific differences in diagnostics and early intervention. Further, we present specific protective measures. This argumentation can also be transferred to other disorders with the onset in childhood and adolescence and thus help to avoid excluding minors from appropriate evidence-based care because of insufficient studies.

Value of a web-based pediatric drug information system to prevent serious adverse drug reactions in child and adolescent psychiatry.

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.

When green enters a room: A scoping review of epidemiological studies on indoor plants and mental health.

BACKGROUND: Increasing numbers of epidemiological studies are investigating the association between outdoor greenery and various health outcomes. However, in the case of indoor plants, although experimental studies seem relatively abundant, epidemiological studies remain scarce, and research considering the mental health effects is even more limited. Thus, we aim to identify and summarise the relevant epidemiological studies on indoor plant exposure and mental health via this scoping review, thereby presenting the current state of knowledge and research niches. METHODS: PubMed and PsycINFO were systematically searched for epidemiological studies on indoor plant exposure and mental health, including mental and behavioural disorders, quality of life, and cognitive function. The publication period was from the inception of these two databases to 22nd June 2022. We extracted information on exposure to indoor plants and mental health-related outcomes from the relevant studies. RESULTS: The systematic search yielded 1186 unique results. Six studies met the inclusion criteria and were finally included in this scoping review. All included studies were Europe-based cross-sectional studies on mental and behavioural disorders. One study was conducted in 2015 and investigated the office environment, whereas the other five were conducted during the COVID-19 pandemic and focused on the home environment. Despite considerable heterogeneity in outcome assessments and indoor plant exposure metrics, all six studies generally reported beneficial associations between having indoor plants and mental health, such as reducing stress, depressive symptoms, and negative emotions. CONCLUSIONS: Epidemiological evidence on exposure to indoor plants and mental health is currently limited. In general, favourable effects of indoor plants are supported, although most relevant studies were conducted in the context of COVID-19. Before conducting more studies to explore the associations, data collection methods must be refined with more elaborate designs that allow for the measurement of more comprehensive metrics of indoor plants. REGISTRATION: Open Science Framework, osf.io/5xr6b.

Serious Adverse Drug Reactions to Antipsychotics in Minors with Multiple Disabilities: Preventability and Potential Cost Savings by Therapeutic Drug Monitoring.

INTRODUCTION: Children and adolescents with multiple disabilities and mental disorders (CAMD) are frequently treated with antipsychotic drugs. However, CAMD are particularly susceptible to serious adverse drug reactions (sADRs). This retrospective study examined the frequency of sADRs to antipsychotics in CAMD. Further, the potential preventability of these sADRs through therapeutic drug monitoring (TDM) and the potential socio-economic benefits of TDM were explored. METHODS: Routine clinical data of all patients treated at a specialized psychiatric clinic for CAMD between January 2017 and December 2018 were retrospectively examined. Data on the occurrence of sADRs (definition according to the European Medicines Agency), their causality with antipsychotics, as well as their preventability (Schumock criteria) were extracted from patient files. The prolongation of the hospital stay due to sADRs was calculated, and the cost savings were estimated if TDM had been applied. The data were based on a subsample of the KiDSafe project, supported by the Innovation Fund of the Joint Federal Committee, grant number 01NVF16021. RESULTS: One hundred two CAMD who were administered at least one antipsychotic drug during inpatient treatment were identified. Of these patients, 22 (21.6%) sADRs with a possible causal relationship with the antipsychotic treatment were documented. Eleven sADRs (50%) could potentially have been prevented through TDM. Mitigating sADRs through TDM likely would have prevented prolonged hospital stays and thus conferred considerable savings for health insurance companies. DISCUSSION: The routine implementation of TDM is urgently recommended for antipsychotic treatment in CAMD to increase drug therapy safety.

Fear conditioning and fear generalization in children and adolescents with anxiety disorders.

Overgeneralization of conditioned fear is associated with anxiety disorders (AD). Most results stem from studies done in adult patients, but studies with children are rare, although the median onset of anxiety disorders lies already in childhood. Thus, the goal of the present study was to examine fear learning and generalization in youth participants, aged 10-17 years, with AD (n = 39) compared to healthy controls (HC) (n = 40). A discriminative fear conditioning and generalization paradigm was used. Ratings of arousal, valence, and US expectancy (the probability of an aversive noise following each stimulus) were measured, hypothesizing that children with AD compared to HC would show heightened ratings of arousal and US expectancy, and decreased positive valence ratings, respectively, as well as overgeneralization of fear. The results indicated that children with AD rated all stimuli as more arousing and less pleasant, and demonstrated higher US expectancy ratings to all stimuli when compared to HC. Thus, rather than displaying qualitatively different generalization patterns (e.g., a linear vs. quadratic slope of the gradient), differences between groups were more quantitative (similar, but parallel shifted gradient). Therefore, overgeneralization of conditioned fear does not seem to be a general marker of anxiety disorders in children and adolescents.

Preventing suicide in post-secondary students: a scoping review of suicide prevention programs.

Suicide among students enrolled in post-secondary education, including university or college, is a major public health concern. Previous research has examined the effectiveness of suicide prevention programs for this population. However, the effective elements of these interventions remain unknown. This study reviewed the literature on suicide prevention programs for post-secondary students, exploring and identifying those elements likely contributing to their effectiveness. A scoping review process was undertaken exploring suicide prevention programs for post-secondary students. Methodological quality of the articles was assessed, and content analysis was used to explore the programs and their effective elements. Twenty seven articles were included in this review, covering a variety of approaches. Gatekeeper training programs were the most common type of suicide prevention program. Programs for post-secondary students may be effective in improving student rates of engagement with mental health services and were associated with greater knowledge, and help-seeking attitudes and behaviors, and gatekeeper-related outcomes. While evidence was found supporting the effectiveness of some interventions such as gatekeeper programs to influence suicide-related knowledge, attitudes and behaviour, further and more rigorous research surrounding suicide prevention programs for post-secondary students is required, with a particular emphasis on student outcomes.

The efficacy of the "Talk-to-Me" suicide prevention and mental health education program for tertiary students: a crossover randomised control trial.

Despite suicide ideation being one of the most frequently reported health issues impacting tertiary students, there is a paucity of research evaluating the efficacy of preventive interventions aimed at improving mental health outcomes for students studying at two tertiary institutes. The current study evaluated the efficacy of the "Talk-to-Me" Mass Open Online Course (MOOC) in improving tertiary students' abilities to support the mental health of themselves and their peers via a randomised controlled trial design, comparing them to a waitlist control group. Overall, 129 tertiary students (M = 25.22 years, SD = 7.43; 80% female) undertaking a health science or education course at two Western Australian universities were randomly allocated to either "Talk-to-Me" (n = 66) or waitlist control (n = 63) groups. The participants' responses to suicidal statements (primary outcome), knowledge of mental health, generalised self-efficacy, coping skills, and overall utility of the program (secondary outcomes) were collected at three timepoints (baseline 10-weeks and 24-weeks from baseline). Assessment time and group interaction were explored using a random-effects regression model, examining changes in the primary and secondary outcomes. Intention-to-treat analysis (N = 129) at 10-weeks demonstrated a significant improvement in generalised self-efficacy for "Talk-to-Me" compared to the control group (ES = 0.36, p = .04), with only the "Talk-to-Me" participants reporting increased knowledge in responding to suicidal ideation (primary outcome). This change was sustained for 24 weeks. Findings provide preliminary evidence suggesting that the "Talk-to-Me" MOOC can effectively improve tertiary students' mental health and knowledge of how to support themselves and others in distress. ACTRN12619000630112, registered 18-03-2019, anzctr.org.au.

Therapeutic drug monitoring in adolescents with anorexia nervosa for safe treatment with adjunct olanzapine.

OBJECTIVE: Medication is commonly used in anorexia nervosa (AN) despite largely missing high grade evidence. Olanzapine (OLZ) is the best-evidenced substance used off-label in this group, with conflicting outcome regarding BMI, clinical and safety parameters. Therefore, it is important to strictly assure quality of treatment with OLZ in AN by using 'Therapeutic Drug Monitoring' according to AGNP-guidelines, including serum levels and adverse drug reactions (ADRs) to support safety for adolescents with AN and attempt to generate an initial age- and disorder-specific therapeutic reference range. METHOD: Sixty-five adolescents with AN (aged 10-18) treated with OLZ (98% female; 97.5% AN-restricting-type) were prospectively observed, ADRs reported, and correlations between dosage and serum levels measured at trough level were calculated, a preliminary therapeutic range defined. RESULTS: Mean dosage of OLZ was 8.15 (SD: 2.91) mg and 0.19 (SD: 0.07) mg/kg respectively, average concentration was 26.57 (SD: 13.46) ng/mL. Correlation between daily dosage/dosage per kg and serum level was 0.72 (**p < 0.001)/0.65 (**p < 0.001), respectively. ADRs with impairment were rare (6.3%). 75% improved clinically (CGI). BMI increased significantly by 1.5 kg/m2 (t = 10.6, p < 0.001). A preliminary therapeutic reference range is 11.9 and 39.9 ng/mL. CONCLUSIONS: OLZ in the hands of specialists is a well-tolerated and safe treatment adjunct for adolescents with AN.

[Particularities and problems of psychopharmacology in childhood and adolescence]. / Besonderheiten und Probleme der Psychopharmakologie im Kindes- und Jugendalter.

The drug treatment of mental illness in childhood and adolescence poses a particular clinical and legal challenge. Reasons for this include the often necessary off-label use and existing knowledge gaps regarding the long-term effects of the neuro-/psychotropic drugs used. In this article, the prerequisites for therapy with neuro/psychotropic drugs, such as the need for age-appropriate inclusion of children and adolescents in the decision-making and education process, as well as the evaluation of medication, the consideration of biological age- and maturation-related factors, and the special measures for off-label use, are discussed. We further discuss general problems in the development and use of neuro-/psychotropic drugs, such as the difficulties in relation to proof of effectiveness, reimbursement and liability issues of off-label administration, and the problems of conducting clinical trials with children and adolescents.

[Experiences of Violence During Inpatient Child and Adolescent Psychiatric Treatment: An Explorative Study with Implications for Child Protection]. / Gewalterfahrungen während stationärer kinder- und jugendpsychiatrischer Behandlung ­ explorative Studie und Implikationen für den Kinderschutz.

Experiences of Violence During Inpatient Child and Adolescent Psychiatric Treatment: An Explorative Study with Implications for Child Protection Abstract. Objective: Educational and medical institutions care for children and adolescents by providing supervision, schooling, education, therapy, and protection. Nevertheless, children in institutional care are exposed to potential danger through maltreatment and abuse. Method: As part of the establishment of the protection concept at the University Hospital for Child and Adolescent Psychiatry in Würzburg, a retrospective patient survey was conducted. The study population consisted of former inpatient clients from 2006 and 2007, who at the time of the catamnesis were of legal age. The survey was conducted by mail. In addition to items on their experiences of violence, the questionnaire included established scales to assess treatment satisfaction and quality of life (FBB-K, WHO-BREF). Results: Of 568 former patients, 87 (15.3 %) provided valid responses (59 female, mean age at the time of the survey: 24.5 years): 35 former patients (40.2 % of the participants) reported experiences of violence during their inpatient treatment (26 victims only, 7 experiences as victims and perpetrators, and 2 perpetrators only). Experiences as victims mainly included emotional violence (34.5 %), but also physical (5.7 %) and sexual violence (10.3 %). Conclusion: We found a significant correlation between experiences of violence, on the one hand, and retrospective treatment satisfaction and current quality of life, on the other hand. The results of the survey underline the importance of establishing protection concepts in clinics and other institutions.

Determination of Guanfacine in Oral Fluid and Serum of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Short Communication.

BACKGROUND: Guanfacine, a selective α2A-adrenoreceptor agonist, is a second-line medication for treating children and adolescents with attention-deficit/hyperkinetic disorder. The dosage administered as milligram per body weight to balance the potential benefits and risks of treatment. Therapeutic drug monitoring (TDM) is useful for identifying a patient's therapeutic window to optimize individual drug dosing and reduce the risk of adverse drug reactions. However, in children and adolescents, intravenous sample collection is especially stressful and thus remains a primary challenge, restricting the use of TDM. Therefore, evaluating alternative specimens to facilitate TDM is a worthwhile task. The aim of this study was to assess the feasibility of using oral fluid for TDM of guanfacine in children and adolescents. METHODS: In this article, 9 patients (median age 8.1 years; 6 boys and 3 girls) undergoing treatment with guanfacine were included. Simultaneously collected oral fluid and serum samples were deproteinized using methanol containing a stable isotope-labeled internal standard before the determination of guanfacine by liquid chromatography-tandem mass spectrometry. Pearson correlation and paired t test were used for statistical analysis. RESULTS: The mean serum guanfacine concentration was 3 times higher than that detected in oral fluid (7.47 ng/mL versus 2.36 ng/mL; t (8) = 5.94; P < 0.001). A strong positive linear correlation (r = 0.758, P = 0.018) was identified between oral fluid and serum concentrations. A strong but nonsignificant negative correlation (r = -0.574, P = 0.106) was detected between the oral fluid pH and oral fluid-to-serum concentration ratio. CONCLUSIONS: The strong correlation between oral fluid and serum concentration and the probable small effect of oral fluid pH on oral fluid-to-serum concentration ratio supports guanfacine as a suitable candidate for TDM in oral fluid.

Therapeutic drug monitoring of sertraline in children and adolescents: A naturalistic study with insights into the clinical response and treatment of obsessive-compulsive disorder.

BACKGROUND: Sertraline is a selective serotonin reuptake inhibitor with specific indications in child and adolescent psychiatry. Notwithstanding its frequent use and clinical benefits, the relationship between pharmacokinetics, pharmacodynamics, efficacy, and tolerability of sertraline across indications, particularly in non-adult patients, is not fully understood. METHOD: This naturalistic therapeutic drug monitoring (TDM) study was conducted in a transdiagnostic sample of children and adolescents treated with sertraline (n = 78; mean age, 14.22 ± 2.39; range, 7-18 years) within the prospective multicenter "TDM-VIGIL" project. Associations between dose, serum concentration, and medication-specific therapeutic and side effects based on the Clinical Global Impression scale were examined. Tolerability was measured qualitatively with the 56-item Pediatric Adverse Event Rating Scale. RESULTS: A strong linear positive dose-serum concentration relationship (with dose explaining 45% of the variance in concentration) and significant effects of weight and co-medication were found. Neither dose nor serum concentration were associated with side effects. An overall mild-to-moderate tolerability profile of sertraline was observed. In contrast with the transdiagnostic analysis that did not indicate an effect of concentration, when split into depression (MDD) and obsessive-compulsive disorder (OCD) diagnoses, the probability of clinical improvement significantly increased as both dose and concentration increased for OCD, but not for MDD. CONCLUSIONS: This TDM-flexible-dose study revealed a significant diagnosis-specific effect between sertraline serum concentration and clinical efficacy for pediatric OCD. While TDM already guides clinical decision-making regarding compliance, dose calibration, and drug-drug interactions, combining TDM with other methods, such as pharmacogenetics, may facilitate a personalized medicine approach in psychiatry.

Serious Adverse Drug Reactions in Children and Adolescents Treated On- and Off-Label with Antidepressants and Antipsychotics in Clinical Practice.

INTRODUCTION: Despite the growing evidence base for psychotropic drug treatment in pediatric patients, knowledge about the benefit-risk ratio in clinical practice remains limited. The 'Therapeutic Drug Monitoring (TDM)-VIGIL' study aimed to evaluate serious adverse drug reactions (ADRs) in children and adolescents treated with antidepressants and/or antipsychotics in approved ('on-label'), and off-label use in clinical practice. METHODS: Psychiatric pediatric patients aged 6-18 years treated with antidepressants and/or antipsychotics either on-label or off-label were prospectively followed between October 2014 and December 2018 within a multicenter trial. Follow-up included standardized assessments of response, serious ADRs and therapeutic drug monitoring. RESULTS: 710 youth (age=14.6±2.2 years, female=66.6%) were observed for 5.5 months on average; 76.3% received antidepressants, 47.5% antipsychotics, and 25.2% both. Altogether, 55.2% of the treatment episodes with antidepressants and 80.7% with antipsychotics were off-label. Serious ADRs occurred in 8.3% (95%CI=6.4-10.6%) of patients, mainly being psychiatric adverse reactions (77.4%), predominantly suicidal ideation and behavior. The risk of serious ADRs was not significantly different between patients using psychotropics off-label and on-label (antidepressants: 8.1% vs. 11.3%, p=0.16; antipsychotics: 8.7% vs 7.5%, p=0.67). Serious ADRs occurred in 16.6% of patients who were suicidal at enrollment versus 5.6% of patients who were not suicidal (relative risk 3.0, 95%CI=1.9-4.9). CONCLUSION: Off-label use of antidepressants and antipsychotics in youth was not a risk factor for the occurrence of serious ADRs in a closely monitored clinical setting. Results from large naturalistic trials like ours can contribute to bridging the gap between knowledge from randomized controlled trials and real-world clinical settings.

Fear conditioning and stimulus generalization in association with age in children and adolescents.

The aim of the study was to investigate age-related differences in fear learning and generalization in healthy children and adolescents (n = 133), aged 8-17 years, using an aversive discriminative fear conditioning and generalization paradigm adapted from Lau et al. (2008). In the current task, participants underwent 24 trials of discriminative conditioning of two female faces with neutral facial expressions, with (CS+) or without (CS-) a 95-dB loud female scream, presented simultaneously with a fearful facial expression (US). The discriminative conditioning was followed by 72 generalization trials (12 CS+, 12 GS1, 12 GS2, 12 GS3, 12 GS4, and 12 CS-): four generalization stimuli depicting gradual morphs from CS+ to CS- in 20%-steps were created for the generalization phases. We hypothesized that generalization in children and adolescents is negatively correlated with age. The subjective ratings of valence, arousal, and US expectancy (the probability of an aversive noise following each stimulus), as well as skin conductance responses (SCRs) were measured. Repeated-measures ANOVAs on ratings and SCR amplitudes were calculated with the within-subject factors stimulus type (CS+, CS-, GS1-4) and phase (Pre-Acquisition, Acquisition 1, Acquisition 2, Generalization 1, Generalization 2). To analyze the modulatory role of age, we additionally calculated ANCOVAs considering age as covariate. Results indicated that (1) subjective and physiological responses were generally lower with increasing age irrespective to the stimulus quality, and (2) stimulus discrimination improved with increasing age paralleled by reduced overgeneralization in older individuals. Longitudinal follow-up studies are required to analyze fear generalization with regard to brain maturational aspects and clarify whether overgeneralization of conditioned fear promotes the development of anxiety disorders or vice versa.

[The Pharmacological Management of Emergencies in Child and Adolescent Psychiatry]. / Das pharmakologische Management kinder- und jugendpsychiatrischer Notfälle.

The Pharmacological Management of Emergencies in Child and Adolescent Psychiatry Abstract. Emergencies in child and adolescent psychiatry are highly prevalent and often pose significant challenges to physicians, since substantial danger to the patient or others must be avoided through the application of largely moderate interventions. Besides using de-escalating strategies and exploiting psychotherapeutic options, the physician frequently employs psychopharmacological interventions. because of a lack of systematically assessed data, however, in emergencies in child and adolescent psychiatry most administrations of psychotropic drugs occur "off label." This review deduces practice-relevant recommendations for the pharmacological management of occurring child and adolescent emergencies such as acute suicidality, acute psychotic episodes, delirium, disorders of consciousness, acute intoxication, and alcohol withdrawal syndrome. We discuss the issue of quality and safety in pharmacological emergency strategies.

Identification of ADHD risk genes in extended pedigrees by combining linkage analysis and whole-exome sequencing.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a complex genetic background, hampering identification of underlying genetic risk factors. We hypothesized that combining linkage analysis and whole-exome sequencing (WES) in multi-generation pedigrees with multiple affected individuals can point toward novel ADHD genes. Three families with multiple ADHD-affected members (Ntotal = 70) and apparent dominant inheritance pattern were included in this study. Genotyping was performed in 37 family members, and WES was additionally carried out in 10 of those. Linkage analysis was performed using multi-point analysis in Superlink Online SNP 1.1. From prioritized linkage regions with a LOD score ≥ 2, a total of 24 genes harboring rare variants were selected. Those genes were taken forward and were jointly analyzed in gene-set analyses of exome-chip data using the MAGMA software in an independent sample of patients with persistent ADHD and healthy controls (N = 9365). The gene-set including all 24 genes together, and particularly the gene-set from one of the three families (12 genes), were significantly associated with persistent ADHD in this sample. Among the latter, gene-wide analysis for the AAED1 gene reached significance. A rare variant (rs151326868) within AAED1 segregated with ADHD in one of the families. The analytic strategy followed here is an effective approach for identifying novel ADHD risk genes. Additionally, this study suggests that both rare and more frequent variants in multiple genes act together in contributing to ADHD risk, even in individual multi-case families.

Betrayed by the nervous system: a comparison group study to investigate the 'unsafe world' model of selective mutism.

The study presented in the following verifies some assumptions of the novel 'unsafe world' model of selective mutism (SM). According to this model, SM is a stress reaction to situations erroneously experienced via cognition without awareness as 'unsafe'. It assumes a high sensitivity to unsafety, whereby the nervous system triggers dissociation or freeze mode at relatively low thresholds. We examine whether there is a correlation between SM, sensory-processing sensitivity and dissociation. We compared a sample of 28 children and adolescents with SM (mean age 12.66 years; 18 females) to 33 controls without SM (mean age 12.45 years; 21 females). Both groups were compared using a medical history sheet, the 'Selective Mutism Questionnaire' (SMQ), a 'Checklist for Speaking Behaviour' (CheckS), the 'Highly Sensitive Person Scale' (HSPS), the 'Child Dissociative Checklist' (CDC), the 'Adolescent Dissociative Experience Scale' (A-DES) and the 'Social Phobia and Anxiety Inventory for Children' (SPAIK). Appropriate parametric and non-parametric tests were conducted to examine differences between groups. The results indicate that sensory-processing sensitivity was significantly higher in the group of children and adolescents with SM [X2(1) = 7.224, p = 0.0007; d = 1.092]. Furthermore, dissociative symptoms were more common in children and adolescents with SM than in controls [F(1, 33) = 13.004, p = 0.001; d = 0.986]. The results indicate that sensory-processing sensitivity and dissociation are important factors of SM that may hold important implications for the treatment. TRIAL REGISTRATION: This study is registered with the ClinicalTrials.gov number NCT04233905.