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Key Points: Question: Can the effects of adolescent psychiatric inpatient treatment as usual for major depressive disorder be enhanced by simultaneous use of morning bright light therapy? Findings: In this randomized clinical trial including 224 adolescents, 4-week inpatient treatment as usual augmented by bright light therapy was not superior to treatment as usual plus placebo red light. Both groups showed significant reductions in depressive symptoms, and there were no serious adverse events during the trial caused by light-related interventions. Meaning: Bright light therapy lacked an edge over placebo in treating adolescent inpatients with depression in this study; further studies should include treatment as usual without placebo to rule out potential placebo effects. This randomized clinical trial evaluates bright light therapy vs treatment as usual for youth with depression. Importance: Major depressive disorder is one of the most common mental disorders among adolescents, entailing severe, long-term psychosocial impairment and a high risk of chronicity. In view of the large number of patients requiring treatment, along with insufficient treatment responses with small effect sizes, innovative adjunctive treatment strategies are urgently needed. Objective: To investigate whether the effect of adolescent psychiatric inpatient treatment as usual for major depressive disorder can be enhanced by simultaneous use of morning bright light therapy. Design, Setting, and Participants: This was a double-blind, placebo-controlled randomized parallel-group trial with enrollment between March 2018 and November 2020 and follow-up completed in May 2021. The study took place among inpatients at 4 university hospitals for child and adolescent psychiatry across Germany. Of 248 eligible youth aged 12 to 18 years fulfilling ICD-10 criteria for major depressive disorder, 227 were randomized to bright light therapy (n = 116) or placebo red light (n = 111); 151 participants completed the study. Interventions: Up to 20 sessions of either morning bright light therapy with an intensity of 10 000 lux or placebo red light (100 lux) in addition to multimodal inpatient treatment as usual over 4 weeks. Main Outcomes and Measures: The primary outcome was the change in Beck Depression Inventory-II (BDI-II) score from baseline to posttreatment in the intention-to-treat sample. Results: Among the 224 patients included in the intention-to-treat analyses (192 girls and 32 boys; mean [SD] age, 15.5 [1.4] years), the mean (SD) BDI-II score at baseline was 37.3 (8.7). BDI-II scores were significantly reduced after 4 weeks (postassessment) by a mean of −7.5 (95% CI, −9.0 to −6.0; Hedges g = 0.71). Bright light therapy had no impact on this change (no significant group × time effect). Loss to follow-up was 31% (n = 69) at 16 weeks and 49% (n = 110) at 28 weeks. There were 10 serious adverse events throughout the whole trial, which were not considered related to study treatment. Conclusions and Relevance: The findings in this study did not indicate superiority of bright light therapy over placebo red light therapy in a large sample of adolescent inpatients with moderate or severe major depressive disorder. Both groups benefited equally from treatment as usual, showing relevant symptom reduction. Trial Registration: German Clinical Trials Register: DRKS00013188 [ABSTRACT FROM AUTHOR]

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Attention deficit hyperactivity disorder (ADHD) is a very common disorder in children and adults. A connection with sleep disorders, and above all, disorders of the circadian rhythm are the subject of research and debate. The circadian system can be represented on different levels. There have been a variety of studies examining 24-h rhythms at the behavioral and endocrine level. At the molecular level, these rhythms are based on a series of feedback loops of core clock genes and proteins. In this paper, we compared the circadian rhythms at the behavioral, endocrine, and molecular levels between children with ADHD and age- and BMI-matched controls, complementing the previous data in adults. In a minimally invasive setting, sleep was assessed via a questionnaire, actigraphy was used to determine the motor activity and light exposure, saliva samples were taken to assess the 24-h profiles of cortisol and melatonin, and buccal mucosa swaps were taken to assess the expression of the clock genes BMAL1 and PER2. We found significant group differences in sleep onset and sleep duration, cortisol secretion profiles, and in the expression of both clock genes. Our data suggest that the analysis of circadian molecular rhythms may provide a new approach for diagnosing ADHD in children and adults. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

E-mental health and home treatment are treatment approaches that have proven to be e􀀀ective, 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 di􀀀erent 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. [ABSTRACT FROM AUTHOR]

Background: Chronotherapeutic treatments for depression, such as bright light therapy (BLT), are non-invasive and produce almost no side effects. However, study evidence for reliable neurobiological changes associated with treatment response is still rare. Several studies using EEG-vigilance indicate higher arousal and a later decline during resting state in adult depressive patients compared to healthy controls. To our knowledge, there are no study reports on EEG-vigilance in depressive youth to date. Methods: A total of 11 adolescents with depression receiving BLT were compared to 11 age and gender-matched patients with depression receiving treatment as usual (TAU). The BLT was administered in the morning for 2 weeks on five consecutive days per week. The depressive symptomatology was assessed using the Beck Depression Inventory (BDI-II) and the resting state electroencephalogram (EEG) of 20 min was recorded. EEG and BDI-II were assessed before and after 10 days of treatment. Vigilance level and vigilance decline were estimated using the VIGALL toolbox. Results: Brain arousal increased after 10 days of bright light therapy in adolescents with depression. Severe depressive symptoms were associated with higher brain arousal levels; the BDI-II sum score correlated negatively with the amount of drowsiness. Limitations: The sample size was small and participants' brain arousal at baseline was not matched and differed between BLT and TAU groups. Conclusion: The BLT might have an additional effect on brain arousal. EEG-vigilance seems to be a reliable and valid marker for neurobiological changes that are probably associated with depression and its treatment and, therefore, might be of clinical relevance. [ABSTRACT FROM AUTHOR]

Objective: Disturbed regulation of vigilance in the wake state seems to play a key role in the development of mental disorders. It is assumed that hyperactivity in adult ADHD is an attempt to increase a general low vigilance level via external stimulation in order to avoid drowsiness. For depression, the avoidance of stimulation is interpreted as a reaction to a tonic increased vigilance state. Although ADHD is assumed to start during childhood, this vigilance model has been barely tested with children diagnosed for ADHD so far. Methods: Resting-state EEG (8 min) measures from two groups of children diagnosed with either ADHD [ N = 76 (16 female, 60 male), age: (mean/SD) 118/33 months] or depression [ N = 94 (73 female, 21 male), age: 184/23 months] were analyzed. Using the VIGALL toolbox, EEG patterns of vigilance level, and regulation were derived and compared between both groups. In correlation analysis, the relations between vigilance measures, attentional test performance (alertness and inhibition), and mental health symptoms were analyzed. Results: Children with ADHD differed from children with most prominent depressive symptoms in brain arousal regulation and level, but EEG vigilance was not related to behavior problems and not related to the attentional test performance. Brain arousal was dependent on the age of the participant in the whole sample; younger children showed lower vigilance stages than teenagers; this effect was not present when analyzed separately for each diagnostic group. EEG assessment time and received medication had no effect on the EEG vigilance. Discussion: Although based on a small sample, this explorative research revealed that EEG vigilance level is different between children with ADHD and with depression. Moreover, even the standard procedure of the clinical routine EEG (resting state) can be used to differentiate brain arousal states between participants with ADHD and depression. Because routine EEG is not specialized to vigilance assessment, it may not be sufficiently sensitive to find vigilance–symptomatology associations. Further research should address developmental changes in EEG measurements in children and use bigger samples of participants within the same age range. [ABSTRACT FROM AUTHOR]

Abstract Most psychotropic drugs used in the treatment of children and adolescents are applied "off label" with a direct risk of under- or overdosing and a delayed risk of long-term side effects. The selection of doses in paediatric psychiatric patients requires a consideration of pharmacokinetic parameters and the development of central nervous system, and warrants specific studies in children and adolescents. Because these are lacking for most of the psychotropic drugs applied in the Child and Adolescent and Psychiatry, therapeutic drug monitoring (TDM) is a valid tool to optimise pharmacotherapy and to enable to adjust the dosage of drugs according to the characteristics of the individual patient. Multi-centre TDM studies enable the identification of age- and development-dependent therapeutic ranges of blood concentrations and facilitate a highly qualified standardized documentation in the child and adolescent health care system. In addition, they will provide data for future research on psychopharmacological treatment in children and adolescents, as a baseline for example for clinically relevant interactions with various co-medications. Therefore, a German-Austrian-Swiss "Competence Network on Therapeutic Drug Monitoring in Child and Adolescent Psychiatry" was founded 1 introducing a comprehensive internet data base for the collection of demographic, safety and efficacy data as well as blood concentrations of psychotropic drugs in children and adolescents.

Objective: The aim of this study is to identify characteristics predicting the use of medication and/or psychotherapy after a first ADHD diagnosis. Method: This cohort study was based on German claims data including 12,250 treatment-naïve children aged 5 to 12 years with an incident ADHD diagnosis in 2010. Logistic regression models were used to estimate associations between children's characteristics at first diagnosis and the chosen treatment within the following 5 years. Results: Medication use was associated with male sex, an ADHD diagnosis "with hyperactivity," comorbid depression, and comorbid developmental and conduct disorders. Male sex and comorbid neurotic and somatoform, conduct, and emotional disorders were associated with psychotherapy only. Receiving both treatments—instead of medication only—was associated with comorbid depression, neurotic and somatoform, conduct, and emotional disorders. Conclusion: In case of equal access to both treatment options, patients, for example, with externalizing symptoms were more prone to receive medication and/or psychotherapy than the average child diagnosed with ADHD. [ABSTRACT FROM AUTHOR]

The article discusses research which analyzed nationwide hospital treatment data on trends in the case numbers in inpatient care for mentally ill minors and whether the diagnostic spectrum changed during the COVID-19 pandemic in Germany. Topics include changes in the numbers of cases with pediatric psychiatric diagnoses treated on an inpatient basis for the first six months of 2019 and of 2021, research findings and limitation of the study.

Objective: Maternal autoantibodies are a risk factor for impaired brain development in offspring. Antibodies (ABs) against the NR1 (GluN1) subunit of the N-methyl-d-aspartate receptor (NMDAR) are among the most frequently diagnosed anti-neuronal surface ABs, yet little is known about effects on fetal development during pregnancy.Methods: We established a murine model of in utero exposure to human recombinant NR1 and isotype-matched nonreactive control ABs. Pregnant C57BL/6J mice were intraperitoneally injected on embryonic days 13 and 17 each with 240μg of human monoclonal ABs. Offspring were investigated for acute and chronic effects on NMDAR function, brain development, and behavior.Results: Transferred NR1 ABs enriched in the fetus and bound to synaptic structures in the fetal brain. Density of NMDAR was considerably reduced (up to -49.2%) and electrophysiological properties were altered, reflected by decreased amplitudes of spontaneous excitatory postsynaptic currents in young neonates (-34.4%). NR1 AB-treated animals displayed increased early postnatal mortality (+27.2%), impaired neurodevelopmental reflexes, altered blood pH, and reduced bodyweight. During adolescence and adulthood, animals showed hyperactivity (+27.8% median activity over 14 days), lower anxiety, and impaired sensorimotor gating. NR1 ABs caused long-lasting neuropathological effects also in aged mice (10 months), such as reduced volumes of cerebellum, midbrain, and brainstem.Interpretation: The data collectively support a model in which asymptomatic mothers can harbor low-level pathogenic human NR1 ABs that are diaplacentally transferred, causing neurotoxic effects on neonatal development. Thus, AB-mediated network changes may represent a potentially treatable neurodevelopmental congenital brain disorder contributing to lifelong neuropsychiatric morbidity in affected children. ANN NEUROL 2019;86:656-670. [ABSTRACT FROM AUTHOR]

Background: The current analyses examined whether the dysregulation profile (DP) 1) could be used to identify children and adolescents at high risk for complex and serious psychopathology and 2) was correlated to other emotional and behavioral problems (such as delinquent behavior or suicide ideation). DP was assessed using both the Child Behavior Checklist (CBCL) and the Youth Self Report (YSR) in a residential care sample.Methods: Children and adolescents (N=374) aged 10-18 years living in residential care in Switzerland completed the YSR, and their professional caregivers completed the CBCL. Participants meeting criteria for DP (T-score ≥67 on the anxious/‌depressed, attention problems, and aggressive behavior scales of the YSR/CBCL) were compared against those who did not for the presence of complex psychopathology (defined as the presence of both emotional and behavioral disorders), and also for the prevalence of several psychiatric diagnoses, suicidal ideation, traumatic experiences, delinquent behaviors, and problems related to quality of life.Results: The diagnostic criteria for CBCL-DP and YSR-DP were met by just 44 (11.8%) and 25 (6.7%) of participants. Only eight participants (2.1%) met the criteria on both instruments. Further analyses were conducted separately for the CBCL-DP and YSR-DP groups. DP was associated with complex psychopathology in only 34.4% of cases according to CBCL and in 60% of cases according to YSR. YSR-DP was somewhat more likely to be associated with psychiatric disorders and associated problems than was the CBCL-DP.Limitations: Because of the relatively small overlap between the CBCL-DP and YSR-DP, analyses were conducted largely with different samples, likely contributing to the different results.Conclusions: Despite a high rate of psychopathology in the population studied, both the YSR-DP and the CBCL-DP were able to detect only a small proportion of those with complex psychiatric disorders. This result questions the validity of YSR-DP and the CBCL-DP in detecting subjects with complex and serious psychopathology. It is possible that different screening instruments may be more effective. [ABSTRACT FROM AUTHOR]