[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.

Prevalence of Somatic Symptoms and Somatoform Disorders among a German Adolescent Psychiatric Inpatient Sample.

Somatoform disorders (SD), commencing during adolescence, represent a major problem in health care systems. While literature underlines the high presence of mental health problems among children and adolescents afflicted by somatic symptoms in the general population, limited evidence is available on the prevalence of comorbid somatic symptoms in child and adolescent psychiatric populations. We assessed the prevalence of somatic symptoms, depression, and anxiety by validated questionnaires in an inpatient cohort. We further screened for the presence of SD. Out of 434 inpatients aged 11-17 years, 371 were included and a total of n = 288 (77.6%) children and adolescents participated in the study. A total of 93.8% of the inpatients reported somatic symptoms within the past six months and still almost half (45.7%) of the sample reported at least one somatic symptom within the last seven days prior to inquiry. Relating to the past six months, 59.5% were positively screened for SD, and 44.6% reported symptoms eligible for positive screening within the past seven days prior to the survey. Somatoform symptomatology was highly associated with anxiety and depression scores, but functional decline was amenable to the number of somatic symptoms only. We provide evidence that somatic symptoms are frequent in children and adolescents being treated in child and adolescent psychiatry and are relevant to everyday functioning. Screening for somatic symptoms should be introduced in the routine diagnostic procedures for early detection of SD in the commencing stages.

Sleep Fosters Odor Recognition in Children with Attention Deficit Hyperactivity Disorder but Not in Typically Developing Children.

Prior experience represents a prerequisite for memory consolidation across various memory systems. In the context of olfaction, sleep was found to enhance the consolidation of odors in adults but not in typically developing children (TDC), likely due to differences in pre-experience. Interestingly, unmedicated children with attention deficit hyperactivity disorder (ADHD), a neurodevelopmental condition related to dopamine dysfunction, showed lower perceptive thresholds for odors, potentially allowing for more odor experience compared to TDC. We investigated sleep-associated odor memory consolidation in ADHD. Twenty-eight children with ADHD and thirty age-matched TDC participated in an incidental odor recognition task. For the sleep groups (ADHD: n = 14, TDC: n = 15), the encoding of 10 target odorants took place in the evening, and the retention of odorants was tested with 10 target odorants and 10 distractor odorants the next morning. In the wake groups (ADHD: n = 14, TDC: n = 15), the time schedule was reversed. Odor memory consolidation was superior in the ADHD sleep group compared to the TDC sleep and the ADHD wake groups. Intensity and familiarity ratings during encoding were substantially higher in ADHD compared to TDC. Sleep-associated odor memory consolidation in ADHD is superior to TDC. Abundant pre-experience due to lower perceptive thresholds is suggested as a possible explanation. Olfaction might serve as a biomarker in ADHD.

Transient Destabilization of Declarative Memory-Opposing Impact of Physical Exercise or Rest after Encoding in Typically Developing Children and Children with Attention Deficit Hyperactivity Disorder but No Difference after Subsequent Sleep.

BACKGROUND: Children are especially sensitive to a broad range of influences and show a remarkable capacity for learning. One prominent example is declarative memory, which may be influenced by a variety of factors and is impaired in attention deficit hyperactivity disorder (ADHD). Exercise and sleep, or both combined, might foster declarative memory. METHODS: Here, 12 typically developing children (TDC) and 12 age-matched children with ADHD participated in an exercise and rest condition before a night in the sleep laboratory. Declarative memory was encoded before exercise or rest and retrieved before and after a night of sleep. RESULTS: Exercise in TDC but rest in ADHD lead to a transient destabilization of declarative memory, while there were no more differences after a night of sleep. Rapid eye movement (REM) sleep latency was prolonged after exercise in both groups. CONCLUSIONS: Exercise leads to opposing effects on immediate declarative memory formation. The factors or contexts that promote or hinder declarative memory formation in children ADHD and TDC differ, and further work is needed to determine the recommendations for declarative learning in children with ADHD.

Slow oscillating transcranial direct current stimulation during non-rapid eye movement sleep improves behavioral inhibition in attention-deficit/hyperactivity disorder.

BACKGROUND: Behavioral inhibition, which is a later-developing executive function (EF) and anatomically located in prefrontal areas, is impaired in attention-deficit and hyperactivity disorder (ADHD). While optimal EFs have been shown to depend on efficient sleep in healthy subjects, the impact of sleep problems, frequently reported in ADHD, remains elusive. Findings of macroscopic sleep changes in ADHD are inconsistent, but there is emerging evidence for distinct microscopic changes with a focus on prefrontal cortical regions and non-rapid eye movement (non-REM) slow-wave sleep. Recently, slow oscillations (SO) during non-REM sleep were found to be less functional and, as such, may be involved in sleep-dependent memory impairments in ADHD. OBJECTIVE: By augmenting slow-wave power through bilateral, slow oscillating transcranial direct current stimulation (so-tDCS, frequency = 0.75 Hz) during non-REM sleep, we aimed to improve daytime behavioral inhibition in children with ADHD. METHODS: Fourteen boys (10-14 years) diagnosed with ADHD were included. In a randomized, double-blind, cross-over design, patients received so-tDCS either in the first or in the second experimental sleep night. Inhibition control was assessed with a visuomotor go/no-go task. Intrinsic alertness was assessed with a simple stimulus response task. To control for visuomotor performance, motor memory was assessed with a finger sequence tapping task. RESULTS: SO-power was enhanced during early non-REM sleep, accompanied by slowed reaction times and decreased standard deviations of reaction times, in the go/no-go task after so-tDCS. In contrast, intrinsic alertness, and motor memory performance were not improved by so-tDCS. CONCLUSION: Since behavioral inhibition but not intrinsic alertness or motor memory was improved by so-tDCS, our results suggest that lateral prefrontal slow oscillations during sleep might play a specific role for executive functioning in ADHD.

Transcranial oscillatory direct current stimulation during sleep improves declarative memory consolidation in children with attention-deficit/hyperactivity disorder to a level comparable to healthy controls.

BACKGROUND: Slow oscillations (<1 Hz) during slow wave sleep (SWS) promote the consolidation of declarative memory. Children with attention-deficit/hyperactivity disorder (ADHD) have been shown to display deficits in sleep-dependent consolidation of declarative memory supposedly due to dysfunctional slow brain rhythms during SWS. OBJECTIVE: Using transcranial oscillating direct current stimulation (toDCS) at 0.75 Hz, we investigated whether an externally triggered increase in slow oscillations during early SWS elevates memory performance in children with ADHD. METHODS: 12 children with ADHD underwent a toDCS and a sham condition in a double-blind crossover study design conducted in a sleep laboratory. Memory was tested using a 2D object-location task. In addition, 12 healthy children performed the same memory task in their home environment. RESULTS: Stimulation enhanced slow oscillation power in children with ADHD and boosted memory performance to the same level as in healthy children. CONCLUSION: These data indicate that increasing slow oscillation power during sleep by toDCS can alleviate declarative memory deficits in children with ADHD.

Sleep promotes consolidation of emotional memory in healthy children but not in children with attention-deficit hyperactivity disorder.

Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline-corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.

Sleep restores daytime deficits in procedural memory in children with attention-deficit/hyperactivity disorder.

Sleep supports the consolidation of declarative and procedural memory. While prefrontal cortex (PFC) activity supports the consolidation of declarative memory during sleep, opposite effects of PFC activity are reported with respect to the consolidation of procedural memory during sleep. Patients with attention-deficit/hyperactivity disorder (ADHD) are characterised by a prefrontal hypoactivity. Therefore, we hypothesised that children with ADHD benefit from sleep with respect to procedural memory more than healthy children. Sixteen children with ADHD and 16 healthy controls (aged 9-12) participated in this study. A modification of the serial-reaction-time task was conducted. In the sleep condition, learning took place in the evening and retrieval after a night of sleep, whereas in the wake condition learning took place in the morning and retrieval in the evening without sleep. Children with ADHD showed an improvement in motor skills after sleep compared to the wake condition. Sleep-associated gain in reaction times was positively correlated with the amount of sleep stage 4 and REM-density in ADHD. As expected, sleep did not benefit motor performance in the group of healthy children. These data suggest that sleep in ADHD normalizes deficits in procedural memory observed during daytime. It is discussed whether in patients with ADHD attenuated prefrontal control enables sleep-dependent gains in motor skills by reducing the competitive interference between explicit and implicit components within a motor task.

Change in delusions is associated with change in "jumping to conclusions".

Evidence has been put forward that premature termination of data collection and jumping to conclusions behavior (JTC) is associated with delusions. However, few investigations have attempted to track associations between changes in delusions and changes in JTC measures. In the current study individuals with schizophrenia spectrum disorders completed a version of the JTC task (involving fishing from lakes as opposed to drawing beads from a jar) at two timepoints 12 weeks apart. The results revealed significant negative correlations between change in task performance (number of requested pieces of information) and change in delusion scores over time. This evidence is consistent with the contention that the JTC task is sensitive to the cognitive systems underlying delusions in schizophrenia spectrum disorders.