Transcranial sonography of subcortical structures in tic/tourette disorder.

Functional neuroimaging studies demonstrate disinhibition of the cortico-striatal-thalamo-cortical circuit. However, structural imaging studies revealed conflicting results, some suggesting smaller volumes of the caudate nucleus (CN) in children with Gilles de la Tourette syndrome (TS). Here we wanted to find out whether transcranial sonography (TCS) detects alterations of raphe nuclei, substantia nigra, lenticular nucleus (LN), or CN in children with Tic disorder or TS (TIC/TS).The study included 25 treatment-naive children (age: 12.2 ± 2.5 years) with a DSM-V based diagnosis of Tic disorder or TS (10 subjects), without other psychiatric or neurologic diagnosis, and 25 healthy controls (age: 12.17 ± 2.57 years), matched for age and sex. Parental rating of behavioral, emotional abnormalities, somatic complaints and social competencies of the participants were assessed using the Child Behavior Check List (CBCL/4-18R). TCS of deep brain structures was conducted through the preauricular acoustic bone windows using a 2.5-MHz phased-array ultrasound system. Fisher's exact test and Mann-Whitney-U test were used for comparisons between TIC/TS patients and healthy volunteers. The number of participants with hyperechogenic area of left CN in the TIC/TS sample was increased, compared to the healthy control group. TIC/TS patients with hyperechogenic CN showed an increased occurrence of thought- and obsessive-compulsive problems. This TCS study revealed pathologic structural changes in CN, its higher occurrence in TIC/TS compared to healthy controls and the relation to comorbidity of thought problems. Further research should focus on the molecular cause of these alterations, probably the disturbed iron metabolism.

Bright Light Therapy as Add-On to Inpatient Treatment in Youth With Moderate to Severe Depression: A Randomized Clinical Trial.

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.

Clock Genes Profiles as Diagnostic Tool in (Childhood) ADHD-A Pilot Study.

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.

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.

Electroconvulsive Therapy in Children and Adolescents in Germany-A Case Series From 3 University Hospitals.

OBJECTIVE: Electroconvulsive therapy (ECT) is a well-established, safe, and efficacious treatment for severe psychiatric disorders. In children and adolescents, it is used much less frequently than in adults, likely because of a lack of knowledge. METHODS: We retrospectively analyzed all patients aged 12 to 17 years who completed a course of ECT at 3 psychiatric university hospitals in Germany between 2010 and 2020. Clinical Global Impression Severity (CGI-S) scores were assessed based on electronic medical records. Changes in CGI-S scores were assessed using a paired samples t test. Predictors for response and remission were assessed using binomial logistic regression. RESULTS: We included 32 patients. The CGI-S scores improved significantly from before to after ECT treatment (6.9 vs 3.9, t = 10.0, P < 0.01). A total of 40.6% of patients responded (CGI ≤ 3) and 21.9% remitted (CGI ≤ 2). The number of ineffective medication trials in the 6 months before ECT treatment was significantly associated with response (odds ratio, 0.54; P = 0.028) and remission (odds ratio, 0.31; P = 0.048). Five patients reported subjective cognitive adverse effects, 2 patients exhibited a prolonged seizure, 1 patient reported headaches, and 1 patient experienced a mild allergic reaction after anesthesia with etomidate. A total of 65.6% of patients experienced no adverse effects at all. CONCLUSIONS: This retrospective analysis found ECT to be effective and safe in children and adolescents irrespective of their main diagnosis. The reported data point to the importance of an early use of ECT for severe psychiatric diseases in child and adolescent psychiatry.

Possible Effects of Bright Light Therapy on Electroencephalogram-Vigilance in the Treatment of Depression in Adolescents: A Pilot Study.

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.

Brain Arousal as Measured by EEG-Assessment Differs Between Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) and Depression.

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.

[Use of electroconvulsive therapy in adolescents - A retrospective survey on 12- to 17-year-old patients at three university hospitals in Germany]. / Elektrokonvulsionstherapie im Kindes- und Jugendalter.

Use of electroconvulsive therapy in adolescents - A retrospective survey on 12- to 17-year-old patients at three university hospitals in Germany Abstract. Abstract. Background: Electroconvulsive therapy (ECT) is a highly effective and well-researched therapy in adult psychiatry and has been successfully used especially as a treatment for severe depressive, catatonic, and psychotic disorders. Although severe disease progressions also occur in child and adolescent psychiatry, ECT is used much less frequently there. This may be because hardly any data have been collected on the use, effectiveness, and tolerability of ECT in child and adolescent psychiatric patients. This article outlines the application, effectiveness, and tolerability of ECT when applied to young adolescents in Germany. Methods: A retrospective survey on ECT in 29 patients under 18 years of age was conducted at three German university centers. All documented cases were recorded and evaluated for effectiveness and tolerability. In addition, a comprehensive PubMed-based database search was carried out. Results and conclusions: Internationally, there are no meta-analyses or randomized controlled studies and hardly any published cases on electroconvulsive therapy in German child and adolescent psychiatry. Our data on ECT show high efficacy in previously treatment-resistant and severely ill patients. Side effects occurred rarely. There was no evidence of differences between adults and adolescents in indication (depression, catatonia, schizophrenia), effectiveness, tolerability, and negative predictors of response to ECT. The results also suggest that the use of ECT in adolescents should be considered earlier in the treatment course.

[Electroconvulsive Therapy - A beneficial and well tolerated therapy in children and adolescents with schizophrenia]. / Elektrokonvulsionstherapie ­ bei Kindern und Jugendlichen mit Schizophrenie wirksam und gut verträglich.

We report four cases of 12- to 17-year-old patients with schizophrenia, two of them suffering from catatonia, which were treated by ECT. Under a combined treatment with either ziprasidone or clozapine, and electroconvulsive therapy (ECT), they improved markedly. Severity and course of acute schizophrenia were evaluated by the Brief Psychiatric rating Scale (BPRS), severity and course of catatonia were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This article underlines the benefit, the safety and the tolerability of ECT in younger patients with schizophrenic disorders.

Methylphenidate promotes the interaction between motor cortex facilitation and attention in healthy adults: A combined study using event-related potentials and transcranial magnetic stimulation.

OBJECTIVE: This study investigated simultaneously the impact of methylphenidate (MPH) on the interaction of inhibitory and facilitative pathways in regions processing motor and cognitive functions. METHOD: Neural markers of attention and response control (event-related potentials) and motor cortical excitability (transcranial magnetic stimulation) and their pharmacological modulation by MPH were measured simultaneously in a sample of healthy adults (n = 31) performing a cued choice reaction test. RESULTS: Methylphenidate modulated attentional gating and response preparation processes (increased contingent negative variation) and response inhibition (increased nogo P3). N1, cue- and go-P3 were not affected by MPH. Motor cortex facilitation, measured with long-interval cortical facilitation, was increased under MPH in the nogo condition and was positively correlated with the P3 amplitude. CONCLUSION: Methylphenidate seems particularly to enhance response preparation processes. The MPH-induced increased motor cortex facilitation during inhibitory task demands was accompanied by increased terminal response inhibition control, probably as a compensatory process.

Treatment of aggressive behavior problems in boys with intellectual disabilities using zuclopenthixol.

OBJECTIVE: Disruptive or challenging behavior problems pose a threat to children and adolescents with intellectual disabilities and their caregivers. Psychopharmacological treatment is mostly studied with new-generation antipsychotics and has been criticized for adverse side effects. This study examined the effect of the classic antipsychotic zuclopenthixol. METHODS: A total of 39 boys (ages 8.0-17.11 years) with learning disabilities were included and examined for a response to zuclopenthixol during a 6 week period of open label treatment. Doses started low and were adapted individually. From responders, zuclopenthixol was randomly withdrawn for 12 weeks. Responses to withdrawal were observed by external raters using the Modified Overt Aggression Scale. RESULTS: Of all patients included into the study, 15 were not randomized because of insufficient therapeutic effect, adverse event, or noncompliance. Kaplan-Meier estimations showed less aggressive behavior problems for the continuing subgroup (n=9) than in the placebo group (n=15). Individual doses stayed <10 mg/day. CONCLUSIONS: Zuclopenthixol proved to be effective in reducing challenging behavior in boys even at low doses.

[Alternative agents used in ADHD]. / Substanzgebundene Alternativen in der Therapie von ADHS.

Attention-deficit/hyperactivity disorder (ADHD) is, with a prevalence of 2% to 6%, one of the most common neurobehavioral disorder affecting children and adolescents, persisting into adulthood. Comorbidity and psychosocial circumstances enter into the choice of intervention strategies. Several agents have been demonstrated effective in treating individuals with ADHD. Direct or indirect attenuation of dopamine and norepinephrine neurotransmission appears closely related to both the stimulant and nonstimulant medications efficacious in ADHD. However, important differences concerning efficacy and side effects exist both between and with the specific classes of agents like neuroleptics, antidepressants, antiepileptics, alpha-agonists, beta-blockers, buspiron, l-dopa, melatonin, pycnogenol, zinc, magnesium, polyunsaturated fatty acids, and homeopathy. Elucidating the various mechanisms of action of ADHD medications may lead to better choices in matching potential responses to the characteristics of individuals. We review the purported mechanism of action and available evidence for selected complementary and alternative medicine therapies for ADHD in childhood and adolescence.

Focal adhesion contact formation by fibroblasts cultured on surface-modified dental implants: an in vitro study.

A major consideration in designing dental implants is to create a surface that provides strong attachment of the implant to bone, connective tissue and epithelium. The aim of the present study was to examine the influence of different treatments of titanium (Ti) implant surfaces on focal adhesion contact (FAC) formation in fibroblast cultures. Human gingival fibroblasts were cultured on glass sheets and polished Ti discs with different surface coatings (applied by physical vapor deposition (PVD): Ti, titanium nitride (TiN), zirconium nitride (ZrN)) or on Ti discs with different surface topographies. For characterization of all surfaces, modified estimation of surface roughness and spacing parameter was carried out using a contact stylus profilometer. Contact angle measurements were carried out to calculate surface energy. Fibroblasts were prepared for transmission electron microscopy at day 3 after seeding, and the number of FACs and the ratio FAC/cellular cross-sections was determined at a length of 300 microm in ultrathin sections. To visualize the extracellular fibronectin and vitronectin molecules and the intracellular actin and vinculin in FAC areas, immunogold labeling was performed. The results revealed a strong correlation between the number of FACs and the surface roughness. The highest number of FACs and the majority of the immunogold-labeled intra- and extracellular matrix molecules were counted on surfaces with the lowest surface roughness: glass sheets coated with either Ti, TiN or ZrN (roughness average=0.03-0.1 microm). These surfaces appear to favor cellular attachment of human gingival fibroblasts and moreover in previous studies the hard coatings have been shown to reduce bacterial adhesion.

Do different implant surfaces exposed in the oral cavity of humans show different biofilm compositions and activities?

Osseointegrated dental implants play an important role in restorative dentistry. However, plaque accumulation may cause inflammatory reactions around the implants, sometimes leading to implant failure. In this in vivo study the influence of two physical hard coatings on bacterial adhesion was examined in comparison with a pure titanium surface. Thin glass sheets coated with titanium nitride (TiN), zirconium nitride (ZrN) or pure titanium were mounted on removable intraoral splints in two adults. After 60 h of intraoral exposure, the biofilms were analyzed to determine the number of bacteria, the types of bacteria [by applying single-strand conformation polymorphism (SSCP analysis) of 16S rRNA genes], and whether or not the bacteria were active (by SSCP analysis of 16S rRNA). The results showed that bacterial cell counts were higher on the pure titanium-coated glass sheets than on the glass sheets coated with TiN or ZrN. The lowest number of bacterial cells was present on theZrN-coated glass. However, the metabolic activity (RNA fingerprints) of bacteria on TiN- and ZrN-coated glass sheets seemed to be lower than the activity of bacteria on the titanium-coated surfaces, whereas SSCP fingerprints based on 16S rDNA revealed that the major 16S bands are common to all of the fingerprints, independently of the surface coating.