Novel Insights into Somatic Comorbidities in Children and Adolescents Across Psychiatric Diagnoses: An Explorative Study.

Many children with psychiatric disorders display somatic symptoms, although these are frequently overlooked. As somatic morbidity early in life negatively influences long-term outcomes, it is relevant to assess comorbidity. However, studies of simultaneous psychiatric and somatic assessment in children are lacking. The aim of this study was to assess the prevalence of somatic comorbidities in a clinical sample of children and adolescents with psychiatric disorders in a naturalistic design. Data were assessed from 276 children with various psychiatric disorders (neurodevelopmental disorders, affective disorders, eating disorders and psychosis) aged 6-18 years. These data were collected as part of routine clinical assessment, including physical examination and retrospectively analyzed. For a subsample (n = 97), blood testing on vitamin D3, lipid spectrum, glucose and prolactin was available. Results of this cross-sectional study revealed that food intake problems (43%) and insomnia (66%) were common. On physical examination, 20% of the children were overweight, 12% displayed obesity and 38% had minor physical anomalies. Blood testing (n = 97) highlighted vitamin D3 deficiency (< 50 nmol/L) in 73% of the children. None of the predefined variables (gender, age, medication and socioeconomic factors) contributed significantly to the prevalence of somatic comorbidities. The main somatic comorbidities in this broad child- and adolescent psychiatric population consisted of (1) problems associated with food intake, including obesity and vitamin D3 deficiency and (2) sleeping problems, mainly insomnia. Child and adolescent psychiatrists need to be aware of potential somatic comorbidities and may promote a healthy lifestyle.

Pivotal Response Treatment with and without robot-assistance for children with autism: a randomized controlled trial.

Pivotal response treatment (PRT) is a promising intervention focused on improving social communication skills in children with autism spectrum disorder (ASD). Since robots potentially appeal to children with ASD and may contribute to their motivation for social interaction, this exploratory randomized controlled trial (RCT) was conducted comparing PRT (PRT and robot-assisted PRT) with treatment-as-usual (TAU). Seventy-three children (PRT: n = 25; PRT + robot: n = 25; TAU: n = 23) with ASD, aged 3-8 years were assessed at baseline, after 10 and 20 weeks of intervention, and at 3-month follow-up. There were no significant group differences on parent- and teacher-rated general social-communicative skills and blindly rated global functioning directly after treatment. However, at follow-up largest gains were observed in robot-assisted PRT compared to other groups. These results suggest that robot-assistance may contribute to intervention efficacy for children with ASD when using game scenarios for robot-child interaction during multiple sessions combined with motivational components of PRT. This trial is registered at https://www.trialregister.nl/trial/4487 ; NL4487/NTR4712 (2014-08-01).

Working memory training in young children with ADHD: a randomized placebo-controlled trial.

BACKGROUND: Until now, working memory training has not reached sufficient evidence as effective treatment for ADHD core symptoms in children with ADHD; for young children with ADHD, no studies are available. To this end, a triple-blind, randomized, placebo-controlled study was designed to assess the efficacy of Cogmed Working Memory Training (CWMT) in young children with ADHD. METHODS: Fifty-one children (5-7 years) with a DSM-IV-TR diagnosis of ADHD (without current psychotropic medication) were randomly assigned to the active (adaptive) or placebo (nonadaptive) training condition for 25 sessions during 5 weeks. The compliance criterion (>20 sessions) was met for 47 children. The primary outcome measure concerned the core behavioural symptoms of ADHD, measured with the ADHD Rating Scale IV (ADHD-RS). Secondary outcome measures were neurocognitive functioning, daily executive functioning, and global clinical functioning. The influence of the increase in difficulty level (Index-Improvement) for the treatment group was also analysed. Clinical trial registration information - 'Working Memory Training in Young ADHD Children'; www.clinicaltrials.gov; NCT00819611. RESULTS: A significant improvement in favour of the active condition was found on a verbal working memory task (p = .041; adapted Digit Span WISC-III, backward condition). However, it did not survive correction for multiple testing. No significant treatment effect on any of the primary or other secondary outcome measurements was found. The Index-Improvement significantly contributed to ADHD-RS and the Behavior Rating Inventory of Executive Function, both rated by the teacher, but revealed no significant group difference. CONCLUSIONS: This study failed to find robust evidence for benefits of CMWT over the placebo training on behavioural symptoms, neurocognitive, daily executive, and global clinical functioning in young children with ADHD.

Does EEG-neurofeedback improve neurocognitive functioning in children with attention-deficit/hyperactivity disorder? A systematic review and a double-blind placebo-controlled study.

BACKGROUND: The number of placebo-controlled randomized studies relating to EEG-neurofeedback and its effect on neurocognition in attention-deficient/hyperactivity disorder (ADHD) is limited. For this reason, a double blind, randomized, placebo-controlled study was designed to assess the effects of EEG-neurofeedback on neurocognitive functioning in children with ADHD, and a systematic review on this topic was performed. METHODS: Forty-one children (8-15 years) with a DSM-IV-TR diagnosis of ADHD were randomly allocated to EEG-neurofeedback or placebo-neurofeedback treatment for 30 sessions, twice a week. Children were stratified by age, electrophysiological state of arousal, and medication use. Neurocognitive tests of attention, executive functioning, working memory, and time processing were administered before and after treatment. Researchers, teachers, children and their parents, with the exception of the neurofeedback-therapist, were all blind to treatment assignment. Outcome measures were the changes in neurocognitive performance before and after treatment. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov: NCT00723684. RESULTS: No significant treatment effect on any of the neurocognitive variables was found. A systematic review of the current literature also did not find any systematic beneficial effect of EEG-neurofeedback on neurocognitive functioning. CONCLUSION: Overall, the existing literature and this study fail to support any benefit of neurofeedback on neurocognitive functioning in ADHD, possibly due to small sample sizes and other study limitations.

Eye Movement Desensitization and Reprocessing in adolescents with autism; Efficacy on ASD symptoms and stress.

Introduction: Eye Movement Desensitization and Reprocessing (EMDR) is a well-established and thoroughly researched treatment method for posttraumatic stress symptoms. When patients with an autism spectrum disorder (ASD) are treated with EMDR for their Posttraumatic Stress Disorder (PTSD), they sometimes report a decrease in the core symptoms of ASD. This explorative pre-post-follow up design study is designed to investigate whether EMDR with a focus on daily experienced stress, is effective in reducing ASD symptoms and stress in adolescents with ASD. Methods: Twenty-one adolescents with ASD (age 12 to 19) were treated with ten sessions EMDR, focusing on events of daily experienced stress. Results: No significant decrease of ASD symptoms was found on the total score of the Social Responsiveness Scale (SRS) as reported by caregivers from baseline to end measurement. However, there was a significant decrease on total caregivers SRS score comparing the baseline to the follow-up measurement. On two subscales, Social Awareness and Social Communication, a significant decrease was found from baseline to follow-up. On the subscales Social Motivation and Restricted Interests and Repetitive Behavior, no significant effects were found. On pre- and posttest scores of total ASD symptoms measured by the Autism Diagnostic Observation Schedule (ADOS-2), no significant effects were found. On the contrary, scores on self-reported Perceived Stress Scale (PSS) showed a significant decrease from baseline to follow-up. Also, 52% of adolescents showed a significant improvement of global clinical functioning at endpoint measurement on the Clinical Global Impression Improvement, rated by an independent child psychiatrist. Discussion: In sum, these results of this uncontrolled study suggest a partial effect of EMDR in adolescents with ASD on ASD symptoms, rated by their caregivers. In addition, the results of this study show that EMDR treatment on daily experienced stress significantly reduce perceived stress as reported by the participants, and improves global clinical functioning. The results also suggest a 'sleeper effect', since no significant effects were found between baseline- and post- treatment measurements, but only between baseline- and follow up three months after the treatment. This finding is in line with other studies investigating psychotherapeutic effects in ASD. Implications for clinical practice and suggestions for future research are discussed.

Vitamin D status in children with a psychiatric diagnosis, autism spectrum disorders, or internalizing disorders.

Background and objective: Multiple studies suggest that children with Autism Spectrum Disorders (ASD) have significantly lower vitamin D3 levels than typically developing children. However, whether vitamin D3 deficiency is more common in children with ASD than in children with other psychiatric disorders remains unclear. This study was conducted to explore the prevalence of vitamin D3 in children with a psychiatric diagnosis including children with ASD or with internalizing disorders (mood and anxiety disorders). In addition, this study investigated the potential associations between vitamin D3 and Body Mass Index (BMI). Materials and methods: Clinical data, including BMI and vitamin D3 levels, of 93 children (6-18 years; n = 47; 51% female) with ASD (n = 58) and internalizing disorders (n = 37) were retrospectively analyzed. Results: In the overall sample, the prevalence of vitamin D3 deficiency (<50 nmol/L) was 77.4%. Additionally, 75.9% of the children with ASD and 79.5% with internalizing disorders had vitamin D3 deficiency. BMI was inversely related to vitamin D3 in the total group (p = 0.016). The multiple regression model for the total group significantly predicted vitamin D3 (p = 0.022). Age contributed significantly to the prediction. Stratified for sex and primary diagnosis, multiple regression models showed that for boys with ASD, higher BMI levels were associated with lower vitamin D3 levels (p = 0.031); in boys with internalizing disorders and in girls, no relation was found between BMI and vitamin D3 levels. Conclusion: In this this cross-sectional, explorative study high rates of vitamin D3 deficiency in children with different psychiatric disorders were found. The results showed an inverse relation between BMI and vitamin D3 levels in the total group. Vitamin D3 deficiency was particularly common in boys with ASD and obesity. Lifestyle factors may contribute to the association between high BMI and low vitamin D3 levels in boys with ASD. Vitamin D3 deficiency is common in patients with psychiatric disorders and it is highly recommended to increase clinicians' awareness of this common and remediable risk factor.

Pivotal Response Treatment (PRT) parent group training for young children with autism spectrum disorder: a pilot study.

Pivotal Response Treatment (PRT) is a promising intervention addressing core symptoms of autism spectrum disorder (ASD), with parent involvement as key component. Parent group-delivered PRT may be an effective treatment model, but currently the evidence is limited. Also, little attention has been paid to therapeutic involvement of multiple important contexts (e.g. home, school, community) of the young child. The current study explores a 14-week protocol of PRT parent group training (PRT-PG), complemented with individual parent-child sessions and involvement of teachers and other childcare providers. Children aged 2-6 years old with ASD and their parents (n = 20) were included. Preliminary results showed a significant increase in spontaneous initiations during a semi-structured therapist-child interaction together with widespread gains in clinical global functioning. No significant improvement on parent-rated general social-communication skills was observed. These findings justify further research on parent group delivered PRT models.

Pivotal Response Treatment (PRT) - Parent Group Training for Young Children with Autism Spectrum Disorder: A Qualitative Study on Perspectives of Parents.

Pivotal Response Treatment (PRT) is considered to be an empirically supported parent-mediated treatment for children with autism spectrum disorder (ASD), but research on parental experiences is lacking. This qualitative study examined the perspectives of parents of young children with ASD who participated in a 14-week PRT with parent group training (PRT-PG). Semi-structured interviews (n = 12) were carried out, based on Grounded Theory principles. Results indicated that facilitators and barriers were related to timing and expectations, training setting and characteristics, and participant characteristics. Perceived effects were related to improved child's social-communication skills and well-being, parental insights into their child's needs and own habitual patterns in communication and behavior, and positive changes in family cohesion. The findings indicate that in general parents value PRT-PG as feasible and effective.

Pivotal Response Treatment for School-Aged Children and Adolescents with Autism Spectrum Disorder: A Randomized Controlled Trial.

Pivotal Response Treatment (PRT) is promising for children with Autism Spectrum Disorder (ASD), but more methodologically robust designed studies are needed. In this randomized controlled trial, forty-four children with ASD, aged 9-15 years, were randomly allocated to PRT (n = 22) or treatment-as-usual (TAU; n = 22). Measurements were obtained after 12- and 20-weeks treatment, and 2-month follow-up. PRT resulted in significant greater improvements on parent-rated social-communicative skills after 12 weeks treatment (p = .004, partial η2 = 0.22), compared to TAU. Furthermore, larger gains in PRT compared to TAU were observed on blindly rated global functioning, and parent-rated adaptive socialization skills and attention problems. Implications for clinical practice and suggestions for future research are discussed.

Self-initiations in young children with autism during Pivotal Response Treatment with and without robot assistance.

LAY ABSTRACT: The initiation of social interaction is often defined as a core deficit of autism spectrum disorder. Optimizing these self-initiations is therefore a key component of Pivotal Response Treatment, an established intervention for children with autism spectrum disorder. However, little is known about the development of self-initiations during intervention and whether this development can be facilitated by robot assistance within Pivotal Response Treatment. The aim of this study was to (1) investigate the effect of Pivotal Response Treatment and robot-assisted Pivotal Response Treatment on self-initiations (functional and social) of young children with autism spectrum disorder over the course of intervention and (2) explore the relation between development in self-initiations and additional gains in general social-communicative skills. Forty-four children with autism spectrum disorder (aged 3-8 years) were included in this study. Self-initiations were assessed during parent-child interaction videos of therapy sessions and coded by raters who did not know which treatment (Pivotal Response Treatment or robot-assisted Pivotal Response Treatment) the child received. General social-communicative skills were assessed before start of the treatment, after 10 and 20 weeks of intervention and 3 months after the treatment was finalized. Results showed that self-initiations increased in both treatment groups, with the largest improvements in functional self-initiations in the group that received robot-assisted Pivotal Response Treatment. Increased self-initiations were related to higher parent-rated social awareness 3 months after finalizing the treatment.

Adherence and acceptability of a robot-assisted Pivotal Response Treatment protocol for children with autism spectrum disorder.

The aim of this study is to present a robot-assisted therapy protocol for children with ASD based on the current state-of-the-art in both ASD intervention research and robotics research, and critically evaluate its adherence and acceptability based on child as well as parent ratings. The robot-assisted therapy was designed based on motivational components of Pivotal Response Treatment (PRT), a highly promising and feasible intervention focused at training "pivotal" (key) areas such as motivation for social interaction and self-initiations, with the goal of establishing collateral gains in untargeted areas of functioning and development, affected by autism spectrum disorders. Overall, children (3-8 y) could adhere to the robot-assisted therapy protocol (Mean percentage of treatment adherence 85.5%), showed positive affect ratings after therapy sessions (positive in 86.6% of sessions) and high robot likability scores (high in 79.4% of sessions). Positive likability ratings were mainly given by school-aged children (H(1) = 7.91, p = .005) and related to the movements, speech and game scenarios of the robot. Parent ratings on the added value of the robot were mainly positive (Mean of 84.8 on 0-100 scale), while lower parent ratings were related to inflexibility of robot behaviour.

How the Individual Alpha Peak Frequency Helps Unravel the Neurophysiologic Underpinnings of Behavioral Functioning in Children With Attention-Deficit/Hyperactivity Disorder.

Attention-deficit/hyperactivity disorder (ADHD) has been associated with an elevated resting-state theta/beta power ratio and elevated theta power. However, the potential confounding effect of a low individual alpha peak frequency (IAPF) on the theta-power estimate has often been disregarded when studying the relationship between ADHD and the theta/beta power ratio or theta power alone. The aim of the present study was to assess whether the theta/beta power ratio and relative theta power are correlated with behavioral functioning in children with ADHD, as expected from previous studies. Subsequently, the influence of IAPF and the amount of supposed overlap between the individually determined alpha-band and the fixed theta-band were studied. For 38 children (aged 8-15 years), electroencephalographic (EEG) and investigator-scored ADHD Rating Scale IV data were available. Additional neurocognitive data were available for 32 children. As expected, the theta/beta power ratio and theta were positively related to the ADHD core symptoms. This relationship strengthened when controlling for IAPF, although correlations did not significantly differ from one another. Eight of 38 children (21%) showed a supposed overlap between their individually determined alpha band and the theta band. Neurocognitive performance did not show any relationship with the theta/beta power ratio or theta. The results of this study confirm that the theta/beta power ratio and theta power are indeed correlated with behavioral symptoms in children with ADHD and underscore the relevance of taking the IAPF into account.

What future research should bring to help resolving the debate about the efficacy of EEG-neurofeedback in children with ADHD.

In recent years a rising amount of randomized controlled trials, reviews, and meta-analyses relating to the efficacy of electroencephalographic-neurofeedback (EEG-NF) in children with attention-deficit/hyperactivity disorder (ADHD) have been published. Although clinical reports and open treatment studies suggest EEG-NF to be effective, double blind placebo-controlled studies as well as a rigorous meta-analysis failed to find support for the efficacy of EEG-NF. Since absence of evidence does not equate with evidence of absence, we will outline how future research might overcome the present methodological limitations. To provide conclusive evidence for the presence or absence of the efficacy of EEG-NF in the treatment of ADHD, there is a need to set up a well-designed study that ensures optimal implementation and embedding of the training, and possibly incorporates different forms of neurofeedback.

A randomized placebo-controlled trial of electroencephalographic (EEG) neurofeedback in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: A double-blind, randomized, placebo-controlled study was designed to assess the efficacy and safety of electroencephalographic (EEG) neurofeedback in children with attention-deficit/hyperactivity disorder (ADHD). The study started in August 2008 and ended in July 2012 and was conducted at Karakter Child and Adolescent Psychiatry University Centre in Nijmegen, The Netherlands. METHOD: Forty-one children (aged 8-15 years) with a DSM-IV-TR diagnosis of ADHD were randomly assigned to treatment with either EEG neurofeedback (n = 22) or placebo neurofeedback (n = 19) for 30 sessions, given as 2 sessions per week. The children were stratified by age, electrophysiologic state of arousal, and medication use. Everyone involved in the study, except the neurofeedback therapist and the principal investigator, was blinded to treatment assignment. The primary outcome was severity of ADHD symptoms on the ADHD Rating Scale IV, scored at baseline, during treatment, and at study end. Clinical improvement as measured by the Clinical Global Impressions-Improvement scale (CGI-I) was a secondary outcome. RESULTS: While total ADHD symptoms improved over time in both groups (F1,39 = 26.56, P < .001), there was no significant treatment effect, ie, group × time interaction (F1,39 = 0.36, P = .554); the same was true for clinical improvement as measured by the CGI-I (P = .092). No clinically relevant side effects were observed. Among the children and their parents, guessing treatment assignment was not better than chance level (P = .224 for children, P = .643 for parents). CONCLUSION: EEG neurofeedback was not superior to placebo neurofeedback in improving ADHD symptoms in children with ADHD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00723684.

The increase in theta/beta ratio on resting-state EEG in boys with attention-deficit/hyperactivity disorder is mediated by slow alpha peak frequency.

Attention-deficit/hyperactivity disorder (ADHD) was found to be characterized by a deviant pattern of electrocortical activity during resting state, particularly increased theta and decreased beta activity. The first objective of the present study is to confirm whether individuals with slow alpha peak frequency contribute to the finding of increased theta activity in ADHD. The second objective is to explore the relation between resting-state brain oscillations and specific cognitive functions. From 49 boys with ADHD and 49 healthy control boys, resting-state EEG during eyes open and eyes closed was recorded, and a variety of cognitive tasks were administered. Theta and beta power and theta/beta ratio were calculated using both fixed frequency bands and individualized frequency bands. As expected, theta/beta ratio, calculated using fixed frequency bands, was significantly higher in ADHD children than control children. However, this group effect was not significant when theta/beta ratio was assessed using individualized frequency bands. No consistent relation was found between resting-state brain oscillations and cognition. The present results suggest that previous findings of increased theta/beta ratio in ADHD may reflect individuals with slow alpha peak frequencies in addition to individuals with true increased theta activity. Therefore, the often reported theta/beta ratio in ADHD can be considered a non-specific measure combining several distinct neurophysiological subgroups such as frontal theta and slowed alpha peak frequencies. Future research should elucidate the functional role of resting-state brain oscillations by investigating neurophysiological subgroups, which may have a clearer relation to cognitive functions than single frequency bands.

Relation between resting EEG to cognitive performance and clinical symptoms in adults with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) in children is characterized by elevated levels of slow wave activity and reduced fast wave activity in resting-state electroencephalogram (EEG). In adults with ADHD, resting-state EEG findings are scarce and inconsistent. The present study examined whether the disparate findings are due EEG recording conditions (i.e., eyes-open vs. eyes-closed). A second goal of the current study was to assess relations between EEG spectral indices to performance measures obtained using a stop-signal task, and to behavioral ADHD symptoms. The present study included 24 adults with ADHD and 24 control adults. The EEG results showed a greater reduction in alpha power from eyes-closed to eyes-open (i.e., alpha attenuation) in ADHD compared to controls. In addition, theta/beta ratio was negatively correlated to the speed of responding to choice stimuli. These findings were interpreted vis-à-vis a biophysical model assuming that the hypo-arousal in ADHD is due to an overdrive of the nucleus coeruleus resulting in inhibitory activity of the thalamic reticular nucleus.