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Vitamin D may play an important role in the etiology of Autism Spectrum Disorders (ASD). Vitamin D is regarded as a neuroactive steroid affecting brain development and function. It plays an essential role in myelination, which is important for connectivity in the brain. Studies have shown that decreased vitamin D levels in patients, decreased maternal vitamin D levels during pregnancy, and decreased exposure to solar UVB might increase the risk for ASD. In addition, autism symptoms and global functioning may improve after vitamin D supplementation. Here, we sought to aggregate information from previous publications on vitamin D levels and ASD, in order to achieve a higher statistical power and thereby to determine the validity of vitamin D deficiency as a risk factor for ASD. For this meta-analysis, 11 studies met the inclusion and exclusion criteria, accounting for a total of 870 ASD patients and 782 healthy controls. Levels of serum 25(OH) D in participants with ASD were significantly lower than controls, suggesting that lower vitamin D level might be a risk factor for ASD.

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.

Background For people with autism spectrum disorder (ASD), daily life can be highly stressful with many unpredictable events that can evoke emotion dysregulation (ED): a strong difficulty with appropriately negative affect regulation. For some of the patients with ASD, treatment as usual does not prove to be effective for ED. They may be at risk of life-long impairment, development of other disorders and loss of motivation for most regular forms of therapy. A highly promising method that may prove effective for therapy-resistant individuals with ASD is Psychotherapy incorporating horses (PIH). PIH uses the interactions of the horse and the patients on the ground and does not include horseriding. While often met with prejudgment and scepticism, reports from parents and therapists as well as a recent systematic review suggest that PIH may have beneficial effects on youths with ASD. Therefore, we examine clinical outcomes both in the short and in the long terms of PIH offered to adolescents with ASD and severe ED despite regular therapy. Methods A total of 35 adolescents aged 11–18 years with ASD will receive PIH during 15 sessions once a week with randomization to five different groups differentiating in baseline phase from 2 to 6 weeks. PIH uses horses to promote social awareness and self-awareness as well as relationship management and self-management. The primary outcome is the response to treatment on the Emotion Dysregulation Index (EDI). The secondary outcome measures include ASD symptom severity, quality of life, self-esteem, global and family functioning, and goal attainment. Assessments take place at the baseline (T0), at the end of baseline phase A (T1), after completion of intervention phase B (T2), after the end of post-measurement phase C (T3) and after one year (T4). Qualitative interviews of participants, parents and therapists will be held to reveal facilitators and barriers of PIH and a cost-effectiveness study will be performed. Discussion This study aims at contributing to clinical practice for adolescents with ASD and persistent emotion regulation problems despite 1.5 year of treatment by offering Psychotherapy incorporating horses in a study with series of randomised, baseline controlled n-of-1 trials. Trial registration www.ClinicalTrials.gov NCT05200351, December 10th 2021.

Background A lifestyle including poor diet, physical inactivity, excessive gaming and inadequate sleep hygiene is frequently seen among Dutch children. These lifestyle behaviors can cause long-term health problems later in life. Unhealthy lifestyle and poor physical health are even more prevalent among children with mental illness (MI) such as autism, attention-deficit/hyperactivity disorder, depression, and anxiety. However, research on lifestyle interventions among children with MI is lacking. As a result, there are currently no guidelines, or treatment programs where children with MI and poor lifestyle can receive effective support. To address these issues and to provide insight into the effectiveness of lifestyle interventions in children with MI and their families, the Movementss study was designed. This paper describes the rationale, study design, and methods of an ongoing randomized controlled trial (RCT) comparing the short-term (12 weeks) and long-term (1 year) effects of a lifestyle intervention with care as usual (CAU) in children with MI and an unhealthy lifestyle. Methods A total of 80 children (6–12 years) with MI according to DSM-V and an unhealthy lifestyle are randomized to the lifestyle intervention group or CAU at a specialized child and adolescent mental hospital. The primary outcome measure is quality of life measured with the KIDSCREEN. Secondary outcomes include emotional and behavior symptoms, lifestyle parameters regarding diet, physical activity, sleep, and screen time, cognitive assessment (intelligence and executive functions), physical measurements (e.g., BMI), parenting styles, and family functioning, prior beliefs, adherence, satisfaction, and cost-effectiveness. Assessments will take place at the start of the study (T0), after 12 weeks (T1), six months (T2), and 12 months of baseline (T3) to measure long-term effects. Discussion This RCT will likely contribute to the currently lacking knowledge on lifestyle interventions in children with MI. Trial registration trialsearch.who.int/ NL9822. Registered at November 2 nd , 2021.

Background There is ongoing debate regarding the treatment of severe and multiple traumatized children and adolescents with post-traumatic stress disorder (PTSD). Many clinicians favor a phase-based treatment approach (i.e., a stabilization phase prior to trauma-focused therapy) over immediate trauma-focused psychological treatment, despite the lack of scientific evidence. Research on the effects of different treatment approaches is needed for children and adolescents with (symptoms of complex) PTSD resulting from repeated sexual and/or physical abuse during childhood. Objective This paper describes the rationale, study design, and methods of the MARS-study, a two-arm randomized controlled trial (RCT) that aims to compare the results of phase-based treatment with those of immediate trauma-focused treatment and determine whether immediate trauma-focused treatment is not worse than phase-based treatment in reducing PTSD symptoms. Methods Participants are individuals between 12 and 18 years who meet the diagnostic criteria for PTSD due to repeated sexual abuse, physical abuse, or domestic violence during childhood. Participants will be blindly allocated to either the phase-based or immediate trauma-focused treatment condition. In the phase-based treatment condition, participants receive 12 sessions of the Dutch version of Skill Training in Affective and Interpersonal Regulation (STAIR-A), followed by 12 sessions of EMDR therapy. In the immediate trauma-focused condition, the participants receive 12 sessions of EMDR therapy. The two groups are compared for several outcome variables before treatment, mid-treatment (only in the phase-based treatment condition), after 12 trauma-focused treatment sessions (post-treatment), and six months post-treatment (follow-up). The main parameter is the presence and severity of PTSD symptoms (Clinician-Administered PTSD Scale for Children and Adolescents, CAPS-CA). The secondary outcome variables are the severity of complex PTSD symptoms (Interpersonal Problems as measured by the Experiences in Close Relationship-Revised, ECR-RC; Emotion Regulation as measured by the Difficulties in Emotion Regulation Scale, DERS; Self Esteem as measured by the Rosenberg Self Esteem Scale, RSES), changes in anxiety and mood symptoms (Revised Anxiety and Depression Scale; RCADS), changes in posttraumatic cognitions (Child Posttraumatic Cognitions Inventory, CPTCI), changes in general psychopathology symptoms (Child Behavior Checklist, CBCL), and Quality of Life (Youth Outcome Questionnaire, Y-OQ-30). Furthermore, parental stress (Opvoedingsvragenlijst, OBVL) and patient-therapist relationship (Feedback Informed Treatment, FIT) will be measured, whereas PTSD symptoms will be monitored in each session during both treatment conditions (Children’s Revised Impact of Event Scale, CRIES-13). Discussion Treating (symptoms of complex) PTSD in children and adolescents with a history of repeated sexual and/or physical abuse during childhood is of great importance. However, there is a lack of consensus among trauma experts regarding the optimal treatment approach. The results of the current study may have important implications for selecting effective treatment options for clinicians working with children and adolescents who experience the effects of exposure to multiple interpersonal traumatic events during childhood. Trial registrations The study was registered on the “National Trial Register (NTR)” with the number NTR7024. This registry was obtained from the International Clinical Trial Registry Platform (ICTRP) and can be accessed through the ICTRP Search Portal ( https://trialsearch.who.int/ ).

Introduction Parents of children with a neurodevelopmental disorder (NDD) experience more stress than parents of typically developing children. In a cocreation process with experts and parents, a low-threshold application that uses exercises based on the principles of positive psychology and mindfulness was developed. This application, called “Adappt,” aims at enhancing the ability to adapt of the parents and caregivers of children with NDDs and at supporting their mental health. This protocol describes the evaluation study of the effectiveness of Adappt, its core working mechanisms and user experiences. Method A pragmatic international multicenter randomized controlled trial will compare the effectiveness of Adappt with a (delayed) waitlist control condition. At least 212 parents or primary caregivers of children younger than 18 years diagnosed with or suspected of a NDD will be randomly assigned to the intervention or waitlist control condition. Participants are excluded if they have severe anxiety or depression levels or are in treatment for mental health issues. Measures will be collected online at baseline, post-intervention (1 month after baseline), and 4 and 7 months after baseline. The primary outcome is the improvement in generic sense of ability to adapt as measured with the Generic Sense of Ability to Adapt Scale (GSAAS; (Front Psychol 14:985408, 2023)) at 4-month follow-up. Secondary outcomes are mental well-being, (parental) distress, and client satisfaction with “Adappt.” Discussion Results of this study will contribute to knowledge on the effectiveness of a low-threshold application for parents of children with a NDD in multiple countries. If the application is found to be effective in improving mental health, recommendations will be made for implementation in health care. Trial registration This study is registered on clinicaltrials.gov (NCT06248762) on February 8, 2024, and the Open Science Framework ( https://osf.io/5znqv ).

Somatic disorders occur more often in adult psychiatric patients than in the general adult population. However, in child and adolescent psychiatry this association is unclear, mainly due to a lack of integration of existing data. To address this issue, we here present a systematic review on medical comorbidity in the two major developmental disorders autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) and formulate clinical recommendations. The literature was searched using the PubMed and PsycINFO databases (2000–1 May 2016) with the keywords “[((child and adolescent) AND (Autism OR Attention Deficit Hyperactivity Disorder* OR ADHD)) AND (“Cardiovascular Diseases” [Mesh] OR “Endocrine System Diseases” [Mesh] OR “Immune System Diseases” [Mesh] OR “Neurobehavioral Manifestations” [Mesh] OR “Gastrointestinal Disorders” [Mesh] OR Somatic OR Autoimmune disease OR Nervous system disease OR Infection OR Infectious disease)]. Two raters independently assessed the quality of the eligible studies. The initial search identified 5278 articles. Based on inclusion and exclusion criteria 104 papers were selected and subsequently subjected to a quality control. This quality was assessed according to a standardized and validated set of criteria and yielded 29 studies for inclusion. This thorough literature search provides an overview of relevant articles on medical comorbidity in ADHD and/or ASD, and shows that medical disorders in these children and adolescents appear to be widespread. Those who work with children with ASD and/or ADHD should be well aware of this and actively promote routine medical assessment. Additionally, case–control studies and population-based studies are needed to provide reliable prevalence estimates. Future studies should furthermore focus on a broader evaluation of medical disorders in children and adolescents with ADHD and/or ASD to improve treatment algorithm in this vulnerable group.

The systematic use of feedback from patients on treatment progress and treatment satisfaction is a promising method to increase treatment effectiveness. The extent to which this also applies to the treatment of children with severe psychiatric problems is not clear. We conducted a Randomized Controlled Trial (RCT) to study the effect of adding Feedback Informed Treatment (FIT) to care as usual in a child psychiatric sample. Quality of Life (QoL) was used as the primary outcome measure and symptom severity as the second. Fifty-one therapists from eight Autism Care Teams in a multi-center facility for Child and Adolescent Psychiatry (Karakter) participated and were cluster randomized to the FIT condition (n = 4 teams) or the Care as Usual (CAU) condition (n = 4 teams). Children aged 6–18 years, mainly with an Autism Spectrum Disorder (ASD) and treated in one of the Autism Care Teams were allocated to the FIT condition (n = 86) or the CAU condition (n = 80). Results indicated that adding FIT leads to an increased QoL [F (2,165) = 3.16, p = 0.045]. No additional effects were observed for symptom severity decrease [F (2,158) = 0.19, p = 0.825]. No interaction with time was found for QoL nor symptom severity. Adding FIT in a child psychiatric setting may increase QoL, but does not appear to decrease symptom severity as compared with CAU. It is suggested that FIT positively changes parents’ expectations. Results should be replicated in other child psychiatric samples and with an extended theoretical model.

Background Adolescents with acute psychiatric disorders are typically treated with long-term clinical admission. However, long term admission may be associated with a variety of negative outcomes. This pilot study presents a new model of care, that is, the combined application of intensive home treatment and the possibility of short term stay at a psychiatric high & intensive care. Methods In total 112 referred adolescents with mixed diagnoses participated in this longitudinal observational design. Clinical outcome was measured by the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) which measures the severity of multiple mental health problems. The HoNOSCA was clinician-rated at intake, after two months and after four months at discharge. Change in HoNOSCA total score was analysed with paired t-tests. Outcome moderators were gender, age, primary diagnosis, clinical admission, home treatment-time, medication and additional therapies. Follow up data were completed for 62 patients after two months and for 53 after four months. Results Participants aged between 11 and 18 years ( M  = 14.8 years, SD = 0.3; 52% female). Mean HoNOSCA total score at intake was 18.8 (SD = 5.2), after two months 13.0 (SD = 5.0); after four months resulting in a score of 9.3 (SD = 5.2). None of the moderators tested showed a significant effect on HoNOSCA scores. However, a control group could not be used because of the severe psychopathology and high risk for suicidality and the lack of an effective treatment intervention for a comparable study group. Conclusion With a symptom decrease of over 50% within four months as measured by the HoNOSCA, including less risk for hospitalization, this new model appears promising and of clinical relevance. Nevertheless, further research regarding stability of treatment outcome is warranted and evaluation of long-term effects of this model in follow-up studies is needed.

The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD), and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD.