Alternative treatments for autism : prevalence and predictors

Autism is a heterogeneous neurodevelopmental disorder for which a large variety of treatments are offered, including alternative treatments. Vaccine-related treatments (treatments falsely claiming to cure autism by addressing its alleged cause: routine childhood vaccines such as MMR) continue to be offered worldwide, despite widespread evidence against the effectiveness and even possible harm related to these treatments. We analysed the use of alternative treatments in two studies: a survey study (N = 1989, autistic adults and parents/legal representatives of individuals with autism) and a clinical care study (N = 4520, patient files from a treatment center for autism). Both studies found a relatively high frequency of alternative treatments (23.0–30.7%) – in children even 46.4% -, mostly in combination with mainstream treatment. In the survey study vaccine-related treatments were used by 3.2% of all individuals with autism (and 6.7% of autistic children), and alternative treatment use was predicted by co-occurring diagnoses, younger age of diagnosis and mainstream treatment use. In the clinical care study, patients who had received treatment from a homeo-/osteopath more often had highly educated parents from Dutch/Western background and were more often enrolled in special education. Alternative treatments are widely used and should be included in treatment guidelines. Parents, practitioners and individuals with autism should be both advised and warned about the benefits and risks of these treatments. More research is needed to better understand the choice for and effect of alternative treatments for autism, and mainstream care should be improved

Treatment of multiple traumatized adolescents by enhancing regulation skills and reducing trauma related symptoms: rationale, study design, and methods of randomized controlled trial (the Mars-study)

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/ )

The short and long-term effects of a lifestyle intervention in children with mental illnesses: a randomized controlled trial (Movementss study)

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

Social responsiveness scale-aided analysis of the clinical impact of copy number variations in autism

Recent array-based studies have detected a wealth of copy number variations (CNVs) in patients with autism spectrum disorders (ASD). Since CNVs also occur in healthy individuals, their contributions to the patient’s phenotype remain largely unclear. In a cohort of children with symptoms of ASD, diagnosis of the index patient using ADOS-G and ADI-R was performed, and the Social Responsiveness Scale (SRS) was administered to the index patients, both parents, and all available siblings. CNVs were identified using SNP arrays and confirmed by FISH or array CGH. To evaluate the clinical significance of CNVs, we analyzed three families with multiple affected children (multiplex) and six families with a single affected child (simplex) in which at least one child carried a CNV with a brain-transcribed gene. CNVs containing genes that participate in pathways previously implicated in ASD, such as the phosphoinositol signaling pathway (PIK3CA, GIRDIN), contactin-based networks of cell communication (CNTN6), and microcephalin (MCPH1) were found not to co-segregate with ASD phenotypes. In one family, a loss of CNTN5 co-segregated with disease. This indicates that most CNVs may by themselves not be sufficient to cause ASD, but still may contribute to the phenotype by additive or epistatic interactions with inherited (transmitted) mutations or non-genetic factors. Our study extends the scope of genome-wide CNV profiling beyond de novo CNVs in sporadic patients and may aid in uncovering missing heritability in genome-wide screening studies of complex psychiatric disorders

Gene-Network Analysis Identifies Susceptibility Genes Related to Glycobiology in Autism

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

DRD3 gene and striatum in autism spectrum disorder

A single-nucleotide polymorphism (SNP) of the DRD3 gene (rs167771) was recently associated with autism spectrum disorders (ASD). Different polymorphisms of rs167771 corresponded to varying degrees of stereotyped behaviour. As DRD3 receptors are relatively overexpressed in the striatum, we investigated whether striatal volume was related to these polymorphisms in autism. We assessed volumes of caudate nucleus and putamen in 86 participants with ASD (mean age 15.3 years). MANCOVA showed an association between alleles of the rs167771 SNP and the volume of striatal structures. Furthermore, greater caudate nucleus volume correlated with stereotyped behaviour. These findings support a relationship between DRD3 gene SNPs, striatum and stereotyped behaviour in ASD

Stop and Change : Inhibition and Flexibility Skills Are Related to Repetitive Behavior in Children and Young Adults with Autism Spectrum Disorders

Cognitive control dysfunctions, like inhibitory and attentional flexibility deficits are assumed to underlie repetitive behavior in individuals with autism spectrum disorders (ASD). In the present study, prepotent response inhibition and attentional flexibility were examined in 64 high-functioning individuals with ASD and 53 control participants. Performance under different task conditions were tested both in response to visual and auditory information, and requiring a motor or verbal response. Individuals with ASD showed significant more control dysfunctions than typically developing participants on the auditory computer task. Inhibitory control and attentional flexibility predicted RRB in everyday life. Specifically, response inhibition in reaction to visual information and task switching in reaction to auditory information predicted motor and sensory stereotyped behavior