Protocol for the development and testing of the schiZotypy Autism Questionnaire (ZAQ) in adults: a new screening tool to discriminate autism spectrum disorder from schizotypal disorder.

BACKGROUND: Autism spectrum disorder (ASD) and schizotypal disorder (SD) both have a heterogenous presentation, with significant overlaps in symptoms and behaviour. Due to elevated recognition and knowledge of ASD worldwide, there is a growing rate of referrals from primary health professionals to specialised units. At all levels of assessment, the differential diagnostic considerations between ASD and SD exert major challenges for clinicians. Although several validated screening questionnaires exist for ASD and SD, none have differential diagnostic properties. Accordingly, in this study, we aim to develop a new screening questionnaire, the schiZotypy Autism Questionnaire (ZAQ), which provides a combined screening for both conditions, while also indicating the relative likelihood of each. METHODS: We aim to test 200 autistic patients and 100 schizotypy patients recruited from specialised psychiatric clinics and 200 controls from the general population (Phase 1). The results from ZAQ will be compared to the clinical diagnoses from interdisciplinary teams at specialised psychiatric clinics. After this initial testing phase, the ZAQ will be validated in an independent sample (Phase 2). CONCLUSIONS: The aim of the study is to investigate the discriminative properties (ASD vs. SD), diagnostic accuracy, and validity of the schiZotypy Autism Questionnaire (ZAQ). FUNDING: Funding was provided by Psychiatric Centre Glostrup, Copenhagen Denmark, Sofiefonden (Grant number: FID4107425), Trygfonden (Grant number:153588), Takeda Pharma. TRIAL REGISTRATION: Clinical Trials, NCT05213286, Registered 28 January 2022, clinicaltrials.gov/ct2/show/NCT05213286?cond = RAADS&draw = 2&rank = 1.

The association between home learning during COVID-19 lockdowns and subsequent school attendance among children with neurodevelopmental conditions.

BACKGROUND: Children with neurodevelopmental conditions have high levels of school absence. During the COVID-19 pandemic, schools closed for many students. The relationship between home learning during school closures and subsequent school attendance requires attention to better understand the impact of pandemic education policy decisions on this population. This study aims to investigate the association between home learning, hybrid learning and school learning during school closures (in January-March 2021) with subsequent school attendance (in May 2021) in children with neurodevelopmental conditions. METHODS: An online survey was completed by 809 parents/carers of 5- to 15-year-old autistic children and/or children with intellectual disability. Regression models examined the association of learning location during school closures with subsequent school absence (i.e., total days missed, persistent absence and school refusal). RESULTS: Children who were learning from home during school closures later missed 4.6 days of a possible 19. Children in hybrid and school learning missed 2.4 and 1.6 school days, respectively. The rates of school absence and persistent absence were significantly higher in the home learning group even after adjusting for confounders. Learning location was not associated with subsequent school refusal. CONCLUSIONS: Policies for school closures and learning from home during public health emergencies may exacerbate school attendance problems in this group of vulnerable children.

Effects of physical activity on behaviour and emotional problems, mental health and psychosocial well-being in children and adolescents with intellectual disability: A systematic review.

BACKGROUND: This systematic review aimed to explore the effects of sport and physical activity on behaviour and emotional problems, mental health and psychosocial well-being of children and adolescents with intellectual disability. METHOD: Five databases were searched systematically (ERIC, MEDLINE, PsycINFO, SportDISCUS and SCOPUS), up to 28 February 2021. Thirty-two studies met criteria for inclusion. RESULTS: Studies in this review included case studies (n = 15), treatment trials (n = 14), cross sectional studies (n = 2) and a cohort study (n = 1). Evidence was positive, though high risk of bias in treatment trials (7 of 14 rated high) meant generalisability of results was limited. CONCLUSIONS: The available evidence suggests a positive relationship between physical activity and improved behaviour and emotional problems, mental health and psychosocial well-being; however, more robust randomised controlled trials are required to confirm this.

Community participation in adults with autism: A systematic review.

BACKGROUND: This systematic review aimed to explore how adults with autism participate in the community, the impact of community participation on quality of life and mental health, and factors that support and hinder participation. METHOD: A systematic review was conducted including studies published from inception to 17 January 2021. RESULTS: Sixty-three reports were included, reporting on 58 studies. Solitary activities, organised group activities, community activities, religious groups and online social participation were identified. The relationship between community participation and quality of life was examined. Barriers and facilitators to increased community participation were identified. Most studies had a moderate to high risk of bias. CONCLUSION: Adults with autism participate in a range of independent and community activities. The impact of community participation on quality of life and mental health warrants further exploration. Future studies should find effective ways of supporting adults with autism to participate in the community.

Attachment and child behaviour and emotional problems in autism spectrum disorder with intellectual disability.

BACKGROUND: Behaviour and emotional problems are highly prevalent in children with autism spectrum disorder (ASD). In typically developing children, attachment quality acts as a risk/protective factor for behavioural outcomes and adjustment, warranting investigation in children with ASD. METHOD: We investigated the relationship between attachment and child behaviour and emotional problems in children with ASD and comorbid intellectual disability. Data were collected from parent-child dyads where children were diagnosed with ASD and ID (n = 28) or other developmental disabilities (n = 20). RESULTS: Children with ASD had higher levels of behaviour and emotional problems and more attachment difficulties than children with other developmental disabilities. Poorer attachment quality contributed uniquely to the variance in child behaviour and emotional problems. CONCLUSIONS: Interventions targeting behaviour and emotional problems in children with ASD may benefit from an attachment model which addresses the child's difficulty in using caregivers as a coregulatory agent of emotions.

Assessment of Placental Cortisol Pathway Gene Expression in Term Pregnant Women with Anxiety.

INTRODUCTION: The aim of this study was to expand on this field of work by examining, within a cohort of pregnant women with diagnosed clinical anxiety, the mRNA expression of a panel of genes associated with the cortisol pathway and comparing them to controls. METHODS: Placental samples were obtained from 24 pregnant women, 12 with a diagnosed anxiety disorder and 12 with no psychiatric history, within 30 min of delivery. Differential expression analysis of 85 genes known to be involved in glucocorticoid synthesis, metabolism or signalling was conducted for the: (1) full sample, (2) those at term without labour (5 cases, 7 controls) and (3) those at term with labour (7 cases, 5 controls). Correlation analyses between gene expression and measures of anxiety and depressive symptom severity were also conducted. RESULTS: No robust difference in placental gene expression between pregnant women with and without anxiety disorder was found nor did we detect robust differences by labour status. However, correlational analyses putatively showed a decrease in PER1 expression was associated with an increase in anxiety symptom severity, explaining up to 32% of the variance in anxiety symptom severity. DISCUSSION: Overall, the strongest correlation was found between a decrease in placental PER1 expression and increased anxiety scores. Labour status was found to have a profound effect on mRNA expression. The placental samples obtained from women following labour produced greater numbers of significant differences in mRNA species expression suggesting that in long-standing anxiety the placenta may respond differently under conditions of chronic stress.

Moderating Effect of Motor Proficiency on the Relationship Between ADHD Symptoms and Sleep Problems in Children With Attention Deficit Hyperactivity Disorder-Combined Type.

OBJECTIVES/BACKGROUND: A high proportion of children with Attention Deficit Hyperactivity Disorder- Combined type (ADHD-CT) experience sleep and motor problems. This study investigated (a) whether motor proficiency moderated the relationship between ADHD symptoms and sleep problems in children with and without ADHD-CT and (b) whether this moderation differed as a function of ADHD diagnosis. PARTICIPANTS: A sample of 70 primary school male children between 8-15 years were recruited; children with ADHD-CT (n = 38; mean age 10 years, 2 months [SD = 1 year, 6 months]) and a typically developing (TD) (n = 32; mean age 9 years, 6 months [SD = 1 year, 5 months]) group. METHODS: Motor proficiency was measured using the Movement Assessment Battery for Children-2nd Edition (MABC-2), ADHD symptoms were measured using the Conners' Parent Rating Scale (CPRS) and parent reported sleep problems were measured using the Children's Sleep Habits Questionnaire (CSHQ). RESULTS: Children who reported higher ADHD symptoms and lower motor proficiency scores reported more sleep problems. The moderation effect only held in children with a diagnosis of ADHD-CT and not in the typically developing group. CONCLUSIONS: These findings indicate that children who experience greater severity of ADHD symptoms who also have lower motor proficiency may be at increased risk of experiencing sleep problems. These findings also illustrate the importance of considering motor proficiency when exploring risk factors for sleep problems in children with ADHD-CT as well as sleep interventions.

Attentional set-shifting and social abilities in children with schizotypal and comorbid autism spectrum disorders.

OBJECTIVE: While diagnostically independent, autism and schizotypal disorders can co-occur. Their concurrent impact on outcomes and phenotypes has not been investigated. We investigated the impact of comorbid autism and schizotypal disorders in children on executive functioning and socio-pragmatic skills - core features of both disorders. METHOD: Executive functioning (assessed with the Cambridge Neuropsychological Test Automated Battery) and socio-pragmatic skills (assessed using the Melbourne Assessment of Schizotypy in Kids) were investigated in a total of 67 (6-12 year old) children with autism ( n = 15; M/F = 10/5), schizotypal disorder ( n = 8; M/F = 5/3) and comorbid autism and schizotypal disorder ( n = 12; M/F = 5/7) and typically developing children ( n = 32; M/F = 17/15). RESULTS: Both the autism and schizotypal disorder groups performed more poorly than the typically developing group on socio-pragmatic skills and overall performance (i.e. number of stages completed) of the intra-/extra-dimensional set-shifting task (all ps < 0.001). Clear distinctions between the autism and schizotypal groups were present in the intra-/extra-dimensional task relative to the typically developing group - the autism group had difficulties with extra-dimensional shifts ( p < 0.001), and the schizotypal disorder group with intra-dimensional shifts ( p = 0.08). Interestingly, the overall performance of the comorbid group on the intra-/extra-dimensional task was not significantly different from the typically developing group, and they were superior to both the autism ( p = 0.019) and schizotypal disorder ( p = 0.042) groups on socio-pragmatic skills. CONCLUSION: The phenotypical overlap between autism and schizotypal disorders may be precipitated by different cognitive styles and/or mechanisms associated with attention and information processing. We propose that sustaining and switching attention represent two poles of irregularities across the autism and schizotypal spectra, which appear to converge in a compensatory manner in the comorbid group. Our findings highlight the importance of investigating children with a dual diagnosis of autism and schizotypal disorders, and raise intriguing questions about possible mechanisms to explain the attenuated impairment observed in the group of children with comorbid autism and schizotpyal disorders.

The Cranky Thermometers: Visual analogue scales measuring irritability in youth.

This study assessed the psychometric properties of two visual analogue scales of irritability, known as the Cranky Thermometers (CT), in both an Australian community secondary-school sample (N = 164) and a sample of adolescents with a depressive disorder (N = 127). The first scale Cranky Now measures current irritability, and the second, Cranky Two Weeks, measures peak irritability within the last two weeks. CT scores were significantly higher in adolescents with major depressive disorder than in the school sample and showed improvement following treatment for depression. Positive associations were found between CT and irritability scores as determined by Kiddie Schedule for Affective Disorders and Schizophrenia (not irritable, sub-threshold, threshold irritability) and Affective Reactivity Index scores. Results suggest that the CTs are rapidly administered, have promising psychometric properties and demonstrate utility in measuring irritability in clinical and community settings.

A randomised, double blind, placebo-controlled trial of a fixed dose of N-acetyl cysteine in children with autistic disorder.

OBJECTIVE: Oxidative stress, inflammation and heavy metals have been implicated in the aetiology of autistic disorder. N-acetyl cysteine has been shown to modulate these pathways, providing a rationale to trial N-acetyl cysteine for autistic disorder. There are now two published pilot studies suggesting efficacy, particularly in symptoms of irritability. This study aimed to explore if N-acetyl cysteine is a useful treatment for autistic disorder. METHOD: This was a placebo-controlled, randomised clinical trial of 500 mg/day oral N-acetyl cysteine over 6 months, in addition to treatment as usual, in children with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of autistic disorder. The study was conducted in Victoria, Australia. The primary outcome measures were the Social Responsiveness Scale, Children's Communication Checklist-Second Edition and the Repetitive Behavior Scale-Revised. Additionally, demographic data, the parent-completed Vineland Adaptive Behavior Scales, Social Communication Questionnaire and clinician-administered Autism Diagnostic Observation Schedule were completed. RESULTS: A total of 102 children were randomised into the study, and 98 (79 male, 19 female; age range: 3.1-9.9 years) attended the baseline appointment with their parent/guardian, forming the Intention to Treat sample. There were no differences between N-acetyl cysteine and placebo-treated groups on any of the outcome measures for either primary or secondary endpoints. There was no significant difference in the number and severity of adverse events between groups. CONCLUSION: This study failed to demonstrate any benefit of adjunctive N-acetyl cysteine in treating autistic disorder. While this may reflect a true null result, methodological issues particularly the lower dose utilised in this study may be confounders.

Augmenting Cognitive Behavior Therapy for School Refusal with Fluoxetine: A Randomized Controlled Trial.

This study investigates whether the augmentation of cognitive behavior therapy (CBT) with fluoxetine improves outcomes in anxious school refusing adolescents (11-16.5 years). Sixty-two participants were randomly allocated to CBT alone, CBT + fluoxetine or CBT + placebo. All treatments were well tolerated; with one suicide-attempt in the CBT + placebo group. All groups improved significantly on primary (school attendance) and secondary outcome measures (anxiety, depression, self-efficacy and clinician-rated global functioning); with gains largely maintained at 6-months and 1-year. Few participants were anxiety disorder free after acute treatment. During the follow-up period anxiety and depressive disorders continued to decline whilst school attendance remained stable, at around 54 %. The only significant between-group difference was greater adolescent-reported treatment satisfaction in the CBT + fluoxetine group than the CBT alone group. These results indicate the chronicity of school refusal, and the need for future research into how to best improve school attendance rates.

Psychopathology of adolescents with an intellectual disability who present to general hospital services.

OBJECTIVE: Adolescents with intellectual disability have increased rates of psychopathology compared with their typically developing peers and present to hospital more frequently for ambulant conditions. The aim of this study is to describe the psychopathology and related characteristics of a sample of adolescents with intellectual disability who presented to general hospital services. METHOD: We investigated a cohort of adolescents with intellectual disability in South East Queensland, Australia between January 2006 and June 2010. Demographic and clinical data were obtained via mailed questionnaires and from general practice notes. Psychopathology was measured with the Short Form of the Developmental Behaviour Checklist. RESULTS: Of 98 individuals presenting to hospital, 71 (72.5%) had significant levels of psychopathology. Unknown aetiology for the intellectual disability was associated with presence of problem behaviours. Adolescents with more severe intellectual disability were more likely to have major problem behaviours. Co-morbid physical health issues were not associated with psychopathology. Only 12 (12.1%) adolescents had undergone specialized mental health intervention. CONCLUSIONS: The general hospital environment may offer opportunities for liaison psychiatry services to screen and provide management expertise for adolescent individuals with intellectual disability presenting for physical health issues.

The developmental trajectory of disruptive behavior in Down syndrome, fragile X syndrome, Prader-Willi syndrome and Williams syndrome.

The aim of this study was to investigate the developmental trajectories of verbal aggression, physical aggression, and temper tantrums in four genetic syndrome groups. Participants were part of the Australian Child to Adult Development Study (ACAD), which collected information from a cohort of individuals with an intellectual disability at five time points over 18 years. Data were examined from a total of 248 people with one of the four following syndromes: Down syndrome, Fragile X syndrome, Prader-Willi syndrome, or Williams syndrome. Changes in behaviors were measured using validated items from the Developmental Behavior Checklist (DBC). The results indicate that, while verbal aggression shows no evidence of diminishing with age, physical aggression, and temper tantrums decline with age before 19 years for people with Down syndrome, Fragile X syndrome, and William syndrome; and after 19 years for people with Prader-Willi syndrome. These findings offer a somewhat more optimistic outlook for people with an intellectual disability than has previously been suggested. Research is needed to investigate the mechanisms predisposing people with PWS to persistence of temper tantrums and physical aggression into adulthood.

The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial.

BACKGROUND: There is increasing interest in oxytocin as a therapeutic to treat social deficits in autism spectrum disorders (ASD). The aim of this study was to investigate the efficacy of a course of oxytocin nasal spray to improve social behavior in youth with ASD. METHODS: In a double-blind, placebo-controlled trial across two Australian university sites between February 2009 and January 2012, 50 male participants aged between 12 and 18 years, with Autistic or Asperger's Disorder, were randomized to receive either oxytocin (n = 26) or placebo (n = 24) nasal sprays (either 18 or 24 International Units), administered twice-daily for 8 weeks. Participants were assessed at baseline, after 4- and 8-weeks of treatment, and at 3-month follow-up. Primary outcomes were change in total scores on the caregiver-completed Social Responsiveness Scale and clinician-ratings on the Clinical Global Impressions-Improvement scale. Secondary assessments included caregiver reports of repetitive and other developmental behaviors and social cognition. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry www.anzctr.org.au ACTRN12609000513213. RESULTS: Participants who received oxytocin showed no benefit following treatment on primary or secondary outcomes. However, caregivers who believed their children received oxytocin reported greater improvements compared to caregivers who believed their child received placebo. Nasal sprays were well tolerated and there was no evidence of increased side effects resulting from oxytocin administration. CONCLUSIONS: This is the first evaluation of the efficacy for a course of oxytocin treatment for youth with ASD. Although results did not suggest clinical efficacy, further research is needed to explore alternative delivery methods, earlier age of intervention, and the influence of caregiver expectation on treatment response.

A comprehensive scoping review of ability and disability in ADHD using the International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY).

This is the first in a series of four empirical investigations to develop International Classification of Functioning, Disability and Health (ICF) Core Sets for Attention Deficit Hyperactivity Disorder (ADHD). The objective here was to use a comprehensive scoping review approach to identify the concepts of functional ability and disability used in the scientific ADHD literature and link these to the nomenclature of the ICF-CY. Systematic searches were conducted using Medline/PubMed, PsycINFO, ERIC and Cinahl, to extract the relevant concepts of functional ability and disability from the identified outcome studies of ADHD. These concepts were then linked to ICF-CY by two independent researchers using a standardized linking procedure. Data from identified studies were analysed until saturation of ICF-CY categories was reached. Eighty studies were included in the final analysis. Concepts contained in these studies were linked to 128 ICF-CY categories. Of these categories, 68 were considered to be particularly relevant to ADHD (i.e., identified in at least 5 % of the studies). Of these, 32 were related to Activities and participation, 31 were related to Body functions, and five were related to environmental factors. The five most frequently identified categories were school education (53 %), energy and drive functions (50 %), psychomotor functions (50 %), attention functions (49 %), and emotional functions (45 %). The broad variety of ICF-CY categories identified in this study underlines the necessity to consider ability and disability in ADHD across all dimensions of life, for which the ICF-CY provides a valuable and universally applicable framework. These results, in combination with three additional preparatory studies (expert survey, focus groups, clinical study), will provide a scientific basis to define the ICF Core Sets for ADHD for multi-purpose use in basic and applied research, and every day clinical practice.

Changing interpretation of chromosomal microarray over time in a community cohort with intellectual disability.

Chromosomal microarray (CMA) is the first-line diagnostic test for individuals with intellectual disability, autism, or multiple congenital anomalies, with a 10-20% diagnostic yield. An ongoing challenge for the clinician and laboratory scientist is the interpretation of variants of uncertain significance (VOUS)-usually rare, unreported genetic variants. Laboratories differ in their threshold for reporting VOUS, and clinical practice varies in how this information is conveyed to the family and what follow-up is arranged. Workflows, websites, and databases are constantly being updated to aid the interpretation of VOUS. There is a growing literature reporting new microdeletion and duplication syndromes, susceptibility, and modifier copy number variants (CNVs). Diagnostic methods are also evolving with new array platforms and genome builds. In 2010, high-resolution arrays (Affymetrix 2.7 M Oligo and SNP, 50 kB resolution) were performed on a community cohort of 67 individuals with intellectual disability of unknown aetiology. Three hundred and one CNVs were detected and analyzed using contemporary resources and a simple scoring system. Thirteen (19%) of the arrays were assessed as potentially pathogenic, 4 (6%) as benign and 50 (75%) of uncertain clinical significance. The CNV data were re-analyzed in 2012 using the contemporary interpretative resources. There was a statistically significant difference in the assessment of individual CNVs (P < 0.0001). An additional eight patients were reassessed as having a potentially pathogenic array (n = 21, 31%) and several additional susceptibility or modifier CNVs were identified. This study highlights the complexity involved in the interpretation of CMA and uniquely demonstrates how, even on the same array platform, it can be subject to change over time.

Psychotropic medication use in adolescents with intellectual disability living in the community.

PURPOSE: Information on the use of psychotropic medications in adolescents with intellectual disability is scant. Such information can guide interventions to improve psychotropic medication use in this population. We investigated the prevalence of, and factors associated with, psychotropic medication use in adolescents with intellectual disability in Australia who live in the community. METHODS: Cross-sectional data were obtained from adolescents with intellectual disability living in the community in South East Queensland, Australia, between February 2007 and September 2010. Self-reported information on medication use was extracted from a health screening tool. Demographic and medical data were collected through parent/caregiver surveys. Medications were classified according to the Anatomical Therapeutic Chemical classification system. Psychopathology was assessed using the Developmental Behaviour Checklist Short Form. Logistic regression analysis was used to assess the association of demographic and medical characteristics with psychotropic medication use. RESULTS: There were 176 participants (median age = 16 years, range = 11-19 years; 55% male). Psychotropics were used by 20% of participants. Psychostimulants were the commonest psychotropic class, used by 9% of participants. Multipsychotropic prescribing was not common with only seven participants using more than one psychotropic agent. After adjusting for potentially confounding variables, use of psychotropic medications was significantly associated with male gender (adjusted odds ratio = 3.6; 95% confidence interval = 1.3-9.5) and having major behaviour problems (3.1; 1.1-8.9). CONCLUSIONS: Adolescents with intellectual disability use a wide range of psychotropic medications. Being male and having major behaviour problems are associated with the use of psychotropic medications. Research examining the rationale for psychotropic prescribing in this population is needed.