Importance:22q11.2 deletion syndrome (22q11DS) is among the strongest genetic risk factors for neuropsychiatric disorders and has marked effects on brain structure. Yet, it remains unclear which neuroanatomical features reflect uniform effects of the deletion versus inter-individual biological processes relevant to psychiatric outcomes. Identifying these features is critical for developing targeted treatments and interventions. Objective:To identify brain regions where 22q11DS exerts its most consistent and most variable impacts, and to test whether these patterns align with normative neurotransmitter receptor distributions and cortical growth trajectories. Design:Multisite cross-sectional case-control study. Setting:T1-weighted brain MRI data were obtained across 15 scanners. MRI data underwent standardized processing, quality control procedures and statistical site-adjustment using ComBat. Participants:A total of N = 438 individuals with 22q11DS (5-54 years, 48% females) and 380 typically developing controls (6-58 years, 48% females). Main Outcomes and Measures:Primary outcomes were global and regional cortical thickness and surface area. Mean and dispersion estimates were calculated using double generalized linear models, correcting for age, age2, sex (and intracranial volume for surface area). Quantile shift functions characterized fine-scale distributional differences. Sensitivity analyses adjustedt for co-occurring neuropsychiatric disorders, antipsychotic use and deletion subtype. Secondary outcomes included spatial correspondence between regional structural alterations and normative maps of neurotransmitter receptor density and cortical expansion. Results:Compared with controls, individuals with 22q11DS showed widespread mean differences in cortical thickness and surface area. Notably, 22q11DS was associated with greater regional heterogeneity in both measures, except for reduced dispersion in the anterior cingulate. Effects were attenuated after covariate adjustment. Cortical thickness differences spatially overlapped with regions enriched for glutamatergic and GABAergic receptors. There was partial evidence linking surface area dispersion patterns to normative cortical growth trajectories. Conclusions and Relevance:22q11DS exerts broad effects on cortical structure consistent with a global developmental mechanism, reflected in widespread mean shifts. Beyond these, region-specific variability, particularly in cortical thickness, suggests individualized neurobiological processes. The anterior cingulate emerges as a region of consistent structural deviation. Overall, structural variability in 22q11DS aligns with normative patterns of excitatory-inhibitory signaling and cortical development, implicating these pathways as potential targets for intervention.

BACKGROUND: Copy number variants (CNVs) may increase the risk for neurodevelopmental conditions. The neurobiological mechanisms that link these high-risk genetic variants to clinical phenotypes are largely unknown. An important question is whether brain abnormalities in individuals who carry CNVs are associated with their degree of penetrance. METHODS: We investigated whether increased CNV penetrance for schizophrenia and other developmental disorders was associated with variations in cortical and subcortical morphology. We pooled T1-weighted brain magnetic resonance imaging and genetic data from 22 cohorts from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-CNV consortium. In the main analyses, we included 9268 individuals (aged 7-90 years, 54% female), from which we identified 398 carriers of 36 neurodevelopmental CNVs at 20 distinct loci. A secondary analysis was performed including additional neuroimaging data from the ENIGMA-22q consortium, including 274 carriers of the 22q11.2 deletion and 291 noncarriers. CNV penetrance was estimated through penetrance scores that were previously generated from large cohorts of patients and controls. These scores represent the probability risk of developing either schizophrenia or other developmental disorders (including developmental delay, autism spectrum disorder, and congenital malformations). RESULTS: For both schizophrenia and developmental disorders, increased penetrance scores were associated with lower surface area in the cerebral cortex and lower intracranial volume. For both conditions, associations between CNV-penetrance scores and cortical surface area were strongest in regions of the occipital lobes, specifically in the cuneus and lingual gyrus. CONCLUSIONS: Our findings link global and regional cortical morphometric features with CNV penetrance, providing new insights into neurobiological mechanisms of genetic risk for schizophrenia and other developmental disorders.

A different communication style, sudden changes in routine, sensory sensitivities, or emotional overload can sometimes lead to behavioural reactions in autistic children. This can trigger emotional dysregulation, resulting in rapid mood changes, meltdowns, self-injury, and/or reactive behaviours that are sometimes labelled as ‘aggressive behaviours’, for example, biting. These types of behaviours can result in stigma for both the child and their parents. We aimed to explore how parents interpret their experiences raising an autistic child who exhibits aggressive behaviours, using a phenomenological epistemological approach. Eight parents of male children who had received a diagnosis of autism completed a semi-structured interview. The transcripts were analysed using interpretative phenomenological analysis. One superordinate theme, ‘Changed expectations’, overarched the five subordinate themes: It’s not the life that was anticipated; Isolation; What does the future hold?; Stigma; and Finding the positive. Parents felt grief for the life they expected compared to the one they were experiencing. Initially, they blamed themselves for their child’s challenging behaviours before accepting that society’s expectations were not always right for their family. Parents also reported feelings of empathy, patience, and joy within themselves and their child. Participants in the study shared that their lived experiences differed from their expectations, often shaped by stigma from themselves, their families, and broader society. They reported social isolation but also some positive personal psychological growth. Future research should explore the lived experience of autistic children who exhibit aggressive behaviours, the stigmas associated with these behaviours, and how these children can be supported. This exploration should be guided by appropriate methodologies developed through co-production with autistic individuals.

22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1-weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source-based morphometry (SBM) pipeline (SS-Detect) to generate structural brain patterns (SBPs) that capture co-varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV-SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel-based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism. Using a novel source-based morphometry method called SS-Detect, we identified 12 structural brain patterns (SBPs) that discriminated individuals with 22q11.2 deletion syndrome from healthy controls. We further demonstrated that deletion size was related to structural covariance patterns; however, history of psychosis did not show a strong relationship with these covariance patterns.image

BACKGROUND:Acquired brain injury (ABI) is associated with social cognitive impairments, yet these impairments are often overlooked during clinical assessments. There are few validated and clinically appropriate measures of social cognition in ABI. The current study examined the validity of the Brief Assessment of Social Skills (BASS) in measuring social cognition following ABI. METHOD:Twenty-eight people with ABI were recruited from local brain injury rehabilitation and support services and completed measures of social cognition, general intellectual ability, and social functioning. Twenty-eight controls demographically matched for age, gender, and years of education also performed these measures. RESULTS:A diagnosis of ABI was significantly associated with poorer performance on five subtests of the BASS. The BASS had moderate correlations with established measures of social cognition and measures characteristics that are distinguishable from general cognition. There was minimal evidence of a relationship between performance on the BASS and social functioning, with a significant relationship between a BASS subscale and informant-reported living skills and total social functioning. Using a series of case studies, the clinical utility of the BASS was emphasized by the development of unique social cognitive profiles across ABI individuals, including impairments in areas not significant at a group level. DISCUSSION:The BASS is a brief and comprehensive measure that is able to detect social cognition impairments in ABI patients. Given the prevalence of impairment in social cognition following ABI and the implications of these abilities on social functioning, this measure can be used in comprehensive neuropsychological assessment to guide and monitor progress toward rehabilitation goals.

Mothers with asthma or atopy have a higher likelihood of having autistic children, with maternal immune activation in pregnancy implicated as a mechanism. This study aimed to determine, in a prospective cohort of mothers with asthma and their infants, whether inflammatory gene expression in pregnancy is associated with likelihood of future autism. Mothers with asthma were recruited to the Breathing for Life Trial. RNA was extracted from blood samples collected at mid-pregnancy. 300 ng total RNA was hybridized with the nCounter Human Inflammation gene expression panel (Nanostring Technologies, 249 inflammation-related genes). Parents completed the First Year Inventory (FYI) at 12-month follow-up, which assessed an infant's likelihood for autism across 2 behavioural domains: social communication and sensory regulation. A total score ≥19.2 indicated increased likelihood for future autism. Inflammatory gene expression was profiled from 24 mothers: four infants scored in the high autism likelihood range; 20 scored in the low autism likelihood range. Six inflammatory genes were differentially expressed and significantly up-regulated in the high autism likelihood group: CYSLTR2, NOX1, C1QA, CXCL10, C8A, IL23R. mRNA count significantly correlated with social communication FYI score for CYSLTR2 (Pearson r = 0.46, p = 0.024) and CXCL10 (r = 0.43, p = 0.036) and with sensory regulation score for ALOX5 (r = -0.43, p = 0.038) and MAFK (r = -0.46, p = 0.022). In this proof-of-concept study, inflammatory gene expression during pregnancy in mothers with asthma was associated with an infant's likelihood of future autism as well as scores relating to social communication and sensory regulation.

Background Asthma during pregnancy is associated with a range of adverse perinatal outcomes. It is also linked to increased rates of neurodevelopmental conditions the offspring. We aimed to assess whether fractional exhaled nitric oxide (F )-based asthma management during pregnancy improves child developmental and behavioural outcomes compared to usual care. Methods The Breathing for Life Trial was a randomised controlled trial that compared F -based asthma management during pregnancy to usual care. Participants were invited to the developmental follow-up, the Breathing for Life Trial – Infant Development study, which followed up infants at 6 weeks, 6 months, and 12 months. The primary outcomes were measured in infants at 12-months using the Bayley-III: Cognitive, Language, and Motor composite scores. Secondary outcomes included Bayley-III social-emotional and adaptive behaviour scores, autism likelihood, and sensory and temperament outcomes. The exposure of interest was the randomised intervention group. Results 220 infants and their 217 participating mothers were recruited to the follow-up; 107 mothers were in the intervention group and 113 were in the control group. There was no evidence of an intervention effect for the primary outcomes: Bayley-III cognitive (Mean=108.9 control, 108.5 intervention, p=0.93), language (Mean=95.9 control, 95.6 intervention, p=0.87) and motor composite scores (Mean=97.2 control, 97.9 intervention, p=0.25). Mean scores for secondary outcomes were also similar among infants born to control and F group mothers, with few results reaching p<0.05. Conclusion In this sample, F -guided asthma treatment during pregnancy did not improve infant developmental outcomes in the first year of life.

Objectives 22q11.2 deletion syndrome (22q11.2DS) is common microdeletion syndrome associated with intellectual and learning disorders, psychiatric disorders, and a complex physical phenotype. The aim of this review was to build upon a previous systematic review on this topic and identify psychological interventions attempting to address the behavioural (including cognitive and emotional) phenotype of the syndrome. Methods Articles were reviewed and organised as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for conducting systematic reviews. The literature search identified 1124 studies, out of which nine studies met the inclusion criteria. The nine studies are summarised in terms of (a) study design and follow-up, (b) populations involved, (c) intervention characteristics, and (d) feasibility. Results The findings indicate that it is important to consider the individual’s needs, developmental stage, and the syndrome-specific behavioural phenotype when implementing (and evaluating) psychological interventions. Conclusions The existing literature has a heavy focus on the delineation of the behavioural phenotype and associated psychiatric comorbidities but there are very few studies exploring how to adapt and implement effective interventions to support the mental health and well-being of people with 22q11.2DS. Future studies are required to evaluate the feasibility of interventions as well as the effectiveness in reducing distress, building skills, and improving quality of life.

There is a paradoxical paradigm operating in neurodiverse families with autistic children, indicating increased stress alongside enrichment of family life. An emerging body of research has shown that the use of family therapy can improve family functioning and relationships in neurodiverse families. The current study uses constructivist grounded theory to explore clinicians' experiences and perceptions of utilising family therapy in the context of autism. Study findings suggest that clinicians integrate therapeutic techniques from diverse family therapy approaches to improve family relations by bridging different ways of learning and communicating as well as facilitating multiple perspectives. Integrating therapeutic techniques across diverse approaches further encompasses working with the systems around the individual with autism. To adapt family therapy in the context of autism, it is suggested that clinicians examine their own perspectives and beliefs about autism and keep a curious stance during the process.

22q11.2 deletion syndrome (22q11.2DS) is a complex and widely variable genetic syndrome involving multisystem physical health problems, significant cognitive and psychosocial challenges, all of which may impact upon learning and academic achievement. In the current study, we explored mothers’ perceptions of their child’s learning within early and primary educational contexts. We conducted 3 online focus groups and 1 online semi-structured interview with a total of 9 mothers of children diagnosed with 22q11.2DS. Mothers were included if their child had a genetic diagnosis of 22q11.2DS and was aged from 3 to 12 years old. The mothers were asked a series of open-ended questions to explore the educational experiences of their child. We adopted an inductive approach to our data analysis and conducted a reflexive thematic analysis resulting in the emergence of 4 major themes (1.) The impact of 22q11.2DS on a child’s learning; (2.) The impact of adaptive behaviour skills on their child’s learning; (3.) The level of support available within the educational setting and; (4.) Mothers’ perceptions about their child’s learning. From these themes, the following 12 sub themes were identified: absences affecting learning; the development of specific learning behaviours; the impact of a 22q11.2 DS diagnosis on their child’s self-perception; toileting, motor issues; communication; sleep; school and teacher support and the presence (or absence) of therapists. Finally, the mothers’ confidence about their child’s learning; mothers’ concerns and comparisons of their child; and mothers’ apprehension about their child’s future were all identified as sub-themes. Children with 22q11.2DS require increased and specific psychosocial support to allow them greater opportunities to fully participate in their learning environments. Mothers perceived the level of support their child received was greater during pre-school compared to that received at primary school. It was clear that a greater understanding of the needs of children with 22q11.2DS, by educators, was needed. Implications for tailored support for school-based learning and educational transitions for young children with 22q11.2DS are discussed.

Objectives Parenting a child with special healthcare needs is associated with significant caregiver stress. Previous research has found that parenting stress and mental health impact outcomes for children with chronic illnesses. Despite this, the importance of managing parents’ stress is often overlooked in the management of chronic health conditions, such as 22q11.2 deletion syndrome (22q11DS). The objective of this study was to investigate the acceptability of the mindful parenting program, Care4Parents. Methods This study was designed as a non-randomised pilot study evaluating the acceptability of an online mindful parenting program Care4Parents, specifically designed for those parenting a child with special health care needs, including medical complexity. There were 20 participants recruited to take part, which involved attending eight online weekly group sessions for 2 h, with a follow-up after 2 months and practice exercises between sessions. Interviews were conducted with 12 participants after the completion of the program. Using attendance data and thematic analysis of semi-structured interviews, the study aimed to determine if the online program Care4Parents would be experienced by participants as acceptable. Results Results indicate preliminary evidence of acceptability, with adequate retention and themes emerging from interviews highlighting the appropriateness of content, delivery, and perceived benefits, including personal growth, peer support, and enhanced coping. ‘ Barriers to engagement ’ was also a theme, and adjustments were discussed based on participant feedback to further enhance the program. Conclusions The analysis of the data indicates that the program was deemed acceptable to participants, therefore warranting further research using quantitative measures to confirm findings and investigate effectiveness.

The present study assessed the validity of one of the first autism-specific anxiety measures, the Anxiety Scale for Children with Autism Spectrum Disorder (ASC-ASD), and compared its ability to predict parent-reported clinical anxiety to a 'traditional' anxiety measure, the Spence Children's Anxiety Scale (SCAS). Whether the inclusion of the child form for each measure improved the predictive ability of the parent forms was also examined. Eighty-seven parents of autistic children, aged 8-12 years, completed the ASC-ASD, the SCAS, and the Social Communication Questionnaire (SCQ), a screener for autism characteristics. Of these parents, 56 had their child complete the ASC-ASD and SCAS. The children with a reported anxiety diagnosis were rated significantly higher by their parents on both the SCAS and the ASC-ASD compared to the non-anxious children. Pearson's correlation coefficients indicated that the ASC-ASD had good divergent and convergent validity, as demonstrated by a poor, non-significant correlation with the SCQ and a strong, significant correlation with the SCAS. Regression analyses indicated that while the ASC-ASD was a significant predictor of parent-reported clinical anxiety in autistic children, the SCAS was not. Neither model was improved with the inclusion of the respective child form. This study is the first to demonstrate the ability of the ASC-ASD to predict child clinical anxiety disorder status and adds to the growing body of evidence for the validity of this measure. The findings also suggest that parent reports of anxiety may be sufficient to identify autistic children warranting further clinical investigation of anxiety in this age group.

INTRODUCTION:Individuals with intellectual disability (ID) are at higher risk of experiencing difficulties with anxiety than the general population. However, there are major barriers for individuals to receive appropriate services. There is a growing understanding of the importance of developing appropriate psychological interventions for this group. The objective of the current review was to systematically evaluate the findings of studies investigating the effectiveness of cognitive behavioural therapy (CBT) for individuals with ID and anxiety. Another aim was to explore which adaptions to CBT and treatment components were currently being utilised within the field. METHOD:The electronic databases of CINAHL, EMBASE, Medline, PsycINFO, Psychology and Behavioural Sciences Collection and Scopus were searched to identify relevant studies. The methodological quality of these studies was assessed using established quality assessment tools by the National Institutes of Health for pre and post studies and case series. RESULTS:Nine studies were included in this systematic review, all of which reported improvements in anxiety severity for some participants (25%-100%; N = 60) following CBT. Only three studies reported moderate effect sizes for CBT interventions on anxiety for individuals with ID. DISCUSSION AND CONCLUSIONS:There is emerging literature supporting the effectiveness of CBT for individuals with mild ID. Findings highlight that CBT for individuals with anxiety and mild ID, including cognitive components, may be feasible and tolerable. While the field is gradually receiving more attention, there are significant methodological flaws present, which limit the conclusions that can be drawn regarding the effectiveness of CBT for individuals with ID. However, there is emerging evidence for techniques such as cognitive restructuring and thought replacement and modifications such as visual aids, modelling and smaller groups based on this review. Future research is warranted to investigate whether individuals with more severe ID can benefit from CBT, as well as further exploring what are the necessary components and modifications.

Coparenting competence (CC) is a concept that describes the sense of collective efficacy that parents experience in raising children. An advantage of CC is that it bridges a gap between family systems thinking and efficacy theory, where extant research and theory have focused on the self-efficacy of one or both parents. This study aimed to develop a self-reported measure of CC.METHODOLOGY:Participants (n = 302), including cohabiting mothers (n = 240) and fathers (n = 62), completed an online survey (112 items) comprising demographic questions, the Coparenting Relationship Scale (CRS), the Parenting Sense of Competence Scale (PSOC), the Strengths and Difficulties Questionnaire (SDQ), and 36 items designed to explore perceptions of CC.RESULTS:Factor analyses on 36-CC items identified 10 items that reliably formed a brief Coparenting Competence Scale (CCS; Alpha = 0.89). Analysis of convergent and divergent validity demonstrated that the CCS measures a unique construct that is linked to parenting self-efficacy, measured by PSOC (r = 0.47), and coparenting quality, assessed by the CRS (r = 0.63). There was a significant association between CCS and SDQ across age groups and an association stronger than that found for the CRS and SDQ in the current cohort.CONCLUSIONS AND IMPLICATIONS:The study found support for the reliability and validity of the CCS. Coparenting competence, assessed by the CCS, was found to be distinct from factors previously used to represent coparenting quality in multivariate scales. The strength of associations between the CCS and SDQ suggests this new measure may have an important role in coparenting research.

Purpose: Mother-infant interactions during the first year of life are crucial to healthy infant development. The infant-directed speech (IDS), and specifically pitch contours, used by mothers during interactions are associated with infant language and social development. However, little research has examined pitch contours towards infants with socio-communication and language differences, such as those displaying early signs of autism spectrum disorder (autism). This study aimed to explore the association of infant autism signs and pitch contours used by mothers with their 12-month-old infants.Method: Mother-infant dyads (n = 109) were recruited from the University of Newcastle BabyLab. Parent-infant dyads completed a 15-min interaction, from which a total of 36,128 pitch contours were measured and correlated with infant autism signs. Infant autism signs were assessed via parent-report (First Year Inventory; Reznick et al., 2007). A subset of high-risk infants (admitted to a neonatal intensive care unit, n = 29) also received an observation-based assessment (Autism Detection in Early Childhood; Young & Nah, 2016).Results: Mothers used fewer sinusoidal contours when they rated their infant as displaying more autism signs (rs = -.30, p = .004) and more autism-related sensory regulation issues (rs = -.31, p = .001). Mothers used fewer flat contours if their infant displayed more researcher-rated autism signs (r2 = -.39, p = .04).Conclusions: This study provides the early evidence that maternal pitch contours in IDS are related to early autism signs in infancy. If our findings are replicated in follow up studies where infants

This systematic review aimed to evaluate the efficacy of psychological therapies for anxiety for people with autism and co-occurring intellectual developmental disorder (AUT + IDD). A systematic search identified 13 studies comprising 49 participants with AUT + IDD, aged between 5 and 41 years. Most studies were single-case experimental designs (n = 7) or case studies or case series (n = 4). Studies implemented cognitive behavioural therapy (n = 4) or exposure therapy techniques (n = 9). All studies reported a reduction in anxiety symptoms, as measured by either quantitative measures or defined as participants meeting end of treatment criterion. However, the conclusions are preliminary due to the methodological limitations of the current literature. The implications of these findings, as well as recommendations for future direction in the field, are discussed.