Pubmed du 21/01/21

jeudi 21 janvier 2021

1. Botha M, Hanlon J, Williams GL. Does Language Matter ? Identity-First Versus Person-First Language Use in Autism Research : A Response to Vivanti. J Autism Dev Disord ;2021 (Jan 20):1-9.

In response to Vivanti’s ’Ask The Editor…’ paper [Journal of Autism and Developmental Disorders, 50(2), 691-693], we argue that the use of language in autism research has material consequences for autistic people including stigmatisation, dehumanisation, and violence. Further, that the debate in the use of person-first language versus identity-first language should centre first and foremost on the needs, autonomy, and rights of autistic people, so in to preserve their rights to self-determination. Lastly, we provide directions for future research.

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2. Cameli C, Viggiano M, Rochat MJ, Maresca A, Caporali L, Fiorini C, Palombo F, Magini P, Duardo RC, Ceroni F, Scaduto MC, Posar A, Seri M, Carelli V, Visconti P, Bacchelli E, Maestrini E. An increased burden of rare exonic variants in NRXN1 microdeletion carriers is likely to enhance the penetrance for autism spectrum disorder. J Cell Mol Med ;2021 (Jan 21)

Autism spectrum disorder (ASD) is characterized by a complex polygenic background, but with the unique feature of a subset of cases ( 15%-30%) presenting a rare large-effect variant. However, clinical interpretation in these cases is often complicated by incomplete penetrance, variable expressivity and different neurodevelopmental trajectories. NRXN1 intragenic deletions represent the prototype of such ASD-associated susceptibility variants. From chromosomal microarrays analysis of 104 ASD individuals, we identified an inherited NRXN1 deletion in a trio family. We carried out whole-exome sequencing and deep sequencing of mitochondrial DNA (mtDNA) in this family, to evaluate the burden of rare variants which may contribute to the phenotypic outcome in NRXN1 deletion carriers. We identified an increased burden of exonic rare variants in the ASD child compared to the unaffected NRXN1 deletion-transmitting mother, which remains significant if we restrict the analysis to potentially deleterious rare variants only (P = 6.07 × 10(-5) ). We also detected significant interaction enrichment among genes with damaging variants in the proband, suggesting that additional rare variants in interacting genes collectively contribute to cross the liability threshold for ASD. Finally, the proband’s mtDNA presented five low-level heteroplasmic mtDNA variants that were absent in the mother, and two maternally inherited variants with increased heteroplasmic load. This study underlines the importance of a comprehensive assessment of the genomic background in carriers of large-effect variants, as penetrance modulation by additional interacting rare variants to might represent a widespread mechanism in neurodevelopmental disorders.

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3. Chan HL, Hsieh YH, Lin CF, Liang HY, Lee SS, Weng JC, Lee MJ, Chen YL, Chen VC, Gossop M. Lower Risk of Burn Injury in Children and Adolescents with Autism Spectrum Disorder : A Nationwide Population-Based Study. J Autism Dev Disord ;2021 (Jan 20)

Little research has examined burn injury in the pediatric population with autism spectrum disorder (ASD). We used data from Taiwan’s National Health Insurance Research Database to identify 15,844 participants aged <18 years with ASD and 130,860 participants without ASD. Our results revealed that the hazard ratios differed across three age ranges. The ASD group had a lower risk of burn injury than the non-ASD group when they were less than 6 years of age, a higher risk from 6 years to 12 years of age, and no difference when they were older than 12 years of age. More research is required to study the characteristics and causes of burn injury in the pediatric population with ASD.

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4. Graña M, Silva M. Impact of Machine Learning Pipeline Choices in Autism Prediction From Functional Connectivity Data. Int J Neural Syst ;2021 (Jan 20):2150009.

Autism Spectrum Disorder (ASD) is a largely prevalent neurodevelopmental condition with a big social and economical impact affecting the entire life of families. There is an intense search for biomarkers that can be assessed as early as possible in order to initiate treatment and preparation of the family to deal with the challenges imposed by the condition. Brain imaging biomarkers have special interest. Specifically, functional connectivity data extracted from resting state functional magnetic resonance imaging (rs-fMRI) should allow to detect brain connectivity alterations. Machine learning pipelines encompass the estimation of the functional connectivity matrix from brain parcellations, feature extraction, and building classification models for ASD prediction. The works reported in the literature are very heterogeneous from the computational and methodological point of view. In this paper, we carry out a comprehensive computational exploration of the impact of the choices involved while building these machine learning pipelines. Specifically, we consider six brain parcellation definitions, five methods for functional connectivity matrix construction, six feature extraction/selection approaches, and nine classifier building algorithms. We report the prediction performance sensitivity to each of these choices, as well as the best results that are comparable with the state of the art.

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5. Green CC, Smith J, Bent CA, Chetcuti L, Sulek R, Uljarević M, Hudry K. Differential predictors of well-being versus mental health among parents of pre-schoolers with autism. Autism ;2021 (Jan 20):1362361320984315.

Raising a child with autism has been linked to mental health difficulties. Poor parental mental health is likely influenced by various factors - including child-, parent-, and family/socioeconomic characteristics. However, little is known about what influences and promotes well-being (as opposed to mental health) among parents of young, newly diagnosed autistic children who may be particularly vulnerable. We examined child-, parent-, and family/socioeconomic factors associated with each of mental health and well-being in a sample of 136 parents of pre-school-aged children. Parental mental health was linked to both child- (i.e. autism symptom severity) and parent-related factors (i.e. personality traits reflecting a tendency to experience negative emotions). By contrast, in additional to mental health difficulties, which were linked to well-being, only other parent-related characteristics (and not child characteristics) were related to well-being. These included personality traits reflecting a tendency to be more extraverted/sociable, and also mindfulness. Other child-related and family/socioeconomic context factors (including household income, parental education level) were not linked to parental mental health or well-being in this sample. These results support the idea that poorer mental health and well-being are not simply the opposite of one another. That is, while these two factors were related, they were linked to different personal characteristics. Perhaps most importantly, the link between well-being and mindfulness - a personal characteristic that parents can improve - suggests mindfulness-based interventions may be helpful in directly supporting parental well-being in the context of raising a young child with autism.

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6. Hoang N, Yuen RKC, Howe J, Drmic I, Ambrozewicz P, Russell C, Vorstman J, Weiss SK, Anagnostou E, Malow BA, Scherer SW. Sleep phenotype of individuals with autism spectrum disorder bearing mutations in the PER2 circadian rhythm gene. Am J Med Genet A ;2021 (Jan 20)

The Per family of genes functions as a primary circadian rhythm maintenance in the brain. Mutations in PER2 are associated with familial advanced sleep-phase syndrome 1 (FASPS1), and recently suggested in delayed sleep phase syndrome and idiopathic hypersomnia. The detection of PER2 variants in individuals with autism spectrum disorder (ASD) and without reported sleep disorders, has suggested a role of circadian-relevant genes in the pathophysiology of ASD. It remains unclear whether these individuals may have, in addition to ASD, an undiagnosed circadian rhythm sleep disorder. The MSSNG database was used to screen whole genome sequencing data of 5,102 individuals with ASD for putative mutations in PER2. Families identified were invited to complete sleep phenotyping consisting of a structured interview and two standardized sleep questionnaires : the Pittsburgh Sleep Quality Index and the Morningness-Eveningness Questionnaire. From 5,102 individuals with ASD, two nonsense, one frameshift, and one de novo missense PER2 variants were identified (0.08%). Of these four, none had a diagnosed sleep disorder. Three reported either a history of, or ongoing sleep disturbances, and one had symptoms highly suggestive of FASPS1 (as did a mutation carrier father without ASD). The individual with the missense variant did not report sleep concerns. The ASD and cognitive profiles of these individuals varied in severity and symptoms. The results support a possible role of PER2-related circadian rhythm disturbances in the dysregulation of sleep overall and sometimes FASPS1. The relationship between dysregulated sleep and the pathophysiology of ASD require further exploration.

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7. Howlin P. Adults with Autism : Changes in Understanding Since DSM-111. J Autism Dev Disord ;2021 (Jan 20)

Over the past four decades there have been significant advances in our understanding of autism, yet services for autistic adults continue to lag far behind those for children, and prospects for employment and independent living remain poor. Adult outcomes also vary widely and while cognitive and language abilities are important prognostic indicators, the influence of social, emotional, familial and many other factors remains uncertain. For this special issue marking the 40th anniversary of DSM-III, the present paper describes the changing perspectives of autism in adulthood that have occurred over this period, explores individual and wider environmental factors related to outcome, and suggests ways in which services need to be changed to improve the future for adults living with autism.

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8. Hoyt CR, L’Hotta AJ, Bauer AH, Chang CH, Varughese TE, Abel RA, King AA. Activity competence among infants and toddlers with developmental disabilities : Rasch analysis of the Infant Toddler Activity Card Sort (ITACS). J Patient Rep Outcomes ;2021 (Jan 21) ;5(1):14.

BACKGROUND : Development is rapid in the first years of life. Developmental delays appearing during this critical period have the potential to persist throughout the child’s life. Available standardized assessments for this age record a child’s ability to successfully complete discrete skills but fail to capture whether the child incorporates those skills into daily routines that are meaningful to the child and family. The Infant Toddler Activity Card Sort (ITACS) is a newly developed photograph-based early intervention tool to measure the participation-related concept of activity competence using caregiver report. The purpose of the present study was to use Rasch analysis to determine if ITACS items comprehensively measure the construct of child activity competence. RESULTS : A total of 60 child/caregiver dyads participated. The dichotomous caregiver-reported responses (present vs. absent) on the 40 individual ITACS items were used in Rasch analysis, and three iterations of the model were completed. The final model included 51 child/caregiver dyads and 67 ITACS assessments with a good spread of individual ability measure (6.47 logits). All items demonstrated adequate infit except for "sleeping" (range 0.68-1.54). Five items (sleeping, eating at restaurants, brushing teeth, crawling, and interact with pets) demonstrated high Mean Square (MNSQ) outfit statistics and one (take a bath) demonstrated low MNSQ outfit. ITACS items demonstrated a good spread of item difficulty measures (6.27 logits), and a clear ceiling was observed. Three activity items (smiling, breastfeeding, and playing with adults) were rarely endorsed as concerns. The activities most likely to be reported as challenging were "crying/communicating" and "going to school". Person and item reliability statistics were adequate (0.79 and 0.80, respectively). The separation between individuals and between items were adequate to good (1.96 and 1.99, respectively). CONCLUSIONS : Findings indicate that ITACS items are measuring a unidimensional construct—activity competence in early childhood. The Rasch analysis of caregiver responses suggest that some activities are more likely to be considered challenging and may be important targets for intervention. These results provide evidence to further validate the ITACS as a caregiver report measure and support its use in the early intervention setting to facilitate caregiver driven goal development.

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9. Jones DR, DeBrabander KM, Sasson NJ. Effects of autism acceptance training on explicit and implicit biases toward autism. Autism ;2021 (Jan 20):1362361320984896.

Autistic adults face prejudice from non-autistic people. They are often judged unfairly and left out of social activities because of their differences. This can make it difficult for autistic people to make friends and find jobs. Some training programs have tried to teach autistic people to act more like non-autistic people to help them gain acceptance. Fewer have focused on teaching non-autistic people how to be more autism friendly. In this study, we used a short training video that teaches people about autism. The video was created with the help of autistic adults and included clips of real autistic people. We found that non-autistic people who watched this video had better knowledge about autism and showed more autism-friendly attitudes than those who watched a video about mental health or those who did not watch any video. They were more open to having a relationship with an autistic person and had more positive beliefs about autism. However, our video did not affect people’s unconscious attitudes about autism. People in our study connected autism with unpleasant traits, even if they had watched the autism training video. This suggests that teaching non-autistic people about autism may promote more autism-friendly attitudes, but some beliefs may be harder to change.

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10. Lebersfeld JB, Swanson M, Clesi CD, O’Kelley SE. Systematic Review and Meta-Analysis of the Clinical Utility of the ADOS-2 and the ADI-R in Diagnosing Autism Spectrum Disorders in Children. J Autism Dev Disord ;2021 (Jan 21)

The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) and the Autism Diagnostic Interview, Revised (ADI-R) have high accuracy as diagnostic instruments in research settings, while evidence of accuracy in clinical settings is less robust. This meta-analysis focused on efficacy of these measures in research versus clinical settings. Articles (n = 22) were analyzed using a hierarchical summary receiver operating characteristics (HSROC) model. ADOS-2 performance was stronger than the ADI-R. ADOS-2 sensitivity and specificity ranged from .89-.92 and .81-.85, respectively. ADOS-2 accuracy in research compared with clinical settings was mixed. ADI-R sensitivity and specificity were .75 and .82, respectively, with higher specificity in research samples (Research = .85, Clinical = .72). A small number of clinical studies were identified, indicating ongoing need for investigation outside research settings.

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11. Luhach K, Kulkarni GT, Singh VP, Sharma B. Effect of papaverine on developmental hyperserotonemia induced autism spectrum disorder related behavioural phenotypes by altering markers of neuronal function, inflammation, and oxidative stress in rats. Clin Exp Pharmacol Physiol ;2021 (Jan 21)

Hyperserotonemia, in the early developmental phase, generates a variety of behavioural and biochemical phenotypes associated with autism spectrum disorder (ASD) in rats. Papaverine is known to provide benefits in various brain conditions. We investigated the role of a selective phosphodiesterase-10A (PDE10A) inhibitor, papaverine on ASD related behavioural phenotypes (social behaviour deficits, repetitive behaviour, anxiety and hyperlocomotion) in developmental hyperserotonemia (DHS) rat model. Also, effects on important biochemical markers related with neuronal function (brain-derived neurotrophic factor (BDNF)-neuronal survival and phosphorylated-cAMP response element binding protein (pCREB)-neuronal transcription factor), brain inflammation (interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α) and brain oxidative stress (TBARS and GSH) were studied in important brain areas (frontal cortex, cerebellum, hippocampus and striatum). Administration of a non-selective serotonin receptor agonist, such as 5-methoxytryptamine (5-MT) to rats prenatally (gestational day 12 - day of parturition) and during early stages (postnatal day (PND) 0 -PND20) of development, resulted in impaired behaviour and brain biochemistry. Administration of papaverine (15/30 mg/kg ip) to 5-MT administered rats from PND21 to PND48, resulted in improvement of behavioural deficits. Also, papaverine administration significantly increased the levels of BDNF, pCREB/CREB, IL-10, GSH and significantly decreased TNF-α, IL-6 and TBARS levels in different brain areas. Papaverine, in both doses rectified important behavioural phenotypes related with ASD, the higher dose (30 mg/kg ip) showed significantly greater improvement than 15 mg/kg ip, possibly by improving neuronal function, brain inflammation and brain oxidative stress. Thus, PDE10A could be a probable target for pharmacological interventions and furthering our understanding of ASD pathogenesis.

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12. McDaniel J, Schuele CM. When Will He Talk ? An Evidence-Based Tutorial for Measuring Progress Toward Use of Spoken Words in Preverbal Children With Autism Spectrum Disorder. Am J Speech Lang Pathol ;2021 (Jan 21):1-18.

Purpose Professionals face substantial challenges determining whether and when children with autism spectrum disorder (ASD) who are not yet using spoken words will use spoken language as their primary means of communication. This tutorial provides speech-language pathologists with practical guidance on how to measure expressive language predictors for progress monitoring and making intervention decisions for children with ASD who are preverbal. Method This tutorial is a repackaging effort that seeks to make the research accessible to clinicians wishing to implement evidence-based practice. Results We describe intentional communication, consonant inventory in communication acts, and responding to joint attention as particularly valuable prelinguistic skills to measure. We explain how and when to efficiently assess progress using published assessments periodically and using brief (5-min) communication samples for more frequent progress monitoring. Conclusions Communication samples can be used to show how a child performs within a therapeutic setting during teaching (treatment data) and outside of the therapeutic setting (generalization probe data). Both types of data are critical for determining whether the child is exhibiting progress and which aspects of intervention are facilitating progress toward use of spoken words. These recommendations also balance the evidence for best practices for progress monitoring and the demands on clinicians’ time and effort. To encourage the measurement of prelinguistic skills of children with ASD who are preverbal in clinical practice, we include (a) example data collection documents, (b) examples with hypothetical data and interpretation, and (c) guidance on communication sampling procedures. Supplemental Material https://doi.org/10.23641/asha.13557836.

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13. Mohammadi MR, Zandifar A, Badrfam R. The Prospective of Autism in the Next Generation ; The Need for Pay Attention to the COVID-19 Pandemic. World J Biol Psychiatry ;2021 (Jan 21):1-4.

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14. Moradimanesh Z, Khosrowabadi R, Eshaghi Gordji M, Jafari GR. Altered structural balance of resting-state networks in autism. Sci Rep ;2021 (Jan 21) ;11(1):1966.

What makes a network complex, in addition to its size, is the interconnected interactions between elements, disruption of which inevitably results in dysfunction. Likewise, the brain networks’ complexity arises from interactions beyond pair connections, as it is simplistic to assume that in complex networks state of a link is independently determined only according to its two constituting nodes. This is particularly of note in genetically complex brain impairments, such as the autism spectrum disorder (ASD), which has a surprising heterogeneity in manifestations with no clear-cut neuropathology. Accordingly, structural balance theory (SBT) affirms that in real-world signed networks, a link is remarkably influenced by each of its two nodes’ interactions with the third node within a triadic interrelationship. Thus, it is plausible to ask whether ASD is associated with altered structural balance resulting from atypical triadic interactions. In other words, it is the abnormal interplay of positive and negative interactions that matters in ASD, besides and beyond hypo (hyper) pair connectivity. To address this question, we explore triadic interactions based on SBT in the weighted signed resting-state functional magnetic resonance imaging networks of participants with ASD relative to healthy controls (CON). We demonstrate that balanced triads are overrepresented in the ASD and CON networks while unbalanced triads are underrepresented, providing first-time empirical evidence for the strong notion of structural balance on the brain networks. We further analyze the frequency and energy distributions of different triads and suggest an alternative description for the reduced functional integration and segregation in the ASD brain networks. Moreover, results reveal that the scale of change in the whole-brain networks’ energy is more narrow in the ASD networks during development. Last but not least, we observe that energy of the salience network and the default mode network are lower in ASD, which may be a reflection of the difficulty in dynamic switching and flexible behaviors. Altogether, these results provide insight into the atypical structural balance of the ASD brain (sub) networks. It also highlights the potential value of SBT as a new perspective in functional connectivity studies, especially in the case of neurodevelopmental disorders.

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15. Pandina G, Ness S, Trudeau J, Stringer S, Knoble N, Lenderking WR, Bangerter A. Qualitative evaluation of the Autism Behavior Inventory : use of cognitive interviewing to establish validity of a caregiver report scale for autism spectrum disorder. Health Qual Life Outcomes ;2021 (Jan 20) ;19(1):26.

PURPOSE : The Autism Behavior Inventory (ABI) is an observer-reported outcome scale measuring core and associated features of autism spectrum disorder (ASD). Extensive scale development (reported elsewhere) took place, in alignment with the Food and Drug Administration’s patient-reported outcome guidance, to address the need for instruments to measure change and severity of ASD symptoms. METHODS : Cognitive interviewing was used to confirm understanding and content validity of the scale prior to its use in clinical trials. Respondents were caregivers of individuals with ASD (N = 50). Interviews used a hybrid of the "think-aloud" and verbal probing approach to assess ABI’s content validity and participant understanding of the instrument, including : item clarity and relevance ; item interpretation ; appropriateness of response scales ; and clarity of instructions. Audio-recordings of the interviews were transcribed for qualitative data analysis. The scale was revised based on participant feedback and tested in a second round of interviews (round 1 N = 38, round 2 N = 12). RESULTS : In total, 67/70 items reached ≥ 90% understandability across participants. Caregivers were able to select an appropriate response from the options available and reported finding the examples helpful. Based on participant feedback, instructions were simplified, 8 items were removed, and 10 items were reworded. The final revised 62-item scale was presented in round 2, where caregivers reported readily understanding the instructions, response options, and 61/62 items reached ≥ 90% understandability. CONCLUSIONS : Cognitive interviews with caregivers of a diverse sample of individuals with ASD confirm the content validity and relevance of the ABI to assess core and associated symptoms of ASD.

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16. Paul S, Arora A, Midha R, Vu D, Roy PK, Belmonte MK. Autistic traits and individual brain differences : functional network efficiency reflects attentional and social impairments, structural nodal efficiencies index systemising and theory-of-mind skills. Mol Autism ;2021 (Jan 21) ;12(1):3.

BACKGROUND : Autism is characterised not only by impaired social cognitive ’empathising’ but also by superior rule-based ’systemising’. These cognitive domains intertwine within the categorical diagnosis of autism, yet behavioural genetics suggest largely independent heritability, and separable brain mechanisms. We sought to determine whether quantitative behavioural measures of autistic traits are dimensionally associated with structural and functional brain network integrity, and whether brain bases of autistic traits vary independently across individuals. METHODS : Thirty right-handed neurotypical adults (12 females) were administered psychometric (Social Responsiveness Scale, Autism Spectrum Quotient and Systemising Quotient) and behavioural (Attention Network Test and theory-of-mind reaction time) measures of autistic traits, and structurally (diffusion tensor imaging) and functionally (500 s of 2 Hz eyes-closed resting fMRI) derived graph-theoretic measures of efficiency of information integration were computed throughout the brain and within subregions. RESULTS : Social impairment was positively associated with functional efficiency (r = .47, p = .006), globally and within temporo-parietal and prefrontal cortices. Delayed orienting of attention likewise was associated with greater functional efficiency (r = - .46, p = .0133). Systemising was positively associated with global structural efficiency (r = .38, p = 0.018), driven specifically by temporal pole ; theory-of-mind reaction time was related to structural efficiency (r = - .40, p = 0.0153) within right supramarginal gyrus. LIMITATIONS : Interpretation of these relationships is complicated by the many senses of the term ’connectivity’, including functional, structural and computational ; by the approximation inherent in group functional anatomical parcellations when confronted with individual variation in functional anatomy ; and by the validity, sensitivity and specificity of the several survey and experimental behavioural measures applied as correlates of brain structure and function. CONCLUSIONS : Functional connectivities highlight distributed networks associated with domain-general properties such as attentional orienting and social cognition broadly, associating more impaired behaviour with more efficient brain networks that may reflect heightened feedforward information flow subserving autistic strengths and deficits alike. Structural connectivity results highlight specific anatomical nodes of convergence, reflecting cognitive and neuroanatomical independence of systemising and theory-of-mind. In addition, this work shows that individual differences in theory-of-mind related to brain structure can be measured behaviourally, and offers neuroanatomical evidence to pin down the slippery construct of ’systemising’ as the capacity to construct invariant contextual associations.

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17. Treise C, Simmons C, Marshall N, Painter M, Perez J. Autism Spectrum Disorder in Early Intervention in Psychosis Services : Implementation and Findings of a 3-step Screening and Diagnostic Protocol. J Psychiatr Pract ;2021 (Jan 21) ;27(1):23-32.

Evidence indicates that autism spectrum disorder (ASD) is underidentified in populations with psychosis, but that clinical presentations of comorbid ASD and psychosis (ASD-P) and specific treatment needs that may relate to this group are not well understood. In fact, recent studies of ASD in first-episode psychosis suggest that there may be a specific clinical presentation of ASD-P. In response, the Cambridgeshire and Peterborough Early Intervention in Psychosis (EIP) service in the UK implemented and evaluated a 3-step ASD screening and diagnostic protocol, using the Autism Spectrum Disorder in Adults Screening Questionnaire (ASDASQ), case note review, and the Autism Diagnostic Observation Schedule (ADOS-2) and the Childhood Autism Spectrum Test (CAST). As a quality improvement project, the evaluation aimed to (1) establish the prevalence of patients with ASD-P, (2) describe characteristics of the clinical presentation of ASD-P and compare them to those of patients suffering from psychosis but no ASD, and (3) determine any differences in treatment between psychosis patients with and without ASD. Notably, at least 9% of the EIP service caseload met the criteria for a diagnosis of ASD-P, with half identified via the implementation of this protocol. The patients with ASD-P had specific clinical presentations and treatment needs that differed from those of patients with psychosis but no ASD. Thus, the findings from this study supported existing evidence concerning the underdetection of ASD in EIP populations. Our findings also added to emerging evidence for a clinical presentation of ASD-P with specific treatment needs. Our protocol has now been established as routine practice, and its implementation has improved the detection and treatment of patients with ASD-P within our EIP service.

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