Pubmed du 22/11/19

vendredi 22 novembre 2019

1. Babinska K, Siklenkova L, Stebelova K, Waczulikova I, Celusakova H, Vidosovicova M, Bartakovicova K, Szapuova Z, Kemenyova P. Urinary levels of 6-sulphatoxymelatonin and their associations with sleep disorders and behavioural impairments in children with autism spectrum disorder. Bratisl Lek Listy ;2019 ;120(11):849-855.

BACKGROUND : Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with sleep disturbances that may result from abnormalities in melatonin production. The correlations of melatonin levels with the severity of sleep disorder and/or severity of ASD were reported. OBJECTIVES : To evaluate urinary levels of the melatonin metabolite, 6-sulphatoxymelatonin (aMT6s), in children with ASD, and their associations with sleep abnormalities and behavioural impairments. METHODS : Study involved 77 children with ASD and 84 controls aged 2.515.5 years. Sleep disorders were assessed by Children’s Sleep Habits Questionnaire. Morning and afternoon levels of aMT6s were determined by radioimmunoassay method. Urinary creatinine levels were assessed by an enzymatic method. RESULTS : The urinary aMT6s/creatinine values indicate that the night-time melatonin levels are significantly lower in ASD than in controls, but there are no significant differences in the daytime levels. In the ASD group, on average, a 6.8-fold difference between night-time and daytime values of urinary aMT6s/creatinine was found, whereas for the controls a 12.5-fold difference was observed, indicating a lower night-time increase in melatonin levels. In ASD group, the difference in night-time-daytime aMT6s/creatinine value correlated with some types of sleep problems, but not with the severity of ASD. CONCLUSION : The results indicate that in ASD there are differences in the patterns of melatonin secretion that may be associated with sleep impairment (Tab. 4, Fig. 2, Ref. 28).

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2. Bogenschutz MD, Dinora PA, Johnson KR. Case Management Workforce Supporting People With Intellectual and Developmental Disabilities : Indications of a New Frontier of the Workforce Crisis. Intellect Dev Disabil ;2019 (Dec) ;57(6):499-511.

Case management (CM) is one of the most commonly used services by individuals with intellectual and developmental disabilities (IDD), but little is known about the workers who provide CM. This study used a mixed methods approach to gain understanding of the CM workforce in one U.S. state. An online survey was completed by 35 IDD service directors (87.5% of directors in the state) ; and 113 CMs and CM supervisors participated in semistructured interviews and focus groups. Results indicated an annual crude separation rate of 28.2%, and participants often complained that turnover resulted in caseload sizes that prevented optimal outcomes for people with IDD. A limited applicant pool, duties focused on regulatory compliance, and inadequate wages were cited as major challenges for CMs.

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3. Carpita B, Carmassi C, Calderoni S, Muti D, Muscarella A, Massimetti G, Cremone IM, Gesi C, Conti E, Muratori F, Dell’Osso L. The broad autism phenotype in real-life : clinical and functional correlates of autism spectrum symptoms and rumination among parents of patients with autism spectrum disorder. CNS Spectr ;2019 (Nov 21):1-9.

OBJECTIVE. : Increasing literature reported higher rates of psychiatric disorders in parents of children with autism spectrum disorder (ASD), as well as of autistic-like features in social and cognitive functioning. However, little attention has been paid to the association between autistic traits (AT) and global functioning in this population. The aim of the present work was to investigate clinical and functional correlates of AT among parents of ASD children, with a specific focus on ruminative thinking. METHODS. : One hundred and twenty parents of ASD children were assessed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the Adult Autism Subthreshold Spectrum (AdAS Spectrum), the Ruminative Response Scale (RRS), the Social and Occupational Functioning Assessment Scale (SOFAS). RESULTS. : Subjects with at least 1 psychiatric disorder (39.2%) showed significantly higher AdAS Spectrum and RRS scores. Subjects with a history of school difficulties and with language development alterations scored significantly higher on specific AdAS Spectrum domains. A significant negative correlation was found between SOFAS and AdAS Spectrum scores, as well as between SOFAS and RRS scores. AdAS Spectrum nonverbal communication domain score was identified has a statistically predictive variable for the presence of psychiatric disorders and lower SOFAS scores. Finally, we found a significant indirect effect of AdAS total score on SOFAS score, which was fully mediated by RRS total score. CONCLUSIONS. : AT in parents of ASD children seem to be associated with a higher vulnerability toward psychopathology and with a lower global functioning. Ruminative thinking may play a role in the relationship between AT and functional outcome.

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4. Colombo-Dougovito AM, Block ME, Zhang X, Strehli I. A multiple-method review of accommodations to gross motor assessments commonly used with children and adolescents on the autism spectrum. Autism ;2019 (Nov 21):1362361319884400.

The purpose of this study is to understand the common accommodations used during standardized motor assessment of children on the autism spectrum. This study was completed in three parts : (1) a narrative review of the literature ; (2) an open-ended survey sent to the first authors of the identified articles ; and (3) a descriptive analysis of responses. Results revealed that 56.7% of the identified articles did not report enough information of assessment procedures, 18.9% followed the assessment manual, 16.9% provided accommodations on a needs basis, and 7.5% used a consistent modified protocol. Individual responses showed that extra demonstrations (n = 5) were the most frequent accommodation, followed by extra breaks (n = 3), picture cards (n = 2), and hand-over-hand assistance (n = 1) ; some respondents stated that they did not provide accommodations. The findings indicate that a clear set of accommodation for motor skill assessments does not exist, though some commonalities were reported. Further research is necessary to understand the impact of accommodations in the assessment process, as well as which accommodations are needed and/or effective.

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5. Contaldo A, Colombi C, Pierotti C, Masoni P, Muratori F. Outcomes and moderators of Early Start Denver Model intervention in young children with autism spectrum disorder delivered in a mixed individual and group setting. Autism ;2019 (Nov 21):1362361319888344.

Several studies have shown the efficacy and effectiveness of the Early Start Denver Model, both in university and in community-based settings. However, a limited number of studies have investigated predictors of outcomes. In this study, we examined outcomes in 32 children diagnosed with autism spectrum disorder after 1 year of community-based Early Start Denver Model intervention, with the aim to identify predictors of treatment objectives acquisition, as measured by the Early Start Denver Model Curriculum Checklist. At a group level, the participants demonstrated improvement in their communication as well as adaptive functioning skills, while they showed a decrease in symptom severity. The large heterogeneity in outcomes identified was related to the pre-treatment non-verbal abilities, symptom severity, action and gesture repertoire, and lexical comprehension. We discussed our results in terms of implications for developing "personalized" interventions for children with autism spectrum disorder.

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6. Huggins CF, Cameron IM, Williams JHG. Different Aspects of Emotional Awareness in Relation to Motor Cognition and Autism Traits. Front Psychol ;2019 ;10:2439.

Emotion is inherently embodied, formulated through bodily sensation, as well as expressed and regulated through action. Both expressing one’s own emotions and understanding the emotional actions of others are common areas of difficulty in autism. Moreover, reduced emotional awareness is also thought to be problematic in autism, and such difficulties may be mediated by impaired motor cognition. We aimed to examine how intensity of emotional experience and ability to differentiate between one’s own emotions relates to motor empathy and autistic traits. We hypothesized that greater motor cognition would be associated with greater emotional intensity and more refined emotion differentiation. Participants from the general population (N = 160) completed the Actions and Feelings Questionnaire (AFQ), a self-report measure assessing motor cognition, alongside the Broad Autism Phenotype Questionnaire and an emotion elicitation task. Motor cognition was significantly associated with more intense emotional experiences but not with ability to differentiate between similar emotions. Autistic traits, particularly social aloofness, predicted less emotion differentiation and lower scores on the animation subscale of the AFQ. We suggest that whereas as intensity of experience may be dependent on sensorimotor representation of emotions, differentiation requires additional cognitive functions such as language understanding. A dissociation between awareness of intensity and differentiation may be critical for understanding emotional difficulties in autism.

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7. Kraemer BR, Odom SL, Tomaszewski B, Hall LJ, Dawalt L, Hume KA, Steinbrenner JR, Szidon K, Brum C. Quality of high school programs for students with autism spectrum disorder. Autism ;2019 (Nov 21):1362361319887280.

The purpose of the study was to examine the quality of high school programs for students with autism spectrum disorder in the United States. The Autism Program Environment Rating Scale-Middle/High School was used to rate the quality of programs for students with autism spectrum disorder in 60 high schools located in three geographic locations in the United States (CA, NC, and WI). Findings indicated that the total quality rating across schools was slightly above the adequate criterion. Higher quality ratings occurred for program environment, learning climate, family participation, and teaming domains. However, quality ratings for intervention domains related to the characteristics of autism spectrum disorder (e.g. communication, social, independence, functional behavior, and transition) were below the adequate quality rating level. Also, quality ratings for transition were significantly higher for modified (primarily self-contained) programs than standard diploma (primarily served in general education) programs. School urbanicity was a significant predictor of program quality, with suburban schools having higher quality ratings than urban or rural schools, controlling for race, school enrollment size, and Title 1 eligibility status. Implications for working with teachers and school teams that support high school students with autism spectrum disorder should include a targeted focus on transition programming that includes a breadth of work-based learning experiences and activities that support social-communication domains.

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8. Lim J, Ryu J, Kang S, Noh HJ, Kim CH. Autism-like behaviors in male mice with a Pcdh19 deletion. Mol Brain ;2019 (Nov 20) ;12(1):95.

Mutations in protocadherin 19 (PCDH19), which is on the X-chromosome, cause the brain disease Epilepsy in Females with Mental Retardation (EFMR). EFMR is also often associated with autism-like symptoms. In mice and humans, epilepsy occurs only in heterozygous females who have a mixture of PCDH19 wild-type (WT) and mutant cells caused by random X-inactivation ; it does not occur in hemizygous PCDH19 mutant males. This unique inheritance pattern strongly suggests the underlying disease mechanism operates via interference between WT and mutant cells rather than being a result of complete loss of PCDH19 functions. Although it remains unclear whether the other symptoms of EFMR also conform to this unique genotype-phenotype relationship, PCDH19 mutant males were recently reported to demonstrate autism-like symptoms. We, therefore, used a Pcdh19 knockout (KO) mouse model to ask whether a complete lack of PCDH19 causes autism-like behaviors. Consistent with the autism observed in EFMR females, we found Pcdh19 heterozygous KO female mice (with mosaic expression of PCDH19) show defects in sociability in the 3-chamber test. Surprisingly, hemizygous Pcdh19 KO male mice (without any PCDH19 expression) exhibit impaired sociability in the 3-chamber test and reduced social interactions in the reciprocal social interaction test. We also observed that, compared to WT mice, mutant mice display more repetitive behaviors, including self-grooming and rearing. These findings indicate that hemizygous Pcdh19 KO male mice show autism-like phenotypes.

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9. Mahendiran T, Brian J, Dupuis A, Muhe N, Wong PY, Iaboni A, Anagnostou E. Meta-Analysis of Sex Differences in Social and Communication Function in Children With Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. Front Psychiatry ;2019 ;10:804.

Background : Sex differences in the prevalence of neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are well documented, but studies examining sex differences in social and communication function remain limited and inconclusive. Objectives : The objective of this study is to conduct a meta-analysis of sex differences in social-communication function in children with ASD or ADHD and typically developing controls. Methods : Using PRISMA, a search was performed on Medline and PSYCHINFO on English-language journals (2000-2017) examining sex differences in social and communication function in ASD and ADHD compared to controls. Inclusion criteria : 1) peer reviewed journal articles, 2) diagnosis of ASD or ADHD and controls, 3) age 6-18 years, 4) measures of social-communication function, and 5) means, standard deviations, and sample sizes reported in order to calculate standardized mean differences (SMD). Results : Eleven original/empirical studies met inclusion criteria for ASD and six for ADHD. No significant sex differences were found between ASD and controls in social (SMD = -0.43 ; p = 0.5 ; CI : -1.58-0.72), or communication function (SMD = 0.86 ; p = 0.5 CI ; -1.57—3.30) and between ADHD and controls in social function (SMD = -0.68 : p = 0.7, CI : -4.17-2.81). No studies evaluated sex differences in communication in ADHD. Significant heterogeneity was noted in all analyses. Type of measure may have partially accounted for some variability between studies. Conclusions : The meta-analysis did not detect sex differences in social and communication function in children with ASD and ADHD ; however, significant heterogeneity was noted. Future larger studies, controlling for measure and with adequate numbers of female participants are required to further understand sex differences in these domains.

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10. Morin-Parent F, Champigny C, Lacroix A, Corbin F, Lepage JF. Hyperexcitability and impaired intracortical inhibition in patients with fragile-X syndrome. Transl Psychiatry ;2019 (Nov 20) ;9(1):312.

Fragile-X syndrome (FXS) is characterized by neurological and psychiatric problems symptomatic of cortical hyperexcitability. Recent animal studies identified deficient gamma-aminobutyricacid (GABA) inhibition as a key mechanism for hyperexcitability in FXS, but the GABA system remains largely unexplored in humans with the disorder. The primary objective of this study was to assess GABA-mediated inhibition and its relationship with hyperexcitability in patients with FXS. Transcranial magnetic stimulation (TMS) was used to assess cortical and corticospinal inhibitory and excitatory mechanisms in 18 patients with a molecular diagnosis of FXS and 18 healthy controls. GABA-mediated inhibition was measured with short-interval intracortical inhibition (GABAA), long-interval intracortical inhibition (GABAB), and the corticospinal silent period (GABAA+B). Net intracortical facilitation involving glutamate was assessed with intracortical facilitation, and corticospinal excitability was measured with the resting motor threshold. Results showed that FXS patients had significantly reduced short-interval intracortical inhibition, increased long-interval intracortical inhibition, and increased intracortical facilitation compared to healthy controls. In the FXS group, reduced short-interval intracortical inhibition was associated with heightened intracortical facilitation. Taken together, these results suggest that reduced GABAA inhibition is a plausible mechanism underlying cortical hyperexcitability in patients with FXS. These findings closely match those observed in animal models, supporting the translational validity of these markers for clinical research.

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11. Niu M, Li Q, Zhang J, Wen F, Dang W, Duan G, Li H, Ruan W, Yang P, Guan C, Tian H, Gao X, Zhang S, Yuan F, Han Y. Characterization of Intestinal Microbiota and Probiotics Treatment in Children With Autism Spectrum Disorders in China. Front Neurol ;2019 ;10:1084.

Background : Most previous studies have found that human intestinal microbiota affect the symptoms of autism spectrum disorder (ASD), especially gastrointestinal (GI) symptoms, but regarding this, there is limited data of non-western ethnicity. Probiotics can reconstitute the host intestinal microbiota and strengthen gastrointestinal function, however, clinical data proving the effect of probiotics treatment on ASD is lacking. Methods : This study explored the significant differences between ASD and neurotypical (NT), and the improvement of applied behavior analysis (ABA) training in combination with probiotics, vs. ABA training only. Results : We found significant differences between the ASD group and the NT group in the evenness of the intestinal microbiota and the relative abundance of the bacterial phyla and genus. At the phylum level, relative abundance of Bacteroidetes in the ASD group was significantly lower than in the NT group. At the genus level, the relative abundance of Bacteroides, Bifidobacterium, Ruminococcus, Roseburia, and Blautia in the ASD group was significantly lower than that in the NT group. After a 4-week ABA training program in combination with probiotics treatment, the ATEC and GI scores decreased more than the control group with ABA training only. Conclusion : Our findings suggest that intestinal microbiota is different between the NT children and the ASD children with or without GI problems. In combination with ABA training, probiotics treatment can bring more benefit to ASD children. Clinical trials with a more rigorous design and larger sample size are indispensable for further validation.

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12. Papadopoulos N, Sciberras E, Hiscock H, Williams K, McGillivray J, Mihalopoulos C, Engel L, Fuller-Tyszkiewicz M, Bellows ST, Marks D, Howlin P, Rinehart N. Sleeping sound with autism spectrum disorder (ASD) : study protocol for an efficacy randomised controlled trial of a tailored brief behavioural sleep intervention for ASD. BMJ Open ;2019 (Nov 19) ;9(11):e029767.

INTRODUCTION : Sleep problems are a characteristic feature of children with autism spectrum disorder (ASD) with 40% to 80% of children experiencing sleep difficulties. Sleep problems have been found to have a pervasive impact on a child’s socio-emotional functioning, as well as on parents’ psychological functioning. The Sleeping Sound ASD project aims to evaluate the efficacy of a brief behavioural sleep intervention in reducing ASD children’s sleep problems in a fully powered randomised controlled trial (RCT). Intervention impact on child and family functioning is also assessed. METHODS AND ANALYSIS : The RCT aims to recruit 234 children with a diagnosis of ASD, aged 5-13 years, who experience moderate to severe sleep problems. Participants are recruited from paediatrician clinics in Victoria, Australia, and via social media. Families interested in the study are screened for eligibility via phone, and then asked to complete a baseline survey online, assessing child sleep problems, and child and family functioning. Participants are then randomised to the intervention group or treatment as usual comparator group. Families in the intervention group attend two face-to-face sessions and a follow-up phone call with a trained clinician, where families are provided with individually tailored behavioural sleep strategies to help manage the child’s sleep problems. Teacher reports of sleep, behavioural and social functioning are collected, and cognitive ability assessed to provide measures blind to treatment group. The primary outcome is children’s sleep problems as measured by the Children’s Sleep Habits Questionnaire at 3 months post-randomisation. Secondary outcomes include parent and child quality of life ; child social, emotional, behavioural and cognitive functioning ; and parenting stress and parent mental health. Cost-effectiveness of the intervention is also evaluated. ETHICS AND DISSEMINATION : Findings from this study will be published in peer-reviewed journals and disseminated at national and international conferences, local networks and online. TRIAL REGISTRATION NUMBER : ISRCTN14077107 (ISRCTN registry dated on 3 March 2017).

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13. Pretzsch CM, Voinescu B, Lythgoe D, Horder J, Mendez MA, Wichers R, Ajram L, Ivin G, Heasman M, Edden RAE, Williams S, Murphy DGM, Daly E, McAlonan GM. Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD) : a single dose trial during magnetic resonance spectroscopy. Transl Psychiatry ;2019 (Nov 20) ;9(1):313.

Autism spectrum disorder (ASD) is a high cost neurodevelopmental condition ; and there are currently no effective pharmacological treatments for its core symptoms. This has led some families and researchers to trial alternative remedies - including the non-intoxicating Cannabis sativa-derived compound cannabidivarin (CBDV). However, how CBDV affects the human brain is unknown. Previous (pre)clinical evidence suggests that CBDV may modulate brain excitatory-inhibitory systems, which are implicated in ASD. Hence, our main aim was to test, for the first time, if CBDV shifts glutamate and/or GABA metabolites - markers of the brain’s primary excitatory and inhibitory system - in both the ’typical’ and autistic brain. Our subsidiary aim was to determine whether, within ASD, brain responsivity to CBDV challenge is related to baseline biological phenotype. We tested this using a repeated-measures, double-blind, randomized-order, cross-over design. We used magnetic resonance spectroscopy (MRS) to compare glutamate (Glx = glutamate + glutamine) and GABA + (GABA + macromolecules) levels following placebo (baseline) and 600 mg CBDV in 34 healthy men with (n = 17) and without (n = 17) ASD. Data acquisition from regions previously reliably linked to ASD (dorsomedial prefrontal cortex, DMPFC ; left basal ganglia, BG) commenced 2 h (peak plasma levels) after placebo/CBDV administration. Where CBDV significantly shifted metabolite levels, we examined the relationship of this change with baseline metabolite levels. Test sessions were at least 13 days apart to ensure CBDV wash-out. CBDV significantly increased Glx in the BG of both groups. However, this impact was not uniform across individuals. In the ASD group, and not in the typically developing controls, the ’shift’ in Glx correlated negatively with baseline Glx concentration. In contrast, CBDV had no significant impact on Glx in the DMPFC, or on GABA+ in either voxel in either group. Our findings suggest that, as measured by MRS, CBDV modulates the glutamate-GABA system in the BG but not in frontal regions. Moreover, there is individual variation in response depending on baseline biochemistry. Future studies should examine the effect of CBDV on behaviour and if the response to an acute dose of CBDV could predict a potential clinical treatment response in ASD.

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14. Satkoske V, Migyanka JM, Kappel D. Autism and Advance Directives : Determining Capability and the Use of Health-Care Tools to Aid in Effective Communication and Decision-Making. Am J Hosp Palliat Care ;2019 (Nov 21):1049909119888621.

With the growing number of individuals with Autism Spectrum Disorder (ASD) reaching the age of consent, health-care providers must be prepared to bridge gaps in their knowledge of ASD. This is especially true for clinicians who may have to determine if a person with ASD has the capacity to engage in end-of-life decision making, complete advance directives, or act as a surrogate decision maker for someone else. This paper provides an overview of the unique characteristics of autism as related to the communication, cognitive processing, and the capability to participate in advance care planning and, when acting as a surrogate decision maker, to consider the values and preferences of others. In addition, we examine the roles and responsibilities of clinician as facilitator of shared health-care decision making communication with the individual who has autism. Consideration is given to determining capacity, planning for atypical responses, the impact or lack of influence of the framing effect, and strategies for presenting information. Finally, we will offer health-care providers information and examples for adapting their existing end-of-life decision-making tools and conversation guides to meet the communication needs of persons with ASD.

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15. Semmel ES, Fox ME, Na SD, Kautiainen R, Latzman RD, King TZ. Caregiver- and Clinician-Reported Adaptive Functioning in Rett Syndrome : a Systematic Review and Evaluation of Measurement Strategies. Neuropsychol Rev ;2019 (Nov 20)

Rett syndrome is the second most common cause of intellectual disability in females worldwide. The severity of many individuals’ impairment limits the effectiveness of traditional assessment. However, clinician and parent reports of adaptive functioning may provide insight into these patients’ abilities. This review aims to synthesize the current literature assessing adaptive functioning in Rett syndrome and evaluate existing measurement tools in this population. A search was conducted on PubMed using the search term "Rett syndrome." Studies that quantitatively assessed adaptive functioning outcomes in Rett syndrome with published and normed questionnaire measures were included. Twenty-three studies met inclusion criteria. Overall results indicate that the population of people with Rett syndrome is highly impaired, both in overall adaptive functioning as well as in specific subdomains (e.g., mobility, activities of daily living). Atypical Rett syndrome groups performed better on measures of adaptive functioning relative to patients with classic Rett syndrome. Our findings identified measurement weaknesses, as many of the studies found floor effects and therefore were unable to capture meaningful variability in outcomes. Individuals with Rett syndrome are highly reliant on caregivers due to disrupted adaptive functioning abilities. Optimizing measurement of adaptive skills in Rett syndrome will facilitate the quantification of meaningful change in skills and the identification of efficacious interventions aimed at improving outcomes and quality of life.

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16. Yankowitz LD, Schultz RT, Parish-Morris J. Pre- and Paralinguistic Vocal Production in ASD : Birth Through School Age. Curr Psychiatry Rep ;2019 (Nov 20) ;21(12):126.

PURPOSE OF REVIEW : We review what is known about how pre-linguistic vocal differences in autism spectrum disorder (ASD) unfold across development and consider whether vocalization features can serve as useful diagnostic indicators. RECENT FINDINGS : Differences in the frequency and acoustic quality of several vocalization types (e.g., babbles and cries) during the first year of life are associated with later ASD diagnosis. Paralinguistic features (e.g., prosody) measured during early and middle childhood can accurately classify current ASD diagnosis using cross-validated machine learning approaches. Pre-linguistic vocalization differences in infants are promising behavioral markers of later ASD diagnosis. In older children, paralinguistic features hold promise as diagnostic indicators as well as clinical targets. Future research efforts should focus on (1) bridging the gap between basic research and practical implementations of early vocalization-based risk assessment tools, and (2) demonstrating the clinical impact of targeting atypical vocalization features during social skill interventions for older children.

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