Pubmed du 15/10/19

mardi 15 octobre 2019

1. Li Y, Zhu Y, Nguchu BA, Wang Y, Wang H, Qiu B, Wang X. Dynamic Functional Connectivity Reveals Abnormal Variability and Hyper-connected Pattern in Autism Spectrum Disorder. Autism Res ;2019 (Oct 15)

Autism spectrum disorder (ASD) is a general neurodevelopmental disorder associated with altered brain connectivity. However, most connectivity analyses in ASD focus on static functional connectivity, largely neglecting brain activity dynamics that have been reported to provide deeper insight into the underlying mechanisms of brain functions. Therefore, we anticipate that the use of dynamic functional connectivity (DFC) with interaction of clustering measures could help characterize ASD severity and reveal more information. In this study, we applied the sliding-window and k-means clustering methods to perform DFC and clustering analyses in ASD and typically developing (TD) groups. Data from 62 ASD and 63 TD children were acquired from the open-access data set Autism Brain Imaging Data Exchange. Our findings revealed higher DFC variability between the posterior cingulate gyrus (PCC) and middle temporal pole (TPOmid) in subjects with ASD. The connection between the PCC and pars opercularis of inferior frontal gyrus (IFGoper) also presented greater variability in ASD, with the increase depending on ASD symptom severity. Furthermore, clustering analysis showed higher averaged dwell time and probability of transition for globally hyper-connected state in the ASD group, which could be related to connection variability between the PCC and IFGoper. Our results demonstrate that both the PCC and IFGoper play crucial roles in characterizing symptom severity and state configuration in ASD, and brain connectivity dynamics may serve as potential indicators of ASD in future studies. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Dynamic functional connectivity (DFC) refers to functional connectivity that changes over a short time. This study found that DFC instability between the posterior cingulate gyrus and pars opercularis of inferior frontal gyrus is associated with abnormal brain pattern configurations and dysfunction of social cognitive processes in autism spectrum disorder (ASD). These findings could contribute to a deeper understanding of the neural mechanisms of ASD and help characterize ASD severity.

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2. Nystrom P, Thorup E, Bolte S, Falck-Ytter T. Joint Attention in Infancy and the Emergence of Autism. Biol Psychiatry ;2019 (Oct 15) ;86(8):631-638.

BACKGROUND : In typical infant development, parents and their children jointly contribute to establishing frequent episodes of joint attention that boost language acquisition and shape social cognition. Here we used novel live eye-tracking technology to evaluate the degree to which autism spectrum disorder (ASD) is related to reduced responding to others’ joint attention bids in infancy (RJA) and to a reduced tendency to initiate joint attention episodes (IJA). Because young infants use their gaze for both RJA and IJA, this approach allowed us to quantify these elusive processes early in life. METHODS : The final sample consisted of 112 infants (54 boys and 58 girls), of whom 81 were at familial risk for ASD and 31 were typically developing low-risk infants. At follow-up (36 months of age), 22 children in the high-risk group were diagnosed with ASD. RESULTS : At 10 months of age, rates of IJA were lower in infants later diagnosed with ASD than in the comparison groups (effect sizes d = 0.78-0.95) and followed an atypical developmental trajectory from 10 to 18 months (p < .002). RJA distinguished infants based on familial ASD risk, albeit not ASD diagnosis. The differences in IJA could not be explained by overall looking time, social preference, eye movement latencies, or number of fixations. CONCLUSIONS : This live eye-tracking study suggests that during an important period for the development of social cognition (10-18 months of age), infants later diagnosed with ASD show marked atypicalities in IJA but not in RJA. The results indicate that IJA is an important target for future prodromal intervention trials.

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3. Solberg BS, Zayats T, Posserud MB, Halmoy A, Engeland A, Haavik J, Klungsoyr K. Patterns of Psychiatric Comorbidity and Genetic Correlations Provide New Insights Into Differences Between Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder. Biol Psychiatry ;2019 (Oct 15) ;86(8):587-598.

BACKGROUND : Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share common genetic factors but seem to have specific patterns of psychiatric comorbidities. There are few systematic studies on adults ; therefore, we compared psychiatric comorbidities in adults with these two neurodevelopmental disorders using population-based data and analyzed their genetic correlations to evaluate underlying factors. METHODS : Using data from Norwegian registries, we assessed patterns of psychiatric disorders in adults with ADHD (n = 38,636 ; 2.3%), ASD (n = 7528 ; 0.4%), and both diagnoses (n = 1467 ; 0.1%) compared with the remaining adult population (n = 1,653,575). We calculated their prevalence ratios (PRs) and differences using Poisson regression, also examining sex-specific relations. Genetic correlations (rg) among ADHD, ASD, and the examined psychiatric disorders were calculated by linkage disequilibrium score regression, exploiting summary statistics from relevant genome-wide association studies. RESULTS : For all psychiatric comorbidities, PRs differed between ADHD and ASD. Associations were strongest in individuals with ADHD and ADHD+ASD for most comorbidities, in both men and women. The relative prevalence increase of substance use disorder was three times larger in ADHD than in ASD (PRADHD, 6.2 ; 95% confidence interval [CI], 6.1-6.4 ; PRASD, 1.9 ; 95% CI, 1.7-2.2 ; p < .001) ; however, the opposite was true for schizophrenia (PRASD, 13.9 ; 95% CI, 12.7-15.2 ; PRADHD, 4.4 ; 95% CI, 4.1-4.7 ; p < .001). Genetic correlations supported these patterns but were significantly different between ADHD and ASD only for the substance use disorder proxies and personality traits (p < .006 for all). CONCLUSIONS : Adults with ADHD, ASD, or both ADHD and ASD have specific patterns of psychiatric comorbidities. This may partly be explained by differences in underlying genetic factors.

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4. Turner TN. Large-Scale Population-Based Assessment of Psychiatric Comorbidities in Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. Biol Psychiatry ;2019 (Oct 15) ;86(8):e25-e27.

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5. Yamane K, Fujii Y, Hijikata N. Support and development of autistic children with selective eating habits. Brain Dev ;2019 (Oct 10)

AIMS : We provided 3 special diets to 40 preschool children with autism at lunchtime and detected improvements in diet-related issues in almost all of the children. The children fell into the following 3 groups : those who selected their diet based on : group1=sensory factors ; group2=visual appearance of foods ; and group3=familiar foods. To identify effective support, we performed developmental and sensory assessments of each group retrospectively. METHOD : There were 7 children in group1, 9 in group2, and 24 in group3. The duration of support was 1-3years. We performed developmental assessments before and after the support period. RESULTS : We found improvement in diet-related issues in almost all children. Initially, the mean developmental age for language understanding differed among group1 (10.8months), group2 (14.7months), and group3 (16.6months). Furthermore, with respect to basic ability in daily life, the mean developmental age in group1 (19.2months) was lower than that in group3 (24.8months). Finally, the mean developmental quotient in group3 (49.6) was higher than that in group1 (36.4) and group2 (40.8). No significant differences were observed in sensory assessment among the groups. CONCLUSIONS : Developmental assessment can be useful for determining the type of support. Group1 support is suitable for children in the pre-language stage. Group2 support is suitable for children who can recognize shapes or understand instructions in simple language. Group3 support is suitable for children who can understand instructions in simple language and a daily routine.

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6. Burnham Riosa P, Khan M, Weiss J. Measuring therapeutic alliance in children with autism during cognitive behavior therapy. Clin Psychol Psychother ;2019 (Oct 15)

Therapeutic alliance (TA), or the collaborative relationship between a therapist and client, has been shown to be an important component of intervention success. The objective of this study was to examine the psychometric properties of the Therapy Process Observational Coding System-Alliance Scale (TPOCS-A). The sample consisted of 20 children (19 males) ages 8 to 12 years with autism and their parents (15 mothers, 5 fathers), who completed a cognitive behavioural intervention designed to improve children’s emotion regulation skills. Two trained coders rated early, middle, and late parent and child alliance using the TPOCS-A after watching video recorded therapy sessions. Therapist-reported child involvement, alliance, and adherence was also assessed. Psychometric findings revealed that the TPOCS-A is a reliable and valid measure of therapeutic alliance for children with autism. The implications of examining TA in empirically supported treatments for this population are discussed.

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7. Layne CS, Young DR, Lee BC, Glaze DG, Schwabe A, Suter B. Kinematics associated with treadmill walking in Rett syndrome. Disabil Rehabil ;2019 (Oct 15):1-9.

Background and purpose : Individuals with Rett syndrome suffer from severely impaired cognitive and motor performance. Current movement-related therapeutic programs often include traditional physical therapy activities and assisted treadmill walking routines for those individuals who are ambulatory. However, there are no quantitative reports of kinematic gait parameters obtained during treadmill walking. The purpose of this research was to characterize the kinematic patterns of the lower limbs during treadmill walking as speed was slowly increased. Methods : Seventeen independently ambulatory females diagnosed with a methyl-CpG-binding protein 2 gene mutation walked on a motorized treadmill while joint kinematics were obtained by a camera-based motion capture system and analysis software. Results : Stride times progressively decreased as treadmill speeds increased. There were significant main effects of speed on sagittal knee and hip ranges of motion and hip velocity. There were large joint asymmetries and variance values relative to other ambulatory patient populations, although variance values decreased as walking speed increased. Conclusions : The results indicate that individuals with Rett syndrome can adapt their kinematic gait patterns in response to increasing treadmill speed, but only within a narrow range of speeds. We suggest that treadmill training for ambulatory individuals with Rett syndrome may promote improved walking kinematics and possibly provide overall health benefits. Implications for rehabilitation Walking is an activity that can counter the negative impacts of the sedentary lifestyle of many individuals with disabilities, including those individuals with Rett syndrome. Documentation of the lower limb kinematic patterns displayed during walking by ambulatory females with Rett syndrome can be used by clinicians to evaluate their patients’ gait performance in response to therapeutic and pharmacological interventions designed to promote walking. The ability to adapt to increases in treadmill speed suggests that a training program of treadmill walking may be effective in promoting improved gait performance in individuals with Rett syndrome.

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8. Jo H, Eckel SP, Chen JC, Cockburn M, Martinez MP, Chow T, Lurmann FW, Funk WE, Xiang AH, McConnell R. Gestational diabetes mellitus, prenatal air pollution exposure, and autism spectrum disorder. Environ Int ;2019 (Oct 11) ;133(Pt A):105110.

BACKGROUND : Ambient air pollution and maternal diabetes may affect common biological pathways underlying adverse neurodevelopmental effects. However, joint effects of maternal diabetes and air pollution on autism spectrum disorder (ASD) have not been studied. OBJECTIVE : We evaluated whether prenatal and early-life air pollution exposure interacts with maternal diabetes status to affect ASD risk. METHODS : This retrospective cohort study included 246,420 singleton children born in Kaiser Permanente Southern California hospitals in 1999-2009. Children were followed from birth until age 5, during which 2471 ASD cases were diagnosed. Ozone (O3), particulate matter<2.5mum (PM2.5) and <10mum in aerodynamic diameter, and nitrogen dioxide measured at regulatory air monitoring stations were interpolated to estimate exposures during preconception and each pregnancy trimester, and first year of life at each child’s birth address. Hazard ratios (HRs) for ASD were estimated adjusting for birth year, KPSC service areas, and relevant maternal and child characteristics. For each exposure window, interactions were tested between pollutants and a 4-category maternal diabetes variable (none, GDM>/=24 and <24weeks’ gestation, and pre-existing type 2 diabetes). For an exposure window with statistically significant global interaction between pollutant and diabetes (p<0.05), pollutant-associated HRs were estimated separately for each category of maternal diabetes. RESULTS : There were associations of ASD with preconception, first and third trimesters, and first year of life PM2.5, but not with other pollutants. There were, however, interactions of maternal diabetes with first trimester and first year of life O3. Increased ASD risk was associated with first trimester O3 among mothers with GDM<24weeks’ gestation [adjusted HR 1.50 per 15.7ppb O3 (95% CI : 1.08-2.09)]. No O3 associations with ASD were observed in other categories of maternal diabetes. CONCLUSIONS : GDM onset early in pregnancy may increase children’s susceptibility to prenatal O3-associated ASD risk. These novel findings merit further investigation.

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9. Parker ML, Diamond RM, Auwood LH. Exploring Exceptions and Discovering Solutions : A Case Presentation of Autism and the Family. Fam Process ;2019 (Oct 15)

As the prevalence of autism spectrum disorder (ASD) continues to rise, there is a rapidly increasing need for treatment services among individuals diagnosed with ASD and families. Currently, the majority of the evidence-based treatments, such as Applied Behavior Analysis, overlook the notable systemic effects of ASD and maintain a problem-focused lens. There is a growing body of research calling for strength-based, relational interventions that build on existing resources to enhance coping, efficacy, and well-being among families affected by ASD. Solution-Focused Brief Therapy (SFBT) is a widely practiced clinical approach that is increasingly being used among clinicians to address the systemic effects of developmental disabilities in the family. However, particular modifications to specific interventions may better accommodate autism-associated deficits in executive functioning (e.g., goal development and impulsivity), perspective taking, or restricted interests when using an SFBT approach. This article offers recommendations for adapting a solution-focused approach by modifying commonly used SFBT interventions to address family-driven treatment goals using a collaborative stance with families of children with ASD. A case presentation is included to demonstrate SFBT as informed by the unique challenges and inherent resources of families affected by ASD that have been identified in the extant literature.

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10. Miot S, Akbaraly T, Michelon C, Couderc S, Crepiat S, Loubersac J, Picot MC, Pernon E, Gonnier V, Jeandel C, Blain H, Baghdadli A. Comorbidity Burden in Adults With Autism Spectrum Disorders and Intellectual Disabilities-A Report From the EFAAR (Frailty Assessment in Ageing Adults With Autism Spectrum and Intellectual Disabilities) Study. Front Psychiatry ;2019 ;10:617.

Background : Autism spectrum disorder (ASD) is an early-onset and lifelong neurodevelopmental condition frequently associated with intellectual disability (ID). Although emerging studies suggest that ASD is associated with premature ageing and various medical comorbidities, as described for ID, data are scarce. Objectives : To determine the comorbidity burden and its association with distinct clinical presentation in terms of ASD severity, adaptive skills, level of autonomy, and drug exposure in a well-phenotyped sample of individuals with ASD-ID-the EFAAR (Frailty Assessment in Ageing Adults with Autism Spectrum and Intellectual Disabilities) cohort. Methods : A total of 63 adults with ASD-ID, with a mean age of 42.9 +/- 15.1 years, were recruited from 2015 to 2017 from nine specialized institutions. They underwent detailed clinical examinations, including screening for comorbidities, ASD severity [Childhood Autism Rating Scale (CARS)], adaptive functioning [Vineland Adaptive Behavior Scale II (VABS-II)], autonomy [activities of daily living (ADLs)], and drug use [polypharmacy and the Drug Burden Index (DBI)]. The comorbidity burden was evaluated using the Cumulative Illness Rating Scale (CIRS-G) and its sub-scores [the severity index (CIRS-SI) and severe comorbidity (CIRS-SC)]. Results : We found a large range of comorbidities, including gastrointestinal disorders and mental and neurological diseases. Overall, 25% of our ASD-ID sample had chronic kidney disease with the associated increased cardiovascular risk factors. The comorbidity burden was high (mean CIRS-G total score of 10.6 +/- 4.8), comparable with that observed among patients older than those in our population hospitalized in geriatric departments. Furthermore, the comorbidity burden positively correlated with age, decreased autonomy, and polypharmacy. Conclusion : The severity of the comorbidity burden associated with premature ageing in adults with ASD and ID highlight their crucial need of personalized medical care.

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11. Stickel S, Weismann P, Kellermann T, Regenbogen C, Habel U, Freiherr J, Chechko N. Audio-visual and olfactory-visual integration in healthy participants and subjects with autism spectrum disorder. Hum Brain Mapp ;2019 (Oct 15) ;40(15):4470-4486.

The human capacity to integrate sensory signals has been investigated with respect to different sensory modalities. A common denominator of the neural network underlying the integration of sensory clues has yet to be identified. Additionally, brain imaging data from patients with autism spectrum disorder (ASD) do not cover disparities in neuronal sensory processing. In this fMRI study, we compared the underlying neural networks of both olfactory-visual and auditory-visual integration in patients with ASD and a group of matched healthy participants. The aim was to disentangle sensory-specific networks so as to derive a potential (amodal) common source of multisensory integration (MSI) and to investigate differences in brain networks with sensory processing in individuals with ASD. In both groups, similar neural networks were found to be involved in the olfactory-visual and auditory-visual integration processes, including the primary visual cortex, the inferior parietal sulcus (IPS), and the medial and inferior frontal cortices. Amygdala activation was observed specifically during olfactory-visual integration, with superior temporal activation having been seen during auditory-visual integration. A dynamic causal modeling analysis revealed a nonlinear top-down IPS modulation of the connection between the respective primary sensory regions in both experimental conditions and in both groups. Thus, we demonstrate that MSI has shared neural sources across olfactory-visual and audio-visual stimulation in patients and controls. The enhanced recruitment of the IPS to modulate changes between areas is relevant to sensory perception. Our results also indicate that, with respect to MSI processing, adults with ASD do not significantly differ from their healthy counterparts.

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12. Kadwa RA, Sahu JK, Singhi P, Malhi P, Mittal BR. Prevalence and Characteristics of Sensory Processing Abnormalities and its Correlation with FDG-PET Findings in Children with Autism. Indian J Pediatr ;2019 (Oct 15)

OBJECTIVE : To study the prevalence and characteristics of Sensory processing abnormalities (SPAs) in children with autism and to study if there is any correlation between sensory processing abnormalities with FDG-PET findings in children with severe autism. METHODS : One hundred children, aged 3-12 y, diagnosed as Autistic spectrum disorder ; ASD (DSM-V) and 100 age and sex matched controls were studied. SPAs were detected using Short sensory profile (SSP) questionnaire. Children with progressive neurological diseases, active epilepsy and structural brain abnormalities were excluded. On Childhood Autism rating scale, 30 children had severe and 70 had mild-moderate autism. The pattern of sensory processing abnormalities in children with severe ASD was compared with mild-moderate ASD. FDG-PET scan was done in children with severe autism and correlated with SPAs. RESULTS : All children with severe autism had sensory processing abnormalities as compared to only 40% children with mild-moderate autism. Underresponsiveness/seeking-sensation was affected in all children with severe ASD and 82% had movement sensitivity. In children with mild-moderate ASD, 45% had auditory filtering, 30% had movement sensitivity and 27% had underresponsiveness/seeking-sensation. FDG-PET was abnormal in 17% of children with severe autism. Diffuse cerebral/ temporal lobe hypometabolism, increased bilateral frontal lobe uptake and moderate reduction in parietal lobe (Lt > Rt) was observed. CONCLUSIONS : All patients with severe autism had SPAs. However, they did not correlate with FDG-PET findings.

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13. Lin FY, Zhu J. Comparison of two discrimination methods in teaching Chinese children with autism. J Appl Behav Anal ;2019 (Oct 14)

In teaching conditional discriminations to children with autism spectrum disorder (ASD), practitioners may progress from simple to conditional discriminations or may teach conditional discriminations from the onset of instruction. Some research indicates that teaching simple discriminations first may be unnecessary and that teaching may more efficiently focus on conditional discriminations exclusively. This study replicated comparisons of simple-to-conditional and conditional-only discrimination training methods in teaching audio-visual conditional discriminations to Chinese preschoolers with ASD. Results indicated the conditional-only training method appeared to be more efficient in teaching these skills.

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14. White SW, Smith IC, Miyazaki Y, Conner CM, Elias R, Capriola-Hall NN. Improving Transition to Adulthood for Students with Autism : A Randomized Controlled Trial of STEPS. J Clin Child Adolesc Psychol ;2019 (Oct 14):1-15.

Emerging adulthood is a period of heightened risk for young people with autism spectrum disorder (ASD). Due in part to a lack of evidence-based services and supports during the transition to adulthood, many emerging adults fail to matriculate into postsecondary education or thrive in productive employment. The Stepped Transition in Education Program for Students with ASD (STEPS) was developed to address the psychosocial, transition-related needs of emerging adults with ASD. Adolescents and emerging adults (n = 59) with ASD were randomly assigned to either STEPS or transition as usual (TAU). Results indicate that STEPS is acceptable to young people with ASD and their parents and that it can be implemented with high fidelity. Among secondary school students, those who completed STEPS exhibited significantly greater gains in transition readiness from high school, and these gains were largely sustained after program completion. Among students enrolled in postsecondary education, STEPS resulted in increased levels of student adaptation to college relative to those in TAU. Programming to address ASD-related challenges can promote successful educational transitions.

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15. Sarber KM, Howard JJM, Dye TJ, Pascoe JE, Simakajornboon N. Sleep-Disordered Breathing in Pediatric Patients With Rett Syndrome. J Clin Sleep Med ;2019 (Oct 15) ;15(10):1451-1457.

STUDY OBJECTIVES : Although respiratory abnormalities occurring during wakefulness are well recognized in patients with Rett syndrome (RS), less has been reported regarding sleep-disordered breathing (SDB) in this population. This study aims to characterize the presenting complaints, types and severity of SDB, and treatment modalities of patients with RS and sleep concerns. METHODS : Retrospective chart review of pediatric patients with RS referred to our academic tertiary care institution from January 2007 to July 2017. RESULTS : Thirteen patients were identified, 11 female (84.6%) ; mean age at polysomnography (PSG) was 10.3 years (standard deviation 4.94). Eleven were white (84.6%), 2 were black (15.4%). The most common presenting symptoms were snoring (10/13, 77%) and witnessed apnea (7/13, 53.8%). On baseline PSG, all patients (100%) exhibited hyperapneas followed by a central apnea during wake. Nine (69.2%) had obstructive sleep apnea (OSA) (obstructive apnea-hypopnea index (oAHI) > 1) ; four had severe OSA (oAHI >/= 10). One had central sleep apnea (central apnea index > 5) and severe OSA. No patients exhibited hypoventilation on baseline PSG. Mean AHI of all patients was 8.77 +/- 8.82 (oAHI 6.51 +/- 6.91) events/h. Mean oxyhemoglobin nadir was 88.52 +/- 5.6%. Treatment modalities included observation : 5 (38%), acetazolamide : 2 (15%), nasal mometasone : 1 (7.7%), adenotonsillectomy : 3 (23.1%), and positive airway pressure : 2 (15%). CONCLUSIONS : Regarding patients with RS referred to the sleep medicine clinic, snoring and witnessed apneas were the most common presenting complaints. In addition to breathing abnormalities during wake, OSA was very common in our cohort. Further studies are needed to examine the pathogenesis of OSA in RS and relationships between disease genotype and respiratory abnormality phenotype.

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16. Singer EV, Shelton AR, Malow BA. Can We Predict Which Children With Autism Will Have Obstructive Sleep Apnea ?. J Clin Sleep Med ;2019 (Oct 15) ;15(10):1389-1390.

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17. Tomkies A, Johnson RF, Shah G, Caraballo M, Evans P, Mitchell RB. Obstructive Sleep Apnea in Children With Autism. J Clin Sleep Med ;2019 (Oct 15) ;15(10):1469-1476.

STUDY OBJECTIVES : To describe the demographic and clinical characteristics of children with autism spectrum disorder (ASD) referred for polysomnography (PSG) and to look for predictors of obstructive sleep apnea (OSA) and severe OSA in these children. METHODS : This is a retrospective case series of children ages 2 to 18 years who underwent PSG between January 2009 and February 2015. Children were excluded if they had major comorbidities, prior tonsillectomy, or missing data. The following information was collected : age, sex, race, height, weight, tonsil size, and prior diagnosis of allergies, asthma, gastroesophageal reflux disease, seizure disorder, developmental delay, cerebral palsy, or attention deficit hyperactivity disorder. Predictors of OSA were evaluated. RESULTS : A total of 45 children were included with a mean (standard deviation [SD]) age of 6.1 years (2.8). The patients were 80% male, 49% Hispanic, 27% African American, 22% Caucasian, and 2.2% other. Of these children 26 (58%) had OSA (apnea-hypopnea index [AHI] > 1 event/h) and 15 (33%) were obese (body mass index, body mass index z-score >/= 95th percentile). The mean (SD) AHI was 7.7 (15.0) events/h (range 1.0-76.6). A total of 9 (20%) had severe OSA (AHI >/= 10 events/h). There were no demographic or clinical predictors of OSA in this group. However, increasing weight served as a predictor of severe OSA and African American or Hispanic children were more likely obese. CONCLUSIONS : The absence of demographic or clinical predictors of OSA supports using general indications for PSG in children with ASD.

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18. Joshi G, DiSalvo M, Wozniak J, Ceranoglu TA, Yule A, Surman C, Fried R, Galdo M, Hoskova B, Belser A, Biederman J. A Prospective Open-Label Trial of Long-Acting Liquid Methylphenidate for the Treatment of Attention Deficit/Hyperactivity Disorder in Intellectually Capable Adults with Autism Spectrum Disorder. World J Biol Psychiatry ;2019 (Oct 14):1-42.

Objectives : This treatment trial is aimed at assessing the short-term tolerability and efficacy of liquid-formulation extended-release methylphenidate (MPH-ER) for the treatment of ADHD in adults with high-functioning autism spectrum disorder (HF-ASD). Methods : Six-week open-label trial (ClinicalTrials.gov : NCT02096952) was conducted in 15 HF-ASD adults (mean age : 24.9 +/- 4.6 ; male : 12 [80%]) suffering from moderate-severe ADHD. MPH-ER was administered based on a flexible titration schedule. Efficacy was assessed on clinician- and self-rated measures. Tolerability was assessed by documenting treatment-emergent adverse events (AEs) and other safety measures. Results : Short-term MPH-ER treatment was associated with significant improvement in ADHD severity (Adult ADHD Investigator Symptom Report Scale [AISRS] mean change [MC] : -22.8 +/- 8.8, p < 0.001 ; Adult ADHD Self-Report Scale [ASRS] MC : -8.2 +/- 15.3, p < 0.001). Twelve (80%) participants were deemed responders, based on >/=30% reduction in AISRS score and an ADHD Clinical Global Impression-Improvement score </=2. MPH-ER was well-tolerated (treatment-limiting AEs : 1/15 ; severe AEs : 1/15) at mean dose of 48.7 +/- 15 mg/day. AEs were transient and experienced by 13/15 (87%) participants at mild to moderate severity. Frequently reported AEs were as typically expected (headache [53%], insomnia [33%], anxiety [33%], decreased appetite [27%]). Conclusions : Our findings suggest that MPH-ER is effective and well-tolerated in the treatment of ADHD in HF-ASD adults.

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