1. Aman MG, Hollway JA, Veenstra-VanderWeele J, Handen BL, Sanders KB, Chan J, Macklin E, Arnold LE, Wong T, Newsom C, Hastie Adams R, Marler S, Peleg N, Anagnostou EA. {{Effects of Metformin on Spatial and Verbal Memory in Children with ASD and Overweight Associated with Atypical Antipsychotic Use}}. {J Child Adolesc Psychopharmacol}. 2018.
OBJECTIVES: Studies in humans and rodents suggest that metformin, a medicine typically used to treat type 2 diabetes, may have beneficial effects on memory. We sought to determine whether metformin improved spatial or verbal memory in children with autism spectrum disorder (ASD) and overweight associated with atypical antipsychotic use. METHODS: We studied the effects of metformin (Riomet((R))) concentrate on spatial and verbal memory in 51 youth with ASD, ages 6 through 17 years, who were taking atypical antipsychotic medications, had gained significant weight, and were enrolled in a trial of metformin for weight management. Phase 1 was a 16-week, randomized, double-blind, placebo-controlled, parallel-group comparison of metformin (500-850 mg given twice a day) versus placebo. During Phase 2, all participants took open-label metformin from week 17 through week 32. We assessed spatial and verbal memory using the Neuropsychological Assessment 2nd Edition (NEPSY-II) and a modified children’s verbal learning task. RESULTS: No measures differed between participants randomized to metformin versus placebo, at either 16 or 32 weeks, after adjustment for multiple comparisons. Sixteen-week change in memory for spatial location on the NEPSY-II was nominally better among participants randomized to placebo. However, patterns of treatment response across all measures revealed no systematic differences in performance, suggesting that metformin had no effect on spatial or verbal memory in these children. CONCLUSIONS: Although further study is needed to support these null effects, the overall impression is that metformin does not affect memory in overweight youth with ASD who were taking atypical antipsychotic medications.
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2. Filipe MG, Frota S, Vicente SG. {{Executive Functions and Prosodic Abilities in Children With High-Functioning Autism}}. {Front Psychol}. 2018; 9: 359.
Little is known about the relationship between prosodic abilities and executive function skills. As deficits in executive functions (EFs) and prosodic impairments are characteristics of autism, we examined how EFs are related to prosodic performance in children with high-functioning autism (HFA). Fifteen children with HFA (M = 7.4 years; SD = 1.12), matched to 15 typically developing peers on age, gender, and non-verbal intelligence participated in the study. The Profiling Elements of Prosody in Speech-Communication (PEPS-C) was used to assess prosodic performance. The Children’s Color Trails Test (CCTT-1, CCTT-2, and CCTT Interference Index) was used as an indicator of executive control abilities. Our findings suggest no relation between prosodic abilities and visual search and processing speed (assessed by CCTT-1), but a significant link between prosodic skills and divided attention, working memory/sequencing, set-switching, and inhibition (assessed by CCTT-2 and CCTT Interference Index). These findings may be of clinical relevance since difficulties in EFs and prosodic deficits are characteristic of many neurodevelopmental disorders. Future studies are needed to further investigate the nature of the relationship between impaired prosody and executive (dys)function.
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3. Green CC, Dissanayake C, Loesch DZ, Bui M, Barbaro J. {{Skeletal Growth Dysregulation in Australian Male Infants and Toddlers With Autism Spectrum Disorder}}. {Autism Res}. 2018.
Recent findings suggest that children with Autism Spectrum Disorder (ASD) are larger in size for head circumference (HC), height, and weight compared to typically developing (TD) children; however, little is known about their rate of growth, especially in height and weight. The current study aimed to: (a) confirm and extend upon previous findings of early generalized overgrowth in ASD; and (b) determine if there were any differences in the rate of growth between infants and toddlers with ASD compared to their TD peers. Measurements of HC, height, and weight were available for 135 boys with ASD and 74 TD boys, from birth through 3 years of age. Size and growth rate in HC, height, and weight were analyzed using a linear mixed-effects model. Infants with ASD were significantly smaller in size at birth for HC, body length, and weight compared to TD infants (all P < 0.05); however, they grew at a significantly faster rate in HC and height in comparison to the TD children (P < 0.001); there was no significant difference between the groups in growth rate for weight (P > 0.05). The results confirmed that male infants and toddlers with ASD exhibit skeletal growth dysregulation early in life. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Recent findings suggest that infants with Autism Spectrum Disorder (ASD) are smaller in size at birth compared to typically developing infants but grow larger than their peers during the first year. Little is known about their rate of growth, especially for height and weight. Our findings confirmed that infants with ASD are smaller in size at birth for head circumference (HC), height, and weight, but grow at a faster rate in HC and height than their peers from birth to 3 years.
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4. Holmes LG, Kirby AV, Strassberg DS, Himle MB. {{Parent Expectations and Preparatory Activities as Adolescents with ASD Transition to Adulthood}}. {J Autism Dev Disord}. 2018.
Community stakeholders, researchers, and providers are increasingly focused on individual, family, and systemic factors that contribute to positive outcomes for adults on the autism spectrum. Parent expectations for their youth’s future are associated with adult outcomes (e.g., employment, school success, independence), yet the mechanism for this effect remains unclear. This study investigated how expectations were related to parent transition-related activities in a sample of 298 parents of adolescents on the autism spectrum (48% female adolescents), stratified by parent-reported IQ (average or above, borderline, or below 70). Parent expectations for the future predicted engagement in some activities intended to enhance adult outcomes when controlling for IQ, gender, age, and household income. The results have implications for how providers discuss expectations and support families in preparing for adulthood.
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5. Liu CX, Li CY, Hu CC, Wang Y, Lin J, Jiang YH, Li Q, Xu X. {{CRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors}}. {Mol Autism}. 2018; 9: 23.
Background: Human genetic and genomic studies have supported a strong causal role of SHANK3 deficiency in autism spectrum disorder (ASD). However, the molecular mechanism underlying SHANK3 deficiency resulting in ASD is not fully understood. Recently, the zebrafish has become an attractive organism to model ASD because of its high efficiency of genetic manipulation and robust behavioral phenotypes. The orthologous gene to human SHANK3 is duplicated in the zebrafish genome and has two homologs, shank3a and shank3b. Previous studies have reported shank3 morphants in zebrafish using the morpholino method. Here, we report the generation and characterization of shank3b mutant zebrafish in larval and adult stages using the CRISPR/Cas9 genome editing technique. Methods: CRISPR/Cas9 was applied to generate a shank3b loss-of-function mutation (shank3b(-/-) ) in zebrafish. A series of morphological measurements, behavioral tests, and molecular analyses were performed to systematically characterize the behavioral and molecular changes in shank3b mutant zebrafish. Results: shank3b(-/-) zebrafish exhibited abnormal morphology in early development. They showed reduced locomotor activity both as larvae and adults, reduced social interaction and time spent near conspecifics, and significant repetitive swimming behaviors. Additionally, the levels of both postsynaptic homer1 and presynaptic synaptophysin were significantly reduced in the adult brain of shank3b-deficient zebrafish. Conclusions: We generated the first inheritable shank3b mutant zebrafish model using CRISPR/Cas9 gene editing approach. shank3b(-/-) zebrafish displayed robust autism-like behaviors and altered levels of the synaptic proteins homer1 and synaptophysin. The versatility of zebrafish as a model for studying neurodevelopment and conducting drug screening will likely have a significant contribution to future studies of human SHANK3 function and ASD.
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6. Lubala TK, Lumaka A, Kanteng G, Mutesa L, Mukuku O, Wembonyama S, Hagerman R, Luboya ON, Lukusa Tshilobo P. {{Fragile X checklists: A meta-analysis and development of a simplified universal clinical checklist}}. {Molecular genetics & genomic medicine}. 2018.
BACKGROUND: Clinical checklists available have been developed to assess the risk of a positive Fragile X syndrome but they include relatively small sample sizes. Therefore, we carried out a meta-analysis that included statistical pooling of study results to obtain accurate figures on the prevalence of clinical predictors of Fragile X syndrome among patients with intellectual disability, thereby helping health professionals to improve their referrals for Fragile X testing. METHODS: All published studies consisting of cytogenetic and/or molecular screening for fragile X syndrome among patients with intellectual disability, were eligible for the meta-analysis. All patients enrolled in clinical checklists trials of Fragile X syndrome were eligible for this review, with no exclusion based on ethnicity or age. Odds ratio values, with 95% confidence intervals as well as Cronbach coefficient alpha, was reported to assess the frequency of clinical characteristics in subjects with intellectual disability with and without the fragile X mutation to determine the most discriminating. RESULTS: The following features were strongly associated with Fragile X syndrome: skin soft and velvety on the palms with redundancy of skin on the dorsum of hand [OR: 16.85 (95% CI 10.4-27.3; alpha:0.97)], large testes [OR: 7.14 (95% CI 5.53-9.22; alpha: 0.80)], large and prominent ears [OR: 18.62 (95% CI 14.38-24.1; alpha: 0.98)], pale blue eyes [OR: 8.97 (95% CI 4.75-16.97; alpha: 0.83)], family history of intellectual disability [OR: 3.43 (95% CI 2.76-4.27; alpha: 0.81)] as well as autistic-like behavior [OR: 3.08 (95% CI 2.48-3.83; alpha: 0.77)], Flat feet [OR: 11.53 (95% CI 6.79-19.56; alpha:0.91)], plantar crease [OR: 3.74 (95% CI 2.67-5.24; alpha: 0.70)]. We noted a weaker positive association between transverse palmar crease [OR: 2.68 (95% CI 1.70-4.18; alpha: 0.51)], elongated face [OR: 3.69 (95% CI 2.84-4.81; alpha: 0.63)]; hyperextensible metacarpo-phalangeal joints [OR: 2.68 (95% CI 2.15-3.34; alpha: 0.57)] and the Fragile X syndrome. CONCLUSION: This study has identified the highest risk features for patients with Fragile X syndrome that have been used to design a universal clinical checklist.
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7. Mazefsky CA, Yu L, White SW, Siegel M, Pilkonis PA. {{The emotion dysregulation inventory: Psychometric properties and item response theory calibration in an autism spectrum disorder sample}}. {Autism Res}. 2018.
Individuals with autism spectrum disorder (ASD) often present with prominent emotion dysregulation that requires treatment but can be difficult to measure. The Emotion Dysregulation Inventory (EDI) was created using methods developed by the Patient-Reported Outcomes Measurement Information System (PROMIS((R)) ) to capture observable indicators of poor emotion regulation. Caregivers of 1,755 youth with ASD completed 66 candidate EDI items, and the final 30 items were selected based on classical test theory and item response theory (IRT) analyses. The analyses identified two factors: (a) Reactivity, characterized by intense, rapidly escalating, sustained, and poorly regulated negative emotional reactions, and (b) Dysphoria, characterized by anhedonia, sadness, and nervousness. The final items did not show differential item functioning (DIF) based on gender, age, intellectual ability, or verbal ability. Because the final items were calibrated using IRT, even a small number of items offers high precision, minimizing respondent burden. IRT co-calibration of the EDI with related measures demonstrated its superiority in assessing the severity of emotion dysregulation with as few as seven items. Validity of the EDI was supported by expert review, its association with related constructs (e.g., anxiety and depression symptoms, aggression), higher scores in psychiatric inpatients with ASD compared to a community ASD sample, and demonstration of test-retest stability and sensitivity to change. In sum, the EDI provides an efficient and sensitive method to measure emotion dysregulation for clinical assessment, monitoring, and research in youth with ASD of any level of cognitive or verbal ability. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This paper describes a new measure of poor emotional control called the Emotion Dysregulation Inventory (EDI). Caregivers of 1,755 youth with ASD completed candidate items, and advanced statistical techniques were applied to identify the best final items. The EDI is unique because it captures common emotional problems in ASD and is appropriate for both nonverbal and verbal youth. It is an efficient and sensitive measure for use in clinical assessments, monitoring, and research with youth with ASD.
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8. Mintz ME. {{A parent-centered approach to autism diagnosis in early childhood}}. {World journal of pediatrics : WJP}. 2018.
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9. Sandtorv LB, Fevang SKE, Nilsen SA, Boe T, Gjestad R, Haugland S, Elgen IB. {{Symptoms Associated With Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorders in School-Aged Children Prenatally Exposed to Substances}}. {Substance abuse : research and treatment}. 2018; 12: 1178221818765773.
Prenatal exposure to substances may influence a child’s neurodevelopment and impact on subsequent mental health. In a hospital-based population of school-aged children prenatally exposed to opiates and a number of illicit substances (n = 57), we evaluated mental health symptoms associated with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) using the Swanson, Nolan, and Pelham Questionnaire, revision IV (SNAP-IV) and the Autism Spectrum Screening Questionnaire (ASSQ) and compared the scores to a reference group which comprised children from the population-based Bergen Child Study (n = 171). Prenatally exposed children had significantly higher SNAP-IV scores associated with ADHD symptoms in both areas of inattention and hyperactivity/impulsivity and also reported a higher ASSQ score related to an increased number of symptoms associated with ASD, compared with the reference group. Of tested predictors of mental health outcomes in the exposed group, the intelligence quotient was a strong predictor of most mental health outcomes, and neonatal abstinence syndrome was a predictor of inattention. In conclusion, prenatally exposed children had more mental health symptoms associated with ADHD and ASD, compared with the reference group.
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10. Uljarevic M, Hedley D, Nevill R, Evans DW, Cai RY, Butter E, Mulick JA. {{Brief report: Poor self-regulation as a predictor of individual differences in adaptive functioning in young children with autism spectrum disorder}}. {Autism Res}. 2018.
The present study examined the link between poor self-regulation (measured by the child behavior checklist dysregulated profile [DP]) and core autism symptoms, as well as with developmental level, in a sample of 107 children with autism spectrum disorder (ASD) aged 19-46 months. We further examined the utility of DP in predicting individual differences in adaptive functioning, relative to the influence of ASD severity, chronological age (CA), and developmental level. Poor self-regulation was unrelated to CA, developmental level, and severity of ADOS-2 restricted and repetitive behaviors, but was associated with lower ADOS-2 social affect severity. Hierarchical regression identified poor self-regulation as a unique independent predictor of adaptive behavior, with more severe dysregulation predicting poorer adaptive functioning. Results highlight the importance of early identification of deficits in self-regulation, and more specifically, of the utility of DP, when designing individually tailored treatments for young children with ASD. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study explored the relationship between poor self-regulation and age, verbal and non-verbal developmental level, severity of autism symptoms and adaptive functioning in 107 children with autism under 4 years of age. Poor self-regulation was unrelated to age, developmental level, and severity of restricted and repetitive behaviors but was associated with lower social affect severity. Importantly, more severe self-regulation deficits predicted poorer adaptive functioning.
