1. Amaral DG, Anderson GM, Bailey A, Bernier R, Bishop S, Blatt G, Canal-Bedia R, Charman T, Dawson G, de Vries PJ, Dicicco-Bloom E, Dissanayake C, Kamio Y, Kana R, Khan NZ, Knoll A, Kooy F, Lainhart J, Levitt P, Loveland K, Minshew N, Mueller RA, Murphy D, Mundy P, Palencia S, Pinto-Martin J, Rattazzi A, Rogers S, Stone WL, Webb SJ, Whitehouse A. {{Gaps in current autism research: The thoughts of the Autism Research Editorial Board and Associate Editors}}. {Autism Res}. 2019.
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2. Bedford SA, Park MTM, Devenyi GA, Tullo S, Germann J, Patel R, Anagnostou E, Baron-Cohen S, Bullmore ET, Chura LR, Craig MC, Ecker C, Floris DL, Holt RJ, Lenroot R, Lerch JP, Lombardo MV, Murphy DGM, Raznahan A, Ruigrok ANV, Smith E, Spencer MD, Suckling J, Taylor MJ, Thurm A, Lai MC, Chakravarty MM. {{Large-scale analyses of the relationship between sex, age and intelligence quotient heterogeneity and cortical morphometry in autism spectrum disorder}}. {Mol Psychiatry}. 2019.
Significant heterogeneity across aetiologies, neurobiology and clinical phenotypes have been observed in individuals with autism spectrum disorder (ASD). Neuroimaging-based neuroanatomical studies of ASD have often reported inconsistent findings which may, in part, be attributable to an insufficient understanding of the relationship between factors influencing clinical heterogeneity and their relationship to brain anatomy. To this end, we performed a large-scale examination of cortical morphometry in ASD, with a specific focus on the impact of three potential sources of heterogeneity: sex, age and full-scale intelligence (FIQ). To examine these potentially subtle relationships, we amassed a large multi-site dataset that was carefully quality controlled (yielding a final sample of 1327 from the initial dataset of 3145 magnetic resonance images; 491 individuals with ASD). Using a meta-analytic technique to account for inter-site differences, we identified greater cortical thickness in individuals with ASD relative to controls, in regions previously implicated in ASD, including the superior temporal gyrus and inferior frontal sulcus. Greater cortical thickness was observed in sex specific regions; further, cortical thickness differences were observed to be greater in younger individuals and in those with lower FIQ, and to be related to overall clinical severity. This work serves as an important step towards parsing factors that influence neuroanatomical heterogeneity in ASD and is a potential step towards establishing individual-specific biomarkers.
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3. Carrasco M, Salazar C, Tiznado W, Ruiz LM. {{Alterations of Mitochondrial Biology in the Oral Mucosa of Chilean Children with Autism Spectrum Disorder (ASD)}}. {Cells}. 2019; 8(4).
Autistic Spectrum Disorder (ASD) is characterized by the impairment of socio-communicative skills and the presence of restricted and stereotyped behavior patterns. Recent researches have revealed the influence of mitochondrial physiology on the development of ASD. Several research groups have identified defects in respiratory complexes, coenzyme-Q10 deficiency, increased oxidative damage, decreased of superoxide dismutase (SOD2). A study on the influence of mitochondrial physiology on the development of ASD can provide new alternatives and challenges. That is why we set ourselves the general objective to initiate studies of mitochondrial physiology in Chilean children with ASD. A sample of oral mucosa was collected in a group of 12 children diagnosed with ASD and 12 children without ASD. In children with ASD, we found a significant increase in mitochondrial DNA levels. Likewise, in these children, an increase in the protein oxidation was observed. Finally, a downward trend in the expression of the HIGD2A and SOD2 genes was observed, while DRP1, FIS1, MFN1, MFN2, and OPA1 gene expression show an upward trend. The increment of mitochondrial DNA, high oxidative stress, and high expression of the MFN2 gene could help as a scanner of the mitochondrial function in children with ASD.
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4. Casanova EL, Switala AE, Dandamudi S, Hickman AR, Vandenbrink J, Sharp JL, Feltus FA, Casanova MF. {{Autism risk genes are evolutionarily ancient and maintain a unique feature landscape that echoes their function}}. {Autism Res}. 2019.
Previous research on autism risk disorder (ASD), developmental regulatory (DevReg), and central nervous system (CNS) genes suggests they tend to be large in size, enriched in nested repeats, and mutation intolerant. The relevance of these genomic features is intriguing yet poorly understood. In this study, we investigated the feature landscape of these gene groups to discover structural themes useful in interpreting their function, developmental patterns, and evolutionary history. ASD, DevReg, CNS, housekeeping, and whole genome control (WGC) groups were compiled using various resources. Multiple gene features of interest were extracted from NCBI/UCSC Bioinformatics. Residual variation intolerance scores, Exome Aggregation Consortium pLI scores, and copy number variation data from Decipher were used to estimate variation intolerance. Gene age and protein-protein interactions (PPI) were estimated using Ensembl and EBI Intact databases, respectively. Compared to WGC: ASD, DevReg, and CNS genes are longer, produce larger proteins, maintain greater numbers/density of conserved noncoding elements and transposable elements, produce more transcript variants, and are comparatively variation intolerant. After controlling for gene size, mutation tolerance, and clinical association, ASD genes still retain many of these same features. In addition, we also found that ASD genes that are extremely mutation intolerant have larger PPI networks. These data support many of the recent findings within the field of autism genetics but also expand our understanding of the evolution of these broad gene groups, their potential regulatory complexity, and the extent to which they interact with the cellular network. Autism Res 2019, 00: 1-10. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism risk genes are more ancient compared to other genes in the genome. As such, they exhibit physical features related to their age, including long gene and protein size and regulatory sequences that help to control gene expression. They share many of these same features with other genes that are expressed in the brain and/or are associated with prenatal development.
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5. Chen J, Liang C, Wei Z, Cui Z, Kong X, Dong CJ, Lai Y, Peng Z, Wan G. {{Atypical longitudinal development of speech-evoked auditory brainstem response in preschool children with autism spectrum disorders}}. {Autism Res}. 2019.
Language impairment is common in children with autism spectrum disorders (ASDs). Previous research has shown that this disability may be, in part, due to atypical auditory processing of speech stimuli. However, how speech sounds are processed in children with ASD remains largely unknown. The present study assessed the developmental pattern of auditory information processing at the level of the brainstem in preschool children with ASD using speech-evoked auditory brainstem response (speech-ABR). Children with ASD (N = 15) and of typical developing (TD) (N = 20), both of preschool age, were enrolled. The speech-ABRs recorded at two different time points (T1 and T2; 9.68 months apart on average) were virtually identical in the TD group. However, in the ASD group, the wave V latency of speech-ABR was significantly shortened and the amplitudes of wave A and C were significantly larger at T2, compared to those recorded at T1 (10.78 months apart on average). Compared to the TD group, the wave V and A latencies were prolonged at T1, whereas the wave E amplitude decreased and wave F latency prolonged at T2. There was a positive partial correlation between the language performance and the wave A amplitude in the ASD group. These results indicate that auditory processing at the subcortical level is well-developed in the TD preschool children, but is immature and abnormal in the children with ASD at the same ages. Thus, aberrant speech processing at the brainstem level may contribute significantly to the language impairment in children with ASD at preschool ages. Autism Res 2019, 00: 1-15. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Language impairment is common in children with autism spectrum disorders (ASDs). We investigated the developmental pattern of subcortical auditory processing by monitoring changes in the speech-evoked auditory brainstem response (speech-ABR) over a period of 10 months in preschool children. Our results show that subcortical auditory processing is impaired and immature in children with ASD compared with age-matched, typically developing children. The results suggest that speech-ABR may be used as an objective measure in evaluating the language performance of children with ASD. The results also suggest that aberrant speech processing at the level of the brainstem may contribute significantly to the language impairment in preschool children with ASD.
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6. Crawford H, Karakatsani E, Singla G, Oliver C. {{The Persistence of Self-injurious and Aggressive Behavior in Males with Fragile X Syndrome Over 8 Years: A Longitudinal Study of Prevalence and Predictive Risk Markers}}. {J Autism Dev Disord}. 2019.
Self-injurious and aggressive behaviors are common in fragile X syndrome (FXS). However, little is known about the persistence of these behaviors and associated risk markers. We established the prevalence and persistence of self-injurious and aggressive behaviors over eight years in males with FXS, and associations with risk markers. Results showed 77% and 69% persistence rates for self-injurious and aggressive behavior, respectively. Baseline levels of repetitive behavior predicted persistent self-injurious behavior. Chronological age, impulsivity and overactivity were associated with persistent aggressive behavior but only impulsivity predicted persistence. This is the first study to document the persistence of self-injurious and aggressive behavior in FXS over the medium to long term and to identify behavioral risk markers that might facilitate targeted early intervention.
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7. Gonzalez-Romero MF, Avina-Galindo AM, Elbe D, Friedlander R, Vila-Rodriguez F. {{Lifesaving Electroconvulsive Therapy for a Child With Autism Spectrum Disorder, Severe Self-Injurious Behavior, and Neuroleptic Malignant Syndrome}}. {The journal of ECT}. 2019.
We present a case of a preteen with autism spectrum disorder and severe self-injurious behavior who developed neuroleptic malignant syndrome on antipsychotics and required urgent electroconvulsive therapy and continued maintenance electroconvulsive therapy for ongoing clinical stability.
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8. Hardan AY, Hendren RL, Aman MG, Robb A, Melmed RD, Andersen KA, Luchini R, Rahman R, Ali S, Jia XD, Mallick M, Lateiner JE, Palmer RH, Graham SM. {{Efficacy and safety of memantine in children with autism spectrum disorder: Results from three phase 2 multicenter studies}}. {Autism}. 2019: 1362361318824103.
Three phase 2 trials were conducted to assess the efficacy and long-term safety of weight-based memantine extended release (ER) treatment in children with autism spectrum disorder. MEM-MD-91, a 50-week open-label trial, identified memantine extended-release treatment responders for enrollment into MEM-MD-68, a 12-week randomized, double-blind, placebo-controlled withdrawal trial. MEM-MD-69 was an open-label extension trial in which participants from MEM-MD-68, MEM-MD-91, and open-label trial MEM-MD-67 were treated 48 weeks with memantine extended release. In MEM-MD-91, 517 (59.6%) participants were confirmed Social Responsiveness Scale responders at week 12; mean Social Responsiveness Scale total raw scores improved two to three times a minimal clinically important difference of 10 points. In MEM-MD-68, there was no difference between memantine and placebo on the primary efficacy parameter, the proportion of patients with a loss of therapeutic response (defined as 10-point increase from baseline in Social Responsiveness Scale total raw score). MEM-MD-69 exploratory analyses revealed mean standard deviation improvement in Social Responsiveness Scale total raw score of 32.4 (26.4) from baseline of the first lead-in study. No new safety concerns were evident. While the a priori-defined efficacy results of the double-blind trial were not achieved, the considerable improvements in mean Social Responsiveness Scale scores from baseline in the open-label trials were presumed to be clinically important.
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9. Hsiung EY, Chien SH, Chu YH, Ho MW. {{Adults with autism are less proficient in identifying biological motion actions portrayed with point-light displays}}. {J Intellect Disabil Res}. 2019.
BACKGROUND: Whether individuals with autism spectrum disorder (ASD) have impairments with biological motion perception has been debated. The present study examined the ability to identify point-light-displayed (PLD) human actions in neurotypical (NT) adults and adults with ASD. METHOD: Twenty-seven adults with ASD (mean age = 28.36) and 30 NT adults (mean age = 22.45) were tested. Both groups viewed 10 different biological motion actions contacting an object/tool and 10 without making contact. Each action was presented twice, and participant’s naming responses and reaction times were recorded. RESULTS: The ASD group had a significantly lower total number of correct items (M = 29.30 +/- 5.08 out of 40) and longer response time (M = 4550 +/- 1442 ms) than NT group (M = 32.77 +/- 2.78; M = 3556 +/- 1148 ms). Both groups were better at naming the actions without objects (ASD group: 17.33 +/- 2.30, NT group: 18.67 +/- 1.30) than those with objects (ASD group: 11.96 +/- 3.57, NT group: 14.10 +/- 1.97). Correlation analyses showed that individuals with higher Autism-spectrum Quotient scale scores tended to make more errors and responded more slowly. CONCLUSION: Adults with ASD were able to identify human point-light display biological motion actions much better than chance; however, they were less proficient compared with NT adults in terms of accuracy and speed, regardless of action type.
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10. Mertz L. {{New Quantitative Approach to Autism Diagnosis}}. {IEEE Pulse}. 2019; 10(2): 34-6.
Only a few years ago, leading autism expert David Amaral described the disorder as a lifelong disability. Today, he acknowledges that description is no longer true. « Research lately shows that a substantial proportion of children with autism spectrum disorder (ASD)-something on the order of 30%-show really substantial improvements in their autism symptoms, » says Amaral, founding research director of the MIND Institute, an autism center at the University of California, Davis, CA (Figure 1). He adds that about 5% of the children, he and his colleagues, study at the MIND Institute actually lose their diagnosis over time.
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11. Morie KP, Jackson S, Zhai ZW, Potenza MN, Dritschel B. {{Mood Disorders in High-Functioning Autism: The Importance of Alexithymia and Emotional Regulation}}. {J Autism Dev Disord}. 2019.
Individuals with autism spectrum disorder (ASD) often have co-morbid anxiety and depression. Alexithymia and emotion regulation difficulties are commonly seen in individuals with ASD and in mood disorders. We hypothesized that alexithymia and emotional regulation would mediate the relationship between autistic features and anxiety/depression symptom severity. We collected data about emotional regulation, alexithymia, autistic symptoms and depression/anxiety in a sample of 64 young adults with ASD. We constructed two serial multiple mediator models, using autistic features as the independent variable and anxiety/depression symptoms as outcome variables. The serial relationship between alexithymia and emotional regulation mediated associations between autistic features and depression and anxiety, separately. The findings suggest that targeting alexithymia may benefit therapies designed to alleviate mood disorders in ASD.
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12. Noriega G. {{Restricted, Repetitive, and Stereotypical Patterns of Behavior in Autism – an fMRI Perspective}}. {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society}. 2019.
The main objective of this work is to determine whether resting-state fMRI can identify functional connectivity differences between individuals with autism who experience severe issues with restricted, repetitive and stereotypical behaviors, those who experience only mild issues, and controls. We use resting-state fMRI data from the ABIDE-I preprocessed repository, with participants grouped according to their ADI-R Restricted, Repetitive, and Stereotyped Patterns of Behavior Subscore. Three processing methods are used for analysis. A time-correlation approach establishes a basic baseline, and we introduce a method based on sliding time windows, with means across time adjusted to consider the fraction of time the correlation measure is above/below average. We complement these with a band-limited coherence approach. For completeness, preprocessing schemes with and without global signal regression are considered. Our results are in line with recent ones which find both over-and under-connectivities in the autistic brain. We find there are indeed significant differences in connectivity between various regions that differentiate between ASD subjects with severe stereotypical/restrictive behavior issues, those with only mild issues, and controls. Interestingly, for some regions the « signature » of subjects in the milder of the ASD groups appears to be distinct (i.e., over-or under-connected) relative to both the more severe ASD group and the controls.
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13. Pattini E, Carnevali L, Troisi A, Matrella G, Rollo D, Fornari M, Sgoifo A. {{Psychological characteristics and physiological reactivity to acute stress in mothers of children with Autism Spectrum Disorder}}. {Stress and health : journal of the International Society for the Investigation of Stress}. 2019.
Stress related to parenting a child with autism spectrum disorder can differently affect caregiver’s physiological reactivity to acute stress. Here, parental stress levels, psychological characteristics and coping strategies were assessed alongside measures of heart rate, heart rate variability, and cortisol during a psychosocial stress test in mothers of children with ASD (M-ASD, n=15) and mothers of typically developing children (n=15). M-ASD reported significantly higher levels of parental stress, anxiety, negative affectivity, social inhibition, and a larger preference for avoidance strategies. M-ASD showed larger heart rate and cortisol responses to the psychosocial stress test. A positive relationship was found between parental stress levels and the magnitude of the cortisol stress response in both groups. The present findings indicate exaggerated physiological reactivity to acute psychosocial stress in M-ASD, and prompt further research to explore the role of individual differences in mediating the effects of parental stress on physiological stress responses.
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14. Tiede G, Walton KM. {{Meta-analysis of naturalistic developmental behavioral interventions for young children with autism spectrum disorder}}. {Autism}. 2019: 1362361319836371.
Naturalistic developmental behavioral intervention is an emerging class of interventions for young children with autism spectrum disorder. The present article is a meta-analysis of outcomes of group-design studies ( n = 27) testing interventions using naturalistic developmental behavioral intervention strategies. Small, significant positive effects of naturalistic developmental behavioral intervention were found for expressive language ( g = 0.32), reduction in symptoms of autism spectrum disorder ( g = -0.38), and play skills ( g = 0.23). Larger effects were found for social engagement ( g = 0.65) and overall cognitive development ( g = 0.48). A marginal effect was found for joint attention ( g = 0.14) and receptive language ( g = 0.28). For joint attention, improvement was moderated by hours of professional involvement. Evidence of publication and reporting bias was present for language outcomes. This meta-analysis grows the evidence base for naturalistic developmental behavioral interventions, particularly in the key areas of social engagement and cognition.
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15. Ward R, Reynolds JE, Pieterse B, Elliott C, Boyd R, Miller L. {{Utilisation of coaching practices in early interventions in children at risk of developmental disability/delay: a systematic review}}. {Disabil Rehabil}. 2019: 1-22.
BACKGROUND: To conduct a systematic review of early intervention programs (0-5 years) utilising coaching practice characteristics, to identify (i) implementation fidelity; (ii) parent training processes, and (iii) outcome measures of capacity building in parents. The coaching practice characteristics of (1) joint planning, (2) observation, (3) action/practice, (4) reflection and (5) feedback identified by Rush and Shelden were utilised. METHOD: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. A comprehensive search of 6 electronic databases was undertaken in March 2016 and updated in February 2018. RESULTS: Of 2397 articles, 18 papers met full inclusion criteria. Of these, 5 were randomised controlled trials. Only one specifically evaluated the impact of parent coaching versus therapist only delivered interventions. Risk of bias and study quality using Downs and Black checklist for clinical trial quality yielded the following descriptive ratings: Seven studies: « Poor » (scores 1-13); Six studies: « Fair » (scores 15-17); and five « Good » (scores 20-24). CONCLUSION: Coaching in early intervention is well accepted. Nevertheless, this review identified a continued lack of operationalised definitions; inconsistency in the reporting of therapist training and adherence to active ingredients/coaching principles; and an absence of outcome measures focused on parent capacity. Implications for Rehabilitation Contemporary early intervention services recognise the importance of engaging parents as active participators in their child’s development. This is evident by the increase in interventions that utilise parent coaching practices. The findings of this systematic review indicate the need for professionals to: *Describe and document fidelity of coaching practices in the delivery of intervention. *Objectively measure changes in parent capacity and self-efficacy as a result of the coaching based intervention. The reporting of parent capacity measures will allow us to truly examine the effectiveness of coaching practices in empowering families to support their child to realise their full potential.
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16. Yamagata B, Itahashi T, Fujino J, Ohta H, Takashio O, Nakamura M, Kato N, Mimura M, Hashimoto RI, Aoki Y. {{Cortical surface architecture endophenotype and correlates of clinical diagnosis of autism spectrum disorder}}. {Psychiatry and clinical neurosciences}. 2019.
AIM: Prior structural MRI studies demonstrated atypical gray matter characteristics in siblings of individuals with autism spectrum disorder (ASD). However, they did not clarify which aspect of gray matter is related to the endophenotype (i.e. genetic vulnerability of) ASD. Further, because they did not enroll siblings of TD people, they may have underestimated the difference between individuals with ASD and their unaffected siblings. The current study aimed to address these gaps. METHODS: We recruited 30 pairs of adult male siblings (15 with an ASD endophenotype, and 15 pairs without) and focused on four gray matter parameters: cortical volume and three surface-based parameters (cortical thickness, fractal dimension, and sulcal depth [SD]). First, we sought to identify a pattern of an ASD endophenotype, comparing the four parameters. Then, we compared individuals with ASD and their unaffected siblings in the cortical parameters to identify neural correlates for the clinical diagnosis accounting for the difference between TD siblings. RESULTS: A sparse logistic regression with a leave-one-pair-out cross-validation showed the highest accuracy for the identification of an ASD endophenotype (73.3%) with the SD compared with the other three parameters. A bootstrapping analysis accounting for the difference in the SD between TD siblings showed a significantly large difference between individuals with ASD and their unaffected siblings in six out of 68 regions-of-interest. CONCLUSIONS: This proof-of-concept study suggests that an ASD endophenotype emerges in SD and that neural bases for ASD diagnosis can be discerned from the endophenotype when accounted for the difference between TD siblings. (250/250 words) This article is protected by copyright. All rights reserved.
