1. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Alshammari MA, Attia SM. {{Neuroprotection by tyrosine kinase inhibitor, tyrphostin AG126, through the suppression of IL-17A, RORgammat, and T-bet signaling, in the BTBR mouse model of autism}}. {Brain Res Bull};2018 (Aug 30)
Autism spectrum disorder (ASD) is an extremely predominant neurodevelopmental disorder expressed as impairment in reciprocal social interaction along with repetitive, restricted, and stereotyped behaviors. The protein tyrosine kinase inhibitor, tyrphostin AG126 (AG126), regulates the expression of several genes that play an important role in the development of neuroinflammatory disorders. Here, we investigate the possible effects of AG126 (5 mg/kg daily through intraperitoneal injection) on self-grooming, marble burying, and hot plate test results in BTBR T + Itpr3tf/J mice (BTBR is a model of autism). We also explore the effects of AG126 administration on IL-17 A, RORgammat, T-bet, and IFN-gamma production in CD4(+) T cells and on CCR6(+) chemokine receptors in splenic cells. We further investigated the effect of AG126 administration on the mRNA and protein expression of IL-17 A, RORgammat, T-bet, IFN-gamma, and NF-kappaB in the brain tissue. Our results demonstrate that treatment of BTBR mice with AG126 reduced repetitive self-grooming scores and lowered hot plate sensitivity potentials. Furthermore, AG126 administration also caused a substantial reduction of IL-17 A, RORgammat, T-bet, and IFN-gamma production in CD4(+) T cells and on CCR6(+) chemokine receptors in splenic cells. BTBR mice treated with AG126 also show decreased mRNA and protein expression levels of IL-17 A, RORgammat, T-bet, IFN-gamma, and NF-kappaB activation in brain tissue. Our results indicate that treating BTBR mice with AG126 leads to protection against neuroimmune dysfunction/dysregulation through the inhibition of cytokines and transcription factor signaling. This mechanism may be useful in the development of future therapies for neuroimmune disorders.
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2. Brewe AM, Reisinger DL, Adlof SM, Roberts JE. {{Initiating joint attention use in infants at high-risk for autism spectrum disorder}}. {J Intellect Disabil Res};2018 (Aug 29)
BACKGROUND: Impairment in initiating joint attention (IJA) is associated with autism spectrum disorder (ASD) in children, although it is unclear when impairments arise. Due to the early development of IJA use and late diagnosis of ASD, groups at high-risk of ASD, such as infants with an older sibling with ASD (ASIBs) and infants with fragile X syndrome (FXS), provide opportunities to study early IJA behaviours for children who are later diagnosed with ASD. This study analysed these two groups to determine if IJA use differed compared with typically developing (TD) peers at 12 months and whether IJA was associated with later ASD outcomes. METHOD: An experimental attention task was used to analyse IJA gaze shifts and gestures in the high-risk groups. Clinical best estimate diagnoses were given to each participant to compare IJA behaviours to ASD severity. RESULTS: No differences in the frequency of IJA gaze shifts and gestures were found between 12-month-old ASIBs and TD controls, but infants with FXS demonstrated a significantly reduced range of IJA gaze shifts relative to TD controls. Additionally, ASD outcomes at 24 months were related to IJA use for infants with FXS at 12 months, but not infant ASIBs, although these findings were explained by differences in nonverbal cognitive development. CONCLUSIONS: Although previous studies have reported delays in IJA use in children with FXS and ASIBs at ages 21 and 14 months, respectively, our results suggest IJA behaviours for these high-risk groups are not distinct from TD children at 12 months. When differences were found at 12 months, they were explained by nonverbal cognitive development, particularly for infants with FXS. Differences in IJA use at 12 months in this study were too small to serve as a potential indicator of later ASD.
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3. Campbell SB, Northrup JB, Tavares AB. {{Resistance to temptation in toddlers at genetic risk for autism spectrum disorder}}. {Autism};2018 (Aug 30):1362361318797264.
Children with autism spectrum disorder often demonstrate difficulties with self-regulation, although studies of this construct in young children with autism spectrum disorder are limited. In this study, developmental changes were examined using a measure of self-regulation appropriate for young children, resistance to temptation. At 22, 28, and 34 months, toddlers with an older sibling with autism spectrum disorder (high risk) and toddlers with typically developing older siblings (low risk) were presented with an appealing toy and instructed not to touch it. Observers coded whether or not children touched the toy and the strategies they used to resist touching it. At 36 months, children were assessed for autism spectrum disorder, yielding three groups: high risk children with autism spectrum disorder, high risk children without autism spectrum disorder, and low risk children. At 22 months, most children, regardless of group, touched the forbidden toy; at 28 and 34 months, many high risk children without autism spectrum disorder and low risk children resisted the temptation to touch the toy, whereas most of the children with autism spectrum disorder did not. Differences in delay strategies were also evident. Some, but not all group differences, were accounted for by differences in language ability. Results highlight one early index of impulse control that differentiates children with emerging autism spectrum disorder from age-mates prior to the third birthday.
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4. Davidovitch M, Chodick G, Shalev V, Eisenberg VH, Dan U, Reichenberg A, Sandin S, Levine SZ. {{Infertility treatments during pregnancy and the risk of autism spectrum disorder in the offspring}}. {Prog Neuropsychopharmacol Biol Psychiatry};2018 (Aug 30);86:175-179.
We aimed to examine the effects of infertility treatments on the risk of Autism Spectrum Disorder (ASD). Data were from a representative national registry on 110,093 male live births in Israel (born: 1999-2008; and ASD: 975, 0.9%). Infertility treatments included In Vitro Fertilization (IVF), and five hormone treatments. Relative risk (RR) was estimated with multivariable logistic models. Results showed that IVF treatment compared with spontaneous conception was not statistically significantly associated with the risk of ASD. Only progesterone hormone treatment was associated with a statistically significant (p<.05) increased risk of ASD (RR=1.51, 95% CI 1.22, 1.86) compared to the group with no progesterone treatment. In conclusion, progesterone exposure during the critical period of fetal life elevated the risk of ASD, possibly reflecting epigenetic modification. Lien vers le texte intégral (Open Access ou abonnement)
5. Deckmann I, Schwingel GB, Fontes-Dutra M, Bambini-Junior V, Gottfried C. {{Neuroimmune Alterations in Autism: A Translational Analysis Focusing on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid}}. {Neuroimmunomodulation};2018 (Aug 29):1-15.
Autism spectrum disorder (ASD) is a highly prevalent developmental disorder characterized by deficits in communication and social interaction and in stereotyped or repetitive behaviors. Besides the classical behavioral dyad, several comorbidities are frequently present in patients with ASD, such as anxiety, epilepsy, sleep disturbances, and gastrointestinal tract dysfunction. Although the etiology of ASD remains unclear, there is supporting evidence for the involvement of both genetic and environmental factors. Valproic acid (VPA) is an anticonvulsant and mood stabilizer that, when used during the gestational period, increases the risk of ASD in the offspring. The animal model of autism induced by prenatal exposure to VPA demonstrates important structural and behavioral features that can be observed in individuals with autism; it is thus an excellent tool for testing new drug targets and developing novel behavioral and drug therapies. In addition, immunological alterations during pregnancy could affect the developing embryo because immune molecules can pass through the placental barrier. In fact, exposure to pathogens during the pregnancy is a known risk factor for ASD, and maternal immune activation can lead to autistic-like features in animals. Interestingly, neuroimmune alterations are common in both autistic individuals and in animal models of ASD. We summarize here the important alterations in inflammatory markers, such as cytokines and chemokines, in patients with ASD and in the VPA animal model.
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6. Eissa N, Jayaprakash P, Azimullah S, Ojha SK, Al-Houqani M, Jalal FY, Lazewska D, Kiec-Kononowicz K, Sadek B. {{The histamine H3R antagonist DL77 attenuates autistic behaviors in a prenatal valproic acid-induced mouse model of autism}}. {Sci Rep};2018 (Aug 30);8(1):13077.
Autistic spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social communication and restricted/repetitive behavior patterns or interests. Antagonists targeting histamine H3 receptor (H3R) are considered potential therapeutic agents for the therapeutic management of different brain disorders, e.g., cognitive impairments. Therefore, the effects of subchronic treatment with the potent and selective H3R antagonist DL77 (5, 10, or 15 mg/kg, i.p.) on sociability, social novelty, anxiety, and aggressive/repetitive behavior in male Tuck-Ordinary (TO) mice with ASD-like behaviors induced by prenatal exposure to valproic acid (VPA, 500 mg/kg, i.p.) were evaluated using the three-chamber test (TCT), marble burying test (MBT), nestlet shredding test (NST), and elevated plus maze (EPM) test. The results showed that VPA-exposed mice exhibited significantly lower sociability and social novelty preference compared to VPA-exposed mice that were pretreated with DL77 (10 or 15 mg/kg, i.p.). VPA-exposed mice presented a significantly higher percentage of buried marbles in MBT and shredded nestlet significantly more in NST compared to the control groups. However, VPA-exposed animals pretreated with DL77 (10 or 15 mg/kg, i.p.) buried a reduced percentage of marbles in MBT and presented a significantly lower percentage of shredding behavior in NST. On the other hand, pretreatment with DL77 (5, 10, or 15 mg/kg, i.p.) failed to restore the disturbed anxiety levels and hyperactivity observed in VPA-exposed animals in EPM, whereas the reference drug donepezil (DOZ, 1 mg/kg, i.p.) significantly palliated the anxiety and reduced the hyperactivity measures of VPA-exposed mice. Furthermore, pretreatment with DL77 (10 or 15 mg/kg, i.p.) modulated oxidative stress status by increasing GSH and decreasing MDA, and it attenuated the proinflammatory cytokines IL-1beta, IL-6 and TNF-alpha exacerbated by lipopolysaccharide (LPS) challenge, in VPA-exposed mouse brain tissue. Taken together, these results provide evidence that modulation of brain histaminergic neurotransmission, such as by subchronic administration of the H3R antagonist DL77, may serve as an effective pharmacological therapeutic target to rescue ASD-like behaviors in VPA-exposed animals, although further investigations are necessary to corroborate and expand these initial data.
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7. El Shemy SA, El-Sayed MS. {{The impact of auditory rhythmic cueing on gross motor skills in children with autism}}. {J Phys Ther Sci};2018 (Aug);30(8):1063-1068.
[Purpose] This study aimed to investigate the effect of auditory rhythmic cueing on gross motor skills in children with autism. [Participants and Methods] A total of 30 autistic children aged 8-10 years with mild to moderate autistic features participated in this study. They were randomly allocated to either the control group (n=15), which underwent a specially designed physical therapy program, or the study group (n=15), which underwent the same program in addition to gait training with rhythmic auditory stimulation. To provide rhythmic auditory stimulation, combination of a metronome beat set to the child’s cadence and rhythmic cueing from the MIDI Cuebase musical program was used. Both groups received 3 sessions per week for 3 months. The Bruininks-Oseretsky Test of Motor Proficiency 2nd Edition was used to assess gross motor skills at baseline and after 3 months of intervention. [Results] The study found statistically significant improvements in bilateral coordination, balance, running speed and agility, and strength in both groups after treatment. Moreover, there were statistically significant differences between the 2 groups, with the study group showing better improvement in all outcome measures. [Conclusion] Gait training with auditory rhythmic cueing elicited a positive effect on the gross motor skills of children with autism.
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8. Ferguson J, Craig EA, Dounavi K. {{Telehealth as a Model for Providing Behaviour Analytic Interventions to Individuals with Autism Spectrum Disorder: A Systematic Review}}. {J Autism Dev Disord};2018 (Aug 28)
Interventions based on applied behaviour analysis are considered evidence based practice for autism spectrum disorders. Due to the shortage of highly qualified professionals required for their delivery, innovative models should be explored, such as telehealth. Telehealth utilises technology for remote training and supervision. The purpose of our study was to systematically review the literature researching telehealth and ABA. We analysed intervention characteristics, outcomes and research quality in 28 studies and identified gaps. Intervention characteristics were: (1) research design (2) participants (3) technology (4) dependent variables (5) aims. Outcomes were favourable with all studies reporting improvements in at least one variable. Quality ratings were significantly low. Implications for future research and practice are discussed in light of identified methodological downfalls.
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9. Gannon CE, Britton TC, Wilkinson EH, Hall SS. {{Improving social gaze behavior in fragile X syndrome using a behavioral skills training approach: a proof of concept study}}. {J Neurodev Disord};2018 (Aug 28);10(1):25.
BACKGROUND: Individuals diagnosed with fragile X syndrome (FXS), the most common known inherited form of intellectual disability, commonly exhibit significant impairments in social gaze behavior during interactions with others. Although this behavior can restrict social development and limit educational opportunities, behavioral interventions designed to improve social gaze behavior have not been developed for this population. In this proof of concept (PoC) study, we examined whether administering a behavioral skills training package-discrete trial instruction (DTI) plus relaxation training-could increase social gaze duration in males with FXS. METHODS: As part of a larger clinical trial, 20 boys with FXS, aged 8 to 18 years, were randomized to receive DTI plus relaxation training administered at one of two prescribed doses over a 2-day period at our research center. Potential improvements in social gaze behavior were evaluated by direct observations conducted across trials during the training, and generalization effects were examined by administering a social challenge before and after the treatment. During the social challenge, social gaze behavior was recorded using an eye tracker and physiological arousal levels were simultaneously recorded by monitoring the child’s heart rate. RESULTS: Levels of social gaze behavior increased significantly across blocks of training trials for six (60%) boys who received the high-dose behavioral treatment and for three (30%) boys who received the low-dose behavioral treatment. Boys who received the high-dose treatment also showed greater improvements in social gaze behavior during the social challenge compared to boys who received the low-dose treatment. There was no effect of the treatment on physiological arousal levels recorded on the heart rate monitor at either dose. CONCLUSIONS: These results suggest that appropriate social gaze behavior can be successfully taught to boys with FXS using a standardized behavioral skills training approach. Future studies will need to evaluate whether younger children with FXS might benefit from this treatment, and/or whether more naturalistic forms of behavioral skills training might be beneficial, before social gaze avoidance becomes established in the child’s repertoire. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02616796 . Registered 30 November 2015.
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10. Kousgaard SJ, Boldsen SK, Mohr-Jensen C, Lauritsen MB. {{The effect of having a child with ADHD or ASD on family separation}}. {Soc Psychiatry Psychiatr Epidemiol};2018 (Aug 28)
PURPOSE: The primary aim of this study was to estimate the risk of parental separation associated with having a child with ADHD or ASD when controlling for a large range of known risk factors for parental separation using Danish registries. METHODS: The study included all children with ADHD or ASD born between 1990 and 1998 in Denmark and a sex and age matched random sample of children from the background population. We followed these children and their parents from birth until the child’s 25th birthday, parental separation or December 31, 2015, whichever came first. Data were analyzed using Cox Proportional Hazard models by estimating hazard ratios (HR) and 95% confidence intervals. Models were adjusted for a range of child, parental, and family variables. RESULTS: The study included the parents of 12,916 children with ADHD, 7496 children with ASD and 18,423 controls. The study found that, even after controlling for a range of potential risk factors, having a child with either ADHD (HR = 1.8, 95% CI 1.6-2.0) or ASD (HR = 1.2, 95% CI 1.1-1.3) significantly increased parents’ risk of separating compared with non-affected families. Other factors associated with parental separation were parental imprisonment, parental psychopathology, low parental education level, low household income and living in a larger city. CONCLUSION: Parents of children diagnosed with ADHD or ASD were more likely to separate than control parents. It is important to improve our knowledge about the particular characteristics of families at risk of separating to prevent distress for the families and their child.
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11. Krieger B, Piskur B, Schulze C, Jakobs U, Beurskens A, Moser A. {{Supporting and hindering environments for participation of adolescents diagnosed with autism spectrum disorder: A scoping review}}. {PLoS One};2018;13(8):e0202071.
The influence of a person’s environment and its modifying potential on participation is well recognized for most childhood disabilities, but scarcely studied for adolescents with autism spectrum disorder (ASD). A scoping review was conducted, the aim of which was to map the existing literature about supporting and hindering environments for the participation of adolescents with ASD. Sources of scientific evidence were searched for in four databases. Inclusion criteria were the perspectives of adolescents between 12 and 21, families, peers, or significant others; ecologic validity; and a clear connection between environment and participation. The publication dates ranged from 2001 to 2014 and partly up to 2018. The International Classification of Functioning, Disability and Health (ICF) served as the guiding framework for inclusion/exclusion during the selection process. Thematic analysis was performed by five independent reviewers. Results were additionally validated by stakeholders. This scoping review identified 5528 articles, and finally included 31 studies. Two main themes were found: « providing security » indicates how the environment, and specifically the parental, physical, and informational environments, have a securing or intimidating effect. The second theme, « helping to connect », indicates which environments support or hinder social relationships or social activities, and hence participation. An additional third main theme, « tension in participation », relates to ambiguities that seem essential to understand participation or isolation of adolescents with ASD. Results show that participation is a value-laden concept. This research widens the field of dealing with adolescents with ASD, as it directs attention towards the responsibility of the environment regarding participation.
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12. Kuru N, Piyal B. {{Perceived social support and quality of life of parents of children with Autism}}. {Niger J Clin Pract};2018 (Sep);21(9):1182-1189.
Background: When examining the incidence of autism, however, children should not be considered independent of their parents, as this collection of disorders also affects the life of their family members. Having a disabled child affects the relationships with the family and friends, and the social and work life of families. The quality of life of these families is discussed in terms of financial aspects, health, support of family members, values, occupation, family relations, and individual support dimensions of developmental disabilities. However, there are very limited studies on the relationship between perceived social support and quality of life of parents of children with autism, and none of these has been conducted in Turkey. Aim: This study aimed to identify the perceived social support and quality of life of the parents of children with autism and to investigate the related factors. Study Design: The sample of the study consists of 90 parents who accepted to join the research studies. The participants enrolled in the study included 90 biological parents (31 mothers; 59 fathers). Eighteen children had both mother and father participate (all participants subsequently will be referred to as « parents »). Methods: This was a descriptive cross-sectional study. A socio-demographic form, the EUROHIS Quality of Life Scale (EUROHIS QOL-8) and the Multi-Dimensional Scale of Perceived Social Support (MSPSS) were used for data collection. Results: The mean score on the EUROHIS QOL-8 was 26.17 +/- 4.91 and that on the MSPSS was 51.06 +/- 20.6. A statistically significant relationship was found between the EUROHIS QOL-8 and MSPSS scores (r = 0.524, P = 0.000). There were significant differences on the average score on the EUROHIS QOL-8 and MSPSS based on fathers’ job status. Conclusion: Our results provide important insights into the family experiences of parents of children with autism, and may aid the development of appropriate interventions to further support them. Providing support and understanding families of children with autism and their experiences, nurses, doctors and health professionals can positively affect their health outcomes. Healthcare professionals should focus on determining the needs of families to accordingly plan and implement appropriate programs.
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13. Lui M, So WC, Tsang YK. {{Neural evidence for reduced automaticity in processing emotional prosody among men with high levels of autistic traits}}. {Physiol Behav};2018 (Aug 26);196:47-58.
This study aimed to examine individual differences in the integration of emotional prosody when processing semantic meaning in speech among men with high and low levels of autistic traits, as measured by the Autism Spectrum Quotient (AQ). The behavioral and neural responses of high- and low-AQ men during semantic valence judgment were compared. The stimuli were positive or negative words spoken with either happy or sad prosody; in other words, the prosody was either congruous or incongruous to the valence of meaning. Participants were required to judge the (positive vs. negative) valence of word meaning as accurately and as quickly as possible while ignoring emotional prosody. Behavioral results showed that high-AQ men responded significantly more slowly than low-AQ men in all stimulus conditions, indicating lower automaticity in processing emotional speech. Neural data revealed that low-AQ men (but not high-AQ men) had significantly increased N200 and N400 amplitudes for incongruous (compared to congruous) stimuli spoken with happy prosody. Our findings supported our hypotheses that high levels of autistic traits are associated with reduced behavioral automaticity and less differential neural resources allocated to processing emotional speech stimuli with different cognitive demands.
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14. Luo T, Liu P, Wang XY, Li LZ, Zhao LP, Huang J, Li YM, Ou JL, Peng XQ. {{Effect of the autism-associated lncRNA Shank2-AS on architecture and growth of neurons}}. {J Cell Biochem};2018 (Aug 30)
The pathogenic mechanism of autism is complex, and current research has shown that long noncoding RNAs (lncRNAs) may play important roles in this process. The antisense lncRNA of SH3 and multiple ankyrin repeat domains 2 (Shank2-AS) is upregulated in patients with autism spectrum disorder (ASD), whereas the expression of its sense strand gene Shank2 is downregulated. In neuronal cells, Shank2-AS and Shank2 can form a double-stranded RNA and inhibit Shank2 expression. Overexpression of Shank2-AS decreases neurite numbers and lengths, thereby inhibiting the proliferation of neuronal cells and promoting their apoptosis. Overexpression of Shank2 inhibits the abovementioned effects of Shank2-AS, and transfection of a vector containing the 10th intron of Shank2 (Shank2-AS is reverse-transcribed from this region) also blocks the function of Shank2-AS. Shank2 small interfering RNA plays a role similar to Shank2-AS. Therefore, Shank2-AS is abnormally expressed in patients with ASD and may affect the structure and growth of neurons by regulating Shank2 expression, thereby facilitating the development of ASD.
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15. Naumann S, Senftleben U, Santhosh M, McPartland J, Webb SJ. {{Neurophysiological correlates of holistic face processing in adolescents with and without autism spectrum disorder}}. {J Neurodev Disord};2018 (Aug 30);10(1):27.
BACKGROUND: Face processing has been found to be impaired in autism spectrum disorders (ASD). One hypothesis is that individuals with ASD engage in piecemeal compared to holistic face processing strategies. To investigate the role of possible impairments in holistic face processing in individuals with autism, the current study investigated behavioral and electroencephalography (EEG) correlates of face processing (P1/N170 and gamma-band activity) in adolescents with ASD and sex-, age-, and IQ-matched neurotypical controls. METHODS: Participants were presented with upright and inverted Mooney stimuli; black and white low information faces that are only perceived as faces when processed holistically. Participants indicated behaviorally the detection of a face. EEG was collected time-locked to the presentation of the stimuli. RESULTS: Adolescents with ASD perceived Mooney stimuli as faces suggesting ability to use holistic processing but displayed a lower face detection rate and slower response times. ERP components suggest slowed temporal processing of Mooney stimuli in the ASD compared to control group for P1 latency but no differences between groups for P1 amplitude and at the N170. Increases in gamma-band activity was similar during the perception of the Mooney images by group, but the ASD group showed prolonged temporal elevation in activity. CONCLUSION: Overall, our results suggest that adolescents with ASD were able to utilize holistic processing to perceive a face within the Mooney stimuli. Delays in early processing, marked by the P1, and elongated elevation in gamma activity indicate that the neural systems supporting holistic processing are slightly altered suggesting a less automatic and less efficient facial processing system. TRIAL REGISTRATION: Non-applicable.
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16. Okuno M, Uehara T. {{Early childhood behavioral features that discriminate autism from other developmental problems in Japan}}. {J Child Adolesc Psychiatr Nurs};2018 (Aug 29)
PROBLEM: The criteria for early detection of autism spectrum disorder (ASD) and its discrimination from other developmental problems (ODP) are not clear. The Social Attention and Communication Study, which identified methods for early identification of ASD in community settings, was modified to the Japanese situation, and we examined its discriminant validity. METHODS: This study followed a cohort of newborns in one town for 4 years. Structured behavioral assessments were added to the standardized health examination and performed five times during toddlerhood. Of the 264 children included in the statistical analysis, four were diagnosed with ASD, and four were diagnosed with ODP. FINDINGS: A canonical discrimination analysis indicated two significant functions. Canonical 1, which involved disturbances of « eye contact » at 27 months and « concept comprehension » at 38 months, characterized both ASD and ODP. Canonical 2, which involved disturbances of « response name call » at 15 months, « showing » at 27 months, and negative loading of vocabulary development at 20 months, discriminated between ASD and ODP. The canonical plot showed good separation, but a few cases were misclassified. CONCLUSIONS: Evaluations of early behavioral signs by public health nurses during general toddler examinations could be useful and convenient.
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17. Pagnozzi AM, Conti E, Calderoni S, Fripp J, Rose SE. {{A systematic review of structural MRI biomarkers in Autism Spectrum Disorder: A Machine Learning perspective}}. {Int J Dev Neurosci};2018 (Aug 30)
Autism Spectrum Disorder (ASD) affects approximately 1% of the population and leads to impairments in social interaction, communication and restricted, repetitive behaviours. Establishing robust neuroimaging biomarkers of ASD using structural magnetic resonance imaging (MRI) is an important step for diagnosing and tailoring treatment, particularly early in life when interventions can have the greatest effect. However currently, there is mixed findings on the structural brain changes associated with autism. Therefore in this systematic review, recent (post-2007), high-resolution (3 T) MRI studies investigating brain morphology associated with ASD have been collated to identify robust neuroimaging biomarkers of ASD. A systematic search was conducted on databases; PubMed, Web of Science and Scopus, resulting in 123 reviewed articles. Patients with ASD were observed to have increased whole brain volume, particularly under 6 years of age. Other consistent changes observed in ASD patients include increased volume in the frontal and temporal lobes, increased cortical thickness in the frontal lobe, increased surface area and cortical gyrification, and increased cerebrospinal fluid volume, as well as reduced cerebellum volume and reduced corpus callosum volume, compared to typically developing controls. Findings were inconsistent regarding the developmental trajectory of brain volume and cortical thinning with age in ASD, as well as potential volume differences in the white matter, hippocampus, amygdala, thalamus and basal ganglia. To elucidate these inconsistencies, future studies should look towards aggregating MRI data from multiple sites or available repositories to avoid underpowered studies, as well as utilising methods which quantify larger-scale image features to reduce the number of statistical tests performed, and hence risk of false positive findings. Additionally, studies should look to perform a thorough validation strategy, to ensure generalisability of study findings, as well as look to leverage the improved image resolution of 3 T scanning to identify subtle brain changes related to ASD.
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18. Pickard K, Reyes N, Reaven J. {{Examining the inclusion of diverse participants in cognitive behavior therapy research for youth with autism spectrum disorder and anxiety}}. {Autism};2018 (Aug 30):1362361318795678.
Results of randomized controlled trials have demonstrated significant reductions in anxiety symptoms following cognitive behavior therapy participation. Although promising, the extent to which previous research has included families from low socioeconomic status or racially/ethnically diverse backgrounds is unknown. Aims of this study are as follows: (1) What is the race, ethnicity, and educational attainment of youth with autism spectrum disorder and their families who have participated in research examining the efficacy of cognitive behavior therapy for anxiety? and (2) How do the demographics of these participants compare to that of the United States census? A total of 14 studies were reviewed that included 473 participants. Chi-square analyses indicated that there are significant differences between the race/ethnicity of youth with autism spectrum disorder participating in cognitive behavior therapy research for anxiety and that of youth in the United States. Standard residuals indicated significant overrepresentation of White youth and significant underrepresentation of Black and Latino youth in cognitive behavior therapy research (all p-values <0.001). Similarly, there were significant differences in the educational attainment of caregivers participating in cognitive behavior therapy research, with a significant underrepresentation of caregivers from low socioeconomic status backgrounds ( p < 0.001). These findings have implications for the development of cognitive behavior therapy interventions for youth with autism spectrum disorder and anxiety that are both rigorous and inclusive. Lien vers le texte intégral (Open Access ou abonnement)
19. Quezada A, Juarez-Ramirez R, Jimenez S, Tapia J, Villarroel R, Munoz R. {{Relations between Touch Target Size and Drag Distance in Mobile Applications for Users with Autism Spectrum Disorders}}. {J Med Syst};2018 (Aug 28);42(10):180.
In recent years, the development of mobile applications for people within the autism spectrum has proliferated to help enhance skills that could be diminished in users with this condition. However, the usability of these applications does not appear to be the focus of development because users with autism can have difficulty with fine motor skills. This article focuses on evaluating the optimal drag distance and the sizes of the interaction elements for users with Autism Spectrum Disorder. To accomplish this goal, a case study was conducted that involved 20 users with Autism Spectrum Disorder and 30 users with typical development, using a prototype generated and two applications for commercial use on 7-in. tablets. For both developed applications, a slight variation can be observed between the different groups of participants. In the interaction with Proyect@ Habilidades, the application has pictograms of 65 pixels and it has a maximum trailing distance of 340 pixels. Moreover, in Proyect@ Retratos, where there is a minimum deviation between users with levels of autism 1 and 2, it also has pictograms of 65 pixels but with a drag distance of 110 pixels. For this reason, according to the results, we suggest that in order to obtain better results in the interaction with applications aimed at users diagnosed with autism spectrum disorders, the applications should have pictograms of a range of 65 pixels with a drag interaction between 110 and 340 pixels. Considering in context a 7-in. tablet with a resolution of 1280 x 800 pixels.
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20. Roleska M, Roman-Urrestarazu A, Griffiths S, Ruigrok ANV, Holt R, van Kessel R, McColl K, Sherlaw W, Brayne C, Czabanowska K. {{Autism and the right to education in the EU: Policy mapping and scoping review of the United Kingdom, France, Poland and Spain}}. {PLoS One};2018;13(8):e0202336.
INTRODUCTION: Autistic people may have different educational needs that need to be met to allow them to develop their full potential. Education and disability policies remain within the competence of EU Member States, with current educational standards and provisions for autistic people implemented locally. This scoping review aims to map EU and national special education policies with the goal of scoping the level of fulfilment of the right to education of autistic people. METHODS: Four EU countries (United Kingdom, France, Poland and Spain) were included in this scoping review study. Governmental policies in the field of education, special education needs and disability law were included. Path dependency framework was used for data analysis; a net of inter-dependencies between international, EU and national policies was created. RESULTS AND DISCUSSION: Each country created policies where the right to free education without discrimination is provided. Poland does not have an autism specific strategy, whereas the United Kingdom, France and Spain have policies specifically designed for autistic individuals. Within the United Kingdom, all countries created different autism plans, nevertheless all aim to reach the same goal-inclusive education for autistic children that leads to the development of their full potential. CONCLUSION: Policy-making across Europe in the field of education has been changing through the years in favour of autistic people. Today their rights are noticed and considered, but there is still room for improvement. Results showed that approaches and policies vastly differ between countries, more Member States should be analysed in a similar manner to gain a broader and clearer view with a special focus on disability rights in Central and Eastern Europe.
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21. White SW, Simmons GL, Gotham KO, Conner CM, Smith IC, Beck KB, Mazefsky CA. {{Psychosocial Treatments Targeting Anxiety and Depression in Adolescents and Adults on the Autism Spectrum: Review of the Latest Research and Recommended Future Directions}}. {Curr Psychiatry Rep};2018 (Aug 28);20(10):82.
PURPOSE OF REVIEW: This synthesis of treatment research related to anxiety and depression in adolescents and adults with autism spectrum disorder (ASD) focuses on the scientific support for various forms of psychosocial interventions, useful adaptations to standard interventions, and engagement of candidate therapeutic mechanisms. RECENT FINDINGS: There is considerable evidence for the efficacy of cognitive-behavioral therapy (CBT) to treat co-occurring problems with anxiety, but there has been relatively little research on treatment of co-occurring depression. Multiple mechanisms of treatment effect have been proposed, but there has been little demonstration of target engagement via experimental therapeutics. Comorbidity between ASD and anxiety and/or mood problems is common. Although there is evidence for the use of CBT for anxiety, little work has addressed how to effectively treat depression. There is emerging support for alternative treatment approaches, such as mindfulness-based interventions. We encourage rigorous, collaborative approaches to identify and manipulate putative mechanisms of change.
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22. Zhang L, Liu L, Wen Y, Ma M, Cheng S, Yang J, Li P, Cheng B, Du Y, Liang X, Zhao Y, Ding M, Guo X, Zhang F. {{Genome-Wide Association Study and Identification of Chromosomal Enhancer Maps in Multiple Brain Regions Related to Autism Spectrum Disorder}}. {Autism Res};2018 (Aug 29)
Autism spectrum disorder (ASD) is a complex developmental disorder with strong genetic components involved. Recent studies have demonstrated the importance of non-coding regulatory variants for complex diseases. To explore the roles of chromosomal enhancer regions in the pathogenesis of ASD, we conducted an integrative analysis of genome-wide association study (GWAS) and brain region related enhancer-gene networks for ASD. The GWAS data of ASD were driven from a published study, involving 7,387 ASD cases and 8,567 controls. The enhancer-gene networks of eight brain regions were used here. The GWAS of ASD was first merged respectively with the enhancer datasets of eight brain regions. Pathway enrichment analysis was then performed to detect ASD associated pathways based on the enhancer-related single nucleotide polymorphism (SNPs) of each brain region. We detected multiple genes with brain region specific or common association signals, such as PGM3 (P value = 1.93 x 10(-5) ) and RWDD2A (P value = 1.93 x 10(-5) ) for hippocampus middle, and ENPP4 (all P values <0.05), and ENPP5 (all P values <0.05) for seven brain regions. By comparing the pathway enrichment analysis results of various brain regions, several cross brain regions pathways were detected for ASD, such as REACTOME_POTASSIUM_CHANNELS (all P values <0.05) for six brain regions and KEGG_CELL_ADHESION_MOLECULES_CAMS (all P values <0.05) for seven brain regions. In addition, several pathways were also identified for specific brain regions, such as REACTOME_CD28_DEPENDENT_PI3K_AKT_SIGNALING (P value = 4.00 x 10(-3) ) for angular gyrus, REACTOME_SIGNALING_BY_CONSTITUTIVELY_ACTIVE_EGFR (P value = 2.22 x 10(-3) ) for anterior caudate, and KEGG_PRION_DISEASES (P value = 1.00 x 10(-4) ) for germinal matrix. Our results provide novel clues for understanding the genetic basis of ASD. LAY SUMMARY: ASD is a complex developmental disorder with strong genetic components, but the pathogenesis of ASD is still unclear. Using the latest GWAS data and enhancer map, we explored the brain region related biological pathways associated with ASD. Our results provide novel clues for revealing the functional relevance of enhancer variants with ASD and understanding the genetic basis of ASD. Lien vers le texte intégral (Open Access ou abonnement)
