1. Akouchekian M, Hakim Shooshtari M, Heidary H, Zahedi Abghari F, Moeinian P. {{The causative variants of amyloidosis in the autism}}. {The International journal of neuroscience}. 2018: 1-6.
PURPOSE: Autism spectrum disorders (ASD) consist of a group of neurodevelopmental disorders that include autistic behavior, Asperger’s syndrome and pervasive developmental disabilities. According to the increasing observations that patients with mitochondrial disorders have symptoms associated with ASD, we have aimed to analyze the role of mitochondrial DNA (mtDNA) variation in autistic patients. MATERIAL AND METHODS: We selected children with autistic behaviors (15-60 CARS Score). The mitochondrial DNA extraction process was done by GeNet Bio DNA extraction kit. The regions of interest were amplified using independent PCR runs. After purification of PCR products, both strands were sequenced by Big Dye Termination system in a directly determined automated sequencing on an ABI 3700 capillary sequencer machine using both primers. All sequencing results were analyzed using bioinformatics’ tools sequencher software 5. RESULTS: In this study, 31 samples were examined, which 15 unique variants were detected in genes related to COXI-III. The most frequent variant (30.76%) were related to COX1 with amino acid change A –> A. The only significant pathogenic variant was C8264G, except for C8264G, all variants seemed to be homoplasmic substitution. CONCLUSION: In our study, among the variations we found, one variant what probably had an interesting association with possible amyloidosis, had been reported in patient with autism previously. It is hoped that with finding more definable genetic and biological markers, the autistic children diagnosis and treatment will be more effective.
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2. Brignell A, Chenausky KV, Song H, Zhu J, Suo C, Morgan AT. {{Communication interventions for autism spectrum disorder in minimally verbal children}}. {The Cochrane database of systematic reviews}. 2018; 11: Cd012324.
BACKGROUND: Autism spectrum disorder (ASD) has an estimated prevalence of around 1.7% of the population. People with ASD often also have language difficulties, and about 25% to 30% of children with ASD either fail to develop functional language or are minimally verbal. The ability to communicate effectively is an essential life skill, and difficulties with communication can have a range of adverse outcomes, including poorer academic achievement, behavioural difficulties and reduced quality of life. Historically, most studies have investigated communication interventions for ASD in verbal children. We cannot assume the same interventions will work for minimally verbal children with ASD. OBJECTIVES: To assess the effects of communication interventions for ASD in minimally verbal children. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase as well as 12 other databases and three trials registers in November 2017. We also checked the reference lists of all included studies and relevant reviews, contacting experts in the field as well as authors of identified studies about other potentially relevant ongoing and unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of communication-focused interventions for children (under 12 years of age) diagnosed with ASD and who are minimally verbal (fewer than 30 functional words or unable to use speech alone to communicate), compared with no treatment, wait-list control or treatment as usual. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: This review includes two RCTs (154 children aged 32 months to 11 years) of communication interventions for ASD in minimally verbal children compared with a control group (treatment as usual). One RCT used a verbally based intervention (focused playtime intervention; FPI) administered by parents in the home, whereas the other used an alternative and augmentative communication (AAC) intervention (Picture Exchange Communication System; PECS) administered by teachers in a school setting.The FPI study took place in the USA and included 70 participants (64 boys) aged 32 to 82 months who were minimally verbal and had received a diagnosis of ASD. This intervention focused on developing coordinated toy play between child and parent. Participants received 12 in-home parent training sessions for 90 minutes per session for 12 weeks, and they were also invited to attend parent advocacy coaching sessions. This study was funded by the National Institute of Child Health and Human Development, the MIND Institute Research Program and a Professional Staff Congress-City University of New York grant. The PECS study included 84 minimally verbal participants (73 boys) aged 4 to 11 years who had a formal diagnosis of ASD and who were not using PECS beyond phase 1 at baseline. All children attended autism-specific classes or units, and most classes had a child to adult ratio of 2:1. Teachers and parents received PECS training (two-day workshop). PECS consultants also conducted six half-day consultations with each class once per month over five months. This study took place in the UK and was funded by the Three Guineas Trust.Both included studies had high or unclear risk of bias in at least four of the seven ‘Risk of bias’ categories, with a lack of blinding for participants and personnel being the most problematic area. Using the GRADE approach, we rated the overall quality of the evidence as very low due to risk of bias, imprecision (small sample sizes and wide confidence intervals) and because there was only one trial identified per type of intervention (i.e. verbally based or AAC).Both studies focused primarily on communication outcomes (verbal and non-verbal). One of the studies also collected information on social communication. The FPI study found no significant improvement in spoken communication, measured using the expressive language domain of the Mullen Scale of Early Learning expressive language, at postintervention. However, this study found that children with lower expressive language at baseline (less than 11.3 months age-equivalent) improved more than children with better expressive language and that the intervention produced expressive language gains in some children. The PECS study found that children enrolled in the AAC intervention were significantly more likely to use verbal initiations and PECS symbols immediately postintervention; however, gains were not maintained 10 months later. There was no evidence that AAC improved frequency of speech, verbal expressive vocabulary or children’s social communication or pragmatic language immediately postintervention. Overall, neither of the interventions (PECS or FPI) resulted in maintained improvements in spoken or non-verbal communication in most children.Neither study collected information on adverse events, other communication skills, quality of life or behavioural outcomes. AUTHORS’ CONCLUSIONS: There is limited evidence that verbally based and ACC interventions improve spoken and non-verbal communication in minimally verbal children with ASD. A substantial number of studies have investigated communication interventions for minimally verbal children with ASD, yet only two studies met inclusion criteria for this review, and we considered the overall quality of the evidence to be very low. In the study that used an AAC intervention, there were significant gains in frequency of PECS use and verbal and non-verbal initiations, but not in expressive vocabulary or social communication immediately postintervention. In the study that investigated a verbally based intervention, there were no significant gains in expressive language postintervention, but children with lower expressive language at the beginning of the study improved more than those with better expressive language at baseline. Neither study investigated adverse events, other communication skills, quality of life or behavioural outcomes. Future RCTs that compare two interventions and include a control group will allow us to better understand treatment effects in the context of spontaneous maturation and will allow further comparison of different interventions as well as the investigation of moderating factors.
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3. Carruthers S, Kinnaird E, Rudra A, Smith P, Allison C, Auyeung B, Chakrabarti B, Wakabayashi A, Baron-Cohen S, Bakolis I, Hoekstra RA. {{A cross-cultural study of autistic traits across India, Japan and the UK}}. {Molecular autism}. 2018; 9: 52.
Background: There is a global need for brief screening instruments that can identify key indicators for autism to support frontline professionals in their referral decision-making. Although a universal set of conditions, there may be subtle differences in expression, identification and reporting of autistic traits across cultures. In order to assess the potential for any measure for cross-cultural screening use, it is important to understand the relative performance of such measures in different cultures. Our study aimed to identify the items on the Autism Spectrum Quotient (AQ)-Child that are most predictive of an autism diagnosis among children aged 4-9 years across samples from India, Japan and the UK. Methods: We analysed parent-reported AQ-Child data from India (73 children with an autism diagnosis and 81 neurotypical children), Japan (116 children with autism and 190 neurotypical children) and the UK (488 children with autism and 532 neurotypical children). None of the children had a reported existing diagnosis of intellectual disability. Discrimination indices (DI) and positive predictive values (PPV) were used to identify the most predictive items in each country. Results: Sixteen items in the Indian sample, 15 items in the Japanese sample and 28 items in the UK sample demonstrated excellent discriminatory power (DI >/= 0.5 and PPV >/= 0.7), suggesting these items represent the strongest indicators for predicting an autism diagnosis within these countries. Across cultures, good performing items were largely overlapping, with five key indicator items appearing across all three countries (can easily keep track of several different people’s conversations, enjoys social chit-chat, knows how to tell if someone listening to him/her is getting bored, good at social chit-chat, finds it difficult to work out people’s intentions). Four items indicated potential cultural differences. One item was highly discriminative in Japan but poorly discriminative (DI < 0.3) in the UK and India, and a further item had excellent discrimination properties in the UK but poorly discriminated in the Indian and Japanese samples. Two additional items were highly discriminative in two cultures but poor in the third. Conclusions: Cross-cultural overlap in the items most predictive of an autism diagnosis supports the general notion of universality in autistic traits whilst also highlighting that there can be cultural differences associated with certain autistic traits. These findings have the potential to inform the development of a brief global screening tool for autism. Further development and evaluation work is needed. Lien vers le texte intégral (Open Access ou abonnement)
4. Laplante DP, Simcock G, Cao-Lei L, Mouallem M, Elgbeili G, Brunet A, Cobham V, Kildea S, King S. {{The 5-HTTLPR polymorphism of the serotonin transporter gene and child’s sex moderate the relationship between disaster-related prenatal maternal stress and autism spectrum disorder traits: The QF2011 Queensland flood study}}. {Development and psychopathology}. 2018: 1-15.
The 5-HTTLPR polymorphism of the serotonin transporter has been shown to play a role in autism spectrum disorders (ASD). Moreover, disaster-related prenatal maternal stress (PNMS) has also been shown to be associated with ASD. However, no study to date has examined whether these two factors, either individually or in combination, are predictive of ASD traits in the same sample. We hypothesized that children, particularly boys, with the LL genotype exposed to high levels of disaster-related PNMS would exhibit higher levels of ASD traits compared to boys with the LS or SS genotypes and girls regardless of genotype. Genotype and ASD levels obtained using the Australian normed Autism Spectrum Rating Scales – Short Form were available for 105 30-month-old children exposed to varying levels of PNMS following the 2011 Queensland Flood. For boys, higher ASD traits were associated with the 5-HTTLPR LL genotype in combination with either a negative maternal appraisal of the flood, or high levels of maternal composite subjective stress, PSTD-like or peritraumatic dissociation symptoms. For girls, maternal peritraumatic dissociation levels in combination with the 5-HTTLPR LS or SS genotype were associated with higher ASD traits. The present findings are the first to demonstrate that children’s genotype moderates effects of disaster-related PNMS on ASD traits, with different pattern according to child sex.
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5. Luebbert C, Real D, Sadowski G. {{Choosing Appropriate Solvents for ASD Preparation}}. {Molecular pharmaceutics}. 2018; 15(11): 5397-409.
Amorphous solid dispersions (ASDs) are often used for formulating poorly water-soluble active pharmaceutical ingredients (APIs). In an ASD, the amorphous API is embedded in a suitable matrix excipient in order to stabilize the amorphous state and control the dissolution performance. ASDs can be prepared by commonly dissolving the API and the polymer in a suitable organic solvent which is evaporated afterward (e.g., via spray drying) aiming at a homogeneous API distribution in the polymer matrix. Sometimes, unexpected solvent influences on the heterogeneity of the dry ASD are observed. Thermodynamic predictions using the Perturbed-Chain Statistical Associating Fluid Theory combined with experimental investigations via Raman spectroscopy, differential scanning calorimetry, and microscopy performed in this work revealed the amorphous phase separation (APS) between the solvent and the polymer as causing the ASD heterogeneities. It will be shown that thermodynamic modeling allows for identifying appropriate solvents that will neither show APS with the polymeric excipient nor at any time of the drying process of ASD formulations.
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6. Tonnsen BL, Wheeler AC, Hamrick LR, Roberts JE. {{Infant Temperament in the FMR1 Premutation and Fragile X Syndrome}}. {Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53}. 2018: 1-11.
Although temperament has been studied for decades as a predictor of psychopathology in the general population, examining temperament in neurogenetic groups has unique potential to inform the genetic and biological factors that may confer risk for psychopathology in later development. The present study examined early temperament in two heritable neurogenetic conditions associated with atypical CGG repeat expansions on the FMR1 gene: the FMR1 premutation (FXpm; 55-200 repeats) and fragile X syndrome (FXS; > 200 repeats). We focus specifically on the FXpm, as the condition is highly prevalent (1:209-291 female individuals, 1:430-855 male individuals) and has been preliminarily associated with increased risk for pediatric psychopathology, including attention problems, autism, and anxiety. In contrast, FXS is a low-incidence disorder (1:7,143 males, 1:11,111 females) often associated with intellectual disability and severe co-occurring psychosocial conditions, particularly in male individuals. Given information on infant clinical phenotypes in the FXpm and FXS is sparse, we aimed to characterize parent-reported infant temperament in infants with the FXpm (n = 22) relative to FXS (n = 24) and controls (n = 24) assessed on 1 to 3 occasions each. Temperament in infants with the FXpm largely fell between TD and FXS groups, with trends toward suppressed negative affect in younger participants, similar to lower negative affect previously reported in FXS. The FXS group consistently demonstrated lower negative affect and surgency than TD controls. These data suggest that FMR1 gene mutations are associated with atypical temperament that emerges as early as infancy, particularly among infants with FXS, warranting further study of whether temperament may index emergent clinical risks in these populations.
