1. Akaltun I, Kara T. {{A case of Nablus mask-like facial syndrome with autism spectrum disorders}}. {Psychiatric genetics}. 2018; 28(4): 75.
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2. Balasubramanian M, Jones R, Milne E, Marshall C, Arundel P, Smith K, Bishop NJ. {{Autism and heritable bone fragility: A true association?}}. {Bone reports}. 2018; 8: 156-62.
Objectives: Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; intelligence is reported to be normal. However, a minority of children seen also show symptomology consistent with an ‘Autism Spectrum Disorder’. A joint genetics and psychology research study was undertaken to identify these patients using ‘Gold Standard’ research tools: Autism Diagnostic Inventory Revised (ADI-R); Autism Diagnostic Observation Schedule (ADOS) and undertake genetic analyses in them. Method: A cohort of n=7 children with autistic traits and severe/complex OI were recruited to the study. The study was set-up to explore whether there was a genetic link between bone fragility and autism in a sub-set of patients with bone fragility identified with autism traits in our complex/severe OI clinic. This was not set-up as a prevalence study but rather an exploration of genetics in association with ADI/ADOS confirmed ASD and bone fragility. ADI& ADOS: Standardised tools were used to confirm autism diagnosis. ADI and ADOS were completed by the Clinical Psychologist; ADI comprises a 93 item semi-structured clinical review with a diagnostic algorithm diagnosing Autism; ADOS is a semi-structured assessment of socialisation, communication and play/imagination which also provides a diagnostic algorithm. Exome sequencing: In patients recruited, those that fulfilled research criteria for diagnosis of autism using above tools were recruited to trio whole exome sequencing (WES). Results: one patient had compound heterozygous variants in NBAS; one patient had a variant in NRX1; one patient had a maternally inherited PLS3 variant; all the other patients in this cohort had pathogenic variants in COL1A1/COL1A2. Conclusions: Although, not set out as an objective, we were able to establish that identifying autism had important clinical and social benefits for patients and their families in ensuring access to services, appropriate schooling, increased understanding of behaviour and support. Lay summary: It is important for clinicians looking after children with brittle bone disease, also referred to as Osteogenesis Imperfecta (OI) to be aware of early features of developmental delay/autistic traits especially with severe forms of OI as the emphasis is on their mobility and bone health. Ensuring appropriate assessment and access to services early-on will enable these patients to achieve their potential. Further investigations of genomics in bone fragility in relation to autism are required and dual diagnosis is essential for high quality clinical and educational provision.
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3. Delion P, Labreuche J, Deplanque D, Cohen D, Duhamel A, Lallie C, Ravary M, Goeb JL, Medjkane F, Xavier J. {{Therapeutic body wraps (TBW) for treatment of severe injurious behaviour in children with autism spectrum disorder (ASD): A 3-month randomized controlled feasibility study}}. {PLoS One}. 2018; 13(6): e0198726.
INTRODUCTION: The use of therapeutic body wraps (TBW) has been reported in small series or case reports, but has become controversial. OBJECTIVES: This is a feasibility, multicentre, randomized, controlled, open-label trial with blinded outcome assessment (PROBE design). SETTING: Children with autism and severe-injurious behaviours (SIB) were enrolled from 13 specialized clinics. INTERVENTIONS: Dry-sheet TBW (DRY group) vs. wet-sheet TBW (WET group). PRIMARY OUTCOME MEASURES: 3-month change in the Aberrant Behaviour Checklist irritability score (ABC-irritability) within per-protocol (PP) sample. RESULTS: From January 2008 to January 2015, we recruited 48 children (age range: 5.9 to 9.9 years, 78.1% male). Seven patients (4 in the DRY group, 3 in the WET group) were dropped from the study early and were excluded from PP analysis. At endpoint, ABC-irritability significantly improved in both groups (means (standard deviation) = -11.15 (8.05) in the DRY group and -10.57 (9.29) in the WET group), as did the other ABC scores and the Children Autism Rating scale score. However, there was no significant difference between groups. All but 5 patients were rated as much or very much improved. A repeated-measures analysis confirmed the significant improvement in ABC-irritability scores according to time (p < .0001), with no significant difference between the two groups (group effect: p = .55; interaction time x group: p = .27). Pooling both groups together, the mean 3-month change from baseline in ABC-irritability score was -10.90 (effect size = 1.59, p < .0001). CONCLUSIONS: We found that feasibility was overall satisfactory with a slow recruitment rate and a rather good attrition rate. TBW was a safe complementary therapy in this population. There was no difference between wet and dry TBW at 3 months, and ABC-irritability significantly decreased with both wet and dry sheet TBW. To assess whether TBW may constitute an alternative to medication or behavioural intervention for treating SIB in ASD patients, a larger randomized comparative trial (e.g. TBW vs. antipsychotics) is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT03164746. Lien vers le texte intégral (Open Access ou abonnement)
4. Hongkaew Y, Medhasi S, Pasomsub E, Ngamsamut N, Puangpetch A, Vanwong N, Chamnanphon M, Limsila P, Suthisisang C, Wilffert B, Sukasem C. {{UGT1A1 polymorphisms associated with prolactin response in risperidone-treated children and adolescents with autism spectrum disorder}}. {The pharmacogenomics journal}. 2018.
The aim of this study was to investigate the association of drug-metabolizing enzyme and transporter (DMET) polymorphisms with the risperidone-induced prolactin response using an overlapping gene model between serum prolactin level and hyperprolactinemia in autism spectrum disorder (ASD) patients. Eighty-four ASD patients who were receiving risperidone for at least 1 month were recruited and then assigned to either the normal prolactin group or the hyperprolactinemia group based on their serum prolactin level. The genotype profile of 1936 (1931 single nucleotide polymorphisms (SNPs) and 5 copy number variation (CNVs) drug metabolism markers was obtained using the Affymetrix DMET Plus GeneChip microarray platform. Genotypes of SNPs used to test the accuracy of DMET genotype profiling were determined using TaqMan SNP Genotyping Assay kits. Eighty-four patients were selected for the allelic association study after microarray analyses (51 in the normal prolactin group, and 33 in the hyperprolactinemia group). An overlapping allelic association analysis of both analyses discovered five DMET SNPs with a suggestive association (P < 0.05) with risperidone-induced prolactin response. Three UGT1A1 SNPs (UGT1A1*80c.-364C > T, UGT1A1*93 c.-3156G > A, and UGT1A1 c.-2950A > G, showed a suggestive association with the risperidone-induced prolactin response and found to be in complete linkage disequilibrium (D’ value of 1). In this DMET microarray platform, we found three UGT1A1 variants with suggestive evidences of association with the risperidone-induced prolactin response both measured by hyperprolactinemia and by prolactin level. However, due to the lack of validation studies confirmation and further exploration are needed in future pharmacogenomic studies.
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5. Jones KL, Pride MC, Edmiston E, Yang M, Silverman JL, Crawley JN, Van de Water J. {{Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism}}. {Mol Psychiatry}. 2018.
Immune dysregulation has been noted consistently in individuals with autism spectrum disorder (ASD) and their families, including the presence of autoantibodies reactive to fetal brain proteins in nearly a quarter of mothers of children with ASD versus <1% in mothers of typically developing children. Our lab recently identified the peptide epitope sequences on seven antigenic proteins targeted by these maternal autoantibodies. Through immunization with these peptide epitopes, we have successfully created an endogenous, antigen-driven mouse model that ensures a constant exposure to the salient autoantibodies throughout gestation in C57BL/6J mice. This exposure more naturally mimics what is observed in mothers of children with ASD. Male and female offspring were tested using a comprehensive sequence of behavioral assays, as well as measures of health and development highly relevant to ASD. We found that MAR-ASD male and female offspring had significant alterations in development and social interactions during dyadic play. Although 3-chambered social approach was not significantly different, fewer social interactions with an estrous female were noted in the adult male MAR-ASD animals, as well as reduced vocalizations emitted in response to social cues with robust repetitive self-grooming behaviors relative to saline treated controls. The generation of MAR-ASD-specific epitope autoantibodies in female mice prior to breeding created a model that demonstrates for the first time that ASD-specific antigen-induced maternal autoantibodies produced alterations in a constellation of ASD-relevant behaviors. Lien vers le texte intégral (Open Access ou abonnement)
6. Khalaj R, Hajizadeh Moghaddam A, Zare M. {{Hesperetin and it nanocrystals ameliorate social behavior deficits and oxido-inflammatory stress in rat model of autism}}. {Int J Dev Neurosci}. 2018; 69: 80-7.
Prenatal exposure to valproic acid (VPA) induces behavioral disorders and enhancement of oxido-inflammatory stress in Autism Spectrum Disorders (ASDs). The aim of this study was to investigate the comparative effects of hesperetin (Hst) and nano-hesperetin on social behavior deficits and oxido-inflammatory indexes in prenatally valproic acid-exposed rat offspring. Pregnant Wistar rats on embryonic day 0 (E0) were segregated into six groups; Group-1 served as vehicle, received distillated water orally (PO) from E1 until the end of lactation and saline intraperitoneally (i.p) on E12.5. Group-2 received sodium valproate (500mg/kg in 0.9% saline, i.p) on E12.5 was considered as VPA-exposed group, Group-3 to 6 were VPA-exposed which received hesperetin and nano-hesperetin (10 and 20mg/kg/day, PO) from E0 until the end of lactation respectively. Social interaction and open field tests were conducted on postnatal day 28 (PND 28) and PND 30, cerebral antioxidant enzymes activity and biochemical indexes, the level of inflammatory factors in plasma and histopathology of cerebellum were estimated on PND 28 and PND 30. Prenatal valproic acid-exposed rat exhibited poor sociability and high level of anxiety-like behaviors (P< 0.05). In addition, increased level of oxidative stress and inflammation were found by determining different oxido-inflammatory markers. Hesperetin and nano-hesperetin treatment improved the behavioral disorder and reduced the oxidative stress in brain and significantly (p< 0.05) plasma's inflammation indexes. In conclusion, it can be state that nano-hesperetin exerts neuroprotective action in comparison with hesperetin and could be efficacious for treatment of VPA animal model of autism during pregnancy and lactation. Lien vers le texte intégral (Open Access ou abonnement)
7. Kim KM, Lim MH, Kwon HJ, Yoo SJ, Kim EJ, Kim JW, Ha M, Paik KC. {{Associations between urinary cotinine and symptoms of attention deficit/hyperactivity disorder and autism spectrum disorder}}. {Environmental research}. 2018; 166: 481-6.
BACKGROUND: The present study investigated associations between urinary cotinine levels as a biomarker of secondhand smoke exposure and symptoms of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). METHODS: A total of 520 child participants (200 with ADHD, 67 with ASD, and 253 normal control subjects) were assessed using the Korean version of the ADHD rating scale (K-ARS), Autism spectrum screening questionnaire (ASSQ), and Behavioral Assessment System for Children, second edition (BASC-2). The Korean version of the computer-based continuous performance test was used to assess cognitive function. Urinary cotinine was evaluated as a biomarker of secondhand smoke exposure. RESULTS: Urinary cotinine levels were significantly and positively associated with K-ARS score (B=4.00, p<0.001), ASSQ score (B=1.71, p=0.030), the behavioral problem subscales of the BASC-2 (B=1.68-3.52, p<0.001-0.045), and omission and commission errors in the continuous performance test (B=6.21-8.42, p<0.001-0.019). Urinary cotinine levels were also associated with the increased odds ratio of ADHD (OR=1.55, 95% CI 1.05-2.30, p=0.028) and ASD (OR=1.89, 95% CI 1.12-3.21, p=0.018). CONCLUSION: Urinary cotinine levels were associated with lower behavioral adaptation and cognitive function and increased odds ratios of ADHD and ASD, indicating a negative effect of secondhand smoke exposure on the symptomatic manifestation of ADHD and ASD. Lien vers le texte intégral (Open Access ou abonnement)
8. Leisman G, Machado C, Machado Y, Chinchilla-Acosta M. {{Effects of Low-Level Laser Therapy in Autism Spectrum Disorder}}. {Advances in experimental medicine and biology}. 2018.
The study examined the efficacy of low-level laser therapy, a form of photobiomodulation, for the treatment of irritability associated with autistic spectrum disorder in children and adolescents aged 5-17 years. Twenty-one of the 40 participants received eight 5-min procedures administered to the base of the skull and temporal areas across a 4-week period (test, i.e., active treatment participants). All the participants were evaluated with the Aberrant Behavior Checklist (ABC), with the global scale and five subscales (irritability/agitation, lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech), and the Clinical Global Impressions (CGI) Scale including a severity-of-illness scale (CGI-S) and a global improvement/change scale (CGI-C). The evaluation took place at baseline, week 2 (interim), week 4 (endpoint), and week 8 (post-procedure) of the study. The adjusted mean difference in the baseline to study endpoint change in the ABC irritability subscale score between test and placebo participants was -15.17 in favor of the test procedure group. ANCOVA analysis found this difference to be statistically significant (F = 99.34, p < 0.0001) compared to the baseline ABC irritability subscale score. The study found that low-level laser therapy could be an effective tool for reducing irritability and other symptoms and behaviors associated with the autistic spectrum disorder in children and adolescents, with positive changes maintained and augmented over time. Lien vers le texte intégral (Open Access ou abonnement)
9. Silbaugh BC, Swinnea S. {{Failure to Replicate the Effects of the High-Probability Instructional Sequence on Feeding in Children With Autism and Food Selectivity}}. {Behav Modif}. 2018: 145445518785111.
Behavioral intervention has positive effects on feeding problems of children with autism and food selectivity (FS), and researchers have evaluated a variety of specific behavioral interventions. Confidence in the effects of some specific interventions on feeding such as the high-probability instructional sequence (HPS) is limited by a lack of replication. Therefore, we assessed the generality of the HPS by replicating the intervention in children with autism and FS. Contrary to prior research, the HPS did not improve feeding responses for three consecutive children enrolled in the study. We discuss the results in relation to publishing failures to replicate without experimental control in applied behavior analysis research.
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10. Sota S, Hatada S, Honjyo K, Takatsuka T, Honer WG, Morinobu S, Sawada K. {{Musical disability in children with autism spectrum disorder}}. {Psychiatry Res}. 2018; 267: 354-9.
Although enhanced musical ability is reported in individuals with autism spectrum disorders (ASD), this observation may be uncommon, and reports of auditory processing deficits suggest musical ability may be impaired. We hypothesized that musical ability would be impaired in children with ASD, that the severity of impairment would correlate with cognitive dysfunction, and with clinical features of illness. We evaluated 26 children with ASD and 27 typically developing (TD) children using the Montreal Battery of Evaluation of Amusia short version (MBEA-s) as well as cognitive tests and clinical evaluations of ASD symptomatology. Mean scores on the MBEA-s were significantly lower in children with ASD. MBEA-s scores did not correlate with cognitive test results in either ASD or TD children, and did not correlate with symptom severity in ASD children. For the ASD children only, the combination of hyperactivity/inattention and working memory resulted in a significant contribution to the variance in the MBEA-s score. The findings indicate that musical ability appears to be impaired in children with ASD, and assessment of musical ability may complement cognitive tests and measures of symptomatology in characterizing the shared neural substrates for these dysfunctions in ASD.
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11. Yamasue H, Okada T, Munesue T, Kuroda M, Fujioka T, Uno Y, Matsumoto K, Kuwabara H, Mori D, Okamoto Y, Yoshimura Y, Kawakubo Y, Arioka Y, Kojima M, Yuhi T, Owada K, Yassin W, Kushima I, Benner S, Ogawa N, Eriguchi Y, Kawano N, Uemura Y, Yamamoto M, Kano Y, Kasai K, Higashida H, Ozaki N, Kosaka H. {{Effect of intranasal oxytocin on the core social symptoms of autism spectrum disorder: a randomized clinical trial}}. {Mol Psychiatry}. 2018.
Although small-scale studies have described the effects of oxytocin on social deficits in autism spectrum disorder (ASD), no large-scale study has been conducted. In this randomized, parallel-group, multicenter, placebo-controlled, double-blind trial in Japan, 106 ASD individuals (18-48 y.o.) were enrolled between Jan 2015 and March 2016. Participants were randomly assigned to a 6-week intranasal oxytocin (48IU/day, n = 53) or placebo (n = 53) group. One-hundred-three participants were analyzed. Since oxytocin reduced the primary endpoint, Autism Diagnostic Observation Schedule (ADOS) reciprocity, (from 8.5 to 7.7; P < .001) but placebo also reduced the score (8.3 to 7.2; P < .001), no between-group difference was found (effect size -0.08; 95% CI, -0.46 to 0.31; P = .69); however, plasma oxytocin was only elevated from baseline to endpoint in the oxytocin-group compared with the placebo-group (effect size -1.12; -1.53 to -0.70; P < .0001). Among the secondary endpoints, oxytocin reduced ADOS repetitive behavior (2.0 to 1.5; P < .0001) compared with placebo (2.0 to 1.8; P = .43) (effect size 0.44; 0.05 to 0.83; P = .026). In addition, the duration of gaze fixation on socially relevant regions, another secondary endpoint, was increased by oxytocin (41.2 to 52.3; P = .03) compared with placebo (45.7 to 40.4; P = .25) (effect size 0.55; 0.10 to 1.0; P = .018). No significant effects were observed for the other secondary endpoints. No significant difference in the prevalence of adverse events was observed between groups, although one participant experienced temporary gynecomastia during oxytocin administration. Based on the present findings, we cannot recommend continuous intranasal oxytocin treatment alone at the current dose and duration for treatment of the core social symptoms of high-functioning ASD in adult men, although this large-scale trial suggests oxytocin's possibility to treat ASD repetitive behavior. Lien vers le texte intégral (Open Access ou abonnement)
