1. Asada K, Tojo Y, Hakarino K, Saito A, Hasegawa T, Kumagaya S. {{Brief Report: Body Image in Autism: Evidence from Body Size Estimation}}. {J Autism Dev Disord}. 2017.
Individuals with autism spectrum disorder (ASD) have difficulties with social interaction and communication. First-hand accounts written by individuals with ASD have shown the existence of other atypical characteristics such as difficulties with body awareness. However, few studies have examined whether such atypicalities are found more generally among individuals with ASD. We examined body image (i.e., self-body awareness) by asking individuals with ASD and typically developing (TD) individuals to estimate their own body size (shoulder width). Results show that TD individuals estimated their shoulder width more accurately than individuals with ASD. This study suggests that individuals with ASD often experience misperceptions in their body size.
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2. Barnevik Olsson M, Holm A, Westerlund J, Lundholm Hedvall A, Gillberg C, Fernell E. {{Children with borderline intellectual functioning and autism spectrum disorder: developmental trajectories from 4 to 11 years of age}}. {Neuropsychiatr Dis Treat}. 2017; 13: 2519-26.
BACKGROUND: Studies on autism have tended to focus either on those with intellectual disability (ie, those with intellectual quotient [IQ] under 70) or on the group that is referred to as « high-functioning », that is, those with borderline, average or above average IQ. The literature on cognition and daily functioning in autism spectrum disorder combined specifically with borderline intellectual functioning (IQ 70-84) is limited. METHODS: From a representative group of 208 preschool children diagnosed with autism spectrum disorder, those 50 children in the group with borderline intellectual functioning at ages 4.5-6.5 years were targeted for follow-up at a median age of 10 years. A new cognitive test was carried out in 30 children. Parents were interviewed with a semi-structured interview together with the Vineland Adaptive Behavior Scales (n=41) and the Autism-Tics, attention-deficit/hyperactivity disorder (AD/HD) and other comorbidities inventory (A-TAC) (n=36). RESULTS: Most children of interviewed parents presented problems within several developmental areas. According to A-TAC and the clinical interview, there were high rates of attention deficits and difficulties with regulating activity level and impulsivity. Vineland Adaptive Behavior Scales composite scores showed that at school age, a majority of the children had declined since the previous assessment at ages between 4.5 and 6.5 years. Almost half the tested group had shifted in their IQ level, to below 70 or above 84. CONCLUSION: None of the children assessed was without developmental/neuropsychiatric problems at school-age follow-up. The results support the need for comprehensive follow-up of educational, medical and developmental/neuropsychiatric needs, including a retesting of cognitive functions. There is also a need for continuing parent/family follow-up and support.
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3. Barton KS, Tabor HK, Starks H, Garrison NA, Laurino M, Burke W. {{Pathways from autism spectrum disorder diagnosis to genetic testing}}. {Genet Med}. 2017.
PurposeThis study examined challenges faced by families and health providers related to genetic testing for autism spectrum disorder (ASD).MethodsThis qualitative study of 14 parents and 15 health providers identified an unstandardized three-step process for families who pursue ASD genetic testing.ResultsStep 1 is the clinical diagnosis of ASD, confirmed by providers practicing alone or in a team. Step 2 is the offer of genetic testing to find an etiology. For those offered testing, step 3 involves the parents’ decision whether to pursue testing. Despite professional guidelines and recommendations, interviews describe considerable variability in approaches to genetic testing for ASD, a lack of consensus among providers, and questions about clinical utility. Many families in our study were unaware of the option for genetic testing; testing decisions by parents appear to be influenced by both provider recommendations and insurance coverage.ConclusionConsideration of genetic testing for ASD should take into account different views about the clinical utility of testing and variability in insurance coverage. Ideally, policy makers from the range of clinical specialties involved in ASD care should revisit policies to clarify the purpose of genetic testing for ASD and promote consensus about its appropriate use.GENETICS in MEDICINE advance online publication, 19 October 2017. doi:10.1038/gim.2017.166.
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4. Billeci L, Narzisi A, Tonacci A, Sbriscia-Fioretti B, Serasini L, Fulceri F, Apicella F, Sicca F, Calderoni S, Muratori F. {{An integrated EEG and eye-tracking approach for the study of responding and initiating joint attention in Autism Spectrum Disorders}}. {Sci Rep}. 2017; 7(1): 13560.
Autism Spectrum Disorders (ASD) are characterised by impairment in joint attention (JA), which has two components: the response to JA and the initiation of JA. Literature suggests a correlation between JA and neural circuitries, although this link is still largely unexplored in ASD. In this pilot study, we aimed at investigating the neural correlates of responding and initiating JA in high-functioning children with ASD and evaluating the changes in brain function and visual pattern after six months of rehabilitative treatment using an integrated EEG/eye-tracking system. Our results showed that initiating and responding JA subtend both overlapping (i.e. frontal and temporal) and specialized (i.e. parietal for responding JA and occipital for initiating JA) neural circuitries. In addition, in a subgroup of subjects, we observed trends of changes in both brain activity and connectivity after rehabilitative treatment in both the two tasks, which were correlated with modifications in gaze measures. These preliminary results, if confirmed in a larger sample, suggest the feasibility of using the proposed multimodal approach to characterise JA-related brain circuitries and visual pattern in ASD individuals and to monitor longitudinal changes in response to rehabilitative intervention.
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5. Bradshaw J, Bearss K, McCracken C, Smith T, Johnson C, Lecavalier L, Swiezy N, Scahill L. {{Parent Education for Young Children With Autism and Disruptive Behavior: Response to Active Control Treatment}}. {J Clin Child Adolesc Psychol}. 2017: 1-11.
This study examines parent and child characteristics in young children with autism spectrum disorder and disruptive behavior who showed a positive response to a parent education program in a randomized clinical trial of parent training. Children with autism spectrum disorder (N = 180) were randomized to parent training (PT) or parent education program (PEP) for 6 months. Using the Clinical Global Impression-Improvement scale, masked independent evaluators rated positive response in 68.5% of children in PT compared to 39.6% in PEP. We compared baseline characteristics and change in parental stress, strain, competence, and mental health for participants who showed a positive response to PEP (PEP-R) to those who did not (PEP-NR). We also compared change in child and parent measures for PEP-R participants to those who showed a positive response to PT (PT-R). At baseline, PEP-R and PEP-NR participants did not differ on any demographic or clinical characteristics. Parents in PEP-R reported significant reductions on the Parenting Stress Index, Caregiver Strain Questionnaire, and Parent Health Questionnaire, and increases on the Parenting Sense of Competence scale. Improvements in child disruptive behavior and parental stress, strain, competence, and mental health for PEP-R participants were similar to PT-R participants. Vineland Daily Living Skills improved only for children in PT-R. PEP was an active control treatment with nearly 40% of participants showing a positive response. Change in child disruptive behavior and parental stress, strain, competence, and mental health were remarkably similar for participants independently rated with a positive response to PEP and PT.
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6. Carlisi CO, Norman L, Murphy CM, Christakou A, Chantiluke K, Giampietro V, Simmons A, Brammer M, Murphy DG, Mataix-Cols D, Rubia K. {{Shared and Disorder-Specific Neurocomputational Mechanisms of Decision-Making in Autism Spectrum Disorder and Obsessive-Compulsive Disorder}}. {Cereb Cortex}. 2017; 27(12): 5804-16.
Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) often share phenotypes of repetitive behaviors, possibly underpinned by abnormal decision-making. To compare neural correlates underlying decision-making between these disorders, brain activation of boys with ASD (N = 24), OCD (N = 20) and typically developing controls (N = 20) during gambling was compared, and computational modeling compared performance. Patients were unimpaired on number of risky decisions, but modeling showed that both patient groups had lower choice consistency and relied less on reinforcement learning compared to controls. ASD individuals had disorder-specific choice perseverance abnormalities compared to OCD individuals. Neurofunctionally, ASD and OCD boys shared dorsolateral/inferior frontal underactivation compared to controls during decision-making. During outcome anticipation, patients shared underactivation compared to controls in lateral inferior/orbitofrontal cortex and ventral striatum. During reward receipt, ASD boys had disorder-specific enhanced activation in inferior frontal/insular regions relative to OCD boys and controls. Results showed that ASD and OCD individuals shared decision-making strategies that differed from controls to achieve comparable performance to controls. Patients showed shared abnormalities in lateral-(orbito)fronto-striatal reward circuitry, but ASD boys had disorder-specific lateral inferior frontal/insular overactivation, suggesting that shared and disorder-specific mechanisms underpin decision-making in these disorders. Findings provide evidence for shared neurobiological substrates that could serve as possible future biomarkers.
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7. Cheng YS, Tseng PT, Chen YW, Stubbs B, Yang WC, Chen TY, Wu CK, Lin PY. {{Supplementation of omega 3 fatty acids may improve hyperactivity, lethargy, and stereotypy in children with autism spectrum disorders: a meta-analysis of randomized controlled trials}}. {Neuropsychiatr Dis Treat}. 2017; 13: 2531-43.
AIM: Deficiency of omega 3 fatty acids may be linked to autism spectrum disorder (ASD). Evidence about the potential therapeutic effects of supplementation of omega 3 fatty acids is lacking in ASD patients. METHODS: We searched major electronic databases from inception to June 21, 2017, for randomized clinical trials, which compared treatment outcomes between supplementation of omega 3 fatty acids and placebo in patients with ASD. An exploratory random-effects meta-analysis of the included studies was undertaken. RESULTS AND CONCLUSION: Six trials were included (n=194). Meta-analysis showed that supplementation of omega 3 fatty acids improved hyperactivity (difference in means =-2.692, 95% confidence interval [CI] =-5.364 to -0.020, P=0.048, studies =4, n=109), lethargy (difference in means =-1.969, 95% CI =-3.566 to -0.372, P=0.016, studies =4, n=109), and stereotypy (difference in means =-1.071, 95% CI =-2.114 to -0.029, P=0.044, studies =4, n=109). No significant differences emerged between supplementation of omega 3 fatty acids and placebo in global assessment of functioning (n=169) or social responsiveness (n=97). Our preliminary meta-analysis suggests that supplementation of omega 3 fatty acids may improve hyperactivity, lethargy, and stereotypy in ASD patients. However, the number of studies was limited and the overall effects were small, precluding definitive conclusions. Future large-scale randomized clinical trials are needed to confirm or refute our findings.
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8. Cho H, Kim CH, Knight EQ, Oh HW, Park B, Kim DG, Park HJ. {{Changes in brain metabolic connectivity underlie autistic-like social deficits in a rat model of autism spectrum disorder}}. {Sci Rep}. 2017; 7(1): 13213.
The neurobiological basis of social dysfunction and the high male prevalence in autism spectrum disorder (ASD) remain poorly understood. Although network alterations presumably underlie the development of autistic-like behaviors, a clear pattern of connectivity differences specific to ASD has not yet emerged. Because the heterogeneous nature of ASD hinders investigations in human subjects, we explored brain connectivity in an etiologically homogenous rat model of ASD induced by exposure to valproic acid (VPA) in utero. We performed partial correlation analysis of cross-sectional resting-state 18F-fluorodeoxyglucose positron emission tomography scans from VPA-exposed and control rats to estimate metabolic connectivity and conducted canonical correlation analysis of metabolic activity and behavior scores. VPA-treated rats exhibited impairments in social behaviors, and this difference was more pronounced in male than female rats. Similarly, current analyses revealed sex-specific changes in network connectivity and identified distinct alterations in the distributed metabolic activity patterns associated with autistic-like social deficits. Specifically, diminished activity in the salience network and enhanced activity in a cortico-cerebellar circuit correlated with the severity of social behavioral deficits. Such metabolic connectivity features may represent neurobiological substrates of autistic-like behavior, particularly in males, and may serve as a pathognomonic sign in the VPA rat model of ASD.
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9. Dang K, Bent S, Lawton B, Warren T, Widjaja F, McDonald MG, Breard M, O’Keefe W, Hendren RL. {{Integrating Autism Care through a School-Based Intervention Model: A Pilot Study}}. {J Clin Med}. 2017; 6(10).
The purpose of this pilot study is to determine the feasibility of monitoring the progress of children with an autism spectrum disorder (ASD) both in school and at home to promote a school-based integrated care model between parents, teachers, and medical providers. This is a prospective cohort study. To monitor progress, outcome measures were administered via an online platform developed for caregivers and teachers of children (n = 30) attending a school specializing in neurodevelopmental disorders and using an integrated medical and education program. Longitudinal analysis showed improvements in a novel scale, the Teacher Autism Progress Scale (TAPS), which was designed to measure key autism-related gains in a school environment (2.1-point improvement, p = 0.004, ES = 0.324). The TAPS showed a strong and statistically significant correlation, with improvement in aberrant behavior (r = -0.50; p = 0.008) and social responsiveness (r = -0.70; p < 0.001). The results also showed non-statistically significant improvements in aberrant behavior, social responsiveness, and quality of life over time at both school and home. To assess feasibility of ongoing progress measurement, we assessed missing data, which showed caregivers were more likely to miss surveys during summer. Results demonstrate the value and feasibility of online, longitudinal data collection in school to assist with individualized education planning and collaborative care for children with ASD. Lessons learned in this pilot will support school outcomes researchers in developing more efficacious, collaborative treatment plans between clinicians, caregivers, and teachers. Lien vers le texte intégral (Open Access ou abonnement)
10. El-Baz F, El-Aal MA, Kamal TM, Sadek AA, Othman AA. {{Study of the C677T and 1298AC polymorphic genotypes of MTHFR Gene in autism spectrum disorder}}. {Electron Physician}. 2017; 9(9): 5287-93.
BACKGROUND: Autism is currently known as « a behaviorally defined syndrome » manifested as impairment in social communication, repetitive routines and restricted interests. There is an increased risk of ASDs associated with common mutations affecting the folate/methylation cycle. AIM: The aim of this study was to identify C677T and 1298AC polymorphic genotypes of MTHFR gene among a sample of Egyptian children with autism and to make a phenotype-genotype correlation for the autistic patients. METHODS: This case-control study was carried out from 2013 through 2015. The study included 31 children with autism and 39 children in a normal control group, the mean age of patients and control was comparable (4.5 years+/- 2) with males predominant in both groups. We used DSM-V-TR criteria, Stanford-Binet intelligence scale V and childhood autism rating scale (CARS) for assessments. Genotyping for MTHFR gene polymorphic loci C677T and 1298AC was performed on amplified DNA by PCR with subsequent reverse hybridization and restriction fragment length polymorphisms analysis. Data were analyzed by SPSS version 11, using Chi-Square, independent-samples t-test, and ANOVA. RESULTS: There was significant relationship between low birth weight and occurrence of autism (p<0.01), and between delayed motor and social milestones in cases of autism compared to controls (p<0.01). Heterozygosity for A1298C polymorphism was highest among patients (41.9%) followed by 35.5% mutant genotype CC and 22.6% normal AA (wild) type and Allele C was detected in patients more than in control (56.45% vs. 11.54%) (p<0.001). For C667T polymorphism, heterozygosity was also highest among patients (48.4%) followed by wild type genotypes C677 (38.7%) and 12.9% for mutant genotypes 667T. Allele T appeared more in patients than control (31.10 %vs. 5.13%) (p<0.00). Heterozygosity for CT and A-C genotypes were detected equally (46.2%) among patients with severe autism (according to CARS). CONCLUSION: There is a significant association between severity and occurrence of autism with MTHFR gene polymorphisms C677T and A1298C. Further studies are needed on a larger scale to explore other genes polymorphisms that may be associated with autism, to correlate the genetic basis of autism. Lien vers le texte intégral (Open Access ou abonnement)
11. Hahn LJ, Brady NC, McCary L, Rague L, Roberts JE. {{Early social communication in infants with fragile X syndrome and infant siblings of children with autism spectrum disorder}}. {Res Dev Disabil}. 2017; 71: 169-80.
BACKGROUND: Little research in fragile X syndrome (FXS) has prospectively examined early social communication. AIMS: To compare early social communication in infants with FXS, infant siblings of children with autism spectrum disorder (ASIBs), and typically developing (TD) infants. METHODS AND PROCEDURES: Participants were 18 infants with FXS, 21 ASIBs, and 22 TD infants between 7.5-14.5 months. Social communication was coded using the Communication Complexity Scale during the administration of Autism Observation Scale for Infants. OUTCOMES AND RESULTS: Descriptively different patterns were seen across the three groups. Overall infants with FXS had lower social communication than ASIBs or TD infants when controlling for nonverbal cognitive abilities. However, infants with FXS had similar levels of social communication as ASIBs or TD infants during peek-a-boo. No differences were observed between ASIBs and TD infants. For all infants, higher social communication was related to lower ASD risk. CONCLUSIONS AND IMPLICATIONS: Findings provide insight into the developmental course of social communication in FXS. The dynamic nature of social games may help to stimulate communication in infants with FXS. Language interventions with a strong social component may be particularly effective for promoting language development in FXS.
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12. Lacivita E, Perrone R, Margari L, Leopoldo M. {{Targets for Drug Therapy for Autism Spectrum Disorder: Challenges and Future Directions}}. {J Med Chem}. 2017; 60(22): 9114-41.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests, and activities. Various factors are involved in the etiopathogenesis of ASD, including genetic factors, environmental toxins and stressors, impaired immune responses, mitochondrial dysfunction, and neuroinflammation. The heterogeneity in the phenotype among ASD patients and the complex etiology of the condition have long impeded the advancement of the development of pharmacological therapies. In the recent years, the integration of findings from mouse models to human genetics resulted in considerable progress toward the understanding of ASD pathophysiology. Currently, strategies to treat core symptoms of ASD are directed to correct synaptic dysfunctions, abnormalities in central oxytocin, vasopressin, and serotonin neurotransmission, and neuroinflammation. Here, we present a survey of the studies that have suggested molecular targets for drug development for ASD and the state-of-the-art of medicinal chemistry efforts in related areas.
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13. Lee J, Spratling R, Helvig A. {{Sleep Characteristics in Mothers of Children With Developmental Disabilities}}. {J Pediatr Health Care}. 2017.
Impaired sleep can contribute to conditions such as cardiometabolic disorders, depression, and decreased immune function. Mothers of children with developmental disabilities (DDs) may be at greater risk for impaired sleep due to the sleep problems of their children. This cross-sectional study described the self-reported sleep characteristics of mothers of children (ages 6-12) with DDs by using a sleep diary and the Pittsburgh Sleep Quality Index (PSQI) as quantitative and qualitative measures of sleep in these mothers. The Consensus Sleep Diary was modified to ascertain how the child’s sleep and needs for care during the night impacted the mother’s sleep. The results showed that mothers had short sleep duration (nearly 40% slept <7 hours per night), woke up an average of 2.2 times per night (most commonly due to caregiving needs of children), and had poor sleep quality (mean PSQI global score of 7.9 [SD=4.8]). The sleep problems of children with DDs may influence mothers' sleep. Lien vers le texte intégral (Open Access ou abonnement)
14. Lefevre A, Mottolese R, Redoute J, Costes N, Le Bars D, Geoffray MM, Leboyer M, Sirigu A. {{Oxytocin Fails to Recruit Serotonergic Neurotransmission in the Autistic Brain}}. {Cereb Cortex}. 2017: 1-10.
Oxytocin (OT), a neuropeptide involved in affiliation has been shown to enhance social skills in patients with autism spectrum disorders (ASD). Nevertheless, OT improvements seem ephemeral. Animal research has demonstrated OT action on serotonin (5-HT), an interaction that we also found in the healthy human brain. Whether such synaptic interplay also occurs in ASD patients is unknown. To address this issue, we mapped the effects of intranasal OT on 5-HT in 18 patients with ASD and 24 healthy controls (HC) in a double blind, placebo controlled, within subject PET-scan experiment. Each participant underwent two scans: baseline and spray (OT or placebo). Using the radiotracer [18 F]MPPF, marking the 5-HT 1A receptor (5-HT1AR), we measured MPPF-Binding Potential (BP) as an index of OT-induced serotonin functional modulation. At baseline ASD patients did not differ from controls for 5-HT1AR concentration and distribution. However, while OT significantly increased MPPF BP in several brain regions of HC, no changes were observed in the ASD group. Serotonin serum concentration analysis corroborated these results. Our findings suggest a disturbed OT-serotonin interaction in autism. This may limit the potential benefits of OT in these patients and open the ways to investigate combined OT-serotonin treatments.
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15. Madipakkam AR, Rothkirch M, Dziobek I, Sterzer P. {{Unconscious avoidance of eye contact in autism spectrum disorder}}. {Sci Rep}. 2017; 7(1): 13378.
Atypical responses to direct gaze are one of the most characteristic hallmarks of autism spectrum disorder (ASD). The cause and mechanism underlying this phenomenon, however, have remained unknown. Here we investigated whether the atypical responses to eye gaze in autism spectrum disorder is dependent on the conscious perception of others’ faces. Face stimuli with direct and averted gaze were rendered invisible by interocular suppression and eye movements were recorded from participants with ASD and an age and sex matched control group. Despite complete unawareness of the stimuli, the two groups differed significantly in their eye movements to the face stimuli. In contrast to the significant positive saccadic index observed in the TD group, indicating an unconscious preference to the face with direct gaze, the ASD group had no such preference towards direct gaze and instead showed a tendency to prefer the face with averted gaze, suggesting an unconscious avoidance of eye contact. These results provide the first evidence that the atypical response to eye contact in ASD is an unconscious and involuntary response. They provide a better understanding of the mechanism of gaze avoidance in autism and might lead to new diagnostic and therapeutic interventions.
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16. Marsh A, Spagnol V, Grove R, Eapen V. {{Transition to school for children with autism spectrum disorder: A systematic review}}. {World J Psychiatry}. 2017; 7(3): 184-96.
AIM: To identify factors that promote a positive start to school for children with autism spectrum disorder (ASD). METHODS: Web of Science, MEDLINE, Scopus, and PsychINFO searches were conducted to identify literature published after 1991 and relevant to school transition processes in children with ASD. Twenty studies were deemed eligible for inclusion. These studies evaluated a range of factors including school readiness, parent and teacher perspectives on transition practices, characteristics of children with ASD that are associated with successful transition to school and the impact of school based intervention programs. RESULTS: A review of these studies showed that children with ASD are less school ready emotionally than their peers and those children with ASD appear to have more externalising behaviours and self-regulation difficulties that affect their school engagement and their relationships with their teachers. There was a paucity of research looking at interventions targeting school readiness. However, school-based behavioural interventions appear to improve cognitive, language and daily living skills, but have less impact on socialisation and peer inclusion. CONCLUSION: Children with ASD face more challenges transitioning to school, particularly with social interaction. Further development and implementation of specific school-based interventions is needed in order to assist children with autism to maximise their success in starting school.
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17. McCauley JB, Harris MA, Zajic MC, Swain-Lerro LE, Oswald T, McIntyre N, Trzesniewski K, Mundy P, Solomon M. {{Self-Esteem, Internalizing Symptoms, and Theory of Mind in Youth With Autism Spectrum Disorder}}. {J Clin Child Adolesc Psychol}. 2017: 1-12.
Self-esteem is a potent indicator of mental health in typically developing (TYP) individuals. It is surprising that there have been few comprehensive investigations of self-esteem in children and adolescents with autism spectrum disorder (ASD), given that they are at high risk for comorbid mental health problems, such as depression and anxiety. The objectives of the current study were to assess how youth with ASD rate their self-esteem compared to age-matched TYP youth and to examine how self-esteem relates to internalizing psychopathology and theory of mind in the two groups. Seventy-three children and adolescents, ages 9 to 17, were administered a battery of questionnaires assessing self-esteem and internalizing symptoms, as well as tasks designed to measure theory of mind. Results indicated that youth with ASD rated their self-esteem significantly lower than did TYP youth. Self-esteem was strongly related to depression in both groups but was negatively related to theory of mind only for youth with ASD. These results may provide important insights into how individuals with ASD form evaluations of their own self-worth and illustrate how increasing self-awareness in individuals with ASD is not without risks.
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18. Moosa A, Shu H, Sarachana T, Hu VW. {{Are endocrine disrupting compounds environmental risk factors for autism spectrum disorder?}}. {Horm Behav}. 2017.
Recent research on the etiology of autism spectrum disorder (ASD) has shifted in part from a singular focus on genetic causes to the involvement of environmental factors and their gene interactions. This shift in focus is a result of the rapidly increasing prevalence of ASD coupled with the incomplete penetrance of this disorder in monozygotic twins. One such area of environmentally focused research is the association of exposures to endocrine disrupting compounds (EDCs) with elevated risk for ASD. EDCs are exogenous chemicals that can alter endogenous hormone activity and homeostasis, thus potentially disrupting the action of sex and other natural hormones at all stages of human development. Inasmuch as sex hormones play a fundamental role in brain development and sexual differentiation, exposure to EDCs in utero during critical stages of development can have lasting neurological and other physiological influences on the developing fetus and, ultimately, the child as well as adult. This review will focus on the possible contributions of EDCs to autism risk and pathogenesis by first discussing the influence of endogenous sex hormones on the autistic phenotype, followed by a review of documented human exposures to EDCs and associations with behaviors relevant to ASD. Mechanistic links between EDC exposures and aberrant neurodevelopment and behaviors are then considered, with emphasis on EDC-induced transcriptional profiles derived from animal and cellular studies. Finally, this review will discuss possible mechanisms through which EDC exposure can lead to persistent changes in gene expression and phenotype, which may in turn contribute to transgenerational inheritance of ASD.
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19. Nomura T, Musial TF, Marshall JJ, Zhu Y, Remmers CL, Xu J, Nicholson DA, Contractor A. {{Delayed Maturation of Fast-Spiking Interneurons Is Rectified by Activation of the TrkB Receptor in the Mouse Model of Fragile X Syndrome}}. {J Neurosci}. 2017; 37(47): 11298-310.
Fragile X syndrome (FXS) is a neurodevelopmental disorder that is a leading cause of inherited intellectual disability, and the most common known cause of autism spectrum disorder. FXS is broadly characterized by sensory hypersensitivity and several developmental alterations in synaptic and circuit function have been uncovered in the sensory cortex of the mouse model of FXS (Fmr1 KO). GABA-mediated neurotransmission and fast-spiking (FS) GABAergic interneurons are central to cortical circuit development in the neonate. Here we demonstrate that there is a delay in the maturation of the intrinsic properties of FS interneurons in the sensory cortex, and a deficit in the formation of excitatory synaptic inputs on to these neurons in neonatal Fmr1 KO mice. Both these delays in neuronal and synaptic maturation were rectified by chronic administration of a TrkB receptor agonist. These results demonstrate that the maturation of the GABAergic circuit in the sensory cortex is altered during a critical developmental period due in part to a perturbation in BDNF-TrkB signaling, and could contribute to the alterations in cortical development underlying the sensory pathophysiology of FXS.SIGNIFICANCE STATEMENT Fragile X (FXS) individuals have a range of sensory related phenotypes, and there is growing evidence of alterations in neuronal circuits in the sensory cortex of the mouse model of FXS (Fmr1 KO). GABAergic interneurons are central to the correct formation of circuits during cortical critical periods. Here we demonstrate a delay in the maturation of the properties and synaptic connectivity of interneurons in Fmr1 KO mice during a critical period of cortical development. The delays both in cellular and synaptic maturation were rectified by administration of a TrkB receptor agonist, suggesting reduced BDNF-TrkB signaling as a contributing factor. These results provide evidence that the function of fast-spiking interneurons is disrupted due to a deficiency in neurotrophin signaling during early development in FXS.
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20. Sabuncuoglu O. {{Towards a further understanding of prenatal thyroid theory of homosexuality: Autoimmune thyroiditis, polycystic ovary syndrome, autism and low birth weight}}. {Ment Illn}. 2017; 9(2): 7325.
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21. Sasson NJ, Morrison KE. {{First impressions of adults with autism improve with diagnostic disclosure and increased autism knowledge of peers}}. {Autism}. 2017: 1362361317729526.
A practical consideration for many intellectually able adults with autism spectrum disorder (ASD) is whether to disclose their diagnostic status or try to mask their autistic characteristics to avoid judgment and discrimination. Here, we assessed first impressions of adults with ASD and typically developing controls ( N = 40) made by typically developing observers ( N = 215) when their diagnostic status was either withheld, accurately provided, or inaccurately provided. First impressions were less favorable for ASD participants compared to typically developing controls across a range of judgments, but were significantly more positive when accurately labeled as ASD compared to when no label was provided, when mislabeled as typically developing, or when mislabeled as having schizophrenia. For typically developing participants, ratings did not change when accurately labeled but improved when mislabeled as ASD. Greater autistic traits for the ASD and typically developing participants were associated with less favorable first impressions, and females were rated more favorably than males. Autism knowledge of the raters, but not age, IQ, or autistic traits, was positively associated with more favorable impressions of ASD participants. Collectively, these findings suggest that first impressions for intellectually able adults with ASD improve with diagnostic disclosure and increased autism understanding on the part of peers.
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22. Sato W, Sawada R, Uono S, Yoshimura S, Kochiyama T, Kubota Y, Sakihama M, Toichi M. {{Impaired detection of happy facial expressions in autism}}. {Sci Rep}. 2017; 7(1): 13340.
The detection of emotional facial expressions plays an indispensable role in social interaction. Psychological studies have shown that typically developing (TD) individuals more rapidly detect emotional expressions than neutral expressions. However, it remains unclear whether individuals with autistic phenotypes, such as autism spectrum disorder (ASD) and high levels of autistic traits (ATs), are impaired in this ability. We examined this by comparing TD and ASD individuals in Experiment 1 and individuals with low and high ATs in Experiment 2 using the visual search paradigm. Participants detected normal facial expressions of anger and happiness and their anti-expressions within crowds of neutral expressions. In Experiment 1, reaction times were shorter for normal angry expressions than for anti-expressions in both TD and ASD groups. This was also the case for normal happy expressions vs. anti-expressions in the TD group but not in the ASD group. Similarly, in Experiment 2, the detection of normal vs. anti-expressions was faster for angry expressions in both groups and for happy expressions in the low, but not high, ATs group. These results suggest that the detection of happy facial expressions is impaired in individuals with ASD and high ATs, which may contribute to their difficulty in creating and maintaining affiliative social relationships.
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23. Tam FI, King JA, Geisler D, Korb FM, Sareng J, Ritschel F, Steding J, Albertowski KU, Roessner V, Ehrlich S. {{Altered behavioral and amygdala habituation in high-functioning adults with autism spectrum disorder: an fMRI study}}. {Sci Rep}. 2017; 7(1): 13611.
Habituation to repeatedly presented stimuli is an important adaptive property of the nervous system. Autism spectrum disorder (ASD) has been associated with reduced neural habituation, for example in the amygdala, which may be related to social impairments. The main focus of this study was to investigate habituation effects on the level of behavioral responses as well as amygdala responses in adults with ASD during a working memory task flanked by task-irrelevant face stimuli. Twenty-two patients with high-functioning autism and 24 healthy controls (HC) were included in this functional magnetic resonance imaging (fMRI) study. We employed an established habituation index to investigate habituation effects. Suggestive of altered habituation, the habituation index showed a decrement of reaction time over the course of the experiment in the HC but not in the ASD group. Similarly, an expected pattern of habituation was evident in amygdala activation in HC but absent in ASD participants. These results provide evidence that habituation may be altered not only on a neural, but also on a behavioral level in ASD. While more research is needed to develop a better understanding of the underlying mechanisms, the current findings support the possibility that deficient habituation may be a biomarker of ASD.
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24. Turner TN, Coe BP, Dickel DE, Hoekzema K, Nelson BJ, Zody MC, Kronenberg ZN, Hormozdiari F, Raja A, Pennacchio LA, Darnell RB, Eichler EE. {{Genomic Patterns of De Novo Mutation in Simplex Autism}}. {Cell}. 2017; 171(3): 710-22 e12.
To further our understanding of the genetic etiology of autism, we generated and analyzed genome sequence data from 516 idiopathic autism families (2,064 individuals). This resource includes >59 million single-nucleotide variants (SNVs) and 9,212 private copy number variants (CNVs), of which 133,992 and 88 are de novo mutations (DNMs), respectively. We estimate a mutation rate of approximately 1.5 x 10-8 SNVs per site per generation with a significantly higher mutation rate in repetitive DNA. Comparing probands and unaffected siblings, we observe several DNM trends. Probands carry more gene-disruptive CNVs and SNVs, resulting in severe missense mutations and mapping to predicted fetal brain promoters and embryonic stem cell enhancers. These differences become more pronounced for autism genes (p = 1.8 x 10-3, OR = 2.2). Patients are more likely to carry multiple coding and noncoding DNMs in different genes, which are enriched for expression in striatal neurons (p = 3 x 10-3), suggesting a path forward for genetically characterizing more complex cases of autism.
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25. Wang J, Gong J, Li L, Chen Y, Liu L, Gu H, Luo X, Hou F, Zhang J, Song R. {{Neurexin gene family variants as risk factors for autism spectrum disorder}}. {Autism Res}. 2017.
Increasing evidence suggests that abnormal synaptic function leads to neuronal developmental disorders and is an important component of the etiology of autism spectrum disorder (ASD). Neurexins are presynaptic cell-adhesion molecules that affect the function of synapses and mediate the conduction of nerve signals. Thus, neurexins are attractive candidate genes for autism. Since gene families have greater power to reveal genetic association than single genes, we designed this case-control study to investigate six genetic variants in three neurexin genes (NRXN1, NRXN2, and NRXN3) in a Chinese population including 529 ASD patients and 1,923 healthy controls. We found that two SNPs were significantly associated with ASD after false discovery rate (FDR) adjustment for multiple comparisons. The NRXN2 rs12273892 polymorphism T allele and AT genotype were significantly associated with increased risk of ASD (respectively: OR = 1.328, 95% CI = 1.133-1.557, P < 0.001; OR = 1.528; 95% CI = 1.249-1.868, P < 0.001). The dominant model showed the same association (OR = 1.495, 95% CI = 1.231-1.816, P < 0.001). The NRXN3 rs12879016 polymorphism played a significant role in ASD susceptibility under the dominant model (OR = 0.747, 95% CI= 0.615-0.908, P = 0.023), with the same trend detected for the G allele and GT genotype (respectively: OR = 0.811, 95% CI = 0.699-0.941, P = 0.036; OR = 0.755, 95% CI = 0.615-0.928, P = 0.035). In conclusion, this study supports the importance of two genetic variants in the neurexin gene family in ASD susceptibility in China. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is highly heritable, and studies have found a number of candidate genes that might contribute to ASD. Neurexins are presynaptic cell-adhesion molecules that affect the function of synapses and mediate the conduction of nerve signals, and they play an important role in normal brain development and become candidate genes for autism. The purpose of our study is to explore the association between variants of the neurexins gene family and ASD in a Chinese population through a case-control study. Lien vers le texte intégral (Open Access ou abonnement)
