1. Chuang HC, Huang TN, Hsueh YP. {{T-Brain-1 – A Potential Master Regulator in Autism Spectrum Disorders}}. {Autism Res}. 2015.
T-Brain-1 (TBR1), a causative gene in autism spectrum disorders (ASDs), encodes a brain-specific T-box transcription factor. It is therefore possible that TBR1 controls the expression of other autism risk factors. The downstream genes of TBR1 have been identified using microarray and promoter analyses. In this study, we annotated individual genes downstream of TBR1 and investigated any associations with ASDs through extensive literature searches. Of 124 TBR1 target genes, 23 were reported to be associated with ASDs. In addition, one gene, Kiaa0319, is a known causative gene for dyslexia, a disorder frequently associated with autism. A change in expression level in 10 of these 24 genes has been previously confirmed. We further validated the alteration of RNA expression levels of Kiaa0319, Baiap2, and Gad1 in Tbr1 deficient mice. Among these 24 genes, four transcription factors Auts2, Nfia, Nr4a2, and Sox5 were found, suggesting that TBR1 controls a transcriptional cascade relevant to autism pathogenesis. A further five of the 24 genes (Cd44, Cdh8, Cntn6, Gpc6, and Ntng1) encode membrane proteins that regulate cell adhesion and axonal outgrowth. These genes likely contribute to the role of TBR1 in regulation of neuronal migration and axonal extension. Besides, decreases in Grin2b expression and increases in Gad1 expression imply that neuronal activity may be aberrant in Tbr1 deficient mice. These analyses provide direction for future experiments to reveal the pathogenic mechanism of autism. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
2. Conti R. {{Compassionate Parenting as a Key to Satisfaction, Efficacy and Meaning Among Mothers of Children with Autism}}. {J Autism Dev Disord}. 2015.
Two studies examine the role of compassionate and self-image parenting goals in the experience of mothers of children with autism. In Study 1, a comparison sample was included. Study 1 included measures of parenting goals, life satisfaction, family life satisfaction, parenting satisfaction, and meaning in life. Study 2 incorporated a measure of parenting efficacy. Study 1 showed that mothers of children with autism were higher than comparison mothers in compassionate parenting goals. In both studies, compassionate parenting predicted positive outcomes including higher parenting satisfaction (both studies), family life satisfaction, meaning in life (Study 1) and higher parenting efficacy (Study 2). These studies support the notion that compassionate parenting is a key to satisfaction for mothers of children with autism.
Lien vers le texte intégral (Open Access ou abonnement)
3. Craig F, Lamanna AL, Margari F, Matera E, Simone M, Margari L. {{Overlap Between Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder: Searching for Distinctive/Common Clinical Features}}. {Autism Res}. 2015.
Recent studies support several overlapping traits between autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), assuming the existence of a combined phenotype. The aim of our study was to evaluate the common or distinctive clinical features between ASD and ADHD in order to identify possible different phenotypes that could have a clinical value. We enrolled 181 subjects divided into four diagnostic groups: ADHD group, ASD group, ASD+ADHD group (that met diagnostic criteria for both ASD and ADHD), and control group. Intelligent quotient (IQ), emotional and behavior problems, ADHD symptoms, ASD symptoms, and adaptive behaviors were investigated through the following test: Wechsler Intelligence Scale for Children, Wechsler Preschool and Primary Scale of Intelligence or Leiter International Performances Scale Revised, Child Behavior Checklist, Conners’ Rating Scales-Revised, SNAP-IV Rating Scale, the Social Communication Questionnaire, Vineland Adaptive Behavior Scales. The ASD+ADHD group differs from ADHD or ASD in some domains such as lower IQ mean level and a higher autistic symptoms severity. However, the ASD+ADHD group shares inattention and hyperactivity deficit and some emotional and behavior problems with the ADHD group, while it shares adaptive behavior impairment with ASD group. These findings provide a new understanding of clinical manifestation of ASD+ADHD phenotype, they may also inform a novel treatment target. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
4. Eigsti IM, Rosset D, Col Cozzari G, da Fonseca D, Deruelle C. {{Effects of motor action on affective preferences in autism spectrum disorders: different influences of embodiment}}. {Dev Sci}. 2015.
In the embodied cognition framework, sensory, motor and emotional experiences are encoded along with sensorimotor cues from the context in which information was acquired. As such, representations retain an initial imprint of the manner in which information was acquired. The current study reports results indicating a lack of embodiment effects in ASD and, further, an association between embodiment differences and ASD symptomatology. The current results are consistent with an embodied account of ASD that goes beyond social experiences and could be driven by subtle deficits in sensorimotor coordination.
Lien vers le texte intégral (Open Access ou abonnement)
5. Ekas NV, Timmons L, Pruitt M, Ghilain C, Alessandri M. {{The Power of Positivity: Predictors of Relationship Satisfaction for Parents of Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2015.
The current study uses the actor-partner interdependence model to examine the predictors of relationship satisfaction for mothers and fathers of children with autism spectrum disorder. Sixty-seven couples completed measures of optimism, benefit finding, coping strategies, social support, and relationship satisfaction. Results indicated that parent’s positive strengths predicted better personal relationship satisfaction. Moreover, parents’ benefit finding, use of emotional support, and perceived social support from their partner also predicted their partner’s relationship satisfaction. The results of this study highlight the importance of focusing on positive factors that can enhance relationship quality. Implications for the development of parent-focused interventions are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
6. Hahamy A, Behrmann M, Malach R. {{The idiosyncratic brain: distortion of spontaneous connectivity patterns in autism spectrum disorder}}. {Nat Neurosci}. 2015.
Autism spectrum disorder (ASD) has been associated with a reduction in resting state functional connectivity, though this assertion has recently been challenged by reports of increased connectivity in ASD. To address these contradictory findings, we examined both inter- and intrahemispheric functional connectivity in several resting state data sets acquired from adults with high-functioning ASD and matched control participants. Our results reveal areas of both increased and decreased connectivity in multiple ASD groups as compared to control groups. We propose that this heterogeneity stems from a previously unrecognized ASD characteristic: idiosyncratic distortions of the functional connectivity pattern relative to the typical, canonical template. The magnitude of an individual’s pattern distortion in homotopic interhemispheric connectivity correlated significantly with behavioral symptoms of ASD. We propose that individualized alterations in functional connectivity organization are a core characteristic of high-functioning ASD, and that this may account for previous discrepant findings.
Lien vers le texte intégral (Open Access ou abonnement)
7. Inoue E, Watanabe Y, Egawa J, Sugimoto A, Nunokawa A, Shibuya M, Igeta H, Someya T. {{Rare heterozygous truncating variations and risk of autism spectrum disorder: whole-exome sequencing of a multiplex family and follow-up study in a Japanese population}}. {Psychiatry Clin Neurosci}. 2015.
AIM: Rare heterozygous truncating variations in multiplex families with autism spectrum disorder (ASD) are suggested to play a major role in genetic etiology of ASD. To further investigate the role of rare heterozygous truncating variations, we performed whole-exome sequencing (WES) in a multiplex ASD family with four affected individuals (two siblings and two maternal cousins), and a follow-up case-control study in a Japanese population. METHODS: WES was performed in four individuals (a proband, his affected and unaffected siblings, and their putative carrier mother) from the multiplex ASD family. Rare heterozygous truncating variations prioritized in WES were genotyped in 243 patients and 667 controls. RESULTS: By WES of the multiplex family, we prioritized two rare heterozygous truncating variations, RPS24 Q191X and CD300LF P261fsX266. However, we did not identify these variations in patients or controls in the follow-up study. CONCLUSION: Our findings suggest that two rare heterozygous truncating variations (RPS24 Q191X and CD300LF P261fsX266) are risk candidates for ASD.
Lien vers le texte intégral (Open Access ou abonnement)
8. Kern JK, Geier D, King P, Sykes L, Mehta J, Geier M. {{Shared Brain Connectivity Issues, Symptoms, and Comorbidities in Autism Spectrum Disorder, Attention Deficit/Hyperactivity Disorder, and Tourette Syndrome}}. {Brain Connect}. 2015.
The prevalence of neurodevelopmental disorders, including autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and Tourette syndrome (TS), has increased over the past two decades. Currently, about 1 in 6 children in the United States is diagnosed with a neurodevelopmental disorder. Evidence suggests that ASD, ADHD, and TS have similar neuropathology, which includes long-range under-connectivity and short-range over-connectivity. They also share similar symptomatology, with considerable overlap in their core and associated symptoms and a frequent overlap in their comorbid conditions. Consequently, it is apparent that ASD, ADHD, and TS diagnoses belong to a broader spectrum of neurodevelopmental illness. Biologically, long-range under-connectivity and short-range over-connectivity are plausibly related to neuronal insult (e.g., neurotoxicity, neuroinflammation, excitotoxicity, sustained microglial activation, proinflammatory cytokines, toxic exposure, oxidative stress, etc.). Therefore, these disorders may a share a similar etiology. The main purpose of this review is to critically examine the evidence that ASD, ADHD, and TS belong to a broader spectrum of neurodevelopmental illness, an abnormal connectivity spectrum disorder (ACSD), which results from neural long-range under-connectivity and short-range over-connectivity. The review also discusses the possible reasons for these neuropathological connectivity findings. In addition, this review examines the role and issue of axonal injury and regeneration in order to better understand the neuropathophysiological interplay between short- and long-range axons in connectivity issues.
Lien vers le texte intégral (Open Access ou abonnement)
9. Madsen GF, Bilenberg N, Jepsen JR, Glenthoj B, Cantio C, Oranje B. {{Normal P50 Gating in Children with Autism, Yet Attenuated P50 Amplitude in the Asperger Subcategory}}. {Autism Res}. 2015.
Autism spectrum disorders (ASD) and schizophrenia are separate disorders, but there is evidence of conversion or comorbid overlap. The objective of this paper was to explore whether deficits in sensory gating, as seen in some schizophrenia patients, can also be found in a group of ASD children compared to neurotypically developed children. An additional aim was to investigate the possibility of subdividing our ASD sample based on these gating deficits. In a case-control design, we assessed gating of the P50 and N100 amplitude in 31 ASD children and 39 healthy matched controls (8-12 years) and screened for differences between groups and within the ASD group. We did not find disturbances in auditory P50 and N100 filtering in the group of ASD children as a whole, nor did we find abnormal P50 and N100 amplitudes. However, the P50 amplitude to the conditioning stimulus was significantly reduced in the Asperger subgroup compared to healthy controls. In contrast to what is usually reported for patients with schizophrenia, we found no evidence for sensory gating deficits in our group of ASD children taken as a whole. However, reduced P50 amplitude to conditioning stimuli was found in the Asperger group, which is similar to what has been described in some studies in schizophrenia patients. There was a positive correlation between the P50 amplitude of the conditioning stimuli and anxiety score in the pervasive developmental disorder not otherwise specified group, which indicates a relation between anxiety and sensory registration in this group. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
10. Marko MK, Crocetti D, Hulst T, Donchin O, Shadmehr R, Mostofsky SH. {{Behavioural and neural basis of anomalous motor learning in children with autism}}. {Brain}. 2015.
Autism spectrum disorder is a developmental disorder characterized by deficits in social and communication skills and repetitive and stereotyped interests and behaviours. Although not part of the diagnostic criteria, individuals with autism experience a host of motor impairments, potentially due to abnormalities in how they learn motor control throughout development. Here, we used behavioural techniques to quantify motor learning in autism spectrum disorder, and structural brain imaging to investigate the neural basis of that learning in the cerebellum. Twenty children with autism spectrum disorder and 20 typically developing control subjects, aged 8-12, made reaching movements while holding the handle of a robotic manipulandum. In random trials the reach was perturbed, resulting in errors that were sensed through vision and proprioception. The brain learned from these errors and altered the motor commands on the subsequent reach. We measured learning from error as a function of the sensory modality of that error, and found that children with autism spectrum disorder outperformed typically developing children when learning from errors that were sensed through proprioception, but underperformed typically developing children when learning from errors that were sensed through vision. Previous work had shown that this learning depends on the integrity of a region in the anterior cerebellum. Here we found that the anterior cerebellum, extending into lobule VI, and parts of lobule VIII were smaller than normal in children with autism spectrum disorder, with a volume that was predicted by the pattern of learning from visual and proprioceptive errors. We suggest that the abnormal patterns of motor learning in children with autism spectrum disorder, showing an increased sensitivity to proprioceptive error and a decreased sensitivity to visual error, may be associated with abnormalities in the cerebellum.
Lien vers le texte intégral (Open Access ou abonnement)
11. Mezzelani A, Raggi ME, Marabotti A, Milanesi L. {{Ochratoxin A as possible factor trigging autism and its male prevalence via epigenetic mechanism}}. {Nutr Neurosci}. 2015.
The role of dysbiosis causing leaky gut with xenobiotic production and absorption is increasingly demonstrated in autism spectrum disorder (ASD) pathogenesis. Among xenobiotics, we focused on ochratoxin A (one of the major food contaminating mycotoxin), that in vitro and in vivo exerts a male-specific neurotoxicity probably via microRNA modulation of a specific target gene. Among possible targets, we focused on neuroligin4X. Interestingly, this gene carries some SNPs already correlated with the disease and with illegitimate microRNA binding sites and, being located on X-chromosome, could explain the male prevalence. In conclusion, we propose a possible gene-environment interaction triggering ASD explaining the epigenetic neurotoxic mechanism activated by ochratoxin A in genetically predisposed children. This mechanism offers a clue for male prevalence of the disease and may have an important impact on prevention and cure of ASD.
Lien vers le texte intégral (Open Access ou abonnement)
12. Neuhaus E, Bernier RA, Beauchaine TP. {{Electrodermal Response to Reward and Non-Reward Among Children With Autism}}. {Autism Res}. 2015.
Pervasive social difficulties among individuals with autism spectrum disorder (ASD) are often construed as deriving from reduced sensitivity to social stimuli. Behavioral and neurobiological evidence suggests that typical individuals show preferential processing of social (e.g., voices, faces) over nonsocial (e.g., nonvocal sounds, images of objects) information, whereas individuals with ASD may not. This reduction in sensitivity may reflect disrupted reward processing [Dawson & Bernier, ], with significant developmental consequences for affected individuals. In this study, we explore effects of social and monetary reward on behavioral and electrodermal responses (EDRs) among 8- to 12-year-old boys with (n = 18) and without (n = 18) ASD, with attention to the potential moderating effects of stimulus familiarity. During a simple matching task, participants with and without ASD had marginally slower reactions during social vs. nonsocial reward, and boys with ASD had less accurate responses than controls. Compared to baseline, reward and non-reward conditions elicited more frequent and larger EDRs for participants as a whole, and both groups showed similar patterns of EDR change within reward blocks. However, boys with and without ASD differed in their EDRs to non-reward, and response amplitude was correlated with social and emotional functioning. These findings provide some support for altered reward responding in ASD at the autonomic level, and highlight the discontinuation of reward as an important component of reward-based learning that may play a role in shaping behavior and guiding specialized brain development to subserve social behavior and cognition across the lifespan. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
13. Taylor MJ, Charman T, Ronald A. {{Where are the strongest associations between autistic traits and traits of ADHD? evidence from a community-based twin study}}. {Eur Child Adolesc Psychiatry}. 2015.
Autism spectrum conditions (ASC) and attention-deficit/hyperactivity disorder (ADHD) regularly co-occur. Twin studies increasingly indicate that these conditions may have overlapping genetic causes. Less is known about the degree to which specific autistic traits relate to specific behaviours characteristic of ADHD. We hence tested, using the classical twin design, whether specific dimensional autistic traits, including social difficulties, communication atypicalities and repetitive behaviours, would display differential degrees of aetiological overlap with specific traits of ADHD, including hyperactivity/impulsivity and inattention. Parents of approximately 4,000 pairs of 12-year-old twins completed the Childhood Autism Spectrum Test and Conners’ Parent Rating Scale. These measures were divided into subscales corresponding to different types of autistic and ADHD behaviours. Twin model fitting suggested that the degree of genetic overlap was particularly strong between communication difficulties and traits of ADHD (genetic correlations = .47-.51), while repetitive behaviours and social difficulties showed moderate (genetic correlations = .12-.33) and modest (.05-.11) genetic overlap respectively. Environmental overlap was low across all subscales (correlations = .01-.23). These patterns were also apparent at the extremes of the general population, with communication difficulties showing the highest genetic overlap with traits of ADHD. These findings indicate that molecular genetic studies seeking to uncover the shared genetic basis of ASC and ADHD would benefit from taking a symptom-specific approach. Furthermore, they could also help to explain why studies of the communication abilities of individuals with ASC and ADHD have produced overlapping findings.
Lien vers le texte intégral (Open Access ou abonnement)
14. Yerys BE, Antezana L, Weinblatt R, Jankowski KF, Strang J, Vaidya CJ, Schultz RT, Gaillard WD, Kenworthy L. {{Neural Correlates of Set-Shifting in Children With Autism}}. {Autism Res}. 2015.
Autism spectrum disorder (ASD) is often associated with high levels of inflexible thinking and rigid behavior. The neural correlates of these behaviors have been investigated in adults and older adolescents, but not children. Prior studies utilized set-shifting tasks that engaged multiple levels of shifting, and depended on learning abstract rules and establishing a strong prepotent bias. These additional demands complicate simple interpretations of the results. We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of set-shifting in 20 children (ages 7-14) with ASD and 19 typically developing, matched, control children. Participants completed a set-shifting task that minimized nonshifting task demands through the use of concrete instructions that provide spatial mapping of stimuli-responses. The shift/stay sets were given an equal number of trials to limit the prepotent bias. Both groups showed an equivalent « switch cost, » responding less accurately and slower to Switch stimuli than Stay stimuli, although the ASD group was less accurate overall. Both groups showed activation in prefrontal, striatal, parietal, and cerebellum regions known to govern effective set-shifts. Compared to controls, children with ASD demonstrated decreased activation of the right middle temporal gyrus across all trials, but increased activation in the mid-dorsal cingulate cortex/superior frontal gyrus, left middle frontal, and right inferior frontal gyri during the Switch vs. Stay contrast. The successful behavioral switching performance of children with ASD comes at the cost of requiring greater engagement of frontal regions, suggesting less efficiency at this lowest level of shifting. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
