1. Gillespie-Smith K, Riby DM, Hancock PJ, Doherty-Sneddon G. {{Children with autism spectrum disorder (ASD) attend typically to faces and objects presented within their picture communication systems}}. {J Intellect Disabil Res};2013 (Apr 19)
BACKGROUND: Children with autism spectrum disorder (ASD) may require interventions for communication difficulties. One type of intervention is picture communication symbols which are proposed to improve comprehension of linguistic input for children with ASD. However, atypical attention to faces and objects is widely reported across the autism spectrum for several types of stimuli. METHOD: In this study we used eye-tracking methodology to explore fixation duration and time taken to fixate on the object and face areas within picture communication symbols. Twenty-one children with ASD were compared with typically developing matched groups. RESULTS: Children with ASD were shown to have similar fixation patterns on face and object areas compared with typically developing matched groups. CONCLUSIONS: It is proposed that children with ASD attend to the images in a manner that does not differentiate them from typically developing individuals. Therefore children with and without autism have the same opportunity to encode the available information. We discuss what this may imply for interventions using picture symbols.
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2. Gilling M, Rasmussen HB, Calloe K, Sequeira AF, Baretto M, Oliveira G, Almeida J, Lauritsen MB, Ullmann R, Boonen SE, Brondum-Nielsen K, Kalscheuer VM, Tumer Z, Vicente AM, Schmitt N, Tommerup N. {{Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders}}. {Front Genet};2013;4:54.
Heterozygous mutations in the KCNQ3 gene on chromosome 8q24 encoding the voltage-gated potassium channel KV7.3 subunit have previously been associated with rolandic epilepsy and idiopathic generalized epilepsy (IGE) including benign neonatal convulsions. We identified a de novo t(3;8) (q21;q24) translocation truncating KCNQ3 in a boy with childhood autism. In addition, we identified a c.1720C > T [p.P574S] nucleotide change in three unrelated individuals with childhood autism and no history of convulsions. This nucleotide change was previously reported in patients with rolandic epilepsy or IGE and has now been annotated as a very rare SNP (rs74582884) in dbSNP. The p.P574S KV7.3 variant significantly reduced potassium current amplitude in Xenopus laevis oocytes when co-expressed with KV7.5 but not with KV7.2 or KV7.4. The nucleotide change did not affect trafficking of heteromeric mutant KV7.3/2, KV7.3/4, or KV7.3/5 channels in HEK 293 cells or primary rat hippocampal neurons. Our results suggest that dysfunction of the heteromeric KV7.3/5 channel is implicated in the pathogenesis of some forms of autism spectrum disorders, epilepsy, and possibly other psychiatric disorders and therefore, KCNQ3 and KCNQ5 are suggested as candidate genes for these disorders.
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3. Girirajan S, Johnson RL, Tassone F, Balciuniene J, Katiyar N, Fox K, Baker C, Srikanth A, Yeoh KH, Khoo SJ, Nauth TB, Hansen R, Ritchie M, Hertz-Picciotto I, Eichler EE, Pessah IN, Selleck SB. {{Global increases in both common and rare copy number load associated with autism}}. {Hum Mol Genet};2013 (Apr 19)
Children with autism have an elevated frequency of large, rare copy number variants (CNVs). However, the global load of deletions or duplications, per se, and their size, location and relationship to clinical manifestations of autism have not been documented. We examined CNV data from 516 individuals with autism or typical development from the population-based Childhood Autism Risks from Genetics and Environment (CHARGE) study. We interrogated 120 regions flanked by segmental duplications (genomic hotspots) for events >50 kbp and the entire genomic backbone for variants >300 kbp using a custom targeted DNA microarray. This analysis was complemented by a separate study of five highly dynamic hotspots associated with autism or developmental delay syndromes, using a finely tiled array platform (>1 kbp) in 142 children matched for gender and ethnicity. In both studies, a significant increase in the number of base pairs of duplication, but not deletion, was associated with autism. Significantly elevated levels of CNV load remained after the removal of rare and likely pathogenic events. Further, the entire CNV load detected with the finely tiled array was contributed by common variants. The impact of this variation was assessed by examining the correlation of clinical outcomes with CNV load. The level of personal and social skills, measured by Vineland Adaptive Behavior Scales, negatively correlated (Spearman’s r = -0.13, P = 0.034) with the duplication CNV load for the affected children; the strongest association was found for communication (P = 0.048) and socialization (P = 0.022) scores. We propose that CNV load, predominantly increased genomic base pairs of duplication, predisposes to autism.
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4. Gongidi P, Johnson C, Dinan D. {{Scurvy in an autistic child: MRI findings}}. {Pediatr Radiol};2013 (Apr 19)
Scurvy results from a deficiency of vitamin C and is rarely seen in the United States. We describe the MRI findings of a case of scurvy in an autistic child with food-avoidant behavior. Advanced imaging is rarely performed in clinically well-understood disease entities such as scurvy. Typical radiographic findings are well described leading to definitive diagnosis, although the findings can be missed or misinterpreted given the rarity of scurvy in daily practice. To our knowledge, MRI features of scurvy in children in the US have been described in only one case report. This case of scurvy in an autistic child with food-avoidant behavior emphasizes that classic nutritional deficiencies, despite their rarity, must be included in the differential diagnosis of at-risk populations.
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5. Parish-Morris J, Chevallier C, Tonge N, Letzen J, Pandey J, Schultz RT. {{Visual attention to dynamic faces and objects is linked to face processing skills: a combined study of children with autism and controls}}. {Front Psychol};2013;4:185.
Although the extant literature on face recognition skills in Autism Spectrum Disorder (ASD) shows clear impairments compared to typically developing controls (TDC) at the group level, the distribution of scores within ASD is broad. In the present research, we take a dimensional approach and explore how differences in social attention during an eye tracking experiment correlate with face recognition skills across ASD and TDC. Emotional discrimination and person identity perception face processing skills were assessed using the Let’s Face It! Skills Battery in 110 children with and without ASD. Social attention was assessed using infrared eye gaze tracking during passive viewing of movies of facial expressions and objects displayed together on a computer screen. Face processing skills were significantly correlated with measures of attention to faces and with social skills as measured by the Social Communication Questionnaire (SCQ). Consistent with prior research, children with ASD scored significantly lower on face processing skills tests but, unexpectedly, group differences in amount of attention to faces (vs. objects) were not found. We discuss possible methodological contributions to this null finding. We also highlight the importance of a dimensional approach for understanding the developmental origins of reduced face perception skills, and emphasize the need for longitudinal research to truly understand how social motivation and social attention influence the development of social perceptual skills.
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6. Pozo P, Sarria E, Brioso A. {{Family quality of life and psychological well-being in parents of children with autism spectrum disorders: a double ABCX model}}. {J Intellect Disabil Res};2013 (Apr 19)
BACKGROUND: This study examined family quality of life (FQOL) and psychological well-being from a multidimensional perspective. The proposed model was based on the double ABCX model, with severity of the disorder, behaviour problems, social support, sense of coherence (SOC) and coping strategies as components. METHOD: One hundred and eighteen parents (59 mothers and 59 fathers) with a child diagnosed with autism spectrum disorders (ASD) participated in the study. Separate path analyses were performed to evaluate models of FQOL and psychological well-being for mothers and fathers. RESULTS: In all models, behaviour problems had a negative indirect effect on adaptation (FQOL and psychological well-being) through SOC. For both mothers and fathers, the severity of the disorder and social support played significant roles in FQOL models. Coping strategies were related with adaptation, active avoidance coping with FQOL for fathers and positive and problem-focused coping with psychological well-being for mothers. CONCLUSIONS: The results of this study highlight the value of the multidimensional approach. The specific patterns of results for mothers and fathers contribute to comprehension of the psychological adaptation of parents. Findings could be taken into account in interventions with families.
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7. Rai D, Lee BK, Dalman C, Golding J, Lewis G, Magnusson C. {{Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study}}. {BMJ};2013;346:f2059.
OBJECTIVE: To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring. DESIGN: Population based nested case-control study. SETTING: Stockholm County, Sweden, 2001-07. PARTICIPANTS: 4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43 277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16 845 controls with data on maternal antidepressant use nested within a cohort (n=589 114) of young people aged 0-17 years. MAIN OUTCOME MEASURE: A diagnosis of autism spectrum disorder, with or without intellectual disability. EXPOSURES: Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards. RESULTS: A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder. CONCLUSIONS: In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases.
8. Ricci S, Businaro R, Ippoliti F, Lo Vasco VR, Massoni F, Onofri E, Troili GM, Pontecorvi V, Morelli M, Rapp Ricciardi M, Archer T. {{Altered Cytokine and BDNF Levels in Autism Spectrum Disorder}}. {Neurotox Res};2013 (Apr 19)
The contribution of neuroimmune functioning and brain-derived neurotrophic factor (BDNF) to functional dysregulation in autism spectrum disorder was assessed in 29 patients under treatment in two specialized centers of Basilicata (Chiaromonte and Matera), Southern Italy, through analysis of serum levels of cytokines and BDNF. Elevated levels of the pro-inflammatory cytokine, including interleukin-1, interleukin-6, interleukin-12, interleukin-23, tumor necrosis factor-alpha and BDNF were observed, regardless of age and gender. Comparisons were made with age- and gender-related healthy controls. The present findings reinforce current notions regarding immunoexcitotoxic mechanisms contributing to the pathophysiology of autistic disorder.
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9. Robertson CE, Kravitz DJ, Freyberg J, Baron-Cohen S, Baker CI. {{Tunnel vision: sharper gradient of spatial attention in autism}}. {J Neurosci};2013 (Apr 17);33(16):6776-6781.
Enhanced perception of detail has long been regarded a hallmark of autism spectrum conditions (ASC), but its origins are unknown. Normal sensitivity on all fundamental perceptual measures-visual acuity, contrast discrimination, and flicker detection-is strongly established in the literature. If individuals with ASC do not have superior low-level vision, how is perception of detail enhanced? We argue that this apparent paradox can be resolved by considering visual attention, which is known to enhance basic visual sensitivity, resulting in greater acuity and lower contrast thresholds. Here, we demonstrate that the focus of attention and concomitant enhancement of perception are sharper in human individuals with ASC than in matched controls. Using a simple visual acuity task embedded in a standard cueing paradigm, we mapped the spatial and temporal gradients of attentional enhancement by varying the distance and onset time of visual targets relative to an exogenous cue, which obligatorily captures attention. Individuals with ASC demonstrated a greater fall-off in performance with distance from the cue than controls, indicating a sharper spatial gradient of attention. Further, this sharpness was highly correlated with the severity of autistic symptoms in ASC, as well as autistic traits across both ASC and control groups. These findings establish the presence of a form of « tunnel vision » in ASC, with far-reaching implications for our understanding of the social and neurobiological aspects of autism.
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10. Rotschafer S, Razak K. {{Altered auditory processing in a mouse model of fragile X syndrome}}. {Brain Res};2013 (Apr 19);1506:12-24.
This study provides the first description of auditory cortical processing in a mouse model of Fragile X Syndrome (FXS). FXS is a genetic cause of intellectual impairment and is an autism spectrum disorder. Human studies with auditory evoked potentials indicate that FXS is associated with abnormal auditory processing. The Fmr1 knock-out (KO) mouse is a useful model for studying FXS. The KO mice show acoustic hypersensitivity and propensity for audiogenic seizures, suggesting altered auditory responses. However, the nature of changes at the neuronal level is not known. Here we conducted in vivo single unit extracellular electrophysiology in the auditory cortex of urethane/xylazine-anesthetized Fmr1 KO mice in response to tones and frequency modulated (FM) sweeps. Using tones as stimuli, we report expanded frequency tuning, enhanced response magnitude, and more variable first spike latencies in Fmr1 KO mice compared to wild-type controls. FM sweep stimuli revealed altered sensitivity to the rate of frequency change indicating abnormal spectrotemporal processing. There was no difference in FM sweep direction selectivity. Consistent with studies of the somatosensory cortex, these data point to hyper-responsiveness of auditory neurons as a key processing abnormality in FXS. Auditory neural responses can serve as outcome measures in preclinical trials of therapeutics for FXS as well as serve as physiological probes to study their mechanisms of action.
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11. Siew WH, Tan KL, Babaei MA, Cheah PS, Ling KH. {{MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome}}. {Front Cell Neurosci};2013;7:41.
Intellectual disability (ID) is one of the many features manifested in various genetic syndromes leading to deficits in cognitive function among affected individuals. ID is a feature affected by polygenes and multiple environmental factors. It leads to a broad spectrum of affected clinical and behavioral characteristics among patients. Until now, the causative mechanism of ID is unknown and the progression of the condition is poorly understood. Advancement in technology and research had identified various genetic abnormalities and defects as the potential cause of ID. However, the link between these abnormalities with ID is remained inconclusive and the roles of many newly discovered genetic components such as non-coding RNAs have not been thoroughly investigated. In this review, we aim to consolidate and assimilate the latest development and findings on a class of small non-coding RNAs known as microRNAs (miRNAs) involvement in ID development and progression with special focus on Down syndrome (DS) and X-linked ID (XLID) [including Fragile X syndrome (FXS)].
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12. Tottenham N, Hertzig ME, Gillespie-Lynch K, Gilhooly T, Millner AJ, Casey BJ. {{Elevated amygdala response to faces and gaze aversion in autism spectrum disorder}}. {Soc Cogn Affect Neurosci};2013 (Apr 16)
Autism spectrum disorders (ASD) are often associated with impairments in judgment of facial expressions. This impairment is often accompanied by diminished eye-contact and atypical amygdala responses to face stimuli. The current study used a within-subjects design to examine the effects of natural viewing and an experimental eye-gaze manipulation on amygdala responses to faces. Individuals with ASD showed less gaze toward the eye-region of faces relative to a control group. Among individuals with ASD, reduced eye-gaze was associated with higher threat ratings of neutral faces. Amygdala signal was elevated in the ASD group relative to controls. This elevated response was further potentiated by experimentally manipulating gaze to the eye-region. Potentiation by the gaze-manipulation was largest for those individuals who exhibited the least amount of naturally occurring gaze towards the eye-region and was associated with their subjective threat ratings. Effects were largest for neutral faces, highlighting the importance of examining neutral faces in the pathophysiology of autism and questioning their use as control stimuli with this population. Overall, our findings provide support for the notion that gaze direction modulates affective response to faces in ASD.
