1. Brown M, Ashcraft P, Arning E, Bottiglieri T, McClintock W, Giancola F, Lieberman D, Hauser NS, Miller R, Roullet JB, Pearl P, Gibson KM. {{Rett syndrome (MECP2) and succinic semialdehyde dehydrogenase (ALDH5A1) deficiency in a developmentally delayed female}}. {Mol Genet Genomic Med};2019 (Mar 4):e629.
BACKGROUND: We present a patient with Rett syndrome (RTT; MECP2) and autosomal-recessive succinic semialdehyde dehydrogenase deficiency (SSADHD; ALDH5A1 (aldehyde dehydrogenase 5a1 = SSADH), in whom the current phenotype exhibits features of SSADHD (hypotonia, global developmental delay) and RTT (hand stereotypies, gait anomalies). METHODS: gamma-Hydroxybutyric acid (GHB) was quantified by UPLC-tandem mass spectrometry, while mutation analysis followed standard methodology of whole-exome sequencing. RESULTS: The biochemical hallmark of SSADHD, GHB was increased in the proband’s dried bloodspot (DBS; 673 microM; previous SSADHD DBSs (n = 7), range 124-4851 microM); control range (n = 2,831), 0-78 microM. The proband was compound heterozygous for pathogenic ALDH5A1 mutations (p.(Asn418IlefsTer39); maternal; p.(Gly409Asp); paternal) and a de novo RTT nonsense mutation in MECP2 (p.Arg255*). CONCLUSION: The major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), is increased in SSADHD but normal in RTT, although there are likely regional changes in GABA receptor distribution. GABAergic anomalies occur in both disorders, each featuring an autism spectrum phenotype. What effect the SSADHD biochemical anomalies (elevated GABA, GHB) might play in the neurodevelopmental/epileptic phenotype of our patient is currently unknown.
Lien vers le texte intégral (Open Access ou abonnement)
2. Dai YG, Miller LE, Ramsey RK, Robins DL, Fein DA, Dumont-Mathieu T. {{Incremental Utility of 24-Month Autism Spectrum Disorder Screening After Negative 18-Month Screening}}. {J Autism Dev Disord};2019 (Mar 4)
The American Academy of Pediatrics recommends Autism Spectrum Disorder (ASD) screening at 18 and 24 months. However, utility of rescreening at 24 months, after a negative 18-month screening, remains unknown. We identified cases of ASD detected at 24 months after a negative 18-month screening (i.e., Catch-24 group; n = 10) and compared them to toddlers detected by 18-month screening (i.e., Early Diagnosis group; n = 203). Repeated ASD-specific screening at 24 months detected children who were missed at their 18-month screening. Thus, our findings support repeated screening for ASD at both 18 and 24 months in order to maximize identification of toddlers with ASD and other neurodevelopmental disorders who require intervention.
Lien vers le texte intégral (Open Access ou abonnement)
3. Fernandes D, Santos SD, Coutinho E, Whitt JL, Beltrao N, Rondao T, Leite MI, Buckley C, Lee HK, Carvalho AL. {{Disrupted AMPA Receptor Function upon Genetic- or Antibody-Mediated Loss of Autism-Associated CASPR2}}. {Cereb Cortex};2019 (Mar 4)
Neuropsychiatric disorders share susceptibility genes, suggesting a common origin. One such gene is CNTNAP2 encoding contactin-associated protein 2 (CASPR2), which harbours mutations associated to autism, schizophrenia, and intellectual disability. Antibodies targeting CASPR2 have also been recently described in patients with several neurological disorders, such as neuromyotonia, Morvan’s syndrome, and limbic encephalitis. Despite the clear implication of CNTNAP2 and CASPR2 in neuropsychiatric disorders, the pathogenic mechanisms associated with alterations in CASPR2 function are unknown. Here, we show that Caspr2 is expressed in excitatory synapses in the cortex, and that silencing its expression in vitro or in vivo decreases the synaptic expression of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and the amplitude of AMPA receptor-mediated currents. Furthermore, Caspr2 loss of function blocks synaptic scaling in vitro and experience-dependent homoeostatic synaptic plasticity in the visual cortex. Patient CASPR2 antibodies decrease the dendritic levels of Caspr2 and synaptic AMPA receptor trafficking, and perturb excitatory transmission in the visual cortex. These results suggest that mutations in CNTNAP2 may contribute to alterations in AMPA receptor function and homoeostatic plasticity, and indicate that antibodies from anti-CASPR2 encephalitis patients affect cortical excitatory transmission.
Lien vers le texte intégral (Open Access ou abonnement)
4. Garcia-Ortiz JE, Zarazua-Nino AI, Hernandez-Orozco AA, Reyes-Oliva EA, Perez-Avila CE, Becerra-Solano LE, Galan-Huerta KA, Rivas-Estilla AM, Cordova-Fletes C. {{Case Report: Whole Exome Sequencing Unveils an Inherited Truncating Variant in CNTN6 (p.Ser189Ter) in a Mexican Child with Autism Spectrum Disorder}}. {J Autism Dev Disord};2019 (Mar 2)
Lien vers le texte intégral (Open Access ou abonnement)
5. Hadad BS, Schwartz S. {{Perception in autism does not adhere to Weber’s law}}. {Elife};2019 (Mar 4);8
Perceptual atypicalities are a widely acknowledged but poorly understood feature of autism. We demonstrate here a striking violation of one of the most adaptive psychophysical computations – Weber’s law – in high-functioning individuals with autism. JNDs based on the best-fitting psychometric functions were measured for size visual judgments (Exp. 1), weight haptic discrimination (Exp. 2), and illusive perception of weight (brightness-weight illusion; Exp. 3). Results for the typically developed group confirmed Weber’s law, demonstrating a linear increase in JNDs with intensity, resulting in constant fractions across intensities. The results for the ASD, in contrast, showed no scaling of JNDs with intensity; instead, fractions decreased linearly with intensity. In striking contrast to its consistency in typical perception, Weber’s law does not hold for visual and haptic perception in autism. These robust modulations in psychophysical computations, demonstrated for different domains of perception, suggest a modality-independent, low-level mechanism driving altered perception in autism.
Lien vers le texte intégral (Open Access ou abonnement)
6. Hong SJ, de Wael RV, Bethlehem RAI, Lariviere S, Paquola C, Valk SL, Milham MP, Di Martino A, Margulies DS, Smallwood J, Bernhardt BC. {{Atypical functional connectome hierarchy in autism}}. {Nat Commun};2019 (Mar 4);10(1):1022.
One paradox of autism is the co-occurrence of deficits in sensory and higher-order socio-cognitive processing. Here, we examined whether these phenotypical patterns may relate to an overarching system-level imbalance-specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. Combining connectome gradient and stepwise connectivity analysis based on task-free functional magnetic resonance imaging (fMRI), we demonstrated atypical connectivity transitions between sensory and higher-order default mode regions in a large cohort of individuals with autism relative to typically-developing controls. Further analyses indicated that reduced differentiation related to perturbed stepwise connectivity from sensory towards transmodal areas, as well as atypical long-range rich-club connectivity. Supervised pattern learning revealed that hierarchical features predicted deficits in social cognition and low-level behavioral symptoms, but not communication-related symptoms. Our findings provide new evidence for imbalances in network hierarchy in autism, which offers a parsimonious reference frame to consolidate its diverse features.
Lien vers le texte intégral (Open Access ou abonnement)
7. Sturrock A, Yau N, Freed J, Adams C. {{Speaking the Same Language? A Preliminary Investigation, Comparing the Language and Communication Skills of Females and Males with High-Functioning Autism}}. {J Autism Dev Disord};2019 (Mar 4)
Understanding the nature of language and communication disorders in High-Functioning Autism Spectrum Disorder (HFASD) populations may provide insight into why females are more likely than males to go undiagnosed. Language and communication skills were compared between 13 females and 13 males (aged 8.11-11.06) with HFASD. Gender-normative data was also ascertained from 26 typically developing children (TD) matched for age and gender. All children had typical range PIQ, slight variation here was controlled for in analysis. Results show females outperforming males in pragmatic and semantic tasks and in certain language-of-emotion tasks. TDs outperformed HFASDs in above-sentence level tasks, but not in basic vocabulary or sentence level tasks. This study highlights specific strengths/weaknesses in language and communication for female HFASD, which could aid more accurate identification of the female autistic phenotype. It indicates the need for larger follow up studies in this area.
Lien vers le texte intégral (Open Access ou abonnement)
8. Wright MF, Wachs S. {{Does Peer Rejection Moderate the Associations among Cyberbullying Victimization, Depression, and Anxiety among Adolescents with Autism Spectrum Disorder?}}. {Children (Basel)};2019 (Mar 4);6(3)
While the consequences of cyberbullying victimization have received some attention in the literature, to date, little is known about the multiple types of strains in adolescents’ lives, such as whether cyberbullying victimization and peer rejection increase their vulnerability to depression and anxiety. Even though some research found that adolescents with disabilities show higher risk for cyberbullying victimization, most research has focused on typically developing adolescents. Thus, the present study focused on examining the moderating effect of peer rejection in the relationships between cyberbullying victimization, depression, and anxiety among adolescents with autism spectrum disorder. There were 128 participants (89% male; ages ranging from 11(-)16 years old) with autism spectrum disorder in the sixth, seventh, or eighth grade at 16 middle schools in the United States. Participants completed questionnaires on cyberbullying victimization, peer rejection, depression, and anxiety. Results revealed that cyberbullying victimization was associated positively with peer rejection, anxiety, and depression among adolescents with autism spectrum disorder. Further, peer rejection was linked positively with depression and anxiety. Peer rejection moderated the positive relationship between cyberbullying victimization and depression, but not anxiety. Implications for prevention programs and future research are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
9. Young RL, Brewer N. {{Brief Report: Perspective Taking Deficits, Autism Spectrum Disorder, and Allaying Police Officers’ Suspicions About Criminal Involvement}}. {J Autism Dev Disord};2019 (Mar 4)
We examined whether perspective taking (or Theory of Mind) deficits that characterize autistic individuals predict whether they have trouble extricating themselves from situations in which police officers erroneously suspect them of a crime. Autistic and typically developing adults listened to scenarios in which they were placed in situations where the police erroneously believe they had been involved in crime. Each scenario contained critical information that, if recognized and provided to the police, would confirm non-involvement in the crime. Autistic adults performed markedly worse than controls on perspective taking measures and the extrication task. Verbal IQ and memory performance accounted for significant variance in extrication performance, and perspective taking explained an additional and significant 15% of variance in extrication performance.
