1. Codina-Sola M, Perez-Jurado LA, Cusco I, Serra-Juhe C. {{Provision of Genetic Services for Autism and its Impact on Spanish Families}}. {J Autism Dev Disord};2017 (Jul 05)
Although a genetic evaluation can identify the etiology in 15-30% of individuals with autism spectrum disorder, several studies show an underuse of genetic services by affected families. We have explored the access to genetic services and perception of genetics and recurrence risk in parents of autistic children in Spain. Despite the high interest in genetics, our results show a remarkable underutilization of genetic services, with only 30% of families having visited a genetic service and 13% of patients having undergone the recommended genetic test. This poor service provision influenced recurrence risk perception and had a great impact on family planning. The National Health System should ensure their access to genetic services allowing them to take informed decisions with precise information.
Lien vers le texte intégral (Open Access ou abonnement)
2. Fluegge K. {{Environmental contributors to modulation of brain estrogen signaling and male gender bias in autism: A reply to the oral contraceptive use hypothesis by Strifert (2015)}}. {Med Hypotheses};2017 (Jul);104:178-181.
Strifert has recently put forward an interesting hypothesis regarding the role of oral contraceptive (OC) use in mothers and risk of offspring autism spectrum disorder (ASD). First, the author reports that combined oral contraceptives (COCs), containing both estrogen and progesterone, were developed in the late 1950s and early 60s, which is a time-frame distinct from Leo Kanner’s documentation of infantile ASD in 1943 that Strifert just briefly mentions. While this important temporal inconsistency of ASD origin does not invalidate the potential role of OC use in contributing to the rise of ASD, it does support the likely possibility of other environmental exposures at play. Second, the epigenetic basis of the hypothesis is that the endocrine-disrupting components (i.e., ethinylestradiol) of OC perturb estrogenic signaling in the fetal brain by triggering aberrant DNA methylation of the estrogen receptor beta (ERbeta) gene, and such methylation patterns may be imprinted to future generations and could theoretically increase subsequent ASD offspring risk. The premise of the hypothesis is challenged, however, with the recognition that MeCP2, a « reader » of DNA methylation sites, is not only associated with age-dependent alteration in ERbeta in females but is also significantly reduced in ASD brain. Furthermore, Strifert does not clearly address how the OC hypothesis accounts for the male bias in ASD. Therefore, the purpose of this correspondence is to address these inconsistencies by proposing a hypothesis that challenges these points. That is, gestational exposure to the agricultural and combustion air pollutant, nitrous oxide (N2O), may be a leading contributor to the development of an ASD phenotype. The mechanism undergirding this hypothesis suggests that compensatory estrogenic activity may mitigate the effects of fetal N2O exposure and thereby confer a protective effect against ASD development in a sex-dependent manner (i.e., male bias in ASD).
Lien vers le texte intégral (Open Access ou abonnement)
3. Garcia-Pino E, Gessele N, Koch U. {{Enhanced Excitatory Connectivity and Disturbed Sound Processing in the Auditory Brainstem of Fragile X Mice}}. {J Neurosci};2017 (Jul 03)
Hypersensitivity to sounds is one of the prevalent symptoms in individuals with Fragile X syndrome (FXS). It manifests behaviorally early during development and is often used as a landmark for treatment efficacy. However, the physiological mechanisms and circuit-level alterations underlying this aberrant behavior remain poorly understood. Using the mouse model of FXS (Fmr1 KO) we demonstrate that functional maturation of auditory brainstem synapses is impaired in FXS. Fmr1 KO mice showed a greatly enhanced excitatory synaptic input strength in neurons of the lateral superior olive (LSO), a prominent auditory brainstem nucleus, which integrates ipsilateral excitation and contralateral inhibition to compute interaural level differences (ILDs). Conversely, the glycinergic, inhibitory input properties remained unaffected. The enhanced excitation was the result of an increased number of cochlear nucleus fibers converging onto one LSO neuron, without changing individual synapse properties. Concomitantly, immunolabeling of excitatory ending markers revealed an increase in the immunolabeled area, supporting abnormally elevated excitatory input numbers. Intrinsic firing properties were only slightly enhanced. In line with the disturbed development of LSO circuitry auditory processing was also affected in adult Fmr1 KO mice as shown with single-unit recordings of LSO neurons. These processing deficits manifested as an increase in firing rate, a broadening of the frequency response area and a shift in the ILD function of LSO neurons. Our results suggest that this aberrant synaptic development of auditory brainstem circuits might be a major underlying cause of the auditory processing deficits in FXS.SIGNIFICANCE STATEMENTFragile X Syndrome (FXS) is the most common inheritable form of intellectual impairment, including autism. A core symptom of FXS is extreme sensitivity to loud sounds. This is one reason why individuals with FXS tend to avoid social interactions, contributing to their isolation. Here, a mouse model of FXS was used to investigate the auditory brainstem where basic sound information is first processed. Loss of the Fragile X mental retardation protein leads to excessive excitatory compared to inhibitory inputs in neurons extracting information about sound levels. Functionally, this elevated excitation results in increased firing rates, and abnormal coding of frequency and binaural sound localization cues. Imbalanced early stage sound level processing could partially explain the auditory processing deficits in FXS.
Lien vers le texte intégral (Open Access ou abonnement)
4. Garrido D, Garcia-Fernandez M, Garcia-Retamero R, Carballo G. {{[Communicative and social-adaptive profile in children with autism spectrum disorder: a new approach based on the DSM-5 criteria]}}. {Rev Neurol};2017 (Jul 16);65(2):49-56.
INTRODUCTION: Following the adoption of the new international diagnosis classification from the Diagnostic and Statistical Manual (DSM-5), autism spectrum disorder (ASD) has been established as a dimensional category that includes other disorders that were previously considered as separate entities. Previous research has shown that some people with this disorder exhibit different communicative and linguistic profiles. Therefore, contradictory results could be found among people who receive the same diagnosis. AIM: To distinguish structural language aspects (expression and comprehension), interactive aspects (pragmatics), and social adaptation between children with an ASD-level 1 of support and children with typical development. SUBJECTS AND METHODS: Seventeen children with Asperger syndrome (according to the DSM-IV-TR), and 20 children with typical development between 7 and 12 years old. We have equated diagnosis of Asperger syndrome with ASD-level 1 of support. We have evaluated intelligence quotient, communication, and social adaptation with direct and indirect standardized parental scales. RESULTS: We have found significant differences in comprehension (p = 0.025), interaction (p = 0.001), and social adaptation (p = 0.001) between the two groups. CONCLUSIONS: Subjects with ASD-level 1 of support demonstrate an average intelligence quotient, and good expressive structure (syntax and semantic level), which may be different from other children who receive the same diagnosis, due to the wide heterogeneity of the disorder. Nevertheless, our subjects have problems related to comprehension of grammar structure, pragmatics, and social adaptation. These difficulties could be related to emotional and social problems.
5. He CX, Cantu DA, Mantri SS, Zeiger WA, Goel A, Portera-Cailliau C. {{Tactile Defensiveness and Impaired Adaptation of Neuronal Activity in the Fmr1 Knock-Out Mouse Model of Autism}}. {J Neurosci};2017 (Jul 05);37(27):6475-6487.
Sensory hypersensitivity is a common symptom in autism spectrum disorders (ASDs), including fragile X syndrome (FXS), and frequently leads to tactile defensiveness. In mouse models of ASDs, there is mounting evidence of neuronal and circuit hyperexcitability in several brain regions, which could contribute to sensory hypersensitivity. However, it is not yet known whether or how sensory stimulation might trigger abnormal sensory processing at the circuit level or abnormal behavioral responses in ASD mouse models, especially during an early developmental time when experience-dependent plasticity shapes such circuits. Using a novel assay, we discovered exaggerated motor responses to whisker stimulation in young Fmr1 knock-out (KO) mice (postnatal days 14-16), a model of FXS. Adult Fmr1 KO mice actively avoided a stimulus that was innocuous to wild-type controls, a sign of tactile defensiveness. Using in vivo two-photon calcium imaging of layer 2/3 barrel cortex neurons expressing GCaMP6s, we found no differences between wild-type and Fmr1 KO mice in overall whisker-evoked activity, though 45% fewer neurons in young Fmr1 KO mice responded in a time-locked manner. Notably, we identified a pronounced deficit in neuronal adaptation to repetitive whisker stimulation in both young and adult Fmr1 KO mice. Thus, impaired adaptation in cortical sensory circuits is a potential cause of tactile defensiveness in autism.SIGNIFICANCE STATEMENT We use a novel paradigm of repetitive whisker stimulation and in vivo calcium imaging to assess tactile defensiveness and barrel cortex activity in young and adult Fmr1 knock-out mice, the mouse model of fragile X syndrome (FXS). We describe evidence of tactile defensiveness, as well as a lack of L2/3 neuronal adaptation in barrel cortex, during whisker stimulation. We propose that a defect in sensory adaptation within local neuronal networks, beginning at a young age and continuing into adulthood, likely contributes to sensory overreactivity in FXS and perhaps other ASDs.
Lien vers le texte intégral (Open Access ou abonnement)
6. Marzolf AL, Peterseim MM, Forcina BD, Papa C, Wilson ME, Cheeseman EW, Trivedi RH. {{Use of the Spot Vision Screener for patients with developmental disability}}. {J aapos};2017 (Jul 05)
PURPOSE: To determine whether the Spot Vision Screener effectively detects amblyopia risk factors (ARF) in patients with developmental disability using the 2013 guidelines of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS). METHODS: Children with developmental disability presenting for complete pediatric ophthalmologic examination were prospectively enrolled between June 2012 and March 2016. The following data were analyzed: presence of ARF according to the AAPOS guidelines, refraction, eye alignment, and other ocular pathology. RESULTS: A total of 100 children (average age, 5.7 years; range, 2.2- 9.2 years) were included. The prevalence of ARF in this cohort was 38%. The sensitivity of the Spot Vision Screener in detecting amblyopia risk factors was 84%; the specificity, 62%. The positive predictive value was 58%; the negative predictive value, 86%. CONCLUSIONS: In our study cohort the Spot Vision Screener provided good sensitivity and adequate specificity for a screening examination. Automated screeners may be useful in screening children with developmental disability.
Lien vers le texte intégral (Open Access ou abonnement)
7. Muskens JB, Velders FP, Staal WG. {{Medical comorbidities in children and adolescents with autism spectrum disorders and attention deficit hyperactivity disorders: a systematic review}}. {Eur Child Adolesc Psychiatry};2017 (Jul 03)
Somatic disorders occur more often in adult psychiatric patients than in the general adult population. However, in child and adolescent psychiatry this association is unclear, mainly due to a lack of integration of existing data. To address this issue, we here present a systematic review on medical comorbidity in the two major developmental disorders autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) and formulate clinical recommendations. The literature was searched using the PubMed and PsycINFO databases (2000-1 May 2016) with the keywords « [((child and adolescent) AND (Autism OR Attention Deficit Hyperactivity Disorder* OR ADHD)) AND (« Cardiovascular Diseases » [Mesh] OR « Endocrine System Diseases » [Mesh] OR « Immune System Diseases » [Mesh] OR « Neurobehavioral Manifestations » [Mesh] OR « Gastrointestinal Disorders » [Mesh] OR Somatic OR Autoimmune disease OR Nervous system disease OR Infection OR Infectious disease)]. Two raters independently assessed the quality of the eligible studies. The initial search identified 5278 articles. Based on inclusion and exclusion criteria 104 papers were selected and subsequently subjected to a quality control. This quality was assessed according to a standardized and validated set of criteria and yielded 29 studies for inclusion. This thorough literature search provides an overview of relevant articles on medical comorbidity in ADHD and/or ASD, and shows that medical disorders in these children and adolescents appear to be widespread. Those who work with children with ASD and/or ADHD should be well aware of this and actively promote routine medical assessment. Additionally, case-control studies and population-based studies are needed to provide reliable prevalence estimates. Future studies should furthermore focus on a broader evaluation of medical disorders in children and adolescents with ADHD and/or ASD to improve treatment algorithm in this vulnerable group.
Lien vers le texte intégral (Open Access ou abonnement)
8. Passias PG, Jalai CM, Line BG, Poorman GW, Scheer JK, Smith JS, Shaffrey CI, Burton DC, Fu KG, Klineberg EO, Hart RA, Schwab F, Lafage V, Bess S. {{Patient profiling can identify adult spinal deformity (ASD) patients at risk for conversion from nonoperative to surgical treatment; initial steps to reduce ineffective ASD management}}. {Spine J};2017 (Jul 05)
BACKGROUND CONTEXT: Non-operative management is a common initial treatment for adult spinal deformity (ASD) patients despite reported superiority of surgery with regard to outcomes. Ineffective medical care is a large source of resource drain on the health system. Characterization of ASD patients likely to elect for operative treatment from nonoperative management may allow for more efficient patient counseling and cost savings. PURPOSE: To identify deformity and disability characteristics of ASD patients that ultimately convert to operative treatment compared to those that remain non-operative and those that initially choose surgery. STUDY DESIGN/SETTING: Retrospective review. PATIENT SAMPLE: 510 ASD patients (189 non-operative, 321 operative) with minimum 2-year follow-up. OUTCOME MEASURES: Oswestry Disability Index (ODI), Short-Form 36 Health Assessment (SF-36), Scoliosis Research Society questionnaire (SRS-22r), and spino-pelvic radiographic alignment. METHODS: Demographic, radiographic and patient-reported outcome measures (PROMs) from a cohort of ASD patients prospectively enrolled into a multi-center database were evaluated. Patients were divided into 3 treatment cohorts: Non-operative (NON=initial non-operative treatment and remained non-operative), Operative (OP=initial operative treatment), and Crossover (CROSS=initial non-operative treatment with subsequent conversion to operative treatment). NON and OP groups were propensity score matched (PSM) to CROSS for to baseline demographics (age, BMI, CCI). Time to crossover was divided into early (<1yr) and late ( >1yr). Outcome measures were compared across and within treatment groups at 4 time points (baseline, 6-week, 1-, and 2-years). RESULTS: Following PSM, 118 patients were included (NON=39, OP=38, CROSS=41). Crossover rate was 21.7% (41/189). Mean time to crossover was 394 days. All groups had similar baseline sagittal alignment, but CROSS had larger PI-LL mismatch than NON (11.9 degrees vs. 3.1 degrees , p=0.032). CROSS and OP had similar baseline PROM scores, however CROSS had worse baseline ODI, PCS, SRS-22r (p<0.05). At time of crossover, CROSS had worse ODI (35.7 vs. 27.8) and SRS Satisfaction (2.6 vs. 3.3) compared to NON (p<0.05). Alignment remained similar for CROSS from baseline to conversion however PROMs (ODI, PCS, SRS Activity/Pain/Total) worsened (p<0.05). Early and late crossover evaluation demonstrated CROSS-early (n=25) had worsening ODI, SRS Activity/Pain at time of crossover (p<0.05). From time of crossover to 2yr follow-up, CROSS-early had less SRS Appearance/Mental improvement compared to OP. Both CROSS-early/late had worse baseline, but greater improvements, in ODI, PCS, SRS Pain/Total compared to NON (p<0.05). Baseline alignment and disability parameters increased crossover odds - Non with Schwab T/L/D curves and ODI>/=40 (OR: 3.05, p=0.031), and Non with high PI-LL modifier grades (‘+’/’++’) and ODI>/=40 (OR: 5.57, p=0.007) were at increased crossover risk. CONCLUSIONS: High baseline and increasing disability over time drives conversion from non-operative to operative ASD care. CROSS patients had similar spinal deformity but worse PROMs than NON. CROSS achieved similar 2-year outcome scores as OP. Profiling at first visit for patients at risk of crossover may optimize physician counseling and cost savings.
Lien vers le texte intégral (Open Access ou abonnement)
9. So WC, Wong MK, Lam CK, Lam WY, Chui AT, Lee TL, Ng HM, Chan CH, Fok DC. {{Using a social robot to teach gestural recognition and production in children with autism spectrum disorders}}. {Disabil Rehabil Assist Technol};2017 (Jul 04):1-13.
While it has been argued that children with autism spectrum disorders are responsive to robot-like toys, very little research has examined the impact of robot-based intervention on gesture use. These children have delayed gestural development. We used a social robot in two phases to teach them to recognize and produce eight pantomime gestures that expressed feelings and needs. Compared to the children in the wait-list control group (N = 6), those in the intervention group (N = 7) were more likely to recognize gestures and to gesture accurately in trained and untrained scenarios. They also generalized the acquired recognition (but not production) skills to human-to-human interaction. The benefits and limitations of robot-based intervention for gestural learning were highlighted. Implications for Rehabilitation Compared to typically-developing children, children with autism spectrum disorders have delayed development of gesture comprehension and production. Robot-based intervention program was developed to teach children with autism spectrum disorders recognition (Phase I) and production (Phase II) of eight pantomime gestures that expressed feelings and needs. Children in the intervention group (but not in the wait-list control group) were able to recognize more gestures in both trained and untrained scenarios and generalize the acquired gestural recognition skills to human-to-human interaction. Similar findings were reported for gestural production except that there was no strong evidence showing children in the intervention group could produce gestures accurately in human-to-human interaction.
Lien vers le texte intégral (Open Access ou abonnement)
10. Watanabe T, Rees G. {{Brain network dynamics in high-functioning individuals with autism}}. {Nat Commun};2017 (Jul 05);8:16048.
Theoretically, autism should be underpinned by aberrant brain dynamics. However, how brain activity changes over time in individuals with autism spectrum disorder (ASD) remains unknown. Here we characterize brain dynamics in autism using an energy-landscape analysis applied to resting-state fMRI data. Whereas neurotypical brain activity frequently transits between two major brain states via an intermediate state, high-functioning adults with ASD show fewer neural transitions due to an unstable intermediate state, and these infrequent transitions predict the severity of autism. Moreover, in contrast to the controls whose IQ is correlated with the neural transition frequency, IQ scores of individuals with ASD are instead predicted by the stability of their brain dynamics. Finally, such brain-behaviour associations are related to functional segregation between brain networks. These findings suggest that atypical functional coordination in the brains of adults with ASD underpins overly stable neural dynamics, which supports both their ASD symptoms and cognitive abilities.
