1. Benjamin DP, McDuffie AS, Thurman AJ, Kover ST, Mastergeorge AM, Hagerman RJ, Abbeduto L. {{Effect of Speaker Gaze on Word Learning in Fragile X Syndrome: A comparison with nonsyndromic ASD}}. {J Speech Lang Hear Res}. 2015.
Purpose: This study examined use of a speaker’s direction of gaze during word learning by boys with fragile X syndrome (FXS), nonsyndromic autism spectrum disorder (ASD), and typical development (TD). Method: A fast-mapping task with Follow-In and Discrepant Labeling conditions was administered. Use of speaker gaze was expected to lead to selecting as the referent of the novel label the object to which the participant attended in Follow-In Trials and the object to which the examiner attended in the Discrepant Labeling Trials. Participants were school-aged boys with FXS (n = 18) or ASD (n = 18) matched on age, IQ, and nonverbal cognition and younger TD boys (n = 18) matched on nonverbal cognition. Results: All groups performed above chance in both conditions, although the TD boys performed closest to the expected pattern. Boys with FXS performed better during Follow-In than in Discrepant Label trials, whereas TD boys and boys with ASD did equally well in both trial types. The type of trial administered first influenced subsequent responding. Error patterns also distinguished the groups. Conclusions: The ability to utilize a speaker’s gaze during word learning is not as well developed in boys with FXS or nonsyndromic ASD as in TD children of the same developmental level.
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2. Braida D, Guerini FR, Ponzoni L, Corradini I, De Astis S, Pattini L, Bolognesi E, Benfante R, Fornasari D, Chiappedi M, Ghezzo A, Clerici M, Matteoli M, Sala M. {{Association between SNAP-25 gene polymorphisms and cognition in autism: functional consequences and potential therapeutic strategies}}. {Transl Psychiatry}. 2015; 5: e500.
Synaptosomal-associated protein of 25 kDa (SNAP-25) is involved in different neuropsychiatric disorders, including schizophrenia and attention-deficit/hyperactivity disorder. Consistently, SNAP-25 polymorphisms in humans are associated with hyperactivity and/or with low cognitive scores. We analysed five SNAP-25 gene polymorphisms (rs363050, rs363039, rs363043, rs3746544 and rs1051312) in 46 autistic children trying to correlate them with Childhood Autism Rating Scale and electroencephalogram (EEG) abnormalities. The functional effects of rs363050 single-nucleotide polymorphism (SNP) on the gene transcriptional activity, by means of the luciferase reporter gene, were evaluated. To investigate the functional consequences that SNAP-25 reduction may have in children, the behaviour and EEG of SNAP-25(+/-) adolescent mice (SNAP-25(+/+)) were studied. Significant association of SNAP-25 polymorphism with decreasing cognitive scores was observed. Analysis of transcriptional activity revealed that SNP rs363050 encompasses a regulatory element, leading to protein expression decrease. Reduction of SNAP-25 levels in adolescent mice was associated with hyperactivity, cognitive and social impairment and an abnormal EEG, characterized by the occurrence of frequent spikes. Both EEG abnormalities and behavioural deficits were rescued by repeated exposure for 21 days to sodium salt valproate (VLP). A partial recovery of SNAP-25 expression content in SNAP-25(+/-) hippocampi was also observed by means of western blotting. A reduced expression of SNAP-25 is responsible for the cognitive deficits in children affected by autism spectrum disorders, as presumably occurring in the presence of rs363050(G) allele, and for behavioural and EEG alterations in adolescent mice. VLP treatment could result in novel therapeutic strategies.
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3. Casanova MF, Sokhadze E, Opris I, Wang Y, Li X. {{Autism Spectrum Disorders: Linking Neuropathological Findings to Treatment with Transcranial Magnetic Stimulation}}. {Acta Paediatr}. 2015.
Postmortem studies in autism spectrum disorder (ASD) individuals indicate the presence of abnormalities within the peripheral neuropil space (PNS) of cortical minicolumns. The geometrical orientation of inhibitory elements within the PNS suggests using repetitive transcranial magnetic stimulation (rTMS) to up-regulate their activity. Several rTMS trials in ASD have shown marked improvements in motor symptomatology, attention, and perceptual binding. CONCLUSION: rTMS is the first therapeutic attempt at ASD aimed at correcting some of its core pathology. This article is protected by copyright. All rights reserved.
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4. Chen JA, Penagarikano O, Belgard TG, Swarup V, Geschwind DH. {{The emerging picture of autism spectrum disorder: genetics and pathology}}. {Annu Rev Pathol}. 2015; 10: 111-44.
Autism spectrum disorder (ASD) is defined by impaired social interaction and communication accompanied by stereotyped behaviors and restricted interests. Although ASD is common, its genetic and clinical features are highly heterogeneous. A number of recent breakthroughs have dramatically advanced our understanding of ASD from the standpoint of human genetics and neuropathology. These studies highlight the period of fetal development and the processes of chromatin structure, synaptic function, and neuron-glial signaling. The initial efforts to systematically integrate findings of multiple levels of genomic data and studies of mouse models have yielded new clues regarding ASD pathophysiology. This early work points to an emerging convergence of disease mechanisms in this complex and etiologically heterogeneous disorder.
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5. Chen YL, Chen SH, Gau SS. {{ADHD and autistic traits, family function, parenting style, and social adjustment for Internet addiction among children and adolescents in Taiwan: A longitudinal study}}. {Res Dev Disabil}. 2015; 39C: 20-31.
This longitudinal study investigated the prevalence, predictors, and related factors for Internet addiction among elementary and junior high school students in Taiwan. A convenient sample of grades 3, 5, and 8 students (n=1153) was recruited from six elementary and one junior high schools. They were assessed during the beginning and the end of the spring semester of 2013. Internet addiction was examined by the Chen Internet Addiction Scale (CIAS). Other factors were screened using the Chinese version of the Autism Spectrum Quotient (AQ) for autistic trait, the Parental Bonding Instrument (PBI) for parenting, the Family APGAR for family support, the Social Adjustment Inventory for Children and Adolescents for social function, and the Swanson, Nolan, and Pelham, version IV scale (SNAP-IV) for ADHD symptoms. The prevalence of Internet addiction decreased from 11.4% to 10.6%. Male, low family support, poor social adjustment, and high ADHD-related symptoms were related to Internet addiction. However, there was an inverse relationship between autistic traits and Internet addiction. Further, its predictivity could be accounted by poor academic performance, male, and protective parenting style. Internet addiction is not uncommon among youths in Taiwan. The predictors identified in this study could be the specific measures for the development of a prevention program for Internet addiction in the youth population.
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6. Du L, Shan L, Wang B, Feng JY, Xu ZD, Jia FY. {{[Serum levels of 25-hydroxyvitamin D in children with autism spectrum disorders]}}. {Zhongguo Dang Dai Er Ke Za Zhi}. 2015; 17(1): 68-71.
OBJECTIVE: To examine serum 25-hydroxyvitamin D levels in children with autism spectrum disorders (ASD) and to explore the relationship between vitamin D level and ASD. METHODS: Serum levels of 25-hydroxyvitamin D levels were determined by the HPLC-MS/MS method in 117 children with newly diagnosed ASD and 109 healthy controls. Vitamin D status were classified into normal (>30 ng/mL), insufficiency (10-30ng/mL) and deficiency (<10 ng/mL) according to 25-hydroxyvitamin D levels. RESULTS: Serum level of 25-hydroxyvitamin D (19+/-9 ng/mL)in children with ASD was significantly lower than that in healthy controls (36+/-13 ng/mL; P<0.01). The rate of vitamin D insufficiency plus deficiency in the ASD group was significantly higher than in the control group (89.7% vs 52.3%; P<0.01). CONCLUSIONS: Vitamin D insufficiency or deficiency is common in children with ASD and might be as one of the environmental or genetic factors for ASD.
7. Fisher PG. {{Autistic disorder and cancer risk}}. {J Pediatr}. 2015; 166(2): 215-7.
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8. Gentile JP, Gillig PM, Stinson K, Jensen J. {{Toward impacting medical and psychiatric comorbidities in persons with intellectual/developmental disabilities: an initial prospective analysis}}. {Innov Clin Neurosci}. 2014; 11(11-12): 22-6.
OBJECTIVE: The purpose of this study was to determine the effectiveness of psychiatric medical services, counseling, and behavioral treatments for adult patients with intellectual disabilities plus behavioral disorders and/or emotional distress. METHODS: Behavioral and medical data were collected at six and 12 months for a consecutive series of 141 adult patients with mild, moderate, or severe/profound intellectual disabilities who had been referred to a dual diagnosis mental health clinic, and treatment outcomes were compared. RESULTS: Most improvement in behavioral problem severity occurred at six months, then plateaued. Treatment improvement for subjects with anxiety disorders was statistically significant across all interventions. In this sample, as expected, patients with intellectual disability had higher incidences of medical illnesses than the general population. CONCLUSIONS: Subjects with more behavioral (overt) symptoms tended to receive referrals for behavioral support, and subjects with less overt symptoms were referred to counseling. In a follow-up study, similar individuals with moderate intellectual disabilities will be seen psychiatrically, but then randomly assigned to either supportive counseling or behavior support, or both. They will be followed prospectively, to determine the relative benefits of supportive psychotherapy, behavior support, or a combination, and for what duration of time the treatment should be continued.
9. Grossman RB, Steinhart E, Mitchell T, McIlvane W. {{« Look who’s talking! » Gaze Patterns for Implicit and Explicit Audio-Visual Speech Synchrony Detection in Children With High-Functioning Autism}}. {Autism Res}. 2015.
Conversation requires integration of information from faces and voices to fully understand the speaker’s message. To detect auditory-visual asynchrony of speech, listeners must integrate visual movements of the face, particularly the mouth, with auditory speech information. Individuals with autism spectrum disorder may be less successful at such multisensory integration, despite their demonstrated preference for looking at the mouth region of a speaker. We showed participants (individuals with and without high-functioning autism (HFA) aged 8-19) a split-screen video of two identical individuals speaking side by side. Only one of the speakers was in synchrony with the corresponding audio track and synchrony switched between the two speakers every few seconds. Participants were asked to watch the video without further instructions (implicit condition) or to specifically watch the in-synch speaker (explicit condition). We recorded which part of the screen and face their eyes targeted. Both groups looked at the in-synch video significantly more with explicit instructions. However, participants with HFA looked at the in-synch video less than typically developing (TD) peers and did not increase their gaze time as much as TD participants in the explicit task. Importantly, the HFA group looked significantly less at the mouth than their TD peers, and significantly more at non-face regions of the image. There were no between-group differences for eye-directed gaze. Overall, individuals with HFA spend less time looking at the crucially important mouth region of the face during auditory-visual speech integration, which is maladaptive gaze behavior for this type of task. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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10. Hellendoorn A, Wijnroks L, van Daalen E, Dietz C, Buitelaar JK, Leseman P. {{Motor functioning, exploration, visuospatial cognition and language development in preschool children with autism}}. {Res Dev Disabil}. 2015; 39C: 32-42.
In order to understand typical and atypical developmental trajectories it is important to assess how strengths or weaknesses in one domain may be affecting performance in other domains. This study examined longitudinal relations between early fine motor functioning, visuospatial cognition, exploration, and language development in preschool children with ASD and children with other developmental delays/disorders. The ASD group included 63 children at T1 (Mage=27.10 months, SD=8.71) and 46 children at T2 (Mage=45.85 months, SD=7.16). The DD group consisted of 269 children at T1 (Mage=17.99 months, SD=5.59), and 121 children at T2 (Mage=43.51 months, SD=3.81). A subgroup nested within the total sample was randomly selected and studied in-depth on exploratory behavior. This group consisted of 50 children, 21 children with ASD (Mage=27.57, SD=7.09) and 29 children with DD (Mage=24.03 months, SD=6.42). Fine motor functioning predicted language in both groups. Fine motor functioning was related to visuospatial cognition in both groups and related to object exploration, spatial exploration, and social orientation during exploration only in the ASD group. Visuospatial cognition and all exploration measures were related to both receptive and expressive language in both groups. The findings are in line with the embodied cognition theory, which suggests that cognition emerges from and is grounded in the bodily interactions of an agent with the environment. This study emphasizes the need for researchers and clinicians to consider cognition as emergent from multiple interacting systems.
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11. Hiremath G, Meadows J, Moore P. {{How Slow Can We Go? 4 Frames Per Second (fps) Versus 7.5 fps Fluoroscopy for Atrial Septal Defects (ASDs) Device Closure}}. {Pediatr Cardiol}. 2015.
Radiation exposure remains a significant concern for ASD device closure. In an effort to reduce radiation exposure, the default fluoroscopy frame rate in our Siemens biplane pediatric catheterization laboratory was reduced to 4 fps in November 2013 from an earlier 7.5 fps fluoro rate. This study aims to evaluate the components contributing to total radiation exposure and compare the procedural success and radiation exposure during ASD device closure using 4 versus 7.5 fps fluoroscopy rates. Twenty ASD device closures performed using 4 fps fluoro rate were weight-matched to 20 ASD closure procedures using 7.5 fps fluoro rate. Baseline characteristics, procedure times and case times were similar in the two groups. Device closure was successful in all but one case in the 4 fps group. The dose area product (DAP), normalized DAP to body weight, total radiation time and fluoro time were lower in the 4 fps group but not statistically different than the 7.5 fps. The number of cine images and cine times were identical in both groups. Fluoroscopy and cineangiography contributed equally to radiation exposure. Fluoroscopy at 4 fps can be safe and effective for ASD device closure in children and adults. There was no increase in procedure time, cine time, fluoro time or complications at this slow fluoro rate. There was a trend toward decreased radiation exposure as measured by indexed DAP although not statistically significant in this small study. Further study with multiple operators using 4 fps fluoroscopy for simple interventional procedures is recommended.
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12. Karmaniolou I, Krishnan R, Galtrey E, Cleland S, Vijayaraghavan R. {{Perioperative management and outcome of patients with Rett syndrome undergoing scoliosis surgery: a retrospective review}}. {J Anesth}. 2015.
BACKGROUND: Rett syndrome is a rare genetically inherited neuromuscular disorder exclusively affecting female patients. Progressive scoliosis is one of the main features of the disease and affected individuals are very likely to need spine correction surgery. METHODS: We undertook a retrospective notes review of patients with Rett syndrome who had undergone spine surgery from 2005 to 2013. Patients were identified through the hospital’s electronic records. The aim of the present study was to identify the anesthetic implications encountered and the perioperative adverse events, in an effort to improve perioperative management and reduce complications. RESULT: We identified twenty-four children who had 29 procedures in total in this period. Frequent chest infections and poorly controlled epilepsy were the main preoperative findings. There were no adverse events during induction and intubation. Common anesthetic/analgesic drugs were used throughout. Postoperatively, gastrointestinal and respiratory tract complications were the most common. Mean intensive care unit stay was 8.1 days and mean time to discharge from hospital was 26.5 days. We had one in-hospital death. CONCLUSIONS: Our case series demonstrates a high incidence of complications in this subpopulation, mainly postoperative. Extreme postoperative vigilance is required and recovery in a high dependency unit is highly recommended.
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13. Lee EJ, Choi SY, Kim E. {{NMDA receptor dysfunction in autism spectrum disorders}}. {Curr Opin Pharmacol}. 2015; 20C: 8-13.
Abnormalities and imbalances in neuronal excitatory and inhibitory synapses have been implicated in diverse neuropsychiatric disorders including autism spectrum disorders (ASDs). Increasing evidence indicates that dysfunction of NMDA receptors (NMDARs) at excitatory synapses is associated with ASDs. In support of this, human ASD-associated genetic variations are found in genes encoding NMDAR subunits. Pharmacological enhancement or suppression of NMDAR function ameliorates ASD symptoms in humans. Animal models of ASD display bidirectional NMDAR dysfunction, and correcting this deficit rescues ASD-like behaviors. These findings suggest that deviation of NMDAR function in either direction contributes to the development of ASDs, and that correcting NMDAR dysfunction has therapeutic potential for ASDs.
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14. Levin AR, Fox NA, Zeanah CH, Jr., Nelson CA. {{Social communication difficulties and autism in previously institutionalized children}}. {J Am Acad Child Adolesc Psychiatry}. 2015; 54(2): 108-15 e1.
OBJECTIVE: To determine the risk of difficulties with social communication and restricted/repetitive behaviors as well as the rate of autism in children institutionalized in early infancy and to assess the impact of a foster care intervention on ameliorating this risk. METHOD: Children abandoned at birth and raised in institutions in Bucharest, Romania were randomly assigned to a care-as-usual group (institutional care, CAUG), or placed in family-centered foster care (FCG) as part of the Bucharest Early Intervention Project (BEIP). At approximately 10 years of age, the Social Communication Questionnaire (SCQ) was administered to caregivers of children in both groups as well as to parents of a typically developing community sample (Never-Institutionalized group [NIG]) residing in Bucharest, Romania. Children scoring >/=12 on the SCQ underwent clinical evaluation for autism spectrum disorder (ASD). RESULTS: Caregivers of children with a history of institutionalization reported that these children had significantly more deviant behavior than never-institutionalized children on all subdomains of the SCQ (all p < 0.001). Children in the FCG had significantly lower scores on the SCQ than children in the CAUG (p < .001), particularly in the reciprocal social interaction domain, indicating that the intervention reduced problems in social communication. Three of 60 CAUG children, 2 of 57 FCG children, and none of the NIG children received a formal ASD diagnosis. CONCLUSION: Early institutional rearing was associated with an increased risk of social communication difficulties and ASD. A family-centered foster care intervention improved social communication skills.
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15. Mazina V, Gerdts J, Trinh S, Ankenman K, Ward T, Dennis MY, Girirajan S, Eichler EE, Bernier R. {{Epigenetics of Autism-related Impairment: Copy Number Variation and Maternal Infection}}. {J Dev Behav Pediatr}. 2015.
OBJECTIVE:: Epidemiological data have suggested maternal infection and fever to be associated with increased risk of autism spectrum disorder (ASD). Animal studies show that gestational infections perturb fetal brain development and result in offspring with the core features of autism and have demonstrated that behavioral effects of maternal immune activation are dependent on genetic susceptibility. The goal of this study was to explore the impact of ASD-associated copy number variants (CNVs) and prenatal maternal infection on clinical severity of ASD within a dataset of prenatal history and complete genetic and phenotypic findings. METHODS:: We analyzed data from the Simons Simplex Collection sample including 1971 children with a diagnosis of ASD aged 4 to 18 years who underwent array comparative genomic hybridization screening. Information on infection and febrile episodes during pregnancy was collected through parent interview. ASD severity was clinically measured through parent-reported interview and questionnaires. RESULTS:: We found significant interactive effects between the presence of CNVs and maternal infection during pregnancy on autistic symptomatology, such that individuals with CNVs and history of maternal infection demonstrated increased rates of social communicative impairments and repetitive/restricted behaviors. In contrast, no significant interactions were found between presence of CNVs and prenatal infections on cognitive and adaptive functioning of individuals with ASD. CONCLUSIONS:: Our findings support a gene-environment interaction model of autism impairment, in that individuals with ASD-associated CNVs are more susceptible to the effects of maternal infection and febrile episodes in pregnancy on behavioral outcomes and suggest that these effects are specific to ASD rather than to global neurodevelopment.
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16. Murdoch JD, Gupta AR, Sanders SJ, Walker MF, Keaney J, Fernandez TV, Murtha MT, Anyanwu S, Ober GT, Raubeson MJ, DiLullo NM, Villa N, Waqar Z, Sullivan C, Gonzalez L, Willsey AJ, Choe SY, Neale BM, Daly MJ, State MW. {{No Evidence for Association of Autism with Rare Heterozygous Point Mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins}}. {PLoS Genet}. 2015; 11(1): e1004852.
Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein-Like 2 (CNTNAP2) in particular, have been widely cited as autism risk genes based on findings from homozygosity mapping, molecular cytogenetics, copy number variation analyses, and both common and rare single nucleotide association studies. However, data specifically with regard to the contribution of heterozygous single nucleotide variants (SNVs) have been inconsistent. In an effort to clarify the role of rare point mutations in CNTNAP2 and related gene families, we have conducted targeted next-generation sequencing and evaluated existing sequence data in cohorts totaling 2704 cases and 2747 controls. We find no evidence for statistically significant association of rare heterozygous mutations in any of the CNTN or CNTNAP genes, including CNTNAP2, placing marked limits on the scale of their plausible contribution to risk.
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17. Ngounou Wetie AG, Wormwood KL, Russell S, Ryan JP, Darie CC, Woods AG. {{A Pilot Proteomic Analysis of Salivary Biomarkers in Autism Spectrum Disorder}}. {Autism Res}. 2015.
Autism spectrum disorder (ASD) prevalence is increasing, with current estimates at 1/68-1/50 individuals diagnosed with an ASD. Diagnosis is based on behavioral assessments. Early diagnosis and intervention is known to greatly improve functional outcomes in people with ASD. Diagnosis, treatment monitoring and prognosis of ASD symptoms could be facilitated with biomarkers to complement behavioral assessments. Mass spectrometry (MS) based proteomics may help reveal biomarkers for ASD. In this pilot study, we have analyzed the salivary proteome in individuals with ASD compared to neurotypical control subjects, using MS-based proteomics. Our goal is to optimize methods for salivary proteomic biomarker discovery and to identify initial putative biomarkers in people with ASDs. The salivary proteome is virtually unstudied in ASD, and saliva could provide an easily accessible biomaterial for analysis. Using nano liquid chromatography-tandem mass spectrometry, we found statistically significant differences in several salivary proteins, including elevated prolactin-inducible protein, lactotransferrin, Ig kappa chain C region, Ig gamma-1 chain C region, Ig lambda-2 chain C regions, neutrophil elastase, polymeric immunoglobulin receptor and deleted in malignant brain tumors 1. Our results indicate that this is an effective method for identification of salivary protein biomarkers, support the concept that immune system and gastrointestinal disturbances may be present in individuals with ASDs and point toward the need for larger studies in behaviorally-characterized individuals. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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18. Pinggera A, Lieb A, Benedetti B, Lampert M, Monteleone S, Liedl KR, Tuluc P, Striessnig J. {{CACNA1D De Novo Mutations in Autism Spectrum Disorders Activate Cav1.3 L-Type Calcium Channels}}. {Biol Psychiatry}. 2014.
BACKGROUND: Cav1.3 voltage-gated L-type calcium channels (LTCCs) are part of postsynaptic neuronal signaling networks. They play a key role in brain function, including fear memory and emotional and drug-taking behaviors. A whole-exome sequencing study identified a de novo mutation, p.A749G, in Cav1.3 alpha1-subunits (CACNA1D), the second main LTCC in the brain, as 1 of 62 high risk-conferring mutations in a cohort of patients with autism and intellectual disability. We screened all published genetic information available from whole-exome sequencing studies and identified a second de novo CACNA1D mutation, p.G407R. Both mutations are present only in the probands and not in their unaffected parents or siblings. METHODS: We functionally expressed both mutations in tsA-201 cells to study their functional consequences using whole-cell patch-clamp. RESULTS: The mutations p.A749G and p.G407R caused dramatic changes in channel gating by shifting (~15 mV) the voltage dependence for steady-state activation and inactivation to more negative voltages (p.A749G) or by pronounced slowing of current inactivation during depolarizing stimuli (p.G407R). In both cases, these changes are compatible with a gain-of-function phenotype. CONCLUSIONS: Our data, together with the discovery that Cav1.3 gain-of-function causes primary aldosteronism with seizures, neurologic abnormalities, and intellectual disability, suggest that Cav1.3 gain-of-function mutations confer a major part of the risk for autism in the two probands and may even cause the disease. Our findings have immediate clinical relevance because blockers of LTCCs are available for therapeutic attempts in affected individuals. Patients should also be explored for other symptoms likely resulting from Cav1.3 hyperactivity, in particular, primary aldosteronism.
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19. Piochon C, Kloth AD, Grasselli G, Titley HK, Nakayama H, Hashimoto K, Wan V, Simmons DH, Eissa T, Nakatani J, Cherskov A, Miyazaki T, Watanabe M, Takumi T, Kano M, Wang SS, Hansel C. {{Corrigendum: Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism}}. {Nat Commun}. 2015; 6: 6014.
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20. Pivovarciova A, Hnilicova S, Ostatnikova D, Mace FC. {{Testosterone and explosive aggression in autism spectrum disorders}}. {Neuro Endocrinol Lett}. 2014; 35(7): 553-8.
Autism spectrum disorders (ASD) are a set of heterogeneous neurodevelopmental conditions, characterized by early-onset difficulties in social communication and unusually restricted, repetitive behavior and interests. Children with ASD have a high rate of irritability and aggressive symptoms which have significant impact on their lives, families and society. The etiology of aggression in humans is likely complex and includes both biological and behavioral causes. Biological approaches have focused on hormones and neurotransmitters that are hypothesized to contribute to the etiology and clinical manifestation of aggressive behavior in humans. Testosterone is a male sex hormone and some studies suggest that it can play a role in the complex etiology of aggressive behavior. Two specific subtypes of aggression have been identified: explosive and non-explosive. Explosive aggression is accompanied by a raged affect and is usually more dangerous and not immediately responsive to behavioral treatment. In our review we would like to provide current findings and discuss potential limitation of research in this area. We propose to determine bio-behavioral model of explosive aggression in children with ASD which will predict which children will be most responsive to potential antiandrogen therapy and behavioral therapy.
21. Richey JA, Damiano CR, Sabatino A, Rittenberg A, Petty C, Bizzell J, Voyvodic J, Heller AS, Coffman MC, Smoski M, Davidson RJ, Dichter GS. {{Neural Mechanisms of Emotion Regulation in Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2015.
Autism spectrum disorder (ASD) is characterized by high rates of comorbid internalizing and externalizing disorders. One mechanistic account of these comorbidities is that ASD is characterized by impaired emotion regulation (ER) that results in deficits modulating emotional responses. We assessed neural activation during cognitive reappraisal of faces in high functioning adults with ASD. Groups did not differ in looking time, pupilometry, or subjective ratings of faces during reappraisal. However, instructions to increase positive and negative emotional responses resulted in less increase in nucleus accumbens and amygdala activations (respectively) in the ASD group, and both regulation instructions resulted in less change in dorsolateral prefrontal cortex activation in the ASD group. Results suggest a potential mechanistic account of impaired ER in ASD.
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22. Selim ME, Abd-Elhakim YM, Al-Ayadhi LY. {{Pancreatic response to gold nanoparticles includes decrease of oxidative stress and inflammation in autistic diabetic model}}. {Cell Physiol Biochem}. 2015; 35(2): 586-600.
BACKGROUND: Gold nanoparticles (AuNPs) have a wide range of applications in various fields. This study provides an understanding of the modulatory effects of AuNPs on an antioxidant system in male Wistar diabetic rats with autism spectrum disorder (ASD). Normal littermates fed by control mothers were injected with citrate buffer alone and served as normal, untreated controls controlin this study. Diabetes mellitus (DM) was induced by administering a single intraperitoneal injection of streptozotocin (STZ) (100 mg/kg) to the pups of (ND) diabetic group, which had been fasted overnight. Autistic pups from mothers that had received a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception were randomly divided into 2 groups (n 2 7/group) as follow; administering single intraperitoneal injection of streptozotocin (STZ) ( (100 mg/kg) to the overnight fasted autistic pups of (AD) autistic diabetic group. The treatment was started on the 5th day after STZ injection with the same dose as in group II and it was considered as 1st day of treatment with gold nanoparticles for 7 days to each rat of (group IV) treated autistic diabetic group(TAD) at a dosage of 2.5 mg/kg. b. wt. RESULTS: At this dose of administration AuNPs, the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were greater in group TAD compared with the control group (P < 0.05). Oxidised glutathione levels were lower (P > 0.05) in the liver of autistic diabetic AuNPs -supplemented rats, whereas reduced glutathione was markedly higher than in control rats, especially after administration of AuNPs. Moreover, the kidney functions in addition to the fat profile scoring supported the protective potential of that dose of AuNPs. The beta cells revealed euchromatic nuclei with no evidence of separation of nuclear membrane. CONCLUSIONS: Our results showed that AuNPs improved many of the oxidative stress parameters (SOD, GPx and, CAT), plasma antioxidant capacity (ORAC) and lipid profile relative to the other parameters. In addition to the apparent reversibility of the pancreatic B cell in group IV which may reflect the regenerative capacity of AuNPs. (c) 2015 S. Karger AG, Basel.
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23. Talalay P, Zimmerman AW. {{Reply to Scahill: Behavioral outcome measures in autism}}. {Proc Natl Acad Sci U S A}. 2015; 112(4): E350.
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24. Yuen RK, Thiruvahindrapuram B, Merico D, Walker S, Tammimies K, Hoang N, Chrysler C, Nalpathamkalam T, Pellecchia G, Liu Y, Gazzellone MJ, D’Abate L, Deneault E, Howe JL, Liu RS, Thompson A, Zarrei M, Uddin M, Marshall CR, Ring RH, Zwaigenbaum L, Ray PN, Weksberg R, Carter MT, Fernandez BA, Roberts W, Szatmari P, Scherer SW. {{Whole-genome sequencing of quartet families with autism spectrum disorder}}. {Nat Med}. 2015.
Autism spectrum disorder (ASD) is genetically heterogeneous, with evidence for hundreds of susceptibility loci. Previous microarray and exome-sequencing studies have examined portions of the genome in simplex families (parents and one ASD-affected child) having presumed sporadic forms of the disorder. We used whole-genome sequencing (WGS) of 85 quartet families (parents and two ASD-affected siblings), consisting of 170 individuals with ASD, to generate a comprehensive data resource encompassing all classes of genetic variation (including noncoding variants) and accompanying phenotypes, in apparently familial forms of ASD. By examining de novo and rare inherited single-nucleotide and structural variations in genes previously reported to be associated with ASD or other neurodevelopmental disorders, we found that some (69.4%) of the affected siblings carried different ASD-relevant mutations. These siblings with discordant mutations tended to demonstrate more clinical variability than those who shared a risk variant. Our study emphasizes that substantial genetic heterogeneity exists in ASD, necessitating the use of WGS to delineate all genic and non-genic susceptibility variants in research and in clinical diagnostics.
