1. Ben-David E, Shifman S. {{Networks of neuronal genes affected by common and rare variants in autism spectrum disorders}}. {PLoS Genet};2012 (Mar);8(3):e1002556.
Autism spectrum disorders (ASD) are neurodevelopmental disorders with phenotypic and genetic heterogeneity. Recent studies have reported rare and de novo mutations in ASD, but the allelic architecture of ASD remains unclear. To assess the role of common and rare variations in ASD, we constructed a gene co-expression network based on a widespread survey of gene expression in the human brain. We identified modules associated with specific cell types and processes. By integrating known rare mutations and the results of an ASD genome-wide association study (GWAS), we identified two neuronal modules that are perturbed by both rare and common variations. These modules contain highly connected genes that are involved in synaptic and neuronal plasticity and that are expressed in areas associated with learning and memory and sensory perception. The enrichment of common risk variants was replicated in two additional samples which include both simplex and multiplex families. An analysis of the combined contribution of common variants in the neuronal modules revealed a polygenic component to the risk of ASD. The results of this study point toward contribution of minor and major perturbations in the two sub-networks of neuronal genes to ASD risk.
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2. Bodner KE, Beversdorf DQ, Saklayen SS, Christ SE. {{Noradrenergic Moderation of Working Memory Impairments in Adults with Autism Spectrum Disorder}}. {J Int Neuropsychol Soc};2012 (Mar 14):1-9.
In addition to having difficulties with social communications, individuals with an autism spectrum disorder (ASD) often also experience impairment in higher-order, executive skills. The present study examined the effects of pharmacological modulation of the norepinephrine system on the severity of such impairments. A sample of 14 high-functioning adults with ASD and a demographically-matched comparison group of 13 typically developing individuals participated. An AX continuous performance test (AX-CPT) was used to evaluate working memory and inhibitory control. AX-CPT performance was assessed following administration of a single dose of propranolol (a beta adrenergic antagonist) and following placebo (sugar pill) administration. Individuals with ASD performed more poorly than non-ASD individuals in the working memory condition (BX trials). Importantly, administration of propranolol attenuated this impairment, with the ASD group performing significantly better in the propranolol condition than the placebo condition. Working memory performance of the non-ASD group was unaffected by propranolol/placebo administration. No group or medication effects were observed for the inhibition condition (AY trials). The present findings suggest that norepinephrine may play a role in some, but not necessarily all, cognitive impairments associated with ASD. Additional research is needed to fully understand whether this role is primarily causal or compensatory in nature. (JINS, 2012, 18, 1-9).
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3. Boucher J, Mayes A, Bigham S. {{Memory in Autistic Spectrum Disorder}}. {Psychol Bull};2012 (Mar 12)
Behavioral evidence concerning memory in forms of high-functioning autism (HFA) and in moderately low-functioning autism (M-LFA) is reviewed and compared. Findings on M-LFA are sparse. However, it is provisionally concluded that memory profiles in HFA and M-LFA (relative to ability-matched controls) are similar but that declarative memory impairments are more extensive in M-LFA than in HFA. Specifically, both groups have diminished memory for emotion- or person-related stimuli. Regarding memory for nonsocial stimuli, both groups probably have mental-age-appropriate nondeclarative memory, and within declarative memory, both groups have mental-age-appropriate immediate free recall of within-span or supraspan lists of unrelated items, as well as cued recall and paired associate learning. By contrast, recognition is largely unimpaired in HFA but moderately impaired in M-LFA, and free recall of meaningful or structured stimuli is moderately impaired in HFA but more severely impaired in M-LFA. Theoretical explanations of data on declarative memory in HFA identify problems in the integrative processing, or the consolidation and storage, of complex stimuli or a specific problem of recollection. Proposed neural substrates include the following: disconnectivity of primary sensory and association areas; dysfunctions of medial prefrontal cortex, hippocampus, or posterior parietal lobe; or combinations of these associated with neural disconnectivity. Hypothetically, perirhinal dysfunction might explain the more extensive declarative memory impairments in M-LFA. Foreseeable consequences of uneven memory abilities in HFA and M-LFA are outlined, including possible effects on language and learning in M-LFA. Finally, priorities for future research are identified, highlighting the urgent need for research on memory in lower functioning individuals. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
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4. Copeland L. {{Help Across the Spectrum: A Developmental Pediatrician’s Perspective on Diagnosing and Treating Autism Spectrum Disorders}}. {J Soc Work Disabil Rehabil};2012 (Jan);11(1):1-32.
Autism spectrum disorders (ASD), a group of neurodevelopmental disorders characterized by marked deficits in social interaction and communication with unusually restricted interests, have a tremendous impact on society and are increasingly being diagnosed. Increased developmental screening, use of standardized diagnostic tests, and a broadening of Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2000) criteria might account for the increased incidence. Evidence-based treatments for children with ASD, reviewed by the National Standards Project, are primarily behavioral interventions with foundations in the sciences of applied behavior analysis and developmental psychology and emphasize improved functional communication and social reciprocity.
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5. Howlin P. {{Understanding savant skills in autism}}. {Dev Med Child Neurol};2012 (Mar 13)
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6. Hurwitz R, Blackmore R, Hazell P, Williams K, Woolfenden S. {{Tricyclic antidepressants for autism spectrum disorders (ASD) in children and adolescents}}. {Cochrane Database Syst Rev};2012;3:CD008372.
BACKGROUND: Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders, ranging in severity and characterised by early onset of delay and deviance in the development of social interaction, and verbal and nonverbal communication. ASD is associated with restricted and/or stereotyped interests or behaviours. Tricyclic antidepressants (TCAs) block noradrenaline and serotonin reuptake, increasing the availability of these neurotransmitters in the central nervous system. Via their impact on serotonin, TCAs have been used in the treatment of autistic symptoms and comorbidities in individuals with ASD. OBJECTIVES: To determine if treatment with tricyclic antidepressants:1) improves the core features of autism, including restricted social interaction, restricted communication, and stereotypical and repetitive behaviours; 2) improves non-core features such as challenging behaviours; 3) improves comorbid states, such as depression and anxiety; 4) causes adverse effects. SEARCH METHODS: We ran the latest searches for this review on 23 May 2011. We searched: Cochrane Central Register of Controlled Trials (CENTRAL), 2011 Issue 2, MEDLINE (1948 to May Week 2, 2011), EMBASE (1980 to 2011 Week 2), PsycINFO (1887 to current), CINAHL (1937 to current). We also searched Dissertation Abstracts International via Dissertation Express, and the metaRegister of Controlled Trials. SELECTION CRITERIA: Randomised controlled trials of any dose, duration and frequency of oral TCAs compared with placebo, in children and adolescents with a diagnosis of ASD, where at least one standardised outcome measure had been used. DATA COLLECTION AND ANALYSIS: Two review authors independently selected and appraised the studies for inclusion and risk of bias. All data were continuous. MAIN RESULTS: Three studies met the inclusion criteria for this review. Two studies used clomipramine and one used tianeptine. All three trials were small, with between 12 and 32 participants. One of the clomipramine trials involved children and young adults, while the other two trials enrolled only children. Due to heterogeneity in study participant characteristics, the TCA medications investigated and the outcome measures used, we were not able to perform any meta-analysis.In only one of the three studies was there any indication that giving children tianeptine could be effective in the short term. In this study, parents and teachers reported that it reduced irritability, hyperactivity, inadequate eye contact and inappropriate speech, but clinician ratings found no significant impact on these symptoms. There were also significant adverse effects, including increased drowsiness and reduced activity levels in these individuals while being treated with tianeptine. The evidence of the impact of clomipramine in the two studies is contradictory. There was evidence of improvement in autistic symptoms, irritability and obsessive-compulsive disorder type symptoms, but conflicting evidence in relation to hyperactivity across the two studies, and no significant changes found with inappropriate speech. There were also adverse effects reported with the use of clomipramine. Although side effect ratings were not significantly different to placebo, there were significant dropout rates in the clomipramine arm of one study. AUTHORS’ CONCLUSIONS: Clinicians considering the use of TCAs need to be aware of the limited and conflicting evidence of effect and the side effect profile when discussing this treatment option with people who have ASD and their carers. Further research is required before TCAs can be recommended for treatment of individuals with ASD.
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7. Hyman SL, Johnson JK. {{Autism and Pediatric Practice: Toward a Medical Home}}. {J Autism Dev Disord};2012 (Mar 13)
The pediatrician sees a child for 11 well child visits by their third birthday. The provision of continuous primary care supports development of trust with parents, provides opportunity for screening and surveillance of autism spectrum disorders (ASD), allows monitoring the progress of children requiring therapy, and a framework to support and educate families. Families of children with ASD are less likely to report that they receive care in a Medical Home, a practice providing coordinated, accessible, continuous, culturally competent care. They report less access to specialty and family focused care compared to other children with special health care needs. It is a major challenge to identify and effect the solutions necessary to bring Medical Home care to all children with ASD.
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8. Irie F, Badie-Mahdavi H, Yamaguchi Y. {{Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate}}. {Proc Natl Acad Sci U S A};2012 (Mar 12)
Heparan sulfate regulates diverse cell-surface signaling events, and its roles in the development of the nervous system recently have been increasingly uncovered by studies using genetic models carrying mutations of genes encoding enzymes for its synthesis. On the other hand, the role of heparan sulfate in the physiological function of the adult brain has been poorly characterized, despite several pieces of evidence suggesting its role in the regulation of synaptic function. To address this issue, we eliminated heparan sulfate from postnatal neurons by conditionally inactivating Ext1, the gene encoding an enzyme essential for heparan sulfate synthesis. Resultant conditional mutant mice show no detectable morphological defects in the cytoarchitecture of the brain. Remarkably, these mutant mice recapitulate almost the full range of autistic symptoms, including impairments in social interaction, expression of stereotyped, repetitive behavior, and impairments in ultrasonic vocalization, as well as some associated features. Mapping of neuronal activation by c-Fos immunohistochemistry demonstrates that neuronal activation in response to social stimulation is attenuated in the amygdala in these mice. Electrophysiology in amygdala pyramidal neurons shows an attenuation of excitatory synaptic transmission, presumably because of the reduction in the level of synaptically localized AMPA-type glutamate receptors. Our results demonstrate that heparan sulfate is critical for normal functioning of glutamatergic synapses and that its deficiency mediates socio-communicative deficits and stereotypies characteristic for autism.
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9. Kana R, Percy A. {{Organization in Autism: Bigger but Not Better}}. {Arch Neurol};2012 (Mar 12)
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10. Miyake K, Hirasawa T, Koide T, Kubota T. {{Epigenetics in autism and other neurodevelopmental diseases}}. {Adv Exp Med Biol};2012;724:91-98.
Autism was previously thought to be caused by environmental factors. However, genetic factors are now considered to be more contributory to the pathogenesis of autism, based on the recent findings of mutations in the genes which encode synaptic molecules associated with the communication between neurons. Epigenetic is a mechanism that controls gene expression without changing DNA sequence but by changing chromosomal histone modifications and its abnormality is associated with several neurodevelopmental diseases. Since epigenetic modifications are known to be affected by environmental factors such as nutrition, drugs and mental stress, autistic diseases are not only caused by congenital genetic defects, but may also be caused by environmental factors via epigenetic mechanism. In this chapter, we introduce autistic diseases caused by epigenetic failures and discuss epigenetic changes by environmental factors and discuss new treatments for neurodevelopmental diseases based on the recent epigenetic findings.
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11. Patterson S, Smith V, Jelen M. {{Autism spectrum disorders: information for pediatricians supporting families of young children on the spectrum}}. {Adv Exp Med Biol};2012;724:51-60.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder affecting in US 1 in 110 individuals.(1) As increasingly younger children are receiving ASD diagnoses, many pediatricians are now faced with the unique needs of parents and other caregivers of newly diagnosed toddlers and young children. This chapter provides an overview of ASD designed to offer information and resources to pediatricians that could, in turn, be provided to families of children newly diagnosed with ASD.
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12. Tordjman S, Anderson GM, Botbol M, Toutain A, Sarda P, Carlier M, Saugier-Veber P, Baumann C, Cohen D, Lagneaux C, Tabet AC, Verloes A. {{Autistic disorder in patients with williams-beuren syndrome: a reconsideration of the williams-beuren syndrome phenotype}}. {PLoS One};2012;7(3):e30778.
BACKGROUND: Williams-Beuren syndrome (WBS), a rare developmental disorder caused by deletion of contiguous genes at 7q11.23, has been characterized by strengths in socialization (overfriendliness) and communication (excessive talkativeness). WBS has been often considered as the polar opposite behavioral phenotype to autism. Our objective was to better understand the range of phenotypic expression in WBS and the relationship between WBS and autistic disorder. METHODOLOGY: The study was conducted on 9 French individuals aged from 4 to 37 years old with autistic disorder associated with WBS. Behavioral assessments were performed using Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) scales. Molecular characterization of the WBS critical region was performed by FISH. FINDINGS: FISH analysis indicated that all 9 patients displayed the common WBS deletion. All 9 patients met ADI-R and ADOS diagnostic criteria for autism, displaying stereotypies and severe impairments in social interaction and communication (including the absence of expressive language). Additionally, patients showed improvement in social communication over time. CONCLUSIONS: The results indicate that comorbid autism and WBS is more frequent than expected and suggest that the common WBS deletion can result in a continuum of social communication impairment, ranging from excessive talkativeness and overfriendliness to absence of verbal language and poor social relationships. Appreciation of the possible co-occurrence of WBS and autism challenges the common view that WBS represents the opposite behavioral phenotype of autism, and might lead to improved recognition of WBS in individuals diagnosed with autism.
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13. Vande Wydeven K, Kwan A, Hardan AY, Bernstein JA. {{Underutilization of Genetics Services for Autism: The Importance of Parental Awareness and Provider Recommendation}}. {J Genet Couns};2012 (Mar 14)
Reasons for the underutilization of genetics services by families of children with autism spectrum disorders (ASD) are not well understood. We report the identification of factors associated with this underuse. Survey-based study of parents and/or guardians of children with ASD. One hundred fifty-five families completed the questionnaire. Thirty-one of 155 (20%) children had seen a genetics professional. Forty-nine of 154 (32%) children had undergone genetic testing. Parents whose child saw a genetics professional were more likely to 1) Have a primary provider refer for or suggest a genetics evaluation 2) Have asked for a referral, and/or 3) Know another person with a genetic cause of ASD. amilies of children with ASD who have not received genetics services are less aware of their availability and utility. They are also less likely to have their provider recommend a clinical genetics evaluation. Efforts should be taken to increase awareness of both health providers and parents regarding the usefulness of genetics services for ASD.
