1. Accordino RE, Kidd C, Politte LC, Henry CA, McDougle CJ. {{Psychopharmacological Interventions in Autism Spectrum Disorder}}. {Expert Opin Pharmacother};2016 (Feb 18)
INTRODUCTION: Individuals with autism spectrum disorder (ASD) commonly present for treatment of emotional and behavioral disturbances associated with ASD’s « core » symptoms. Psychotropic medications are widely utilized in alleviating associated emotional and behavioral symptoms. Areas covered: Emotional and behavioral disturbances associated with ASD include irritability/severely disruptive behavior, which comprises the heaviest symptom burden; hyperactivity and other Attention-Deficit-Hyperactivity-Disorder (ADHD)-type symptoms; repetitive/stereotyped behaviors; and social withdrawal. Existing evidence for medications for each of these symptom clusters will be examined in this review. Expert opinion: Psychopharmacological treatment of core and associated symptoms in ASD is challenging, in large part because of the heterogeneity in the presentation of ASD. Furthermore, children and adolescents with ASD are more vulnerable to the side effects of psychopharmacological intervention than their age-matched, typically developing counterparts. Currently, risperidone and aripiprazole are the only medications that have been (relatively) reliably shown to help treat certain symptom clusters associated with ASD, namely severely disruptive behavior and hyperactivity. Recent studies have begun to look at medications with mechanisms that are novel in the treatment of ASD and that may address underlying pathophysiology and/or core symptoms such as glutamate-modulating agents. Overall, randomized, placebo-controlled studies of medications for the treatment of ASD are scarce.
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2. Akcakaya NH, Tekturk P, Cagatay A, Tur EK, Yapici Z. {{Atypical enterovirus encephalitis causing behavioral changes and autism-like clinical manifestations: case report}}. {Acta Neurol Belg};2016 (Feb 19)
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3. Becker MM, Bosa C, Oliveira-Freitas VL, Goldim JR, Ohlweiler L, Roesler R, Schwartsmann G, Riesgo RS. {{Improvement of autism spectrum disorder symptoms in three children by using gastrin-releasing peptide}}. {J Pediatr (Rio J)};2016 (Feb 15)
OBJECTIVE: To evaluate the safety, tolerability and potential therapeutic effects of gastrin-releasing peptide in three children with autistic spectrum disorder. METHODS: Case series study with the intravenous administration of gastrin-releasing peptide in the dose of 160pmol/kg for four consecutive days. To evaluate the results, parental impressions the Childhood Autism Rating Scale (CARS) and the Clinical Global Impression (CGI) Scale. Each child underwent a new peptide cycle after two weeks. The children were followed for four weeks after the end of the infusions. RESULTS: The gastrin-releasing peptide was well tolerated and no child had adverse effects. Two children had improved social interaction, with a slight improvement in joint attention and the interaction initiatives. Two showed reduction of stereotypes and improvement in verbal language. One child lost his compulsion to bathe, an effect that lasted two weeks after each infusion cycle. Average reduction in CARS score was 2.8 points. CGI was « minimally better » in two children and « much better » in one. CONCLUSIONS: This study suggests that the gastrin-releasing peptide is safe and may be effective in improving key symptoms of autism spectrum disorder, but its results should be interpreted with caution. Controlled clinical trials-randomized, double-blinded, and with more children-are needed to better evaluate the possible therapeutic effects of gastrin-releasing peptide in autism.
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4. Biran J, Levkowitz G. {{Zebrafish Reel in Phenotypic Suppressors of Autism}}. {Neuron};2016 (Feb 17);89(4):673-675.
Chemical genetics can help decipher novel pathways underlying neurodevelopmental psychiatric impairments. Hoffman et al. (2016) utilized behavioral profiling of psychoactive compounds in zebrafish and identified estrogens as suppressors of a phenotype resulting from loss of an autism risk gene.
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5. Charman T, Chakrabarti B. {{Commentary: Not just genes – reclaiming a role for environmental influences on aetiology and outcome in autism. A commentary on Mandy and Lai (2016)}}. {J Child Psychol Psychiatry};2016 (Mar);57(3):293-295.
Mandy and Lai (2015) do the field a service in ‘reclaiming’ the role of pre- and postnatal environmental influences on the aetiology and course of autism spectrum conditions (ASC). This follows several decades where now discredited theories about putative psychogenic and biological disease models held sway, not least in the public mind. We discuss issues that arise from their review; including the need to identify how large the environmental influences on ASC are likely to be; the specificity of these environmental influences to ASC as opposed to a broader range of neurodevelopmental conditions and outcomes; how best to study complex interactions between genetic and environmental influences; and the promise of novel insights into their mechanisms of action. The review highlights current research that aims to better our understanding of the role of environmental factors in the aetiology and course of ASC and, in the near future, may offer the potential for personalised medicine approaches to intervention based on these discoveries.
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6. Cotter M, Archibald AD, McClaren BJ, Burgess T, Francis D, Hills L, Martyn M, Oertel R, Slater H, Cohen J, Metcalfe SA. {{Clinical audit of genetic testing and referral patterns for fragile X and associated conditions}}. {Am J Med Genet A};2016 (Feb 18)
An audit was conducted of laboratory/clinical databases of genetic tests performed between January 2003 and December 2009, and for 2014, as well as referrals to the clinical service and a specialist multidisciplinary clinic, to determine genetic testing request patterns for fragile X syndrome and associated conditions and referrals for genetic counseling/multidisciplinary management in Victoria, Australia. An expanded allele (full mutation, premutation or intermediate) was found in 3.7% of tests. Pediatricians requested approximately 70% of test samples, although fewer general practitioners and more obstetricians/gynecologists ordered tests in 2014. Median age at testing for individuals with a full mutation seeking a diagnosis without a fragile X family history was 4.3 years (males) and 9.4 years (females); these ages were lower when pediatricians ordered the tests (2.1 years and 6.1 years, respectively). Individuals with a premutation were generally tested at a later age (median age: males, 33.2 years; females, 36.4 years). Logistic regression showed that a family history of ID (OR 3.28 P = 0.005, CI 1.77-5.98) was the only indication to independently increase the likelihood of a test-positive (FM or PM) result. Following testing, approximately 25% of full mutation or premutation individuals may not have attended clinical services providing genetic counseling or multidisciplinary management for these families. The apparent delay in fragile X syndrome diagnosis and lack of appropriate referrals for some may result in less than optimal management for these families. These findings suggest continued need for awareness and education of health professionals around diagnosis and familial implications of fragile X syndrome and associated conditions. (c) 2016 Wiley Periodicals, Inc.
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7. Domes G, Spenthof I, Radtke M, Isaksson A, Normann C, Heinrichs M. {{Autistic traits and empathy in chronic vs. episodic depression}}. {J Affect Disord};2016 (Feb 8);195:144-147.
OBJECTIVES: Difficulties in social interaction are characteristic for depressive disorders and one of the cardinal symptoms of Autism Spectrum Disorders (ASD). It has been proposed that chronically depressed persons have profoundly impaired empathic abilities in comparison to episodically depressed persons, and that specifically they exhibit a deficit in cognitive empathy, but not in affective empathy, a pattern also reported in ASD. This study aimed to explore autistic traits and empathy deficits in chronic depression, and identify specific differences to episodic depression. METHOD: Autistic traits and multimodal empathy were assessed in chronically depressed patients (n=59), episodically depressed patients (n=40), and a healthy control group (n=55) using standardized questionnaires. RESULTS: Regardless of the disorder’s chronicity, depressed patients exhibited higher levels of autistic traits and lower levels of perspective-taking than healthy controls. Chronically depressed patients reported significantly higher impairment in social skills and higher levels of personal distress in social interactions than episodic patients. DISCUSSION: Our results suggest that patients with chronic depression share two distinct characteristics, namely lower levels of social skills and higher levels of distress in tense social situations than patients with episodic depression. Future studies will need to determine whether the elevated autistic traits in chronic depression are specific to chronic depression, or represent the general tendency to withdraw from social situations. We conclude that chronically depressed patients are not specifically impaired in understanding another person’s state of mind, but are unable to deal with another person’s suffering or negative affective state.
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8. Dunn SA, Freeth M, Milne E. {{Electrophysiological Evidence of Atypical Spatial Attention in Those with a High Level of Self-reported Autistic Traits}}. {J Autism Dev Disord};2016 (Feb 20)
Selective attention is atypical in individuals with autism spectrum conditions. Evidence suggests this is also the case for those with high levels of autistic traits. Here we investigated the neural basis of spatial attention in those with high and low levels of self-reported autistic traits via analysis of ERP deflections associated with covert attention, target selection and distractor suppression (the N2pc, NT and PD). Larger N2pc and smaller PD amplitude was observed in those with high levels of autistic traits. These data provide neural evidence for differences in spatial attention, specifically, reduced distractor suppression in those with high levels of autistic traits, and may provide insight into the experience of perceptual overload often reported by individuals on the autism spectrum.
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9. Fein D, Robins D, Barton M. {{Testing two screening instruments for autism spectrum disorder}}. {Dev Med Child Neurol};2016 (Mar);58(3):314-315.
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10. Granich J, Lin A, Hunt A, Wray J, Dass A, Whitehouse AJ. {{Obesity and associated factors in youth with an autism spectrum disorder}}. {Autism};2016 (Feb 17)
Weight status on children and youth with autism spectrum disorder is limited. We examined the prevalence of overweight/obesity in children and youth with autism spectrum disorder, and associations between weight status and range of factors. Children and youth with autism spectrum disorder aged 2-16 years (n = 208) and their parents participated in this study. Body mass index was calculated using the Centers for Disease Control and Prevention growth charts and the International Obesity Task Force body mass index cut-offs. The Autism Diagnostic Observation Schedule was administered. Parents completed questionnaires about socio-demographics, diagnosed comorbidities, sleep disturbances, social functioning and medication of youth with autism spectrum disorder. The prevalence of overweight/obesity in participants with autism spectrum disorder was 35%. One quarter of obese children and youth (25.6%) had obese parents. There was a significant association between children and youth’s body mass index and maternal body mass index (r = 0.25, n = 199, p < 0.001). The gender and age, parental education, family income, ethnicity, autism spectrum disorder severity, social functioning, psychotropic and complementary medication use of children and youth with autism spectrum disorder were not statistically associated with their weight status. Findings suggest the need for clinical settings to monitor weight status of children and youth with autism spectrum disorder in a bid to manage or prevent overweight/obesity in this population. Incorporating a family system approach to influence health behaviours among children and youth with autism spectrum disorder especially for specific weight interventions is warranted and should be further explored.
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11. Gul H, Erol N, Pamir Akin D, Ustun Gullu B, Akcakin M, Alpas B, Oner O. {{EMOTIONAL AVAILABILITY IN EARLY MOTHER-CHILD INTERACTIONS FOR CHILDREN WITH AUTISM SPECTRUM DISORDERS, OTHER PSYCHIATRIC DISORDERS, AND DEVELOPMENTAL DELAY}}. {Infant Ment Health J};2016 (Feb 19)
Emotional availability (EA) is a method to assess early parent-child dyadic interactions for emotional awareness, perception, experience, and expression between child and parent that describe global relational quality (Z. Biringen & M. Easterbrooks, ). The current study aimed to examine the effects of an infant’s diagnosis of autism spectrum disorders (ASDs), other psychiatric disorders (OPD), and developmental delay (DD) on the maternal EA Scale (EAS; Z. Biringen & M. Easterbrooks, ; Z. Biringen, J.L. Robinson, & R.N. Emde, ) scores and the relative contributions of infant’s age, gender, diagnosis, developmental level, and maternal education on EAS scores in a clinical Turkish sample. Three hundred forty-five infant-mother dyads participated in this study. Results of the research indicated that EAS adult scores were associated with maternal education and infant’s diagnosis whereas child scores were associated with infant’s age, diagnosis, and developmental level. Infants’ involvement and responsiveness to the mother were lower in the group with ASD. Children with OPD, particularly when their mothers have lower education, might be at increased risk of having problems in parent-child interactions. Young ASD subjects with developmental delay are in greatest need of support to increase reactions toward their mother. These findings underscore the importance of using all of the EA dimensions rather than only one measure on children in high-risk populations.
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12. Hall SS, Wright HF, Mills DS. {{What Factors Are Associated with Positive Effects of Dog Ownership in Families with Children with Autism Spectrum Disorder? The Development of the Lincoln Autism Pet Dog Impact Scale}}. {PLoS One};2016;11(2):e0149736.
Scientific literature exploring the value of assistance dogs to children with autism spectrum disorder (ASD) is rapidly emerging. However, there is comparably less literature reporting the effects of pet (as opposed to assistance) dogs to these children. In particular, there are no known validated scales which assess how children may alter their behaviours in the presence of the dog, to evaluate the efficacy of pet dogs to these families. Additionally, given the highly individualised nature of ASD it is likely that some children and families gain more benefits from dog ownership than others, yet no research has reported the effect of individual differences. This pilot study reports the development of a 28-item scale based on the perceived impact of a pet dog on a child with autism by parents (Lincoln Autism Pet Dog Impact Scale-LAPDIS). The scale is comprised of three mathematically derived factors: Adaptability, Social Skills and Conflict Management. We assessed how individual differences (aspects) may be associated with scores on these three factors. Family Aspects and Dog Aspects were not significantly associated with ratings on the three factors, but Child Aspects (including: contact with horses, child age, disability level and language abilities) were related to impact of the dog on all factors. Training Aspects were related to scores on Social Skills (formal training with children with ASD and dogs and attendance at PAWS workshops run by Dogs for Good). These results suggest that individual differences associated with the child and the training approach may be important considerations for a positive impact from dog ownership on families with children with ASD. Differences in family features and the dog may not be so important, but may be worthy of further investigations given the early stage of development in this field.
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13. Hendren RL, James SJ, Widjaja F, Lawton B, Rosenblatt A, Bent S. {{Randomized, Placebo-Controlled Trial of Methyl B12 for Children with Autism}}. {J Child Adolesc Psychopharmacol};2016 (Feb 18)
OBJECTIVE: Children with autism spectrum disorder (ASD) have been reported to have reduced ability to methylate DNA and elevated markers of oxidative stress. We sought to determine if methyl B12, a key metabolic cofactor for cellular methylation reactions and antioxidant defense, could improve symptoms of ASD. METHODS: A total of 57 children with ASD were randomly assigned to 8 weeks of treatment with methyl B12 (75 mug/kg) or saline placebo every 3 days in a subcutaneous injection. The primary outcome measure was overall improvement in symptoms of ASD as measured by the Clinical Global Impressions-Improvement (CGI-I) score. Secondary outcome measures included changes in the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS). Laboratory measures of methionine methylation and antioxidant glutathione metabolism were assessed at baseline and 8 weeks. RESULTS: A total of 50 children (mean age 5.3 years, 79% male) completed the study. The primary outcome measure – the clinician rated CGI-I score – was statistically significantly better (lower) in the methyl B12 group (2.4) than in the placebo group (3.1) (0.7 greater improvement in the methyl B12 group, 95% CI 1.2-0.2, p = 0.005). Clinical improvement among children treated with methyl B12 was positively correlated with increases in plasma methionine (p = 0.05), decreases in S-adenosyl-l-homocysteine (SAH) (p = 0.007) and improvements in the ratio of S-adenosylmethionine (SAM) to SAH (p = 0.007), indicating an improvement in cellular methylation capacity. No improvements were observed in the parent-rated ABC or SRS. CONCLUSIONS: Methyl B12 treatment improved clinician-rated symptoms of ASD that were correlated with improvements in measures of methionine metabolism and cellular methylation capacity. Clinical Trial Registry: Efficacy Study of Subcutaneous Methyl B12 in Children with Autism: NCT01039792 ( clinicaltrials.gov1 ).
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14. Klusek J, McGrath SE, Abbeduto L, Roberts JE. {{Pragmatic Language Features of Mothers With the FMR1 Premutation Are Associated With the Language Outcomes of Adolescents and Young Adults With Fragile X Syndrome}}. {J Speech Lang Hear Res};2016 (Feb 18):1-13.
Purpose: Pragmatic language difficulties have been documented as part of the FMR1 premutation phenotype, yet the interplay between these features in mothers and the language outcomes of their children with fragile X syndrome is unknown. This study aimed to determine whether pragmatic language difficulties in mothers with the FMR1 premutation are related to the language development of their children. Method: Twenty-seven mothers with the FMR1 premutation and their adolescent/young adult sons with fragile X syndrome participated. Maternal pragmatic language violations were rated from conversational samples using the Pragmatic Rating Scale (Landa et al., 1992). Children completed standardized assessments of vocabulary, syntax, and reading. Results: Maternal pragmatic language difficulties were significantly associated with poorer child receptive vocabulary and expressive syntax skills, with medium effect sizes. Conclusions: This work contributes to knowledge of the FMR1 premutation phenotype and its consequences at the family level, with the goal of identifying modifiable aspects of the child’s language-learning environment that may promote the selection of treatments targeting the specific needs of families affected by fragile X. Findings contribute to our understanding of the multifaceted environment in which children with fragile X syndrome learn language and highlight the importance of family-centered intervention practices for this group.
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15. Kung KT, Constantinescu M, Browne WV, Noorderhaven RM, Hines M. {{No relationship between early postnatal testosterone concentrations and autistic traits in 18 to 30-month-old children}}. {Mol Autism};2016;7:15.
BACKGROUND: Some previous research has suggested that testosterone prenatally contributes to gender differences in autistic traits, but little is known about the role of testosterone during early postnatal development (mini-puberty). Two prior studies found no sex difference in testosterone postnatally in saliva samples and detected little to no relationship between testosterone postnatally and autistic traits in toddlers. These findings may reflect late measurements of testosterone at 3 to 4 months of age, after the peak of mini-puberty at 1 to 3 months of age. The present study examined the relationship between testosterone at 1 to 3 months of age and autistic traits at 18 to 30 months of age. FINDINGS: Testosterone was measured in saliva samples collected from children at 1 to 3 months of age. When the children (40 boys, 47 girls) reached 18 to 30 months of age, parents completed the Quantitative Checklist for Autism in Toddlers (Q-CHAT). Boys had higher concentrations of testosterone postnatally and higher Q-CHAT scores than girls. However, testosterone did not correlate with Q-CHAT scores in boys, girls, or the entire sample. CONCLUSIONS: The current results suggest that testosterone during the early postnatal period does not contribute to later autistic traits. Given our relatively small samples and therefore limited power, however, further research could usefully examine if testosterone in saliva samples collected during the peak of mini-puberty in larger groups predicts autistic traits or other traits that show gender differences.
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16. Moulton E, Barton M, Robins DL, Abrams DN, Fein D. {{Early Characteristics of Children with ASD Who Demonstrate Optimal Progress Between Age Two and Four}}. {J Autism Dev Disord};2016 (Feb 19)
Although for many children, Autism Spectrum Disorder (ASD) is a lifelong disability, a subset of children with ASD lose their diagnosis and show typical cognitive and adaptive abilities. The ages at which this transition can occur is not known, but it sometimes occurs quite early. Participants in the current study were 207 children with an ASD at age two who were reevaluated at age four. Eighty-three percent retained an ASD diagnosis at reevaluation and 9 % showed « optimal progress »: clear ASD at age two but not at age four, and average cognition, language, communication and social skills at age four. Early child-level factors predicted optimal progress: diagnosis of PDD-NOS, fewer repetitive behaviors, less severe symptomatology and stronger adaptive skills.
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17. Schuch JB, Paixao-Cortes VR, Friedrich DC, Tovo-Rodrigues L. {{The contribution of protein intrinsic disorder to understand the role of genetic variants uncovered by autism spectrum disorders exome studies}}. {Am J Med Genet B Neuropsychiatr Genet};2016 (Feb 19)
Several autism spectrum disorders (ASD) exome studies suggest that coding single nucleotide variants (SNVs) play an important role on ASD etiology. Usually, the pathogenic effect of missense mutations is estimated through predictors that lose accuracy for those SNVs placed in intrinsically disordered regions of protein. Here, we used bioinformatics tools to investigate the effect of mutations described in ASD published exome studies (549 mutations) in protein disorder, considering post-translational modification, PEST and Molecular Recognition Features (MoRFs) motifs. Schizophrenia and type 2 diabetes (T2D) datasets were created for comparison purposes. The frequency of mutations predicted as disordered was comparable among the three datasets (38.1% in ASD, 35.7% in schizophrenia, 46.4% in T2D). However, the frequency of SNVs predicted to lead a gain or loss of functional sites or change intrinsic disorder tendencies was higher in ASD and schizophrenia than T2D (46.9%, 36.4%, and 23.1%, respectively). The results obtained by SIFT and PolyPhen-2 indicated that 38.9% and 34.4% of the mutations predicted, respectively, as tolerated and benign showed functional alterations in disorder properties. Given the frequency of mutations placed in IDRs and their functional impact, this study suggests that alterations in intrinsic disorder properties might play a role in ASD and schizophrenia etiologies. They should be taken into consideration when researching the pathogenicity of mutations in neurodevelopmental and psychiatric diseases. Finally, mutations with functional alterations in disorder properties must be potential targets for in vitro and in vivo functional studies. (c) 2016 Wiley Periodicals, Inc.
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18. Sharda M, Foster NE, Tryfon A, Doyle-Thomas KA, Ouimet T, Anagnostou E, Evans AC, Zwaigenbaum L, Lerch JP, Lewis JD, Hyde KL. {{Language Ability Predicts Cortical Structure and Covariance in Boys with Autism Spectrum Disorder}}. {Cereb Cortex};2016 (Feb 17)
There is significant clinical heterogeneity in language and communication abilities of individuals with Autism Spectrum Disorders (ASD). However, no consistent pathology regarding the relationship of these abilities to brain structure has emerged. Recent developments in anatomical correlation-based approaches to map structural covariance networks (SCNs), combined with detailed behavioral characterization, offer an alternative for studying these relationships. In this study, such an approach was used to study the integrity of SCNs of cortical thickness and surface area associated with language and communication, in 46 high-functioning, school-age children with ASD compared with 50 matched, typically developing controls (all males) with IQ > 75. Findings showed that there was alteration of cortical structure and disruption of fronto-temporal cortical covariance in ASD compared with controls. Furthermore, in an analysis of a subset of ASD participants, alterations in both cortical structure and covariance were modulated by structural language ability of the participants, but not communicative function. These findings indicate that structural language abilities are related to altered fronto-temporal cortical covariance in ASD, much more than symptom severity or cognitive ability. They also support the importance of better characterizing ASD samples while studying brain structure and for better understanding individual differences in language and communication abilities in ASD.
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19. Werling DM, Parikshak NN, Geschwind DH. {{Gene expression in human brain implicates sexually dimorphic pathways in autism spectrum disorders}}. {Nat Commun};2016;7:10717.
Autism spectrum disorder (ASD) is more prevalent in males, and the mechanisms behind this sex-differential risk are not fully understood. Two competing, but not mutually exclusive, hypotheses are that ASD risk genes are sex-differentially regulated, or alternatively, that they interact with characteristic sexually dimorphic pathways. Here we characterized sexually dimorphic gene expression in multiple data sets from neurotypical adult and prenatal human neocortical tissue, and evaluated ASD risk genes for evidence of sex-biased expression. We find no evidence for systematic sex-differential expression of ASD risk genes. Instead, we observe that genes expressed at higher levels in males are significantly enriched for genes upregulated in post-mortem autistic brain, including astrocyte and microglia markers. This suggests that it is not sex-differential regulation of ASD risk genes, but rather naturally occurring sexually dimorphic processes, potentially including neuron-glial interactions, that modulate the impact of risk variants and contribute to the sex-skewed prevalence of ASD.
