1. Anderberg E, Cox JC, Neeley Tass ES, Erekson DM, Gabrielsen TP, Warren JS, Cline J, Petersen D, South M. {{Sticking with it: Psychotherapy outcomes for adults with autism spectrum disorder in a university counseling center setting}}. {Autism Res};2017 (Aug 17)
Young adults with autism spectrum disorders (ASD) experience high rates of comorbid mental health concerns in addition to distress arising from the core symptoms of autism. Many adults with ASD seek psychological treatment in outpatient facilities in their communities that are not specifically geared toward individuals with ASD. However, few studies have looked at the effectiveness of standard psychotherapeutic care in adults with ASD. This study aimed to discover how individuals with ASD fare in psychotherapy within a college counseling setting, compared to their neurotypical peers. Clients with ASD (n = 76) or possible ASD (n = 91) were retrospectively identified from counseling center case notes. Data from the Outcome Questionnaire-45 (OQ) were retrieved for each therapy session as a measure of client distress. Clients with ASD showed no difference in level of distress at intake compared to their neurotypical peers (n = 21,546), and improved about the same amount from pre- to post-treatment. However, students with ASD stayed in treatment for significantly more sessions than neurotypical clients, and took significantly longer to achieve maximum improvement on OQ reports. Results are discussed with implications for university and other community based treatment settings. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study aimed to discover how individuals with autism spectrum disorders (ASD) fare in psychotherapy within a university counseling setting, compared to their neurotypical peers. Clients with ASD showed no difference in level of distress at intake compared to their neurotypical peers, and improved about the same amount from pre- to post-treatment. However, students with ASD stayed in treatment for significantly more sessions than neurotypical clients, and took significantly longer to achieve maximum improvement on Outcome Questionnaire-45 reports.
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2. Boutrus M, Maybery MT, Alvares GA, Tan DW, Varcin KJ, Whitehouse AJO. {{Investigating facial phenotype in autism spectrum conditions: The importance of a hypothesis driven approach}}. {Autism Res};2017 (Aug 17)
Atypical facial characteristics have been observed in many disorders associated with developmental disability. While autism spectrum conditions (ASC) have not previously been thought to be associated with a distinct facial phenotype, an emerging research literature is casting doubt on this assumption. The identification of differences in the facial phenotype of individuals with ASC may contribute to efforts to promote early identification of the condition and help elucidate etiological pathways. With the aim of identifying facial phenotypes associated with ASC, this commentary evaluated facial features purported to distinguish ASC from typical development. Although there is little consensus across the reviewed studies for the majority of facial characteristics described, preliminary evidence suggests increased facial asymmetry may be more common in ASC. There is also evidence to suggest that there are morphologically distinct subgroups within ASC that correspond with different cognitive and behavioral symptomatology. However, in light of the various inconsistencies in the reported literature, and based on an accumulating understanding of etiological pathways proposed to be associated with ASC, we propose an alternative paradigm for investigating facial phenotypes in ASC. A series of studies are outlined to demonstrate the promise of a research program that has taken a hypothesis-driven approach to examine facial phenotypes associated with increased exposure to prenatal testosterone and to ASC. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This commentary reviewed studies that found differences in the facial features of individuals with autism spectrum conditions (ASC) compared to typically developing individuals. While there is little agreement between studies, there is some support for asymmetrical facial features associated with ASC, and preliminary evidence that particular facial features relate to specific patterns of cognitive and behavioral symptoms. However, in light of inconsistencies between studies and based on accumulating understanding of etiological pathways, we propose an alternative approach to investigating facial differences in ASC.
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3. Hubbard DJ, Faso DJ, Assmann PF, Sasson NJ. {{Production and perception of emotional prosody by adults with autism spectrum disorder}}. {Autism Res};2017 (Aug 17)
This study examined production and perception of affective prosody by adults with autism spectrum disorder (ASD). Previous research has reported increased pitch variability in talkers with ASD compared to typically developing (TD) controls in grammatical speaking tasks (e.g., comparing interrogative vs. declarative sentences), but it is unclear whether this pattern extends to emotional speech. In this study, speech recordings in five emotion contexts (angry, happy, interested, sad, and neutral) were obtained from 15 adult males with ASD and 15 controls (Experiment 1), and were later presented to 52 listeners (22 with ASD) who were asked to identify the emotion expressed and rate the level of naturalness of the emotion in each recording (Experiment 2). Compared to the TD group, talkers with ASD produced phrases with greater intensity, longer durations, and increased pitch range for all emotions except neutral, suggesting that their greater pitch variability was specific to emotional contexts. When asked to identify emotion from speech, both groups of listeners were more accurate at identifying the emotion context from speech produced by ASD speakers compared to TD speakers, but rated ASD emotional speech as sounding less natural. Collectively, these results reveal differences in emotional speech production in talkers with ASD that provide an acoustic basis for reported perceptions of oddness in the speech presentation of adults with ASD. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study examined emotional speech communication produced and perceived by adults with autism spectrum disorder (ASD) and typically-developing (TD) controls. Compared to the TD group, talkers with ASD produced emotional phrases that were louder, longer, and more variable in pitch. Both ASD and TD listeners were more accurate at identifying emotion in speech produced by ASD speakers compared to TD speakers, but rated ASD emotional speech as sounding less natural.
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4. Li B, Sharma A, Meng J, Purushwalkam S, Gowen E. {{Applying machine learning to identify autistic adults using imitation: An exploratory study}}. {PLoS One};2017;12(8):e0182652.
Autism spectrum condition (ASC) is primarily diagnosed by behavioural symptoms including social, sensory and motor aspects. Although stereotyped, repetitive motor movements are considered during diagnosis, quantitative measures that identify kinematic characteristics in the movement patterns of autistic individuals are poorly studied, preventing advances in understanding the aetiology of motor impairment, or whether a wider range of motor characteristics could be used for diagnosis. The aim of this study was to investigate whether data-driven machine learning based methods could be used to address some fundamental problems with regard to identifying discriminative test conditions and kinematic parameters to classify between ASC and neurotypical controls. Data was based on a previous task where 16 ASC participants and 14 age, IQ matched controls observed then imitated a series of hand movements. 40 kinematic parameters extracted from eight imitation conditions were analysed using machine learning based methods. Two optimal imitation conditions and nine most significant kinematic parameters were identified and compared with some standard attribute evaluators. To our knowledge, this is the first attempt to apply machine learning to kinematic movement parameters measured during imitation of hand movements to investigate the identification of ASC. Although based on a small sample, the work demonstrates the feasibility of applying machine learning methods to analyse high-dimensional data and suggest the potential of machine learning for identifying kinematic biomarkers that could contribute to the diagnostic classification of autism.
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5. Mahmood U, Ahn S, Yang EJ, Choi M, Kim H, Regan P, Cho K, Kim HS. {{Dendritic Spine Anomalies and PTEN Alterations in a Mouse Model of VPA-induced Autism Spectrum Disorder}}. {Pharmacol Res};2017 (Aug 17)
Mounting evidence suggests that the etiology of autism spectrum disorders (ASDs) is profoundly influenced by exposure to environmental factors, although the precise molecular and cellular links remain ill-defined. In this study, we examined how exposure to valproic acid (VPA) during pregnancy is associated with an increased incidence of ASD. A mouse model was established by injecting VPA at embryonic day 13, and its behavioral phenotypes including impaired social interaction, increased repetitive behaviors and decreased nociception were observed at postnatal days 21-42. VPA-treated mice showed dysregulation of synaptic structure in cortical neurons, including a reduced proportion of filopodium-type and stubby spines and increased proportions of thin and mushroom-type spines, along with a decreased spine head size. We also found that VPA-treatment led to decreased expression of phosphate and tensin homolog (PTEN) and increased levels of p-AKT protein in the hippocampus and cortex. Our data suggest that there is a correlation between VPA exposure and dysregulation of PTEN with ASD-like behavioral and neuroanatomical changes, and this may be a potential mechanism of VPA-induced ASD.
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6. Na ES, De Jesus-Cortes H, Martinez-Rivera A, Kabir ZD, Wang J, Ramesh V, Onder Y, Rajadhyaksha AM, Monteggia LM, Pieper AA. {{D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome}}. {PLoS One};2017;12(8):e0183026.
Rett syndrome (RTT), a leading cause of intellectual disability in girls, is predominantly caused by mutations in the X-linked gene MECP2. Disruption of Mecp2 in mice recapitulates major features of RTT, including neurobehavioral abnormalities, which can be reversed by re-expression of normal Mecp2. Thus, there is reason to believe that RTT could be amenable to therapeutic intervention throughout the lifespan of patients after the onset of symptoms. A common feature underlying neuropsychiatric disorders, including RTT, is altered synaptic function in the brain. Here, we show that Mecp2tm1.1Jae/y mice display lower presynaptic function as assessed by paired pulse ratio, as well as decreased long term potentiation (LTP) at hippocampal Schaffer-collateral-CA1 synapses. Treatment of Mecp2tm1.1Jae/y mice with D-cycloserine (DCS), an FDA-approved analog of the amino acid D-alanine with antibiotic and glycinergic activity, corrected the presynaptic but not LTP deficit without affecting deficient hippocampal BDNF levels. DCS treatment did, however, partially restore lower BDNF levels in the brain stem and striatum. Thus, treatment with DCS may mitigate the severity of some of the neurobehavioral symptoms experienced by patients with Rett syndrome.
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7. Vita DJ, Broadie K. {{ESCRT-III Membrane Trafficking Misregulation Contributes To Fragile X Syndrome Synaptic Defects}}. {Sci Rep};2017 (Aug 17);7(1):8683.
The leading cause of heritable intellectual disability (ID) and autism spectrum disorders (ASD), Fragile X syndrome (FXS), is caused by loss of the mRNA-binding translational suppressor Fragile X Mental Retardation Protein (FMRP). In the Drosophila FXS disease model, we found FMRP binds shrub mRNA (human Chmp4) to repress Shrub expression, causing overexpression during the disease state early-use critical period. The FXS hallmark is synaptic overelaboration causing circuit hyperconnectivity. Testing innervation of a central brain learning/memory center, we found FMRP loss and Shrub overexpression similarly increase connectivity. The ESCRT-III core protein Shrub has a central role in endosome-to-multivesicular body membrane trafficking, with synaptic requirements resembling FMRP. Consistently, we found FMRP loss and Shrub overexpression similarly elevate endosomes and result in the arrested accumulation of enlarged intraluminal vesicles within synaptic boutons. Importantly, genetic correction of Shrub levels in the FXS model prevents synaptic membrane trafficking defects and strongly restores innervation. These results reveal a new molecular mechanism underpinning the FXS disease state.
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8. Youssef EA, Berry-Kravis E, Czech C, Hagerman RJ, Hessl D, Wong CY, Rabbia M, Deptula D, John A, Kinch R, Drewitt P, Lindemann L, Marcinowski M, Langland R, Horn C, Fontoura P, Santarelli L, Quiroz JA. {{Effect of the mGluR5-NAM Basimglurant on Behavior in Adolescents and Adults with Fragile X Syndrome in a Randomized, Double-Blind, Placebo-Controlled Trial: FragXis Phase 2 Results}}. {Neuropsychopharmacology};2017 (Aug 17)
Preclinical data suggests that inhibition of the mGluR5 receptor might hold therapeutic benefits in Fragile X syndrome (FXS). Treatment of Fmr1 knockout mice with mGluR5-negative allosteric modulators (NAMs) has been reported to correct a broad range of phenotypes related to FXS. The early short-term clinical trials with mGluR5 NAMs, including basimglurant, assessing the effects in individuals with FXS, were supportive of further exploration in larger, well-controlled trials. We evaluated basimglurant, a potent and selective mGluR5 NAM, in a 12-week, double-blind, parallel-group study of 183 adults and adolescents (aged 14-50, mean 23.4 years) with FXS. Individuals with an FMR1 full mutation were randomized to placebo or one of two doses of basimglurant. The primary efficacy endpoint was the change from baseline in behavioral symptoms using the Anxiety Depression and Mood Scale (ADAMS) total score. All treatment arms showed marked behavioral improvements from baseline to week 12 with less improvement in the basimglurant 1.5 mg arm than placebo; however, basimglurant 0.5 mg was inferior to placebo in the ADAMs total score. Treatment with basimglurant was overall well-tolerated. A higher incidence of adverse events classified as psychiatric disorders were reported in patients treated with basimglurant, including three patients with hallucinations or psychosis. In this phase 2 clinical trial, basimglurant did not demonstrate improvement over placebo. Evaluation of the overall risk-benefit in younger patient populations is an important consideration for the design of potential further investigations of efficacy with this class of medications.Neuropsychopharmacology accepted article preview online, 17 August 2017. doi:10.1038/npp.2017.177.
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9. Zeleke WA, Hughes T, Chitiyo M. {{The Path to an Autism Spectrum Disorders Diagnosis in Ethiopia: Parent Perspective}}. {Am J Orthopsychiatry};2017 (Aug 17)
This study explores the common characteristics of children with autism spectrum disorders (ASDs) and the available diagnostic and intervention currently practiced for children with ASDs in Ethiopia based on parents’ experience. Data gathered from 100 parents in Ethiopia detail the difficulties families face when they suspect their child has an autism spectrum disorder (ASD). The data indicate Ethiopian parents pursued a diagnosis of ASD after noting common ASD behaviors such as hand flapping and unusual attachments to objects. Poor social interactions were the least likely to symptoms to prompt an ASD evaluation. The large majority of parents indicated they were unaware of the services provided to their children and indicated poor parent-agency coordination. Parents noted very limited formal support systems to help cope with the stigma of having a child with ASD. Implication for future research and intervention are discussed. (PsycINFO Database Record
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10. Zou Y, Lu Q, Zheng D, Chu Z, Liu Z, Chen H, Ruan Q, Ge X, Zhang Z, Wang X, Lou W, Huang Y, Wang Y, Huang X, Liu Z, Xie W, Zhou Y, Yao P. {{Prenatal levonorgestrel exposure induces autism-like behavior in offspring through ERbeta suppression in the amygdala}}. {Mol Autism};2017;8:46.
BACKGROUND: Autism spectrum disorder (ASD) is characterized by impairments in social communication and restricted or repetitive behaviors or interests. ASD is now diagnosed in more than one out of 100 children and is biased towards males by a ratio of at least 4:1. Many possible explanations and potential causative factors have been reported, such as genetics, sex, and environmental factors, although the detailed mechanisms of ASD remain unclear. METHODS: The dams were exposed through oral contraceptives to either vehicle control (VEH) alone, levonorgestrel (LNG) alone, ethinyl estradiol (EE) alone, or a combination of LNG/EE for 21 days during their pregnancy. The subsequent 10-week-old offspring were used for autism-like behavior testing, and the limbic tissues were isolated for analysis. In another experimental group, 8-week-old male offspring were treated by infusion of ERbeta overexpression/knockdown lentivirus in the amygdala, and the offspring were analyzed after 2 weeks. RESULTS: We show that prenatal exposure of either LNG alone or a LNG/EE combination, but not EE alone, results in suppression of ERbeta (estrogen receptor beta) and its target genes in the amygdala with autism-like behavior in male offspring, while there is a much smaller effect on female offspring. However, we find that there is no effect on the hippocampus and hypothalamus. Further investigation shows that ERbeta suppression is due to LNG-mediated altered methylation on the ERbeta promoter and results in tissue damage with oxidative stress and the dysfunction of mitochondria and fatty acid metabolism, which subsequently triggers autism-like behavior. Overexpression of ERbeta in the amygdala completely restores LNG-induced ERbeta suppression and autism-like behaviors in offspring, while ERbeta knockdown mimics this effect, indicating that ERbeta expression in the amygdala plays an important role in autism-like behavior development. CONCLUSIONS: We conclude that prenatal levonorgestrel exposure induces autism-like behavior in offspring through ERbeta suppression in the amygdala. To our knowledge, this is the first time the potential effect of oral contraceptives on the contribution of autism-like behavior in offspring has been discovered.
