1. Bal VH, Kim SH, Cheong D, Lord C. {{Daily living skills in individuals with autism spectrum disorder from 2 to 21 years of age}}. {Autism};2015 (Apr 28)
Daily living skills (DLS), such as personal hygiene, meal preparation, and money management, are important to independent living. Research suggests that many individuals with autism spectrum disorder exhibit impairments in daily living skills relative to their cognitive skills. This study examined predictors of daily living skills attainment and trajectories of daily living skills in a longitudinal sample referred for possible autism spectrum disorder and followed from 2 to 21 years of age. Consistent with previous studies, participants with autism spectrum disorder and nonspectrum diagnoses showed continual development of daily living skills throughout childhood and adolescence. Early childhood nonverbal mental age was the strongest predictor of daily living skills attainment for both diagnostic groups. Group-based modeling suggested two distinct trajectories of daily living skills development for participants with autism spectrum disorder. Skill levels for both groups of young adults with autism spectrum disorder remained considerably below age level expectations. Whereas the « High-DLS » group gained approximately 12 years in daily living skills from T2 to T21, the « Low-DLS » group’s daily living skills improved 3-4 years over the 16- to 19-year study period. Nonverbal mental age, receptive language, and social-communication impairment at 2 years predicted High- versus Low-DLS group membership. Receiving greater than 20 h of parent-implemented intervention before age 3 was also associated with daily living skills trajectory. Results suggest that daily living skills should be a focus of treatment plans for individuals with autism spectrum disorder, particularly adolescents transitioning to young adulthood.
Lien vers le texte intégral (Open Access ou abonnement)
2. Chen L, Chen K, Lavery LA, Baker SA, Shaw CA, Li W, Zoghbi HY. {{MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome}}. {Proc Natl Acad Sci U S A};2015 (Apr 28);112(17):5509-5514.
Epigenetic mechanisms, such as DNA methylation, regulate transcriptional programs to afford the genome flexibility in responding to developmental and environmental cues in health and disease. A prime example involving epigenetic dysfunction is the postnatal neurodevelopmental disorder Rett syndrome (RTT), which is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2). Despite decades of research, it remains unclear how MeCP2 regulates transcription or why RTT features appear 6-18 months after birth. Here we report integrated analyses of genomic binding of MeCP2, gene-expression data, and patterns of DNA methylation. In addition to the expected high-affinity binding to methylated cytosine in the CG context (mCG), we find a distinct epigenetic pattern of substantial MeCP2 binding to methylated cytosine in the non-CG context (mCH, where H = A, C, or T) in the adult brain. Unexpectedly, we discovered that genes that acquire elevated mCH after birth become preferentially misregulated in mouse models of MeCP2 disorders, suggesting that MeCP2 binding at mCH loci is key for regulating neuronal gene expression in vivo. This pattern is unique to the maturing and adult nervous system, as it requires the increase in mCH after birth to guide differential MeCP2 binding among mCG, mCH, and nonmethylated DNA elements. Notably, MeCP2 binds mCH with higher affinity than nonmethylated identical DNA sequences to influence the level of Bdnf, a gene implicated in the pathophysiology of RTT. This study thus provides insight into the molecular mechanism governing MeCP2 targeting and sheds light on the delayed onset of RTT symptoms.
Lien vers le texte intégral (Open Access ou abonnement)
3. Cochran DM, Sikoglu EM, Hodge SM, Edden RA, Foley A, Kennedy DN, Moore CM, Frazier JA. {{Relationship Among Glutamine, gamma-Aminobutyric Acid, and Social Cognition In Autism Spectrum Disorders}}. {J Child Adolesc Psychopharmacol};2015 (Apr 28)
OBJECTIVE: An imbalance of excitatory and inhibitory neurotransmission in autism spectrum disorder (ASD) has been proposed. We compared glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) of 13 males with ASD and 14 typically developing (TD) males (ages 13-17), and correlated these levels with intelligence quotient (IQ) and measures of social cognition. METHODS: Social cognition was evaluated by administration of the Social Responsiveness Scale (SRS) and the Reading the Mind in the Eyes Test (RMET). We acquired proton magnetic resonance spectroscopy (1H-MRS) data from the bilateral ACC using the single voxel point resolved spectroscopy sequence (PRESS) to quantify Glu and Gln, and Mescher-Garwood point-resolved spectroscopy sequence (MEGA-PRESS) to quantify GABA levels referenced to creatine (Cr). RESULTS: There were higher Gln levels (p=0.04), and lower GABA/Cre levels (p=0.09) in the ASD group than in the TD group. There was no difference in Glu levels between groups. Gln was negatively correlated with RMET score (rho=-0.62, p=0.001) and IQ (rho=-0.56, p=0.003), and positively correlated with SRS scores (rho=0.53, p=0.007). GABA/Cre levels were positively correlated with RMET score (rho=0.34, p=0.09) and IQ (rho=0.36, p=0.07), and negatively correlated with SRS score (rho=-0.34, p=0.09). CONCLUSIONS: These data suggest an imbalance between glutamatergic neurotransmission and GABA-ergic neurotransmission in ASD. Higher Gln levels and lower GABA/Cre levels were associated with lower IQ and greater impairments in social cognition across groups.
Lien vers le texte intégral (Open Access ou abonnement)
4. Dubin AH, Lieberman-Betz R, Michele Lease A. {{Investigation of Individual Factors Associated with Anxiety in Youth with Autism Spectrum Disorders}}. {J Autism Dev Disord};2015 (Apr 28)
As youth with autism spectrum disorder (ASD) are more likely to experience anxiety than youth in the general population, investigation of associated factors is important for diagnosis and treatment. The present study extended prior research by examining factors associated with caregiver-reported anxiety in 2662 youth (mean age = 8.82 years) with ASD. Logistic regression analyses indicated increases in age, social problems, and cognitive functioning predicted high anxiety group membership. Cognitive functioning moderated the relation of adaptive social behaviors and anxiety. Results from the present study provide support for previously identified factors associated with anxiety; however, further investigation is necessary to uncover additional factors and to explore their relation to anxiety across individuals with ASD with varying levels of cognitive functioning.
Lien vers le texte intégral (Open Access ou abonnement)
5. Duda M, Kosmicki JA, Wall DP. {{Testing the accuracy of an observation-based classifier for rapid detection of autism risk}}. {Transl Psychiatry};2015;5:e556.
Lien vers le texte intégral (Open Access ou abonnement)
6. Hagen E, Shprung D, Minakova E, Washington J, 3rd, Kumar U, Shin D, Sankar R, Mazarati A. {{Autism-Like Behavior in BTBR Mice Is Improved by Electroconvulsive Therapy}}. {Neurotherapeutics};2015 (Apr 28)
Autism is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. Incidence of autism is higher than earlier estimates, and treatments have limited efficacy and are costly. Limited clinical and experimental evidence suggest that patients with autism may benefit from electroconvulsive therapy (ECT). We examined the therapeutic potential of ECT in BTBR T+ tf/j mice, which represent a validated model of autism. A series of 13 electroconvulsive shocks (ECS) delivered twice a day over 7 days reversed core autism-like behavioral abnormalities-impaired sociability, social novelty, and repetitive behavior-when the animals were tested 24 h after the last ECS. The effect lasted up to 2 weeks after ECT. Neither single ECS nor a series of 6 ECS modified animals’ behavior. Chronic infusion into the lateral brain ventricle of a preferential oxytocin receptor blocker (2S)-2-Amino-N-[(1S,2S,4R)-7,7-dimethyl-1-[[[4-(2-methylphenyl)-1-piperazinyl]sul fonyl]methyl]bicyclo[2.2.1]hept-2-yl]-4-(methylsulfonyl)butanamide hydrochloride abolished ECT-induced improvement of sociability and mitigated improvement of social novelty but did not affect ECT-induced reversal of repetitive behavior. These proof-of-principle experiments suggest that ECT may, indeed, be useful in the treatment of autism, and that its therapeutic effects may be mediated, in part, by central oxytocin signaling.
Lien vers le texte intégral (Open Access ou abonnement)
7. Harfterkamp M, van der Meer D, van der Loo-Neus G, Buitelaar JK, Minderaa RB, Hoekstra PJ. {{No Evidence for Predictors of Response to Atomoxetine Treatment of Attention-Deficit/Hyperactivity Disorder Symptoms in Children and Adolescents with Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol};2015 (Apr 28)
Lien vers le texte intégral (Open Access ou abonnement)
8. Logan SL, Carpenter L, Leslie RS, Garrett-Mayer E, Hunt KJ, Charles J, Nicholas JS. {{Aberrant Behaviors and Co-occurring Conditions as Predictors of Psychotropic Polypharmacy among Children with Autism Spectrum Disorders}}. {J Child Adolesc Psychopharmacol};2015 (Apr 28)
OBJECTIVES: The purpose of this study was to identify rates and predictors of psychotropic medication polypharmacy among Medicaid-eligible children in South Carolina with autism spectrum disorder (ASD) from 2000 to 2008. METHODS: Population-based surveillance data were linked with state Medicaid records to obtain a detailed demographic, behavioral, educational, clinical, and diagnostic data set for all Medicaid-eligible 8-year-old children (n=629) who were identified and diagnosed with ASD using standardized criteria. Polypharmacy was defined as having interclass psychotropic medication claims overlapping for >/=30 consecutive days at any time during the 2-year study period. Multivariable logistic regression was used to model predictors of any polypharmacy, and for the three most common combinations. RESULTS: Overall, 60% (n=377) used any psychotropic medication, and 41% (n=153) of those had interclass polypharmacy. Common combinations were attention-deficit/hyperactivity disorder (ADHD) medications with an antidepressant (A/AD), antipsychotic (A/AP) or a mood stabilizer (A/MS). Black children had lower odds of any polypharmacy, as did those eligible for Medicaid because of income or being foster care versus those eligible because of disability. There were no significant associations between polypharmacy and social deficits in ASD for any combination, although children with communication deficits diagnostic of ASD had lower odds of any polypharmacy and A/AP polypharmacy. Children with argumentative, aggressive, hyperactive/impulsive, or self-injurious aberrant behaviors had higher odds of polypharmacy, as did children with diagnosed co-occurring ADHD, anxiety or mood disorders, or conduct/oppositional defiant disorder (ODD) in Medicaid records. CONCLUSIONS: Future research is warranted to investigate how child-level factors impact combination psychotropic medication prescribing practices and outcomes in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
9. Lundstrom S, Reichenberg A, Anckarsater H, Lichtenstein P, Gillberg C. {{Autism phenotype versus registered diagnosis in Swedish children: prevalence trends over 10 years in general population samples}}. {BMJ};2015;350:h1961.
OBJECTIVE: To compare the annual prevalence of the autism symptom phenotype and of registered diagnoses for autism spectrum disorder during a 10 year period in children. DESIGN: Population based study. SETTING: Child and Adolescent Twin Study and national patient register, Sweden. PARTICIPANTS: 19 993 twins (190 with autism spectrum disorder) and all children (n=1 078 975; 4620 with autism spectrum disorder) born in Sweden over a 10 year period from 1993 to 2002. MAIN OUTCOME MEASURES: Annual prevalence of the autism symptom phenotype (that is, symptoms on which the diagnostic criteria are based) assessed by a validated parental telephone interview (the Autism-Tics, ADHD and other Comorbidities inventory), and annual prevalence of reported diagnoses of autism spectrum disorder in the national patient register. RESULTS: The annual prevalence of the autism symptom phenotype was stable during the 10 year period (P=0.87 for linear time trend). In contrast, there was a monotonic significant increase in prevalence of registered diagnoses of autism spectrum disorder in the national patient register (P<0.001 for linear trend). CONCLUSIONS: The prevalence of the autism symptom phenotype has remained stable in children in Sweden while the official prevalence for registered, clinically diagnosed, autism spectrum disorder has increased substantially. This suggests that administrative changes, affecting the registered prevalence, rather than secular factors affecting the pathogenesis, are important for the increase in reported prevalence of autism spectrum disorder.
Lien vers le texte intégral (Open Access ou abonnement)
10. Must A, Phillips S, Curtin C, Bandini LG. {{Barriers to Physical Activity in Children With Autism Spectrum Disorders: Relationship to Physical Activity and Screen Time}}. {J Phys Act Health};2015 (Apr 28)
BACKGROUND: Individual, social, and community barriers to physical activity (PA) experienced by children with autism spectrum disorder (ASD) make PA participation more difficult and may contribute to increased screen time. METHODS: We compared the prevalence of parent-reported barriers to PA among 58 typically developing (TD) children and 53 children with an ASD, 3-11 years, and assessed the association between barriers and PA participation and screen time among children with ASD. RESULTS: Parents of children with ASD reported significantly more barriers than parents of TD children. Based on parent-report, 60% of children with ASD required too much supervision compared to no TD children (p<0.001). Parents of children with ASD were more likely to report that adults lack skills needed to include their child (58%), that their child has few friends (45%), and that other children exclude their child (23%). The number of parent-reported barriers to PA was inversely correlated with the hours spent in PA per year (r=-0.27, p=0.05) and positively related to total screen time (r=0.32, p<0.03). CONCLUSIONS: These findings underscore the need for community-based PA programs designed to meet the special requirements of this population and policies that compel schools and other government-supported organizations for inclusion and/or targeted programming.
Lien vers le texte intégral (Open Access ou abonnement)
11. Palmer CJ, Seth AK, Hohwy J. {{The felt presence of other minds: Predictive processing, counterfactual predictions, and mentalising in autism}}. {Conscious Cogn};2015 (Apr 28)
The mental states of other people are components of the external world that modulate the activity of our sensory epithelia. Recent probabilistic frameworks that cast perception as unconscious inference on the external causes of sensory input can thus be expanded to enfold the brain’s representation of others’ mental states. This paper examines this subject in the context of the debate concerning the extent to which we have perceptual awareness of other minds. In particular, we suggest that the notion of perceptual presence helps to refine this debate: are others’ mental states experienced as veridical qualities of the perceptual world around us? This experiential aspect of social cognition may be central to conditions such as autism spectrum disorder, where representations of others’ mental states seem to be selectively compromised. Importantly, recent work ties perceptual presence to the counterfactual predictions of hierarchical generative models that are suggested to perform unconscious inference in the brain. This enables a characterisation of mental state representations in terms of their associated counterfactual predictions, allowing a distinction between spontaneous and explicit forms of mentalising within the framework of predictive processing. This leads to a hypothesis that social cognition in autism spectrum disorder is characterised by a diminished set of counterfactual predictions and the reduced perceptual presence of others’ mental states.
Lien vers le texte intégral (Open Access ou abonnement)
12. Tilot AK, Frazier TW, 2nd, Eng C. {{Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder}}. {Neurotherapeutics};2015 (Apr 28)
Germline mutations in PTEN, which encodes a widely expressed phosphatase, was mapped to 10q23 and identified as the susceptibility gene for Cowden syndrome, characterized by macrocephaly and high risks of breast, thyroid, and other cancers. The phenotypic spectrum of PTEN mutations expanded to include autism with macrocephaly only 10 years ago. Neurological studies of patients with PTEN-associated autism spectrum disorder (ASD) show increases in cortical white matter and a distinctive cognitive profile, including delayed language development with poor working memory and processing speed. Once a germline PTEN mutation is found, and a diagnosis of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome made, the clinical outlook broadens to include higher lifetime risks for multiple cancers, beginning in childhood with thyroid cancer. First described as a tumor suppressor, PTEN is a major negative regulator of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling pathway-controlling growth, protein synthesis, and proliferation. This canonical function combines with less well-understood mechanisms to influence synaptic plasticity and neuronal cytoarchitecture. Several excellent mouse models of Pten loss or dysfunction link these neural functions to autism-like behavioral abnormalities, such as altered sociability, repetitive behaviors, and phenotypes like anxiety that are often associated with ASD in humans. These models also show the promise of mTOR inhibitors as therapeutic agents capable of reversing phenotypes ranging from overgrowth to low social behavior. Based on these findings, therapeutic options for patients with PTEN hamartoma tumor syndrome and ASD are coming into view, even as new discoveries in PTEN biology add complexity to our understanding of this master regulator.
