1. Agostoni C, Nobile M, Ciappolino V, Delvecchio G, Tesei A, Turolo S, Crippa A, Mazzocchi A, Altamura CA, Brambilla P. {{The Role of Omega-3 Fatty Acids in Developmental Psychopathology: A Systematic Review on Early Psychosis, Autism, and ADHD}}. {Int J Mol Sci};2017 (Dec 4);18(12)
In this systematic review, we will consider and debate studies that have explored the effects of omega-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of omega-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far.
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2. Ali Z, Zulfiqar S, Klar J, Wikstrom J, Ullah F, Khan A, Abdullah U, Baig S, Dahl N. {{Homozygous GRID2 missense mutation predicts a shift in the D-serine binding domain of GluD2 in a case with generalized brain atrophy and unusual clinical features}}. {BMC Med Genet};2017 (Dec 6);18(1):144.
BACKGROUND: Spinocerebellar ataxias comprise a large and heterogeneous group of disorders that may present with isolated ataxia, or ataxia in combination with other neurologic or non-neurologic symptoms. Monoallelic or biallelic GRID2 mutations were recently reported in rare cases with cerebellar syndrome and variable degree of ataxia, ocular symptoms, hypotonia and developmental delay. CASE PRESENTATION: We report on a consanguineous family with autosomal recessive childhood onset of slowly progressive cerebellar ataxia and delayed psychomotor development in three siblings. MRI of an adult and affected family member revealed slightly widened cerebral and cerebellar sulci, suggesting generalized brain atrophy, and mild cerebellar atrophy. Using whole exome sequencing we identified a novel homozygous missense variant [c.2128C > T, p.(Arg710Trp)] in GRID2 that segregates with the disease. The missense variant is located in a conserved region encoding the extracellular serine-binding domain of the GluD2 protein and predicts a change in conformation of the protein. CONCLUSION: The widespread supratentorial brain abnormalities, absence of oculomotor symptoms, increased peripheral muscle tone and the novel missense mutation add to the clinical and genetic variability in GRID2 associated cerebellar syndrome. The neuroradiological findings in our family indicate a generalized neurodegenerative process to be taken into account in other families segregating complex clinical features and GRID2 mutations.
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3. Bjornsdotter M, Davidovic M, Karjalainen L, Starck G, Olausson H, Wentz E. {{Grey matter correlates of autistic traits in women with anorexia nervosa}}. {J Psychiatry Neurosci};2017 (Dec 7);43(1):1-8.
Background: Patients with anorexia nervosa exhibit higher levels of behaviours typically associated with autism-spectrum disorder (ASD), but the neural basis is unclear. We sought to determine whether elevated autistic traits in women with anorexia nervosa may be reflected in cortical morphology. Methods: We used voxel-based morphometry (VBM) to examine regional grey matter volumes in high-resolution MRI structural brain scans in women with anorexia nervosa and matched healthy controls. The Autism-spectrum Quotient (AQ) scale was used to assess autistic traits. Results: Women with anorexia nervosa (n = 25) had higher AQ scores and lower bilateral superior temporal sulcus (STS) grey matter volumes than the control group (n = 25). The AQ scores correlated negatively with average left STS grey matter volume in women with anorexia nervosa. Limitations: We did not control for cognitive ability and examined only women with ongoing anorexia nervosa. Conclusion: Elevated autistic traits in women with anorexia nervosa are associated with morphometric alterations of brain areas linked to social cognition. This finding provides neurobiological support for the behavioural link between anorexia nervosa and ASD and emphasizes the importance of recognizing autistic traits in preventing and treating -anorexia nervosa.
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4. Chretien B, Bourgine J, Hamel Senecal L, Bretaudeau-Deguigne M, Boels D, Lelong-Boulouard V, Le Boisselier R. {{Severe Serotonin Syndrome in an Autistic New Psychoactive Substance User After Consumption of Pills Containing Methoxphenidine and alpha-Methyltryptamine}}. {J Clin Psychopharmacol};2018 (Feb);38(1):94-96.
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5. Deshpande A, Yadav S, Dao DQ, Wu ZY, Hokanson KC, Cahill MK, Wiita AP, Jan YN, Ullian EM, Weiss LA. {{Cellular Phenotypes in Human iPSC-Derived Neurons from a Genetic Model of Autism Spectrum Disorder}}. {Cell Rep};2017 (Dec 5);21(10):2678-2687.
A deletion or duplication in the 16p11.2 region is associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. In addition to clinical characteristics, carriers of the 16p11.2 copy-number variant (CNV) manifest opposing neuroanatomical phenotypes-e.g., macrocephaly in deletion carriers (16pdel) and microcephaly in duplication carriers (16pdup). Using fibroblasts obtained from 16pdel and 16pdup carriers, we generated induced pluripotent stem cells (iPSCs) and differentiated them into neurons to identify causal cellular mechanisms underlying neurobiological phenotypes. Our study revealed increased soma size and dendrite length in 16pdel neurons and reduced neuronal size and dendrite length in 16pdup neurons. The functional properties of iPSC-derived neurons corroborated aspects of these contrasting morphological differences that may underlie brain size. Interestingly, both 16pdel and 16pdup neurons displayed reduced synaptic density, suggesting that distinct mechanisms may underlie brain size and neuronal connectivity at this locus.
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6. Dolskiy AA, Pustylnyak VO, Yarushkin AA, Lemskaya NA, Yudkin DV. {{Inhibitors of Histone Deacetylases Are Weak Activators of the FMR1 Gene in Fragile X Syndrome Cell Lines}}. {Biomed Res Int};2017;2017:3582601.
Fragile X syndrome is the most common cause of inherited intellectual disability in humans. It is a result of CGG repeat expansion in the 5′ untranslated region (5′ UTR) of the FMR1 gene. This gene encodes the FMRP protein that is involved in neuronal development. Repeat expansion leads to heterochromatinization of the promoter, gene silencing, and the subsequent absence of FMRP. To date, there is no specific therapy for the syndrome. All treatments in clinic practice provide symptomatic therapy. The development of drug therapy for Fragile X syndrome treatment is connected with the search for inhibitors of enzymes that are responsible for heterochromatinization. Here, we report a weak transcriptional activity of the FMR1 gene and the absence of FMRP protein after Fragile X syndrome cell lines treatment with two FDA approved inhibitors of histone deacetylases, romidepsin and vorinostat. We demonstrate that romidepsin, an inhibitor of class I histone deacetylases, does not activate FMR1 expression in patient cell cultures, whereas vorinostat, an inhibitor of classes I and II histone deacetylases, activates a low level of FMR1 expression in some patient cell lines.
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7. Fukuyama H, Kumagaya SI, Asada K, Ayaya S, Kato M. {{Publisher Correction: Autonomic versus perceptual accounts for tactile hypersensitivity in autism spectrum disorder}}. {Sci Rep};2017 (Dec 5);7(1):17276.
A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
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8. Gilbert J, Man HY. {{Fundamental Elements in Autism: From Neurogenesis and Neurite Growth to Synaptic Plasticity}}. {Front Cell Neurosci};2017;11:359.
Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders with a high prevalence and impact on society. ASDs are characterized by deficits in both social behavior and cognitive function. There is a strong genetic basis underlying ASDs that is highly heterogeneous; however, multiple studies have highlighted the involvement of key processes, including neurogenesis, neurite growth, synaptogenesis and synaptic plasticity in the pathophysiology of neurodevelopmental disorders. In this review article, we focus on the major genes and signaling pathways implicated in ASD and discuss the cellular, molecular and functional studies that have shed light on common dysregulated pathways using in vitro, in vivo and human evidence. Highlights Autism spectrum disorder (ASD) has a prevalence of 1 in 68 children in the United States.ASDs are highly heterogeneous in their genetic basis.ASDs share common features at the cellular and molecular levels in the brain.Most ASD genes are implicated in neurogenesis, structural maturation, synaptogenesis and function.
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9. Kim SA, Kim BN, Kim JW, Shin MS, Park TW, Son JW, Chung US, Park M. {{Polymorphism in the Promoter Region of SEMA5A Is Associated with Sociality Traits in Korean Subjects with Autism Spectrum Disorders}}. {Psychiatry Investig};2017 (Nov);14(6):876-878.
In this study, we evaluated the association between autism spectrum disorders (ASDs) and 10 single-nucleotide polymorphisms (SNPs) in the 5′ region of the semaphorin 5A gene (SEMA5A) for 250 Korean trios including children with ASDs. Family-based association testing and haplotype analysis revealed a statistically significant association between rs194085 and multiple sociality traits with Korean ASDs in the dominant model (p<0.001, corrected p=0.035). This indicates that genetic variations in the 5' region of SEMA5A play a role in the genetic predisposition to sociality traits in Korean ASDs. Lien vers le texte intégral (Open Access ou abonnement)
10. Kramer JM, Hwang IT, Levin M, Acevedo-Garcia D, Rosenfeld L. {{Identifying environmental barriers to participation: Usability of a health-literacy informed problem-identification approach for parents of young children with developmental disabilities}}. {Child Care Health Dev};2017 (Dec 7)
BACKGROUND: Parents of very young children recently diagnosed with developmental disabilities (DD) need to identify environmental barriers to their children’s participation and adopt an adaptive orientation to solving these problems. Given the health service disparities for diverse families, parents may benefit from easy to use problem-identification approaches that address environmental barriers stemming from community and policy contexts. This feasibility study evaluated the usability of a health literacy-informed, structured, environment-focused problem-identification approach for parents of young children with DD. METHODS: We used purposeful, convenience sampling to enrol 9 mothers of children ages 1-3 with DD (4 racial/ethnic minorities, 3 high school education, 4 annual household income <$20,000). We developed a structured problem-identification approach guided by a social ecological model featuring home, community, and policy contexts. The approach was applied to 3 short stories during a narrative elicitation interview. Two researchers independently coded parent responses for the type of barrier and solution identified with and without the approach. RESULTS: Parents identified 121 environmental barriers without the approach. When using the approach and prompted to consider home, community, and policy barriers, parents identified an additional 222 environmental barriers; the greatest number of barriers were aligned with International Classification of Functioning, Disability, and Health-Children and Youth environment Chapter 5 "Services, systems, and policies." Using the approach, parents with a postgraduate education and annual household income >$80,000 identified the most environmental barriers, and parents reporting the lowest annual household incomes identified the fewest environmental barriers. When parents attributed participation challenges to an environmental barrier, ~57% of solutions required parents to interact with individuals at the community or policy level. CONCLUSIONS: This study suggests that parents with a range of background characteristics can use a structured, environment-focused problem-identification approach. With the approach, parents are more likely to attribute participation challenges to environmental barriers and adopt a problem-solving orientation focused on changes to the community and policy context. Key Messages In this study, the structured, environment-focused problem-identification approach led parents to identify additional environmental barriers, particularly policy barriers, which they did not consider during independent problem identification. Parents with previous exposure to professionals who helped identify and resolve environmental barriers to their children’s participation may most benefit from the structured, environment-focused problem-identification approach. Parents’ ability to attribute participation restrictions to environmental barriers is linked to parents’ orientation to solving participation challenges using community and policy level solutions.
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11. Larson FV, Arrand JR, Tantam D, Jones PB, Holland AJ. {{Copy number variants in people with autism spectrum disorders and co-morbid psychosis}}. {Eur J Med Genet};2017 (Dec 7)
The genetic association between autism spectrum disorder (ASD) and psychotic disorders such as schizophrenia is complicated and mirrors the clinical overlap between these conditions to some degree. However, no studies to date have examined the genetics of individuals dually diagnosed with both ASD and psychosis. In this study, we present findings of copy number variants (CNVs) from a study of 116 well-characterised individuals with this dual diagnosis. DNA was extracted and arrayed using the Affymetrix CytoScan HD 2.8M array or the Affymetrix Cytogenetics arrays and compared with existing samples from the Database of Genomic Variants and the Simons Simplex Collection of CNVs from individuals with ASD and their families. Twenty-seven novel CNVs >/=20k base pairs were identified in the sample, most occurring in only a single individual, although two were found in two female participants. Forty-nine rare CNVs (<1.5% rate in general population) were also found at significantly higher frequencies than expected. The findings may provide evidence for areas of further study in the understanding of the development of both ASD and psychosis due to the number of affected genetic regions that have not previously been linked to these conditions. Lien vers le texte intégral (Open Access ou abonnement)
12. Martin L, McKenzie K, Ouellette-Kuntz H. {{Once frail, always frail? Frailty transitions in home care users with intellectual and developmental disabilities}}. {Geriatr Gerontol Int};2017 (Dec 7)
AIM: Frailty is understood as a dynamic non-linear process, and used to indicate age-related decline. Recent work has shown that adults with intellectual and developmental disabilities experience higher rates of frailty at much earlier ages than the general population. The present study describes transitions in frailty status (i.e. non-frail, pre-frail, frail) over 1 year, and explores the association between baseline frailty status and worsening/death over time. METHODS: Results are based on secondary analysis of 2893 individuals with intellectual and developmental disabilities receiving community-based home care services in Ontario (Canada). Frailty status is based on a validated 42-item frailty index (FI); where FI 0.30 indicates frail. Baseline characteristics of frailty groups at baseline were compared using the chi(2) -test/analysis of variance. Relative risk of worsening/dying was calculated using a modified Poisson regression model. RESULTS: Initially, 67.0% of participants were non-frail, 16.2% were pre-frail and 16.8% were frail. Of those non-frail at baseline, 84.3% remained non-frail, 11.8% worsened and 3.9% died. Among those initially pre-frail, 37.0% remained stable, 35.3% improved, 18.2% worsened and 9.6% died. Although similar proportions of frail individuals improved (37.4%) or remained stable (36.8%), 25.9% had died. After controlling for other factors, being pre-frail at baseline was associated with an increase in the risk of worsening or death (RR 1.24, 95% CI 1.04-1.49). CONCLUSIONS: While many experience worsening of frailty status, stability and improvement are viable goals of care. Future research should examine the rate at which non-frail, pre-frail and frail individuals accumulate deficits, as well as the impact of home care services on frailty. Geriatr Gerontol Int 2017; **: **-**.
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13. Metcalfe SA, Delatycki MB, Cohen J, Archibald AD, Emery JD. {{Fragile X population carrier screening}}. {Genet Med};2017 (Dec 7)
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14. Mo W, Liu J, Zhang Z, Yu H, Yang A, Qu F, Hu P, Liu Z, Hu F. {{A study of single nucleotide polymorphisms in CD157, AIM2 and JARID2 genes in Han Chinese children with autism spectrum disorder}}. {Nord J Psychiatry};2017 (Dec 7):1-5.
PURPOSE: Autism spectrum disorder (ASD) is a group of developmental brain disorders caused by genetic and environmental factors. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) in genes related to immune function were associated with ASD in Chinese Han children. MATERIALS AND METHODS: A total of 201 children with ASD and 200 age- and gender-matched healthy controls were recruited from September 2012 to June 2106. A TaqMan probe-based approach was used to genotype SNPs corresponding to rs28532698 and rs4301112 in CD157, rs855867 in AIM2, and rs2237126 in JARID2. Case-control and case-only studies were performed to determine the contribution of SNPs to the predisposition of disease and its severity, respectively. RESULTS: Our results revealed that the genotypes and allele frequencies of these SNPs were not significantly associated with childhood ASD and its severity in this population. CONCLUSIONS: Results of our study suggest that these SNPs are not predictors of childhood ASD in the Chinese Han population. The discrepant results suggest the predictor roles of SNPs have to be determined in different ethnic populations due to genetic heterogeneity of ASD.
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15. Olliac B, Crespin G, Laznik MC, Cherif Idrissi El Ganouni O, Sarradet JL, Bauby C, Dandres AM, Ruiz E, Bursztejn C, Xavier J, Falissard B, Bodeau N, Cohen D, Saint-Georges C. {{Infant and dyadic assessment in early community-based screening for autism spectrum disorder with the PREAUT grid}}. {PLoS One};2017;12(12):e0188831.
BACKGROUND: The need for early treatment of autism spectrum disorders (ASD) necessitates early screening. Very few tools have been prospectively tested with infants of less than 12 months of age. The PREAUT grid is based on dyadic assessment through interaction and shared emotion and showed good metrics for predicting ASD in very-high-risk infants with West syndrome. METHODS: We assessed the ability of the PREAUT grid to predict ASD in low-risk individuals by prospectively following and screening 12,179 infants with the PREAUT grid at four (PREAUT-4) and nine (PREAUT-9) months of age. A sample of 4,835 toddlers completed the Checklist for Autism in Toddlers (CHAT) at 24 months (CHAT-24) of age. Children who were positive at one screening (N = 100) were proposed a clinical assessment (including the Children Autism Rating Scale, a Developmental Quotient, and an ICD-10-based clinical diagnosis if appropriate) in the third year of life. A randomly selected sample of 1,100 individuals who were negative at all screenings was followed by the PMI team from three to five years of age to identify prospective false negative cases. The clinical outcome was available for 45% (N = 45) of positive children and 52.6% (N = 579) of negative children. RESULTS: Of the 100 children who screened positive, 45 received a diagnosis at follow-up. Among those receiving a diagnosis, 22 were healthy, 10 were diagnosed with ASD, seven with intellectual disability (ID), and six had another developmental disorder. Thus, 50% of infants positive at one screening subsequently received a neurodevelopmental diagnosis. The PREAUT grid scores were significantly associated with medium and high ASD risk status on the CHAT at 24 months (odds ratio of 12.1 (95%CI: 3.0-36.8), p < 0.001, at four months and 38.1 (95%CI: 3.65-220.3), p < 0.001, at nine months). Sensitivity (Se), specificity, negative predictive values, and positive predictive values (PPVs) for PREAUT at four or nine months, and CHAT at 24 months, were similar [PREAUT-4: Se = 16.0 to 20.6%, PPV = 25.4 to 26.3%; PREAUT-9: Se = 30.5 to 41.2%, PPV = 20.2 to 36.4%; and CHAT-24: Se = 33.9 to 41.5%, PPV = 27.3 to 25.9%]. The repeated use of the screening instruments increased the Se but not PPV estimates [PREAUT and CHAT combined: Se = 67.9 to 77.7%, PPV = 19.0 to 28.0%]. CONCLUSIONS: The PREAUT grid can contribute to very early detection of ASD and its combination with the CHAT may improve the early diagnosis of ASD and other neurodevelopmental disorders. Lien vers le texte intégral (Open Access ou abonnement)
16. Peristeri E, Andreou M, Tsimpli IM. {{Syntactic and Story Structure Complexity in the Narratives of High- and Low-Language Ability Children with Autism Spectrum Disorder}}. {Front Psychol};2017;8:2027.
Although language impairment is commonly associated with the autism spectrum disorder (ASD), the Diagnostic Statistical Manual no longer includes language impairment as a necessary component of an ASD diagnosis (American Psychiatric Association, 2013). However, children with ASD and no comorbid intellectual disability struggle with some aspects of language whose precise nature is still outstanding. Narratives have been extensively used as a tool to examine lexical and syntactic abilities, as well as pragmatic skills in children with ASD. This study contributes to this literature by investigating the narrative skills of 30 Greek-speaking children with ASD and normal non-verbal IQ, 16 with language skills in the upper end of the normal range (ASD-HL), and 14 in the lower end of the normal range (ASD-LL). The control group consisted of 15 age-matched typically-developing (TD) children. Narrative performance was measured in terms of both microstructural and macrostructural properties. Microstructural properties included lexical and syntactic measures of complexity such as subordinate vs. coordinate clauses and types of subordinate clauses. Macrostructure was measured in terms of the diversity in the use of internal state terms (ISTs) and story structure complexity, i.e., children’s ability to produce important units of information that involve the setting, characters, events, and outcomes of the story, as well as the characters’ thoughts and feelings. The findings demonstrate that high language ability and syntactic complexity pattern together in ASD children’s narrative performance and that language ability compensates for autistic children’s pragmatic deficit associated with the production of Theory of Mind-related ISTs. Nevertheless, both groups of children with ASD (high and low language ability) scored lower than the TD controls in the production of Theory of Mind-unrelated ISTs, modifier clauses and story structure complexity.
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17. Rosen TE, Lerner MD. {{Error-related brain activity and anxiety symptoms in youth with autism spectrum disorder}}. {Autism Res};2017 (Dec 6)
Individuals with autism spectrum disorder (ASD) often experience symptoms associated with generalized anxiety disorder, obsessive-compulsive disorder, and social anxiety disorder. In other populations, these same symptoms are associated with a larger error-related negativity (ERN), an event-related potential that reflects endogenous threat sensitivity. As such, it is possible that the ERN may relate to the clinical presentation of anxiety in ASD. However, studies examining these associations in youth with ASD have yielded mixed results. The present study aimed to clarify this relationship by examining the ERN in relation to these specific anxiety symptoms in ASD, and by accounting for typical covariates (e.g., age, verbal abilities, depression, ASD symptoms) of the ERN. Fifty-one youth, ages 8-17, with ASD and intact cognitive ability completed a modified Flanker task, from which the ERN component was obtained. Measures of anxiety, verbal abilities, depression, and ASD symptoms were collected from participants and parents. Results revealed that greater self-reported social anxiety symptoms, specifically performance fears but not humiliation/rejection fears, were associated with an increased neural response to errors, as measured by the ERN. This relationship remained after controlling for other anxiety symptoms, as well as age, verbal IQ, depression symptoms, and ASD symptoms. Findings suggest that heightened threat sensitivity may be characteristic of individuals with ASD who exhibit social fearfulness. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The error-related negativity (ERN) is a physiological measure of the brain’s response to errors which is thought to reflect threat sensitivity and has been implicated in anxiety disorders in individuals without autism spectrum disorder (ASD). The present study revealed that the ERN is related to social anxiety symptoms, specifically performance fears, in a sample of youth with ASD. Findings suggest that heightened threat sensitivity may be characteristic of individuals with ASD who exhibit social fearfulness.
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18. Schuetze M, Rohr CS, Dewey D, McCrimmon A, Bray S. {{Reinforcement Learning in Autism Spectrum Disorder}}. {Front Psychol};2017;8:2035.
Early behavioral interventions are recognized as integral to standard care in autism spectrum disorder (ASD), and often focus on reinforcing desired behaviors (e.g., eye contact) and reducing the presence of atypical behaviors (e.g., echoing others’ phrases). However, efficacy of these programs is mixed. Reinforcement learning relies on neurocircuitry that has been reported to be atypical in ASD: prefrontal-sub-cortical circuits, amygdala, brainstem, and cerebellum. Thus, early behavioral interventions rely on neurocircuitry that may function atypically in at least a subset of individuals with ASD. Recent work has investigated physiological, behavioral, and neural responses to reinforcers to uncover differences in motivation and learning in ASD. We will synthesize this work to identify promising avenues for future research that ultimately can be used to enhance the efficacy of early intervention.
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19. Steinmetz AB, Stern SA, Kohtz AS, Descalzi G, Alberini CM. {{Insulin-like Growth Factor II Targets the mTOR Pathway to Reverse Autism-like Phenotypes in Mice}}. {J Neurosci};2017 (Dec 7)
Autism spectrum disorder (ASD) is a developmental disability characterized by impairments in social interaction and repetitive behavior, and is also associated with cognitive deficits. There is no current treatment that can ameliorate most of the ASD symptomatology; thus, identifying novel therapies is urgently needed. We used male BTBR T(+)Itpr3(tf) /J (BTBR) mice, a model that reproduces most of the core behavioral phenotypes of ASD, to test the effects of systemic administration of insulin like growth factor II (IGF-II), a polypeptide that crosses the blood brain barrier and acts as a cognitive enhancer. We show that systemic IGF-II treatments reverse the typical defects in social interaction, cognitive/executive functions, and repetitive behaviors reflective of ASD-like phenotypes. In BTBR mice, IGF-II, via IGF-II- receptor, but not via IGF-I- receptor, reverses the abnormal levels of the AMPK-mTOR-S6K pathway and of active translation at synapses. Thus, IGF-II may represent a novel potential therapy for ASD.SIGNIFICANCE STATEMENTCurrently, there is no effective treatment for autism spectrum disorder (ASD), a developmental disability affecting a high number of children. Using a mouse model that expresses most of the key core as well as associated behavioral deficits of ASD, that are, social, cognitive, and repetitive behaviors, we report that a systemic administration of the polypeptide insulin like growth factor II (IGF-II) reverses all these deficits. The effects of IGF-II occur via IGF-II receptors, and not IGF-I receptors, and target both basal and learning-dependent molecular abnormalities found in several ASD mice models, including those of identified genetic mutations. We suggest that IGF-II represents a potential novel therapeutic target for ASD.
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20. Tachibana Y, Miyazaki C, Ota E, Mori R, Hwang Y, Kobayashi E, Terasaka A, Tang J, Kamio Y. {{A systematic review and meta-analysis of comprehensive interventions for pre-school children with autism spectrum disorder (ASD)}}. {PLoS One};2017;12(12):e0186502.
BACKGROUND: There has an increasing number of published trials on psychosocial intervention programmes for pre-school children with autism spectrum disorder (ASD). To achieve better quality of unbiased evidence for the effectiveness of ASD interventions, it is necessary to conduct a comprehensive review that covers studies with adequate quality standards, such as randomised controlled trials (RCTs), and different types of intervention In this study, we categorize interventions for ASD as behavioural, social-communication focused, and multimodal developmental based on Howlin’s classification of early interventions for children with ASD. The aim of this study was to compare these three models and investigate the strengths and weaknesses of each type of intervention and to identify the approaches that contribute to a successful outcome for children with autism. METHODS: We performed a systematic review and meta-analysis. We included RCTs targeting children with ASD 6 years old or younger. A random effects model was used to present the effect estimate for the outcomes. This study also performed combined meta-analyses of all the three models to investigate the overall effectiveness of the intervention programmes. RESULTS: 32 randomized controlled studies were found to be eligible for inclusion. The synthesized data included 594 children from 14 RCTs. There was no statistically significant difference in the effects on autism general symptoms between the social-communication-focused model and the multimodal developmental model (p = 0.83). The results suggest that there is evidence of an effect on ‘reciprocity of social interaction towards others’ (standard mean difference [95% confidential interval] = 0.53[0.29,0.78], p<0.01) and 'parental synchrony' (SMD = 0.99[0.70,1.29], p<0.01). CONCLUSION: The small number of studies included in the present study limited the ability to make inferences when comparing the three models and investigating the strengths and weaknesses of each type of intervention with respect to important outcomes. Since the outcome of 'reciprocity of social interaction towards others' could be a dependent variable that might be context-bound to interactions with the child's parent, we cannot conclude the interventions for pre-school children with ASD have significant effects on a generalized skill to engage in reciprocal interactions with others. However, the outcomes of 'reciprocity of social interaction towards others' and 'parental synchrony' may be promising targets for interventions involving pre-school children with ASD. TRIAL REGISTRATION: Prospero CRD42011001349. Lien vers le texte intégral (Open Access ou abonnement)
21. Wei L, Zhong S, Nie S, Gong G. {{Aberrant development of the asymmetry between hemispheric brain white matter networks in autism spectrum disorder}}. {Eur Neuropsychopharmacol};2017 (Dec 7)
Atypical brain asymmetry/lateralization has long been hypothesized for autism spectrum disorder (ASD), and this model has been repeatedly supported by various neuroimaging studies. Recently, hemispheric network topologies have been found to be asymmetric, thereby providing a new avenue for investigating brain asymmetries under various conditions. To date, however, how network topological asymmetries are altered in ASD remains largely unexplored. To clarify this, the present study included ASD individuals from the newly released Autism Brain Imaging Data Exchange II database (58 right-handed male ASD individuals aged 5 to 26 years and 70 age- and IQ-matched typically developing (TD) individuals). Diffusion and structural magnetic resonance imaging were used to construct hemispheric white matter networks, and graph-theory approaches were applied to quantify topological efficiencies for hemispheric networks. Statistical analyses revealed a decreased rightward asymmetry of network efficiencies with increasing age in the TD group, but not in the ASD group. More specifically, the TD group did not exhibit an age-related increase in network efficiency in the right hemisphere, but the ASD group did. For the left hemisphere, no difference between the groups was observed for the developmental trajectory of network efficiencies. Intriguingly, within the ASD group, more severe restricted and repetitive behavior in ASD was found to be correlated with less rightward asymmetry of network local efficiency. These findings provide suggestive evidence of atypical network topological asymmetries and offer important insights into the abnormal development of ASD brains.
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22. Wu H, Zhang Q, Gao J, Sun C, Wang J, Xia W, Cao Y, Hao Y, Wu L. {{Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in the valproic acid rat model of autism}}. {Psychopharmacology (Berl)};2017 (Dec 7)
RATIONALE: Autism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early childhood, and it is growing up to be a major cause of disability in children. However, the etiology and treatment of ASD are not well understood. In our previous study, we found that serum levels of sphingosine 1-phosphate (S1P) were increased significantly in children with autism, indicating that S1P levels may be involved in ASD. OBJECTIVE: The objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism. METHODS: We utilized a valproic acid (VPA) -induced rat model of autism to evaluate the levels of S1P and the expression of sphingosine kinase (SphK), a key enzyme for S1P production, in serum and hippocampal tissue. Furthermore, we assessed cognitive functional changes and histopathological and neurochemical alterations in VPA-exposed rats after SphK blockade to explore the possible link between increased levels of S1P and neurobehavioral changes in autism. RESULTS: We found that SphK2 and S1P are upregulated in hippocampal tissue from VPA-exposed rats, while pharmacological inhibition of SphK reduced S1P levels, attenuated spatial learning and memory impairments, increased the expression of phosphorylated CaMKII and CREB and autophagy-related proteins, inhibited cytochrome c release, decreased the expression of apoptosis related proteins, and protected against neuronal loss in the hippocampus. CONCLUSION: We have demonstrated that an increased level of SphK2/S1P is involved in the spatial learning and memory impairments of autism, and this signaling pathway represents a novel therapeutic target and direction for future studies.
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23. Yoshimura Y, Kikuchi M, Hayashi N, Hiraishi H, Hasegawa C, Takahashi T, Oi M, Remijn GB, Ikeda T, Saito DN, Kumazaki H, Minabe Y. {{Altered human voice processing in the frontal cortex and a developmental language delay in 3- to 5-year-old children with autism spectrum disorder}}. {Sci Rep};2017 (Dec 7);7(1):17116.
The inferior frontal and superior temporal areas in the left hemisphere are crucial for human language processing. In the present study, we investigated the magnetic mismatch field (MMF) evoked by voice stimuli in 3- to 5-year-old typically developing (TD) children and children with autism spectrum disorder (ASD) using child-customized magnetoencephalography (MEG). The children with ASD exhibited significantly decreased activation in the left superior temporal gyrus compared with the TD children for the MMF amplitude. If we classified the children with ASD according to the presence of a speech onset delay (ASD – SOD and ASD – NoSOD, respectively) and compared them with the TD children, both ASD groups exhibited decreased activation in the left superior temporal gyrus compared with the TD children. In contrast, the ASD – SOD group exhibited increased activity in the left frontal cortex (i.e., pars orbitalis) compared with the other groups. For all children with ASD, there was a significant negative correlation between the MMF amplitude in the left pars orbitalis and language performance. This investigation is the first to show a significant difference in two distinct MMF regions in ASD – SOD children compared with TD children.
