Pubmed du 17/04/20

vendredi 17 avril 2020

1. Abdelzaher LA, Hussein OA, Ashry IEM. The Novel Potential Therapeutic Utility of Montelukast in Alleviating Autistic Behavior Induced by Early Postnatal Administration of Thimerosal in Mice. Cellular and molecular neurobiology. 2020.

BACKGROUND AND AIM : Thimerosal (THIM) is a mercury-containing preservative widely used in many biological and medical products including many vaccines. It has been accused of being a possible etiological factor for some neurodevelopmental disorders such as autistic spectrum disorders (ASDs). In our study, the potential therapeutic effect of montelukast, a leukotriene receptor antagonist used to treat seasonal allergies and asthma, on THIM mice model (ASDs model) was examined. METHODOLOGY : Newborn mice were randomly distributed into three groups : (Group 1) Control (Cont.) group received saline injections. (Group 2) THIM-treated (THIM) group received THIM intramuscular (IM) at a dose of 3000 mug Hg/kg on postnatal days 7, 9, 11, and 15. (Group 3) Montelukast-treated (Monte) group received THIM followed by montelukast sodium (10 mg/kg/day) intraperitoneal (IP) for 3 weeks. Mice were evaluated for growth development, social interactions, anxiety, locomotor activity, and cognitive function. Brain histopathology, alpha 7 nicotinic acetylcholine receptors (alpha7nAChRs), nuclear factor kappa B p65 (NF-kappaB p65), apoptotic factor (Bax), and brain injury markers were evaluated as well. RESULTS : THIIM significantly impaired social activity and growth development. Montelukast mitigated THIM-induced social deficit probably through alpha7nAChRs upregulation, NF-kappaB p65, Bax, and brain injury markers downregulation, thus suppressing THIM-induced neuronal toxicity and inflammation. CONCLUSION : Neonatal exposure to THIM can induce growth retardation and abnormal social interactions similar to those observed in ASDs. Some of these abnormalities could be ameliorated by montelukast via upregulation of alpha7nAChRs that inhibited NF-kappaB activation and significant suppression of neuronal injury and the associated apoptosis.

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2. Barnett BR, Casey CP, Torres-Velazquez M, Rowley PA, Yu JJ. Convergent brain microstructure across multiple genetic models of schizophrenia and autism spectrum disorder : A feasibility study. Magnetic resonance imaging. 2020.

Neuroimaging studies of psychiatric illness have revealed a broad spectrum of structural and functional perturbations that have been attributed in part to the complex genetic heterogeneity underpinning these disorders. These perturbations have been identified in both preclinical genetic models and in patients when compared to control populations, but recent work has also demonstrated strong evidence for genetic, molecular, and structural convergence of several psychiatric diseases. We explored potential similarities in neural microstructure in preclinical genetic models of ASD (Fmr1, Nrxn1, Pten) and schizophrenia (Disc1 svDelta2) and in age- and sex-matched control animals with diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). Our findings demonstrate a convergence in brain microstructure across these four genetic models with both tract-based and region-of-interest based analyses, which continues to buttress an emerging understanding of converging neural microstructure in psychiatric disease.

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3. Bhat AN. Is Motor Impairment in Autism Spectrum Disorder Distinct From Developmental Coordination Disorder ? A Report From the SPARK Study. Physical therapy. 2020 ; 100(4) : 633-44.

BACKGROUND : Motor impairments are pervasive in Autism Spectrum Disorder (ASD) ; however, children with ASD rarely receive a dual diagnosis of Developmental Coordination Disorder (DCD). The Simons Foundation SPARK study engaged families affected by ASD through an online study. OBJECTIVES : The DCD parent questionnaire (DCDQ) was used to assess the prevalence of a risk for motor impairment or DCD in children with ASD between 5 and 15 years of age. DESIGN : This study utilizes parent reports from a large database of children with ASD. METHODS : A total of 16,705 parents of children with ASD completed the DCDQ. We obtained our final SPARK dataset (n = 11,814) after filtering out invalid data, using stronger cut-offs to confirm ASD traits, and excluding children with general neuromotor impairments/intellectual delays. We compared DCDQ total and subscale scores from the SPARK dataset with published norms for each age between 5 and 15 years. RESULTS : The proportion of children with ASD at risk for a motor impairment was very high at 86.9%. Children with ASD did not outgrow their motor impairments and continued to present with a risk for DCD even into adolescence. Yet, only 31.6% of children were receiving physical therapy services. LIMITATIONS : Our analysis of a large database of parent-reported outcomes using the DCDQ did not involve follow-up clinical assessments. CONCLUSIONS : Using a large sample of children with ASD, this study shows that a risk for motor impairment or DCD was present in most children with ASD and persists into adolescence ; however, only a small proportion of children with ASD were receiving physical therapist interventions. A diagnosis of ASD must trigger motor screening, evaluations, and appropriate interventions by physical and occupational therapists to address the functional impairments of children with ASD while also positively impacting their social communication, cognition, and behavior. Using valid motor measures, future research must determine if motor impairment is a fundamental feature of ASD.

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4. Brisini KSC, Solomon DH. Relational Uncertainty and Taking Conflict Personally : Comparing Parents of Children with and Without Autism Spectrum Disorder. J Autism Dev Disord. 2020.

Previous research suggests that parents of children with ASD experience greater marital conflict than parents of children with neurotypical development (NTD). This study examines how relational uncertainty is associated with taking conflict personally among parents of children with or without ASD. Parents of children with ASD (N = 298) and parents of children with NTD (N = 316) completed an online survey. They reported their relational uncertainty, recalled a conflict related to their child, and completed measures of taking conflict personally. The study provides evidence that spouses’ experiences of relational uncertainty may be associated with conflict about topics related to their child. In addition, experiences of self uncertainty may have a greater impact for the parents of children with ASD than parents of children with NTD.

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5. Gorenstein M, Giserman-Kiss I, Feldman E, Isenstein EL, Donnelly L, Wang AT, Foss-Feig JH. Brief Report : A Job-Based Social Skills Program (JOBSS) for Adults with Autism Spectrum Disorder : A Pilot Randomized Controlled Trial. J Autism Dev Disord. 2020.

Adults with autism spectrum disorder (ASD) have low employment rates ; even those who are employed have low wages and limited hours. This study evaluated the effectiveness of the Job-Based Social Skills (JOBSS) curriculum, a manualized, 15-week, group-delivered intervention for adults with ASD. The intervention aimed to increase social-pragmatic skills necessary to obtain and maintain employment. Twenty-two adults were randomly assigned to either JOBSS intervention or wait-list control groups. Results showed significant improvement in social cognition, as reported by caregivers, among JOBSS group participants compared to wait-list control participants. Forty-five percent of intervention participants gained employment in the six months following participation. This curriculum has potential to improve social skills of adults with ASD, thereby increasing successful employment.

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6. Kalmbach D, Wood W, Peters BC. Parental Perspectives of Occupational Therapy in an Equine Environment for Children with Autism Spectrum Disorder. Occupational therapy in health care. 2020 : 1-23.

This paper reports on the qualitative phase of a mixed methods study of occupational therapy in an equine environment for children with autism spectrum disorder (ASD). The study’s quantitative phase found that this intervention improved the occupational performance, social motivation, social communication, and self-regulation of some children with ASD. The study’s qualitative phase, reported herein, subsequently aimed to describe parental perspectives on children’s experiences of the intervention and its influences on everyday life. Using a qualitative descriptive research approach, five parents participated in two rounds of semi-structured interviews. Interview data were analyzed using theoretical thematic analysis. Although parents expressed some concerns about the intervention, overall they found the intervention to be appropriate and acceptable. Next research steps include creation of a manual for the intervention and assessment of feasibility across a broader range of practice sites, occupational therapists, children with ASD, and their parents.

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7. Kamp-Becker I, Stroth S, Stehr T. [Autism spectrum disorder in childhood and adults : diagnosis and differential diagnoses]. Der Nervenarzt. 2020.

Autistic disorders are summarized in DSM5 under the term autism spectrum disorder (ASD) and are severe, lifelong, pervasive neurodevelopmental disorders. Core features manifested even in childhood are impairments in social interaction and communication as well as restricted and repetitive behavior. The intensity of symptoms, language and cognitive impairments vary but the majority of affected individuals have below average intelligence and 80% have at least one comorbid disorder. The diverse pathology and heterogeneity in phenotypes are caused by a complex genetic etiology, which is associated with a reduced synaptic plasticity of neural networks. The disorder is associated with a clearly reduced quality of life as well as a high familial burden. The differential diagnostics have a high relevance and the diagnosis should be carried out by specialized institutions. Behavioral therapeutic interventions are indicated.

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8. Khayatzadeh-Mahani A, Wittevrongel K, Petermann L, Graham ID, Zwicker JD. Stakeholders’ engagement in co-producing policy-relevant knowledge to facilitate employment for persons with developmental disabilities. Health research policy and systems. 2020 ; 18(1) : 39.

BACKGROUND : Persons with developmental disabilities (PWDD) face a number of individual, environmental and societal barriers when seeking employment. Integrated knowledge translation (IKT) involves ongoing and dynamic interactions between researchers and stakeholders for the purpose of engaging in mutually beneficial research to address these types of multi-faceted barriers. There is a knowledge gap in the IKT literature on effective stakeholder engagement strategies outside of the dissemination stage to inform policy. In this paper, we report on a number of engagement strategies employed over a 2-year period to engage a wide range of stakeholders in different stages of an IKT project that aimed to investigate the ’wicked’ problem of employment for PWDD. METHOD : Our engagement plan included multiple linked strategies and was designed to ensure the meaningful engagement of, and knowledge co-production with, stakeholders. We held two participatory consensus-building stakeholder policy dialogue events to co-produce knowledge utilising the nominal group technique and the modified Delphi technique. A total of 31 and 49 stakeholders engaged in the first and second events, respectively, from six key stakeholder groups. Focused engagement strategies were employed to build on the stakeholder dialogues for knowledge mobilisation and included a focus group attended only by PWDD, a stakeholder workshop attended only by policy/decision-makers, a webinar attended by human resources professionals and employers, and a current affairs panel attended by the general public. RESULTS : Our findings suggest that the level of engagement for each stakeholder group varies depending on the goal and need of the project. Our stakeholder dialogue findings highlight the inherent challenges in co-framing and knowledge co-production through the meaningful engagement of multiple stakeholders who hold different ideas and interests. Focused outreach is needed to foster relationships and trust for meaningful engagement. CONCLUSIONS : In addition to providing guidance on how to implement adaptable meaningful engagement strategies, these findings contribute to discussions on how IKT projects are planned and funded. More studies to explore effective mechanisms for engaging a wide range of stakeholders in IKT research are needed. More evidence of successful engagement strategies employed by researchers to achieve meaningful knowledge co-production is also key to advancing the discipline.

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9. Kirby AV, Diener ML, Adkins DE, Wright C. Transition preparation activities among families of youth on the autism spectrum : Preliminary study using repeated assessments across a school year. PLoS One. 2020 ; 15(4) : e0231551.

Much is still unknown about the transition to adulthood for youth with autism spectrum disorder (ASD), including what preparation activities best support positive adult outcomes. Parents play a crucial role in the transition planning and preparation process, yet the existing literature lacks detailed information about parent perceptions about transition preparation activities. To examine family transition preparation activities, we conducted a ten-month study of the transition preparation process of 15 families of youth with ASD across an academic year. Youth were ages 14-17 and 93% male. We collected data on transition preparation activity time spent and parent satisfaction over twenty data collection points. We used multi-level modeling to determine longitudinal trajectories of parent-reported preparation for the transition to adulthood based on endorsed transition preparation activities. Findings from this preliminary study revealed that discussions about the future were the most commonly endorsed activities, while social activities were most associated with increased parental perception of transition preparation over time. This study expands understanding of various transition preparation activities engaged in by families of youth with ASD during high school, though research with a larger and more diverse sample is needed to extend findings.

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10. Kolodny T, Schallmo MP, Gerdts J, Edden RAE, Bernier RA, Murray SO. Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder. Autism Res. 2020.

The balance of excitation and inhibition in neural circuits is hypothesized to be increased in autism spectrum disorder, possibly mediated by altered signaling of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), yet empirical evidence in humans is inconsistent. We used edited magnetic resonance spectroscopy (MRS) to quantify signals associated with both GABA and the excitatory neurotransmitter glutamate in multiple regions of the sensory and sensorimotor cortex, including primary visual, auditory, and motor areas in adult individuals with autism and in neurotypical controls. Despite the strong a priori hypothesis of reduced GABA in autism spectrum disorder, we found no group differences in neurometabolite concentrations in any of the examined regions and no correlations of MRS measure with psychophysical visual sensitivity or autism symptomatology. We demonstrate high data quality that is comparable across groups, with a relatively large sample of well-characterized participants, and use Bayesian statistics to corroborate the lack of any group differences. We conclude that levels of GABA and Glx (glutamate, glutamine, and glutathione) in the sensory and sensorimotor cortex, as measured with MRS at 3T, are comparable in adults with autism and neurotypical individuals. LAY SUMMARY : gamma-Aminobutyric acid (GABA) and glutamate are the main inhibitory and excitatory neurotransmitters in the human brain, respectively, and their balanced interaction is necessary for neural function. Previous research suggests that the GABA and glutamate systems might be altered in autism. In this study, we used magnetic resonance spectroscopy to measure concentrations of these neurotransmitters in the sensory areas in the brains of young adults with autism. In contradiction to the common hypothesis of reduced GABA in autism, we demonstrate that concentrations of both GABA and glutamate, in all the brain regions examined, are comparable in individuals with autism and in neurotypical adults. (c) 2020 International Society for Autism Research, Wiley Periodicals, Inc.

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11. Moliadze V, Brodski-Guerniero A, Schuetz M, Siemann J, Lyzhko E, Schlitt S, Kitzerow J, Langer A, Kaiser J, Naumer MJ, Wibral M, Chan J, Freitag CM, Siniatchkin M. Significance of Beta-Band Oscillations in Autism Spectrum Disorders During Motor Response Inhibition Tasks : A MEG Study. Brain topography. 2020.

In Autism Spectrum Disorders (ASD), impaired response inhibition and lack of adaptation are hypothesized to underlie core ASD symptoms, such as social communication and repetitive, stereotyped behavior. Thus, the aim of the present study was to compare neural correlates of inhibition, post-error adaptation, and reaction time variability in ASD and neuro-typical control (NTC) participants by investigating possible differences in error-related changes of oscillatory MEG activity. Twelve male NTC (mean age 20.3 +/- 3.7) and fourteen male patients with ASD (mean age 17.8 +/- 2.9) were included in the analysis. Subjects with ASD showed increased error-related reaction time variability. MEG analysis revealed decreased beta power in the ASD group in comparison to the NTC group over the centro-parietal channels in both, the pre-stimulus and post-response interval. In the ASD group, mean centro-parietal beta power negatively correlated with dimensional autism symptoms. In both groups, false alarms were followed by an early increase in temporo-frontal theta to alpha power ; and by a later decrease in alpha to beta power at central and posterior sensors. Single trial correlations were additionally studied in the ASD group, who showed a positive correlation of pre-stimulus beta power with post-response theta, alpha, and beta power, particularly after hit trials. On a broader scale, the results deliver important insights into top-down control deficits that may relate to core symptoms observed in ASD.

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12. Pascucci T, Colamartino M, Fiori E, Sacco R, Coviello A, Ventura R, Puglisi-Allegra S, Turriziani L, Persico AM. P-cresol Alters Brain Dopamine Metabolism and Exacerbates Autism-Like Behaviors in the BTBR Mouse. Brain Sci. 2020 ; 10(4).

Background : Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction/communication, stereotypic behaviors, restricted interests, and abnormal sensory-processing. Several studies have reported significantly elevated urinary and foecal levels of p-cresol in ASD children, an aromatic compound either of environmental origin or produced by specific gut bacterial strains. Methods : Since p-cresol is a known uremic toxin, able to negatively affect multiple brain functions, the present study was undertaken to assess the effects of a single acute injection of low- or high-dose (1 or 10 mg/kg i.v. respectively) of p-cresol in behavioral and neurochemical phenotypes of BTBR mice, a reliable animal model of human ASD. Results : P-cresol significantly increased anxiety-like behaviors and hyperactivity in the open field, in addition to producing stereotypic behaviors and loss of social preference in BTBR mice. Tissue levels of monoaminergic neurotransmitters and their metabolites unveiled significantly activated dopamine turnover in amygdala as well as in dorsal and ventral striatum after p-cresol administration ; no effect was recorded in medial-prefrontal cortex and hippocampus. Conclusion : Our study supports a gene x environment interaction model, whereby p-cresol, acting upon a susceptible genetic background, can acutely induce autism-like behaviors and produce abnormal dopamine metabolism in the reward circuitry.

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13. Pivetti M, Melotti G, Mancini C. Vaccines and autism : a preliminary qualitative study on the beliefs of concerned mothers in Italy. International journal of qualitative studies on health and well-being. 2020 ; 15(1) : 1754086.

Purpose : While a large body of evidence has shown that the administration of the measles-mumps-rubella (MMR) vaccine is not associated with an increased risk of autism spectrum disorder (ASD), a hesitant attitude towards childhood vaccination is still present among the public. In this study, we aim to investigate the mothers’ perceptions of the cause of their child’s ASD in order to increase our understanding of vaccine hesitancy.Methods : This study draws on the analysis of 18 semi-structured interviews of mothers of children with ASD on the causes of autism.Results : The interview material was content-analysed. The main themes were 1) childhood vaccines ; 2) genetics ; 3) specific conditions of the mother or the newborn at the moment of delivery ; 4) environmental factors such as the mother’s lifestyle or her diet. The link between vaccines and autism was prevalent. About one third of the mothers reported that their child’s ASD was a consequence of a combination of two or more factors, i.e., childhood vaccines and specific conditions of the newborn or the mother at the moment of delivery.Conclusion : This study provides preliminary insights into recurring sets of beliefs concerning the causes of ASD among the mothers of affected children.

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14. Reeves PT, Susi A, Hisle-Gorman E, Gorman GH, Nylund C. Brief Report : Association of Complicated Appendicitis in Children with Autism Spectrum Disorders. J Autism Dev Disord. 2020.

Appendicitis is the most common surgical emergency in children and can lead to significant complications. The aim of our study was to determine whether children with autism spectrum disorders (ASD) are at increased risk for appendicitis and its complications compared to neurotypical (NT) peers. From 2000 to 2013, 292,572 children were included (n = 48,762 ASD). ASD children exhibited an incidence of 8.66 appendicitis cases per 10,000 person-years, P > 0.05. There was an increased risk of perforation in ASD children age 15-17 years-old (OR 2.25 ; 95% CI 1.15-4.42) as well as an increased odds of sepsis (OR 3.44, 95% CI 1.43-8.27). Providers should display heightened awareness for the risk of complicated appendicitis in children with ASD.

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15. Steenfeldt-Kristensen C, Jones CA, Richards C. The Prevalence of Self-injurious Behaviour in Autism : A Meta-analytic Study. J Autism Dev Disord. 2020.

Self-injurious behaviour is purportedly common in autism, but prevalence rates have not yet been synthesised meta-analytically. In the present study, data from 14,379 participants in thirty-seven papers were analysed to generate a pooled prevalence estimate of self-injury in autism of 42% (confidence intervals 0.38-0.47). Hand-hitting topography was the most common form of self-injury (23%), self-cutting topography the least common (3%). Sub-group analyses revealed no association between study quality, participant intellectual disability or age and overall prevalence rate of self-injury. However, females obtained higher prevalence rates than males (p = .013) and hair pulling and self-scratching were associated with intellectual disability (p = .008 and p = .002, respectively). The results confirm very high rates of self-injury in autism and highlight within group risk-markers.

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16. Van Dijck A, Barbosa S, Bermudez-Martin P, Khalfallah O, Gilet C, Martinuzzi E, Elinck E, Kooy RF, Glaichenhaus N, Davidovic L. Reduced serum levels of pro-inflammatory chemokines in fragile X syndrome. BMC neurology. 2020 ; 20(1) : 138.

BACKGROUND : Fragile X syndrome (FXS) is the most frequent cause of inherited intellectual disability and the most commonly identified monogenic cause of autism. Recent studies have shown that long-term pathological consequences of FXS are not solely confined to the central nervous system (CNS) but rather extend to other physiological dysfunctions in peripheral organs. To gain insights into possible immune dysfunctions in FXS, we profiled a large panel of immune-related biomarkers in the serum of FXS patients and healthy controls. METHODS : We have used a sensitive and robust Electro Chemi Luminescence (ECL)-based immunoassay to measure the levels of 52 cytokines in the serum of n = 25 FXS patients and n = 29 healthy controls. We then used univariate statistics and multivariate analysis, as well as an advanced unsupervised clustering method, to identify combinations of immune-related biomarkers that could discriminate FXS patients from healthy individuals. RESULTS : While the majority of the tested cytokines were present at similar levels in FXS patients and healthy individuals, nine chemokines, CCL2, CCL3, CCL4, CCL11, CCL13, CCL17, CCL22, CCL26 and CXCL10, were present at much lower levels in FXS patients. Using robust regression, we show that six of these biomarkers (CCL2, CCL3, CCL11, CCL22, CCL26 and CXCL10) were negatively associated with FXS diagnosis. Finally, applying the K-sparse unsupervised clustering method to the biomarker dataset allowed for the identification of two subsets of individuals, which essentially matched the FXS and healthy control categories. CONCLUSIONS : Our data show that FXS patients exhibit reduced serum levels of several chemokines and may therefore exhibit impaired immune responses. The present study also highlights the power of unsupervised clustering methods to identify combinations of biomarkers for diagnosis and prognosis in medicine.

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17. Xie R, Sun X, Yang L, Guo Y. Characteristic Executive Dysfunction for High-Functioning Autism Sustained to Adulthood. Autism Res. 2020.

The comprehensiveness and severity of executive dysfunction in high-functioning autism (HFA) spectrum disorder have not reached a unified conclusion especially in patients in adulthood. Clarifying this issue is critical for guiding clinical diagnosis and targeted intervention. The primary objective of the present meta-analysis was to study the characteristics of executive function (EF) in adults with HFA compared to typically developing (TD) adults, by taking five key components into consideration, including inhibition, working memory, flexibility, planning, and fluency. The PubMed and Embase databases were searched to identify peer-reviewed studies that compared EF in adults with and without HFA from 1980 to November 2018. Hedges’ g effect sizes were computed to measure the primary outcome. Moderators like age, sex, and diagnostic tools were controlled using meta-regressions. Forty-two studies satisfying the selection criteria were included, which resulted in a large sample size of 2419 participants. A moderate overall effect size for reduced EF across domains was found in adults with HFA, compared with TD (g = 0.57, 95% confidence interval 0.47-0.66). Subsequently, a broad executive dysfunction was found in adults with HFA in this study (flexibility [g = 0.69], planning [g = 0.64], inhibition [g = 0.61], working memory [g = 0.48], fluency [g = 0.42]), with the predominated impairment on flexibility and planning. Taken together, these results provide evidence for the executive dysfunction hypothesis and may assist in the clinical diagnosis and targeted intervention, suggesting the necessity of sustained intervention on EF for individuals with HFA from childhood to adulthood. LAY SUMMARY : The meta-analysis explored the characteristics of EF in adults with high-functioning autism (HFA) comparing to typically developing controls. Moderate effect sizes for reduced EF across domains were found in adults with HFA, with the flexibility and planning being the most predominately impaired. A comprehensive measurement of EF in adults with HFA has important clinical implications for the diagnosis, treatment, prognosis, and a fundamental understanding for developmental trajectory of these patients.

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18. Yoshihara Y, Lisi G, Yahata N, Fujino J, Matsumoto Y, Miyata J, Sugihara GI, Urayama SI, Kubota M, Yamashita M, Hashimoto R, Ichikawa N, Cahn W, van Haren NEM, Mori S, Okamoto Y, Kasai K, Kato N, Imamizu H, Kahn RS, Sawa A, Kawato M, Murai T, Morimoto J, Takahashi H. Overlapping but Asymmetrical Relationships Between Schizophrenia and Autism Revealed by Brain Connectivity. Schizophr Bull. 2020.

Although the relationship between schizophrenia spectrum disorder (SSD) and autism spectrum disorder (ASD) has long been debated, it has not yet been fully elucidated. The authors quantified and visualized the relationship between ASD and SSD using dual classifiers that discriminate patients from healthy controls (HCs) based on resting-state functional connectivity magnetic resonance imaging. To develop a reliable SSD classifier, sophisticated machine-learning algorithms that automatically selected SSD-specific functional connections were applied to Japanese datasets from Kyoto University Hospital (N = 170) including patients with chronic-stage SSD. The generalizability of the SSD classifier was tested by 2 independent validation cohorts, and 1 cohort including first-episode schizophrenia. The specificity of the SSD classifier was tested by 2 Japanese cohorts of ASD and major depressive disorder. The weighted linear summation of the classifier’s functional connections constituted the biological dimensions representing neural classification certainty for the disorders. Our previously developed ASD classifier was used as ASD dimension. Distributions of individuals with SSD, ASD, and HCs s were examined on the SSD and ASD biological dimensions. We found that the SSD and ASD populations exhibited overlapping but asymmetrical patterns in the 2 biological dimensions. That is, the SSD population showed increased classification certainty for the ASD dimension but not vice versa. Furthermore, the 2 dimensions were correlated within the ASD population but not the SSD population. In conclusion, using the 2 biological dimensions based on resting-state functional connectivity enabled us to discover the quantified relationships between SSD and ASD.

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19. Yu H, Zhang Z, Liu J, Hu P, Liu Z. Association study between genetic variants in vitamin D metabolism related genes and childhood autism spectrum disorder. Metabolic brain disease. 2020.

Vitamin D deficiency has been implicated as a risk factor for autism spectrum disorder (ASD). This case-controlled study was to determine the association between single nucleotide polymorphisms (SNPs) in genes encoding vitamin D metabolism related enzymes and childhood ASD in a Chinese Han population. Both autistic children and age-and gender-matched healthy controls were recruited from September 2012-November 2017. The severity of ASD was evaluated by the childhood autism rating scale (CARS). Taqman probe based real-time PCR was applied to examine genotypes. The association between SNPs and the risk of ASD or the disease severity was examined through the logistic regression. This study recruited 249 children with ASD and 353 healthy controls. The G/A genotype (P = 0.0112) or the G allele (P = 0.0117) of CYP24A1 rs17219315, and the G/A genotype of CYP27B1 rs4646536 (P = 0.0341) were significantly associated with an increased risk of ASD. In addition, multivariate analysis found that A allele of both CYP2R1 rs12794714 (P = 0.0159) and CYP27B1 rs4646536 (P = 0.0268) were significantly associated with the severity of ASD. Genetic polymorphisms in vitamin D metabolism related enzymes are associated with the risk of childhood ASD and the severity of the disease.

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20. Zeif D, Yechiam E. Autism is not associated with poor or enhanced performance on the Iowa Gambling Task : A Meta-Analysis. Neurosci Biobehav Rev. 2020.

Individuals with Autism Spectrum Disorder (ASD) report difficulties in making routine decisions. Yet there is a controversy about whether their decision performance is impaired or enhanced compared to typically developing individuals. We focused on studies of the Iowa Gambling Task (IGT) where contrary arguments have been made in this regard. In a meta-analysis, we examined differences between high functioning individuals with ASD and controls in decision performance (choice of long-term advantageous options) and choice switching on the IGT. The analysis encompassed 14 studies involving 433 participants with ASD and 500 controls. The results showed virtually no difference in IGT performance between groups (d = 0.04), except for a slight disadvantage in the first block of trials for the ASD group (d = -0.16). We also found a non-significant trend towards increased choice switching in the ASD group (d = -0.37) that may be examined in future research. In sum, decision performance on the IGT is similar in individuals with ASD and controls, though their strategy may differ.

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