1. Bernardo BA, Lanphear BP, Venners SA, Arbuckle TE, Braun JM, Muckle G, Fraser WD, McCandless LC. {{Assessing the Relation between Plasma PCB Concentrations and Elevated Autistic Behaviours using Bayesian Predictive Odds Ratios}}. {Int J Environ Res Public Health}. 2019; 16(3).
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive or stereotypic behaviours. In utero exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs), may play a role in the etiology of ASD. We examined the relation between plasma PCB concentrations measured during pregnancy and autistic behaviours in a subset of children aged 3(-)4 years old in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pregnancy and birth cohort of 546 mother-infant pairs from Canada (enrolled: 2008(-)2011). We quantified the concentrations of 6 PCB congeners that were detected in >40% of plasma samples collected during the 1st trimester. At age 3(-)4 years, caregivers completed the Social Responsiveness Scale-2 (SRS), a valid and reliable measure of children’s reciprocal social and repetitive behaviours and restricted interests. We examined SRS scores as both a continuous and binary outcome, and we calculated Bayesian predictive odds ratios for more autistic behaviours based on a latent variable model for SRS scores >60. We found no evidence of an association between plasma PCB concentrations and autistic behaviour. However, we found small and imprecise increases in the mean SRS score and odds of more autistic behaviour for the highest category of plasma PCB concentrations compared with the lowest category; for instance, an average increase of 1.4 (95%PCI: -0.4, 3.2) in the mean SRS (exposure contrast highest versus lowest PCB category) for PCB138 translated to an odds ratio of 1.8 (95%PCI: 1.0, 2.9). Our findings illustrate the importance of measuring associations between PCBs and autistic behaviour on both continuous and binary scales.
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2. Davis JM, Heft I, Scherer SW, Sikela JM. {{A Third Linear Association Between Olduvai (DUF1220) Copy Number and Severity of the Classic Symptoms of Inherited Autism}}. {Am J Psychiatry}. 2019: appiajp201818080993.
OBJECTIVE:: The authors previously reported that the copy number of sequences encoding an Olduvai protein domain subtype (CON1) shows a linear association with the severity of social deficits and communication impairment in individuals with autism. In this study, using an improved measurement method, the authors replicated this association in an independent population. METHOD:: The authors obtained whole genome sequence (WGS) data and phenotype data on 215 individuals from the Autism Speaks MSSNG project. They derived copy number from WGS data using a modified sequence read-depth technique. A linear mixed-effects model was used to test the association between Olduvai CON1 copy number and symptom severity as measured by the Autism Diagnostic Interview-Revised. The authors then combined data from previous studies (N=524) for final analyses. RESULTS:: A significant linear association was observed between CON1 copy number and social diagnostic score (SDS) (beta=0.24) and communicative diagnostic score (CDS) (beta=0.23). Using the combined data, the authors present strong significant associations of CON1 dosage with SDS (beta=0.18) and CDS (beta=0.13). The authors also implicate Olduvai subtypes found in two genes, NBPF1 and NBPF14 (R(2)=6.2%). Associations were preferentially found in multiplex versus simplex families. CONCLUSIONS:: The finding of a third dose-dependent association between Olduvai sequences and autism severity, preferentially in multiplex families, provides strong evidence that this highly duplicated and underexamined protein domain family plays an important role in inherited autism.
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3. Duffy FH, Als H. {{Autism, spectrum or clusters? An EEG coherence study}}. {BMC neurology}. 2019; 19(1): 27.
BACKGROUND: Autism prevalence continues to grow, yet a universally agreed upon etiology is lacking despite manifold evidence of abnormalities especially in terms of genetics and epigenetics. The authors postulate that the broad definition of an omnibus ‘spectrum disorder’ may inhibit delineation of meaningful clinical correlations. This paper presents evidence that an objectively defined, EEG based brain measure may be helpful in illuminating the autism spectrum versus subgroups (clusters) question. METHODS: Forty objectively defined EEG coherence factors created in prior studies demonstrated reliable separation of neuro-typical controls from subjects with autism, and reliable separation of subjects with Asperger’s syndrome from all other subjects within the autism spectrum and from neurotypical controls. In the current study, these forty previously defined EEG coherence factors were used prospectively within a large (N = 430) population of subjects with autism in order to determine quantitatively the potential existence of separate clusters within this population. RESULTS: By use of a recently published software package, NbClust, the current investigation determined that the 40 EEG coherence factors reliably identified two distinct clusters within the larger population of subjects with autism. These two clusters demonstrated highly significant differences. Of interest, many more subjects with Asperger’s syndrome fell into one rather than the other cluster. CONCLUSIONS: EEG coherence factors provide evidence of two highly significant separate clusters within the subject population with autism. The establishment of a unitary « Autism Spectrum Disorder » does a disservice to patients and clinicians, hinders much needed scientific exploration, and likely leads to less than optimal educational and/or interventional efforts.
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4. Kim H, Keifer C, Rodriguez-Seijas C, Eaton N, Lerner M, Gadow K. {{Quantifying the Optimal Structure of the Autism Phenotype: A Comprehensive Comparison of Dimensional, Categorical, and Hybrid Models}}. {J Am Acad Child Adolesc Psychiatry}. 2018.
OBJECTIVE: The two primary – seemingly contradictory – strategies for classifying child psychiatric syndromes are categorical and dimensional; conceptual ambiguities appear to be greatest for polythetic syndromes such as autism spectrum disorder (ASD). Recently, a compelling alternative has emerged that integrates both categorical and dimensional approaches (ie, hybrid model) thanks to the increasing sophistication of analytic procedures. This study aimed to quantify the optimal phenotypic structure of ASD by comprehensively comparing categorical, dimensional, and hybrid models. METHOD: The sample comprised 3,825 youth, who were consecutive referrals to a university developmental disabilities or child psychiatric outpatient clinic. Caregivers completed the Child and Adolescent Symptom Inventory-4R (CASI-4R), which includes an ASD symptom rating scale. A series of latent class analyses, exploratory and confirmatory factor analyses, and factor mixture analyses was conducted. Replication analyses were conducted in an independent sample (N=2,503) of children referred for outpatient evaluation. RESULTS: Based on comparison of 44 different models, results indicated that the ASD symptom phenotype is best conceptualized as multi-dimensional versus a categorical or categorical-dimensional hybrid construct. ASD symptoms were best characterized as falling along three dimensions (ie, social interaction, communication, and repetitive behavior) on the CASI-4R. CONCLUSION: Findings reveal an optimal structure with which to characterize the ASD phenotype using a single, parent-report measure, supporting presence of multiple correlated symptom dimensions that traverse formal diagnostic boundaries and quantify the heterogeneity of ASD. These findings inform understanding of how neurodevelopmental disorders can extend beyond discrete categories of development and represent continuously-distributed traits across the range of human behaviors.
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5. Maskey M, Rodgers J, Grahame V, Glod M, Honey E, Kinnear J, Labus M, Milne J, Minos D, McConachie H, Parr JR. {{A Randomised Controlled Feasibility Trial of Immersive Virtual Reality Treatment with Cognitive Behaviour Therapy for Specific Phobias in Young People with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2019.
We examined the feasibility and acceptability of using an immersive virtual reality environment (VRE) alongside cognitive behaviour therapy (CBT) for young people with autism experiencing specific phobia. Thirty-two participants were randomised to treatment or control. Treatment involved one session introducing CBT techniques and four VRE sessions, delivered by local clinical therapists. Change in target behaviour was independently rated. Two weeks after treatment, four treatment participants (25%) and no control participants were responders; at 6 months after treatment, six (38%) treatment and no control participants were responders. At 6 months post-treatment, symptoms had worsened for one treatment and five control (untreated) participants. Brief VRE exposure with CBT is feasible and acceptable to deliver through child clinical services and is effective for some participants.
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6. Mirza R, Sharma B. {{Benefits of Fenofibrate in prenatal valproic acid-induced autism spectrum disorder related phenotype in rats}}. {Brain Res Bull}. 2019.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with two major behavioral symptoms i.e. repetitive behavior and social-communication impairment. The unknown etiology of ASD is responsible for the difficulty in identifying the possible therapeutic modulators for ASD. Valproic acid (VPA) is an anticonvulsant drug in both human and rodents with teratogenic effects during pregnancy. Therefore, prenatal exposure of VPA induced autism spectrum disorder like phenotypes in both human and rodents. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is widely localized in the brain. This research investigates the utility of fenofibrate, a selective agonist of PPAR-alpha in prenatal VPA-induced experimental ASD in Wistar rats. The prenatal VPA has induced social impairment (three chambers social behavior apparatus), repetitive behavior (Y-maze), hyperlocomotion (actophotometer), anxiety (elevated plus maze) and low exploratory activity (hole board test). Also, prenatal VPA treated rats have shown higher levels of oxidative stress (increased in thiobarbituric acid reactive species and decreased in reduced glutathione level) and inflammation (increased in interleukin-6, tumor necrosis factor-alpha and decreased in interleukin-10) in the cerebellum, brainstem and prefrontal cortex. Treatment with fenofibrate significantly attenuated prenatal VPA-induced social impairment, repetitive behavior, hyperactivity, anxiety, and low exploratory activity. Furthermore, fenofibrate also decreased the prenatal VPA-induced oxidative stress and inflammation in brain regions. Hence, it may be concluded that fenofibrate may provide neurobehavioral and biochemical benefits in prenatal VPA-induced autism phenotypes in rats.
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7. Plaza-Diaz J, Gomez-Fernandez A, Chueca N, Torre-Aguilar MJ, Gil A, Perez-Navero JL, Flores-Rojas K, Martin-Borreguero P, Solis-Urra P, Ruiz-Ojeda FJ, Garcia F, Gil-Campos M. {{Autism Spectrum Disorder (ASD) with and without Mental Regression is Associated with Changes in the Fecal Microbiota}}. {Nutrients}. 2019; 11(2).
New microbiome sequencing technologies provide novel information about the potential interactions among intestinal microorganisms and the host in some neuropathologies as autism spectrum disorders (ASD). The microbiota(-)gut(-)brain axis is an emerging aspect in the generation of autistic behaviors; evidence from animal models suggests that intestinal microbial shifts may produce changes fitting the clinical picture of autism. The aim of the present study was to evaluate the fecal metagenomic profiles in children with ASD and compare them with healthy participants. This comparison allows us to ascertain how mental regression (an important variable in ASD) could influence the intestinal microbiota profile. For this reason, a subclassification in children with ASD by mental regression (AMR) and no mental regression (ANMR) phenotype was performed. The present report was a descriptive observational study. Forty-eight children aged 2(-)6 years with ASD were included: 30 with ANMR and 18 with AMR. In addition, a control group of 57 normally developing children was selected and matched to the ASD group by sex and age. Fecal samples were analyzed with a metagenomic approach using a next-generation sequencing platform. Several differences between children with ASD, compared with the healthy group, were detected. Namely, Actinobacteria and Proteobacteria at phylum level, as well as, Actinobacteria, Bacilli, Erysipelotrichi, and Gammaproteobacteria at class level were found at higher proportions in children with ASD. Additionally, Proteobacteria levels showed to be augmented exclusively in AMR children. Preliminary results, using a principal component analysis, showed differential patterns in children with ASD, ANMR and AMR, compared to healthy group, both for intestinal microbiota and food patterns. In this study, we report, higher levels of Actinobacteria, Proteobacteria and Bacilli, aside from Erysipelotrichi, and Gammaproteobacteria in children with ASD compared to healthy group. Furthermore, AMR children exhibited higher levels of Proteobacteria. Further analysis using these preliminary results and mixing metagenomic and other « omic » technologies are needed in larger cohorts of children with ASD to confirm these intestinal microbiota changes.
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8. Ruane A, Carr A, Moffat V, Finn T, Murphy A, O’Brien O, Groarke H, O’Dwyer R. {{A randomised controlled trial of the Group Stepping Stones Triple P training programme for parents of children with developmental disabilities}}. {Clinical child psychology and psychiatry}. 2019: 1359104519827622.
The central aim of this study was to examine the effectiveness of Group Stepping Stones Triple P (GSSTP) in an Irish context for families of children with both developmental disabilities and internalising and externalising behavioural problems. Parents of 84 children (mean age = 5.73; SD = 2.06) with developmental disabilities and co-occurring behaviour problems attending Irish public health services were randomly assigned to a 9-week GSSTP group or a waiting list control (WLC) group. All parents completed self-report measures before (Time 1) and after (Time 2) the programme and parents in the GSSTP group were assessed at 3- to 5-month follow-up (Time 3). At Time 2, clinical improvement and reliable change rates on the primary dependent variables (summary scales of the Developmental Behaviour Checklist and Strengths and Difficulties Questionnaire) were significantly higher in the GSSTP group than in the WLC group. At Time 2, mean scores of the GSSTP group showed significant, small to medium improvements relative to the WLC group on parent-reported child behaviour problems, parenting skills and confidence, and parental adjustment. Most of these improvements were maintained at 3- to 5-month follow-up. These results indicate that GSSTP is a promising intervention for improving child behaviour and parenting outcomes in a mixed-disability group in an Irish context.
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9. van den Boomen C, Fahrenfort JJ, Snijders TM, Kemner C. {{Slow segmentation of faces in Autism Spectrum Disorder}}. {Neuropsychologia}. 2019.
Atypical visual segmentation, affecting object perception, might contribute to face processing problems in Autism Spectrum Disorder (ASD). The current study investigated impairments in visual segmentation of faces in ASD. Thirty participants (ASD: 16; Control: 14) viewed texture-defined faces, houses, and homogeneous images, while electroencephalographic and behavioral responses were recorded. The ASD group showed slower face-segmentation related brain activity and longer segmentation reaction times than the control group, but no difference in house-segmentation related activity or behavioral performance. Furthermore, individual differences in face-segmentation but not house-segmentation correlated with score on the Autism Quotient. Segmentation is thus selectively impaired for faces in ASD, and relates to the degree of ASD traits. Face segmentation relates to recurrent connectivity from the fusiform face area (FFA) to the visual cortex. These findings thus suggest that atypical connectivity from the FFA might contribute to delayed face processing in ASD.
