1. Crawford S. {{On the origins of autism: The Quantitative Threshold Exposure hypothesis}}. {Med Hypotheses};2015 (Oct 16)
The Quantitative Threshold Exposure (QTE) hypothesis is a multifactorial threshold model that accounts for the cumulative effects of risk factor exposure in both the causation of autism spectrum disorder (ASD) and its dramatic increase over the past 30years. The QTE hypothesis proposes that ASD is triggered by the cumulative effects of high-level exposure to endogenous and environmental factors that act as antigens to impair normal immune system (IS) and associated central nervous system (CNS) functions during critical developmental stages. The quantitative threshold parameters that comprise a cumulative risk for the development of ASD are identified by the assessment of documented epidemiological factors that, in sum, determine the likelihood that ASD will occur as a result of their effects on critically integrated IS and CNS pathways active during prenatal, neo-natal and early childhood brain maturation. The model proposes an explanation for the relationship between critical developmental stages of brain/immune system development in conjunction with the quantitative effects of genetic and environmental risk factors that may interface with these critical developmental windows. This model may be useful even when the individual contributions of specific risk factors cannot be quantified, as it proposes that the combined quantitative level of exposure to risk factors for ASD rather than exposure to any one risk factor per se defines threshold occurrence rates.
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2. Dewinter J, Vermeiren R, Vanwesenbeeck I, Van Nieuwenhuizen C. {{Parental Awareness of Sexual Experience in Adolescent Boys With Autism Spectrum Disorder}}. {J Autism Dev Disord};2015 (Oct 19)
Parent report and adolescent self-report data on lifetime sexual experience in adolescents with ASD were compared in 43 parent-adolescent dyads. Parents tended to underestimate the lifetime sexual experience of their sons, particularly solo sexual experiences such as masturbation and experience with orgasm. Parental underestimation and unawareness of adolescents’ sexual experience may influence communication and education about sex and sexuality in families. These findings have implications for the interpretation of earlier research, based on parent and caregiver reports, on sexuality in adolescents with ASD.
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3. Dougherty CC, Evans DW, Myers SM, Moore GJ, Michael AM. {{A Comparison of Structural Brain Imaging Findings in Autism Spectrum Disorder and Attention-Deficit Hyperactivity Disorder}}. {Neuropsychol Rev};2015 (Oct 19)
ASD and ADHD are regarded as distinct disorders in the current DSM-5. However, recent research and the RDoC initiative are recognizing considerable overlap in the clinical presentation of ASD, ADHD, and other neurodevelopmental disorders. In spite of numerous neuroimaging findings in ASD and ADHD, the extent to which either of the above views are supported remains equivocal. Here we compare structural MRI and DTI literature in ASD and ADHD. Our main findings reveal both distinct and shared neural features. Distinct expressions were in total brain volume (ASD: increased volume, ADHD: decreased volume), amygdala (ASD: overgrowth, ADHD: normal), and internal capsule (ASD: unclear, ADHD: reduced FA in DTI). Considerable overlap was noted in the corpus callosum and cerebellum (lower volume in structural MRI and decreased FA in DTI), and superior longitudinal fasciculus (reduced FA in DTI). In addition, we identify brain regions which have not been studied in depth and require more research. We discuss relationships between brain features and symptomatology. We conclude by addressing limitations of current neuroimaging research and offer approaches that account for clinical heterogeneity to better distinguish brain-behavior relationships.
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4. Durbin A, Sirotich F, Lunsky Y, Durbin J. {{Unmet Needs of Adults in Community Mental Health Care With and Without Intellectual and Developmental Disabilities: A Cross-Sectional Study}}. {Community Ment Health J};2015 (Oct 19)
The cross-sectional study compared the clinical and need profiles for clients with and without intellectual and developmental disabilities (IDD) in seven mental health case management programs in Toronto, Canada on March 31, 2013. Unmet needs in domains within four broad clusters were measured by staff using an internationally utilized tool, the Camberwell Assessment of Need. Among the 2560 clients, 8.3 % had a co-occurring IDD. For most assessed domains rates of unmet need were not different for persons with and without IDD. However, the IDD group had greater unmet needs for adaptive functioning/skills and cognitive needs [self-care (p = 0.023), education (p < 0.001), transportation (p < 0.001), and information on condition (p = 0.038)]. While clients with IDD and psychiatric diagnoses often receive poor quality care, in the case management programs examined their rates of unmet need were similar to individuals without IDD across most assessed domains, including in the areas of addictions and physical health care.
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5. Fairthorne J, de Klerk N, Leonard H. {{Brief Report: Burden of Care in Mothers of Children with Autism Spectrum Disorder or Intellectual Disability}}. {J Autism Dev Disord};2015 (Oct 19)
Compared to other mothers, mothers of children with autism spectrum disorder (ASD) or intellectual disability (ID) have higher rates of treatment episodes for psychiatric disorders. We aimed to estimate the maternal burden of care by comparing the length of hospitalisations for psychiatric disorders and the treatment rates for psychiatric disorders after the birth in mothers of children with ASD/ID and no psychiatric history to that of other mothers with no psychiatric history. Mothers of children with ID of known cause (not Down syndrome) and mothers of children ASD without ID emerged as particularly vulnerable. Mothers of children with Down syndrome were resilient. The development of specialised organisations to provide support to mothers of children with ID of known cause (not Down syndrome) and mothers of children with ASD without ID could assist them to maintain their mental health.
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6. Hellings JA, Jadhav M, Jain S, Jadhav S, Genovese A. {{Low Dose Loxapine: Neuromotor Side Effects and Tolerability in Autism Spectrum Disorders}}. {J Child Adolesc Psychopharmacol};2015 (Oct);25(8):618-624.
OBJECTIVE: New and repurposed drugs are urgently needed to treat individuals with autism spectrum disorders (ASD). Loxapine (LOX) in low doses of 5-15 mg/day resembles an atypical antipsychotic (Stahl 2002 ). Our recent open pilot study of LOX found significant behavioral improvements and overall weight neutrality in 16 adolescents and adults with ASD. The present study examined an outpatient sample for LOX neuromotor tolerability. METHODS: Consecutive outpatients with Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision (DSM-IV-TR) ASD diagnoses receiving LOX were examined for tardive dyskinesia (TD) and extrapyramidal side effects (EPS) using the Dyskinesia Identification System: Condensed User Scale (DISCUS), and for akathisia using the Barnes Akathisia Rating Scale. Data were also then retrospectively extracted from clinic charts regarding age, gender, diagnoses, LOX doses, treatment duration, concomitant medications, and LOX dosage reductions. RESULTS: Thirty-four subjects (25 male, 9 female) participated. Mean age was 23.4 years at LOX initiation (range 8-52). Thirteen subjects (38.2%) received loxapine for >/=5 years. Mean LOX dose was 8.9 mg/day (range 5-30 mg) and mean duration was 4.2 years (range 0.8-13). Fourteen subjects (41.2%) received concomitant atypical antipsychotics. Benztropine was prescribed in 5 of 34 subjects (14.7%). Three subjects manifested tics at baseline, but lower final DISCUS scores. Subject 26, with Prader-Willi syndrome, manifested TD. Apart from LOX 5 mg daily he received paroxetine 40 mg daily, which reduces LOX metabolism significantly. Akathisia objective scores were positive in 6 subjects (17.6%): Subject 2 scored 3 (pacing was present also at baseline); subjects 6, 7, and 11 each scored 1; and subjects 18 and 23 each scored 2. Six of 9 subjects (66.7%) with expressive language were positive for subjective akathisia. CONCLUSIONS: Low dose LOX was well tolerated, with lower than expected TD rates. This confirms clinical resemblance to an atypical antipsychotic. Individuals with neuromuscular problems including Prader-Willi Syndrome receiving LOX require close monitoring. Further study of LOX in ASD is warranted.
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7. Pennisi P, Tonacci A, Tartarisco G, Billeci L, Ruta L, Gangemi S, Pioggia G. {{Autism and social robotics: A systematic review}}. {Autism Res};2015 (Oct 20)
Social robotics could be a promising method for Autism Spectrum Disorders (ASD) treatment. The aim of this article is to carry out a systematic literature review of the studies on this topic that were published in the last 10 years. We tried to address the following questions: can social robots be a useful tool in autism therapy? We followed the PRISMA guidelines, and the protocol was registered within PROSPERO database (CRD42015016158). We found many positive implications in the use of social robots in therapy as for example: ASD subjects often performed better with a robot partner rather than a human partner; sometimes, ASD patients had, toward robots, behaviors that TD patients had toward human agents; ASDs had a lot of social behaviors toward robots; during robotic sessions, ASDs showed reduced repetitive and stereotyped behaviors and, social robots manage to improve spontaneous language during therapy sessions. Therefore, robots provide therapists and researchers a means to connect with autistic subjects in an easier way, but studies in this area are still insufficient. It is necessary to clarify whether sex, intelligence quotient, and age of participants affect the outcome of therapy and whether any beneficial effects only occur during the robotic session or if they are still observable outside the clinical/experimental context. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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8. Reiner O, Karzburn E, Kshirsagar A, Kaibuchi K. {{Regulation of Neuronal Migration, an Emerging Topic in Autism Spectrum Disorders (ASD)}}. {J Neurochem};2015 (Oct 20)
Autism Spectrum Disorders (ASD) encompass a group of neurodevelopmental diseases that demonstrate strong heritability, however the inheritance is not simple and many genes have been associated with these disorders. ASD is regarded as a neurodevelopmental disorder, and abnormalities at different developmental stages are part of the disease etiology. This review provides a general background on neuronal migration during brain development and discusses recent advancements in the field connecting ASD and aberrant neuronal migration. This article is protected by copyright. All rights reserved.
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9. Ruzich E, Allison C, Chakrabarti B, Smith P, Musto H, Ring H, Baron-Cohen S. {{Sex and STEM Occupation Predict Autism-Spectrum Quotient (AQ) Scores in Half a Million People}}. {PLoS One};2015;10(10):e0141229.
This study assesses Autism-Spectrum Quotient (AQ) scores in a ‘big data’ sample collected through the UK Channel 4 television website, following the broadcasting of a medical education program. We examine correlations between the AQ and age, sex, occupation, and UK geographic region in 450,394 individuals. We predicted that age and geography would not be correlated with AQ, whilst sex and occupation would have a correlation. Mean AQ for the total sample score was m = 19.83 (SD = 8.71), slightly higher than a previous systematic review of 6,900 individuals in a non-clinical sample (mean of means = 16.94) This likely reflects that this big-data sample includes individuals with autism who in the systematic review score much higher (mean of means = 35.19). As predicted, sex and occupation differences were observed: on average, males (m = 21.55, SD = 8.82) scored higher than females (m = 18.95; SD = 8.52), and individuals working in a STEM career (m = 21.92, SD = 8.92) scored higher than individuals non-STEM careers (m = 18.92, SD = 8.48). Also as predicted, age and geographic region were not meaningfully correlated with AQ. These results support previous findings relating to sex and STEM careers in the largest set of individuals for which AQ scores have been reported and suggest the AQ is a useful self-report measure of autistic traits.
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10. Schipul SE, Just MA. {{Diminished Neural Adaptation during Implicit Learning in Autism}}. {Neuroimage};2015 (Oct 17)
Neuroimaging studies have shown evidence of disrupted neural adaptation during learning in individuals with autism spectrum disorder (ASD) in several types of tasks, potentially stemming from frontal-posterior cortical underconnectivity (Schipul et al., 2012). The aim of the current study was to examine neural adaptations in an implicit learning task that entails participation of frontal and posterior regions. Sixteen high-functioning adults with ASD and sixteen neurotypical control participants were trained on and performed an implicit dot pattern prototype learning task in a functional magnetic resonance imaging (fMRI) session. During the preliminary exposure to the type of implicit prototype learning task later to be used in the scanner, the ASD participants took longer than the neurotypical group to learn the task, demonstrating altered implicit learning in ASD. After equating task structure learning, the two groups’ brain activation differed during their learning of a new prototype in the subsequent scanning session. The main findings indicated that neural adaptations in a distributed task network were reduced in the ASD group, relative to the neurotypical group, and were related to ASD symptom severity. Functional connectivity was reduced and did not change as much during learning for the ASD group, and was related to ASD symptom severity. These findings suggest that individuals with ASD show altered neural adaptations during learning, as seen in both activation and functional connectivity measures. This finding suggests why many real-world implicit learning situations may pose special challenges for ASD.
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11. Spek AA. {{[Eating problems in individuals with autism spectrum disorder (ASD) but no intellectual impairment]}}. {Tijdschr Psychiatr};2015;57(10):749-756.
BACKGROUND: Little is known about the co-occurrence – in individuals – of autism spectrum disorder (ASD) and eating disorders and eating problems. Consequently, clinicians do not have enough information about how to diagnose or treat the combination of ASD and eating problems. AIM: To discuss the scientific literature and clinical experiences relating to eating disorders and eating problems in people who have ASD but no intellectual impairment. METHOD: The scientific literature was searched by means of PubMed, Medline and PsycINFO, and clinical experiences were discussed. RESULTS: The combination of ASS and anorexia nervosa seems to be a strong predictor that the eating disorder will follow a chronic course. It is not clear how often bulimia nervosa occurs in persons with ASD. Eating problems in persons with ASD often seem to be related to sensory sensitivity, eating preferences and motor problems. So far, little is known about the treatment of eating disorders and eating problems in individuals with ASD. CONCLUSION: When diagnosing and treating eating disorders and eating problems in individuals with ASD, it is important to take information processing and behaviour characteristics of ASD into account. Further research is needed, particularly in order to cast more light on treatment possibilities.
12. Stanish H, Curtin C, Must A, Phillips S, Maslin M, Bandini L. {{Enjoyment, Barriers, and Beliefs About Physical Activity in Adolescents With and Without Autism Spectrum Disorder}}. {Adapt Phys Activ Q};2015 (Oct);32(4):302-317.
The authors compared physical activity enjoyment, perceived barriers, beliefs, and self-efficacy between adolescents with autism spectrum disorder (ASD) and typically developing (TD) adolescents. A questionnaire was verbally administered to 35 adolescents with ASD and 60 TD adolescents. Compared with TD adolescents, fewer adolescents with ASD enjoyed team sports (65% vs. 95%, p < .001) and physical education (84% vs. 98%, p = .02). A greater proportion of adolescents with ASD perceived that physical activities were too hard to learn (16% vs. 0%, p < .01), and fewer believed that physical activity was a way to make friends (68% vs. 97%, p < .001). Fewer adolescents with ASD preferred to do physical activity in their free time (25% vs. 58%, p < .01). Most adolescents with ASD felt that physical activity is fun (84%), but the proportion was lower than in TD adolescents (98%, p = .03). Some perceptions about physical activity were similar between the 2 groups, but differences identified may inform program development.
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13. Subramanian M, Timmerman CK, Schwartz JL, Pham DL, Meffert MK. {{Characterizing autism spectrum disorders by key biochemical pathways}}. {Front Neurosci};2015;9:313.
The genetic and phenotypic heterogeneity of autism spectrum disorders (ASD) presents a substantial challenge for diagnosis, classification, research, and treatment. Investigations into the underlying molecular etiology of ASD have often yielded mixed and at times opposing findings. Defining the molecular and biochemical underpinnings of heterogeneity in ASD is crucial to our understanding of the pathophysiological development of the disorder, and has the potential to assist in diagnosis and the rational design of clinical trials. In this review, we propose that genetically diverse forms of ASD may be usefully parsed into entities resulting from converse patterns of growth regulation at the molecular level, which lead to the correlates of general synaptic and neural overgrowth or undergrowth. Abnormal brain growth during development is a characteristic feature that has been observed both in children with autism and in mouse models of autism. We review evidence from syndromic and non-syndromic ASD to suggest that entities currently classified as autism may fundamentally differ by underlying pro- or anti-growth abnormalities in key biochemical pathways, giving rise to either excessive or reduced synaptic connectivity in affected brain regions. We posit that this classification strategy has the potential not only to aid research efforts, but also to ultimately facilitate early diagnosis and direct appropriate therapeutic interventions.
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14. Tassone F. {{Advanced technologies for the molecular diagnosis of fragile X syndrome}}. {Expert Rev Mol Diagn};2015 (Oct 21):1-9.
Fragile X syndrome (FXS), a trinucleotide repeat disorder, is the most common heritable form of cognitive impairment. Since the discovery of the FMR1 gene in 1991, great strides have been made in the field of molecular diagnosis for FXS. Cytogenetic analysis, which was the method of diagnosis in the early 1990, was replaced by Southern blot and PCR analysis albeit with some limitations. In the past few years many PCR-based methodologies, able to amplify large full mutation expanded alleles, with or without methylation, have been proposed. Reviewed here are the advantages, disadvantages and limitations of the most recent developments in the field of FXS diagnosis.
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15. Urbain C, Vogan VM, Ye AX, Pang EW, Doesburg SM, Taylor MJ. {{Desynchronization of fronto-temporal networks during working memory processing in autism}}. {Hum Brain Mapp};2015 (Oct 20)
BACKGROUND: Mounting evidence suggests that autism is a network disorder, characterized by atypical brain connectivity, especially in the context of high level cognitive processes such as working memory (WM). Accordingly, atypical WM processes have been related to the social and cognitive deficits observed in children with autism spectrum disorder (ASD). METHODS: We used magnetoencephalography (MEG) to investigate connectivity differences during a high memory load (2-back) WM task between 17 children with ASD and 20 age-, sex-, and IQ-matched controls. RESULTS: We identified reduced inter-regional alpha-band (9-15 Hz) phase synchronization in children with ASD during the WM task. Reduced WM-related brain synchronization encompassed fronto-temporal networks (ps < 0.04 corrected) previously associated with challenging high-level conditions (i.e. the left insula and the anterior cingulate cortex (ACC)) and memory encoding and/or recognition (i.e. the right middle temporal gyrus and the right fusiform gyrus). Additionally, we found that reduced connectivity processes related to the right fusiform were correlated with the severity of symptoms in children with ASD, suggesting that such atypicalities could be directly related to the behavioural deficits observed. DISCUSSION: This study provides new evidence of atypical long-range synchronization in children with ASD in fronto-temporal areas that crucially contribute to challenging WM tasks, but also emotion regulation and social cognition processes. Thus, these results support the network disorder hypothesis of ASD and argue for a specific pathophysiological contribution of brain processes related to working memory and executive functions on the symptomatology of autism. Hum Brain Mapp, 2015. (c) 2015 Wiley Periodicals, Inc.
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16. Wang Y, Zhao X, Ju W, Flory M, Zhong J, Jiang S, Wang P, Dong X, Tao X, Chen Q, Shen C, Zhong M, Yu Y, Brown WT, Zhong N. {{Genome-wide differential expression of synaptic long noncoding RNAs in autism spectrum disorder}}. {Transl Psychiatry};2015;5:e660.
A genome-wide differential expression of long noncoding RNAs (lncRNAs) was identified in blood specimens of autism spectrum disorder (ASD). A total of 3929 lncRNAs were found to be differentially expressed in ASD peripheral leukocytes, including 2407 that were upregulated and 1522 that were downregulated. Simultaneously, 2591 messenger RNAs (mRNAs), including 1789 upregulated and 821 downregulated, were also identified in ASD leukocytes. Functional pathway analysis of these lncRNAs revealed neurological pathways of the synaptic vesicle cycling, long-term depression and long-term potentiation to be primarily involved. Thirteen synaptic lncRNAs, including nine upregulated and four downregulated, and 19 synaptic mRNAs, including 12 upregulated and seven downregulated, were identified as being differentially expressed in ASD. Our identification of differential expression of synaptic lncRNAs and mRNAs suggested that synaptic vesicle transportation and cycling are important for the delivery of synaptosomal protein(s) between presynaptic and postsynaptic membranes in ASD. Finding of 19 lncRNAs, which are the antisense, bi-directional and intergenic, of HOX genes may lead us to investigate the role of HOX genes involved in the development of ASD. Discovery of the lncRNAs of SHANK2-AS and BDNF-AS, the natural antisense of genes SHANK2 and BDNF, respectively, indicates that in addition to gene mutations, deregulation of lncRNAs on ASD-causing gene loci presents a new approach for exploring possible epigenetic mechanisms underlying ASD. Our study also opened a new avenue for exploring the use of lncRNA(s) as biomarker(s) for the early detection of ASD.
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17. Yerys BE, Gordon EM, Abrams DN, Satterthwaite TD, Weinblatt R, Jankowski KF, Strang J, Kenworthy L, Gaillard WD, Vaidya CJ. {{Default mode network segregation and social deficits in autism spectrum disorder: Evidence from non-medicated children}}. {Neuroimage Clin};2015;9:223-232.
Functional pathology of the default mode network is posited to be central to social-cognitive impairment in autism spectrum disorders (ASD). Altered functional connectivity of the default mode network’s midline core may be a potential endophenotype for social deficits in ASD. Generalizability from prior studies is limited by inclusion of medicated participants and by methods favoring restricted examination of network function. This study measured resting-state functional connectivity in 22 8-13 year-old non-medicated children with ASD and 22 typically developing controls using seed-based and network segregation functional connectivity methods. Relative to controls the ASD group showed both under- and over-functional connectivity within default mode and non-default mode regions, respectively. ASD symptoms correlated negatively with the connection strength of the default mode midline core-medial prefrontal cortex-posterior cingulate cortex. Network segregation analysis with the participation coefficient showed a higher area under the curve for the ASD group. Our findings demonstrate that the default mode network in ASD shows a pattern of poor segregation with both functional connectivity metrics. This study confirms the potential for the functional connection of the midline core as an endophenotype for social deficits. Poor segregation of the default mode network is consistent with an excitation/inhibition imbalance model of ASD.
