1. Alabdali A, Al-Ayadhi L, El-Ansary A. {{A key role for an impaired detoxification mechanism in the etiology and severity of autism spectrum disorders}}. {Behav Brain Funct}. 2014; 10(1): 14.
BACKGROUND: Autism Spectrum Disorders (ASD) is a syndrome with a number of etiologies and different mechanisms that lead to abnormal development. The identification of autism biomarkers in patients with different degrees of clinical presentation (i.e., mild, moderate and severe) will give greater insight into the pathogenesis of this disease and will enable effective early diagnostic strategies and treatments for this disorder. METHODS: In this study, the concentration of two toxic heavy metals, lead (Pb) and mercury (Hg), were measured in red blood cells, while glutathione-s-transferase (GST) and vitamin E, as enzymatic and non-enzymatic antioxidants, respectively, were measured in the plasma of subgroups of autistic patients with different Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS) scores. The results were compared to age- and gender-matched healthy controls. RESULTS: The obtained data showed that the patients with autism spectrum disorder had significantly higher Pb and Hg levels and lower GST activity and vitamin E concentrations compared with the controls. The levels of heavy metals (Hg and Pb), GST and vitamin E were correlated with the severity of the social and cognitive impairment measures (SRS and CARS). Receiver Operating Characteristics (ROC) analysis and predictiveness curves indicated that the four parameters show satisfactory sensitivity, very high specificity and excellent predictiveness. Multiple regression analyses confirmed that higher levels of Hg and Pb, together with lower levels of GST and vitamin E, can be used to predict social and cognitive impairment in patients with autism spectrum disorders. CONCLUSION: This study confirms earlier studies that implicate toxic metal accumulation as a consequence of impaired detoxification in autism and provides insight into the etiological mechanism of autism.
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2. Goffin D, Brodkin ES, Blendy JA, Siegel SJ, Zhou Z. {{Cellular origins of auditory event-related potential deficits in Rett syndrome}}. {Nat Neurosci}. 2014.
Dysfunction in sensory information processing is a hallmark of many neurological disorders, including autism spectrum disorders, schizophrenia and Rett syndrome (RTT). Using mouse models of RTT, a monogenic disorder caused by mutations in MECP2, we found that the large-scale loss of MeCP2 from forebrain GABAergic interneurons led to deficits in auditory event-related potentials and seizure manifestation, whereas the restoration of MeCP2 in specific classes of interneurons ameliorated these deficits.
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3. Hauth I, de Bruijn YG, Staal W, Buitelaar JK, Rommelse NN. {{Testing the Extreme Male Brain Theory of Autism Spectrum Disorder in a Familial Design}}. {Autism Res}. 2014.
Autism Spectrum Disorder (ASD) may be an extreme manifestation of some male-typical traits in both neuroanatomy and cognition. Using the ratio of the second to fourth digit (2D:4D) and digit length as biomarkers of (pre- and postnatal) testosterone levels, examined was whether hypermasculinized digit ratios and/or lengths were familial traits in ASD and investigated their relation to sexually dimorphic cognitive abilities. 2D:4D ratios and digit lengths of 216 children with ASD, 202 unaffected siblings, and 360 parents were compared with those of 174 control children and their 146 parents. Generalized Estimation Equations, Generalized Linear Models, and Linear Mixed Models were used to investigate parent-offspring relationships and group differences. In ASD probands and their relatives alike, digit length relative to overall height was significantly increased in comparison to controls. No significant group differences were found between affected and unaffected subjects, or between males and females. Additionally, 2D:4D ratios increased with age. No (consistent) associations were found between 2D:4D ratio or digit lengths and systemizing and empathizing skills. The findings emphasize the role of familially based elevated pre- and postnatal testosterone levels in the liability for ASD, but challenge the use of 2D:4D ratio as a proxy of prenatal testosterone exposure solely. Given that many genes influence digit length, the exact mechanisms underlying a familial predisposition toward increased digit length in ASD are as yet unknown and needs to be explored in future studies. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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4. Inaba Y, Schwartz CE, Bui QM, Li X, Skinner C, Field M, Wotton T, Hagerman RJ, Francis D, Amor DJ, Hopper JL, Loesch DZ, Bretherton L, Slater HR, Godler DE. {{Early Detection of Fragile X Syndrome: Applications of a Novel Approach for Improved Quantitative Methylation Analysis in Venous Blood and Newborn Blood Spots}}. {Clin Chem}. 2014.
BACKGROUND: Standard fragile X syndrome (FXS) diagnostic tests that target methylation of the fragile X mental retardation 1 (FMR1) CpG island 5` of the CGG expansion can be used to predict severity of the disease in males from birth, but not in females.METHODS: We describe methylation specific-quantitative melt analysis (MS-QMA) that targets 10 CpG sites, with 9 within FMR1 intron 1, to screen for FXS from birth in both sexes. The novel method combines the qualitative strengths of high-resolution melt and the high-throughput, quantitative real-time PCR standard curve to provide accurate quantification of DNA methylation in a single assay. Its performance was assessed in 312 control (CGG <40), 143 premutation (PM) (CGG 56-170), 197 full mutation (FM) (CGG 200-2000), and 33 CGG size and methylation mosaic samples.RESULTS: In male and female newborn blood spots, MS-QMA differentiated FM from control alleles, with sensitivity, specificity, and positive and negative predictive values between 92% and 100%. In venous blood of FM females between 6 and 35 years of age, MS-QMA correlated most strongly with verbal IQ impairment (P = 0.002). In the larger cohort of males and females, MS-QMA correlated with reference methods Southern blot and MALDI-TOF mass spectrometry (P < 0.05), but was not significantly correlated with age. Unmethylated alleles in high-functioning FM and PM males determined by both reference methods were also unmethylated by MS-QMA.CONCLUSIONS: MS-QMA has an immediate application in FXS diagnostics, with a potential use of its quantitative methylation output for prognosis in both sexes.
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5. McElhanon BO, McCracken C, Karpen S, Sharp WG. {{Gastrointestinal Symptoms in Autism Spectrum Disorder: A Meta-analysis}}. {Pediatrics}. 2014.
BACKGROUND: In pediatric settings, parents often raise concerns about possible gastrointestinal (GI) symptoms in autism spectrum disorder (ASD), yet the specificity of these concerns are not well studied. OBJECTIVE: To conduct a meta-analysis of research investigating GI symptoms among children with ASD. METHODS: We searched Medline, PsycINFO, and PubMed databases (1980-2012) in peer-reviewed journals. Analysis involved studies with a comparison group presenting quantitative data on GI symptoms using combinations of terms for ASD and GI indicators. The systematic search yielded 15 studies. We calculated effect sizes and 95% confidence intervals (CIs) using a random-effects model. RESULTS: Children with ASD experience significantly more general GI symptoms than comparison groups, with a standardized mean difference of 0.82 (0.24) and a corresponding odds ratio (OR) of 4.42 (95% CI, 1.90-10.28). Analysis also indicated higher rates of diarrhea (OR, 3.63; 95% CI, 1.82-7.23), constipation (OR, 3.86; 95% CI, 2.23-6.71), and abdominal pain (OR, 2.45; 95% CI, 1.19-5.07). CONCLUSIONS: Results indicate greater prevalence of GI symptoms among children with ASD compared with control children. Identified studies involved high methodological variability and lack of comprehensive data prohibited analysis of GI pathophysiologies (eg, gastroesophageal reflux) typically associated with organic etiologies, limiting conclusions about the underpinnings of the observed association. Future research must address critical questions about the causes and long-term impact of GI symptoms in ASD. Such analyses will require more systematic research and clinical activities, including improved diagnostic screening, standardized assessment, and exploration of potential moderators (eg, dietary restrictions).
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6. Pineda JA, Carrasco K, Datko M, Pillen S, Schalles M. {{Neurofeedback training produces normalization in behavioural and electrophysiological measures of high-functioning autism}}. {Philos Trans R Soc Lond B Biol Sci}. 2014; 369(1644): 20130183.
Autism spectrum disorder (ASD) is a neurodevelopmental condition exhibiting impairments in behaviour, social and communication skills. These deficits may arise from aberrant functional connections that impact synchronization and effective neural communication. Neurofeedback training (NFT), based on operant conditioning of the electroencephalogram (EEG), has shown promise in addressing abnormalities in functional and structural connectivity. We tested the efficacy of NFT in reducing symptoms in children with ASD by targeting training to the mirror neuron system (MNS) via modulation of EEG mu rhythms. The human MNS has provided a neurobiological substrate for understanding concepts in social cognition relevant to behavioural and cognitive deficits observed in ASD. Furthermore, mu rhythms resemble MNS phenomenology supporting the argument that they are linked to perception and action. Thirty hours of NFT on ASD and typically developing (TD) children were assessed. Both groups completed an eyes-open/-closed EEG session as well as a mu suppression index assessment before and after training. Parents filled out pre- and post-behavioural questionnaires. The results showed improvements in ASD subjects but not in TDs. This suggests that induction of neuroplastic changes via NFT can normalize dysfunctional mirroring networks in children with autism, but the benefits are different for TD brains.
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7. Vivanti G, Rogers SJ. {{Autism and the mirror neuron system: insights from learning and teaching}}. {Philos Trans R Soc Lond B Biol Sci}. 2014; 369(1644): 20130184.
Individuals with autism have difficulties in social learning domains which typically involve mirror neuron system (MNS) activation. However, the precise role of the MNS in the development of autism and its relevance to treatment remain unclear. In this paper, we argue that three distinct aspects of social learning are critical for advancing knowledge in this area: (i) the mechanisms that allow for the implicit mapping of and learning from others’ behaviour, (ii) the motivation to attend to and model conspecifics and (iii) the flexible and selective use of social learning. These factors are key targets of the Early Start Denver Model, an autism treatment approach which emphasizes social imitation, dyadic engagement, verbal and non-verbal communication and affect sharing. Analysis of the developmental processes and treatment-related changes in these different aspects of social learning in autism can shed light on the nature of the neuropsychological mechanisms underlying social learning and positive treatment outcomes in autism. This knowledge in turn may assist in developing more successful pedagogic approaches to autism spectrum disorder. Thus, intervention research can inform the debate on relations among neuropsychology of social learning, the role of the MNS, and educational practice in autism.
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8. Watkins N, Sparling E. {{The Effectiveness of the Snug Vest on Stereotypic Behaviors in Children Diagnosed With an Autism Spectrum Disorder}}. {Behav Modif}. 2014.
Various reviews of the effects of sensory integration therapy (SIT) have concluded that such interventions fail to reduce stereotypy. However, a new, and as yet untested, SIT iteration, an inflatable wearable vest known as the Snug Vest purports to decrease such repetitive behavior. In the current study, three children who emitted different forms of stereotypy participated in an alternating treatments design in which each participant wore a fully inflated vest and either a fully deflated vest or no vest. The results of the study show that the Snug Vest failed to reduce any participants’ stereotypy. We highlight our findings in the context of professional practice and discuss several potential limitations.
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9. Wong LM, Goodrich-Hunsaker NJ, McLennan Y, Tassone F, Zhang M, Rivera SM, Simon TJ. {{Eye movements reveal impaired inhibitory control in adult male fragile x premutation carriers asymptomatic for fxtas}}. {Neuropsychology}. 2014.
Objective: Fragile X premutation carriers (fXPCs) have an expansion of 55 -200 CGG repeats in the FMR1 gene. Male fXPCs are at risk for developing a neurodegenerative motor disorder (FXTAS) often accompanied by inhibitory control impairments, even in fXPCs without motor symptoms. Inhibitory control impairments might precede, and thus indicate elevated risk for motor impairment associated with FXTAS. We tested whether inhibitory impairments are observable in fXPCs by assessing oculomotor performance. Method: Participants were males aged 18-48 years asymptomatic for FXTAS. FXPCs (n = 21) and healthy age-matched controls (n = 22) performed four oculomotor tasks. In a Fixation task, participants fixated on a central cross and maintained gaze position when a peripheral stimulus appeared. In a Pursuit task, participants maintained gaze on a square moving at constant velocity. In a Prosaccade task, participants fixated on a central cross, then looked at a peripheral stimulus. An Antisaccade task was identical to the Prosaccade task, except participants looked in the direction opposite the stimulus. Inhibitory cost was the difference in saccade latency between the Antisaccade and Prosaccade tasks. Results: Relative to controls, fXPCs had longer saccade latency in the Antisaccade task. In fXPCs, inhibitory cost was positively associated with vermis area in lobules VI-VII. Conclusion: Antisaccades require inhibitory control to inhibit reflexive eye movements. We found that eye movements are sensitive to impaired inhibitory control in fXPCs asymptomatic for FXTAS. Thus, eye movements may be useful in assessing FXTAS risk or disease progression. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
