1. Bauman MD, Schumann CM. {{Is ‘bench-to-bedside’ realistic for autism? An integrative neuroscience approach}}. {Neuropsychiatry}. 2013 Apr;3(2):159-68.
Given the prevalence and societal impact of autism spectrum disorder (ASD), there is an urgent need to develop innovative treatments that will improve core social deficits, for which there is currently no reliable pharmacological treatment, prevention or cure. Development of novel biological interventions will depend upon the successful translation of basic neuroscience research into safe and effective medicines. This article outlines steps to bring neuroscience research from ‘the bench’ to treatment at ‘bedside’, from phenotyping the disorder to animal models to patient treatment. Although these steps appear simplistic, this is a daunting challenge because of the inherent complexity of the human brain, our lack of understanding of disease neurobiology underlying ASD, and the incredible heterogeneity of the disorder. For ASD, perhaps more than any other neurological or psychiatric disorder, progress will depend on integrative multidisciplinary approaches between basic scientists from varying neuroscience disciplines and clinicians to make ‘bench to bedside’ treatment a reality.
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2. Bellebaum C, Brodmann K, Thoma P. {{Active and observational reward learning in adults with autism spectrum disorder: relationship with empathy in an atypical sample}}. {Cognitive neuropsychiatry}. 2013 Sep 2.
Introduction Autism spectrum disorders (ASDs) are characterised by disturbances in social behaviour. A prevailing hypothesis suggests that these problems are related to deficits in assigning rewarding value to social stimuli. The present study aimed to examine monetary reward processing in adults with ASDs by means of event-related potentials (ERPs). Methods Ten individuals with mild ASDs (Asperger’s syndrome and high-functioning autism) and 12 healthy control subjects performed an active and an observational probabilistic reward-learning task. Results Both groups showed similar overall learning performance. With respect to reward processing, subjects with ASDs exhibited a general reduction in feedback-related negativity (FRN) amplitude, irrespective of feedback valence and type of learning (active or observational). Individuals with ASDs showed lower scores for cognitive empathy, while affective empathy did not differ between groups. Correlation analyses revealed that higher empathy (both cognitive and affective) negatively affected performance in observational learning in controls and in active learning in ASDs (only cognitive empathy). No relationships were seen between empathy and ERPs. Conclusions Reduced FRN amplitudes are discussed in terms of a deficit in fast reward processing in ASDs, which may indicate altered reward system functioning.
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3. Brosnan M, Chapman E, Ashwin C. {{Adolescents with Autism Spectrum Disorder Show a Circumspect Reasoning Bias Rather than ‘Jumping-to-Conclusions’}}. {J Autism Dev Disord}. 2013 Sep 4.
People with autism spectrum disorders (ASD) often take longer to make decisions. The Autism-Psychosis Model proposes that people with autism and psychosis show the opposite pattern of results on cognitive tasks. As those with psychosis show a jump-to-conclusions reasoning bias, those with ASD should show a circumspect reasoning bias. Jumping-to-conclusions was assessed in a sample of 20 adolescents with ASD and 23 age-matched controls using the jumping-to-conclusions beads task. Both groups demonstrated equivalent levels of confidence in decision-making, however the ASD group required more beads than controls before making their decision. Furthermore, there was a positive correlation between the beads required and degree of autism symptoms. Consistent with the Autism-Psychosis Model, a more circumspect reasoning bias was evident in ASD.
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4. Ladd-Acosta C, Hansen KD, Briem E, Fallin MD, Kaufmann WE, Feinberg AP. {{Common DNA methylation alterations in multiple brain regions in autism}}. {Molecular psychiatry}. 2013 Sep 3.
Autism spectrum disorders (ASD) are increasingly common neurodevelopmental disorders defined clinically by a triad of features including impairment in social interaction, impairment in communication in social situations and restricted and repetitive patterns of behavior and interests, with considerable phenotypic heterogeneity among individuals. Although heritability estimates for ASD are high, conventional genetic-based efforts to identify genes involved in ASD have yielded only few reproducible candidate genes that account for only a small proportion of ASDs. There is mounting evidence to suggest environmental and epigenetic factors play a stronger role in the etiology of ASD than previously thought. To begin to understand the contribution of epigenetics to ASD, we have examined DNA methylation (DNAm) in a pilot study of postmortem brain tissue from 19 autism cases and 21 unrelated controls, among three brain regions including dorsolateral prefrontal cortex, temporal cortex and cerebellum. We measured over 485 000 CpG loci across a diverse set of functionally relevant genomic regions using the Infinium HumanMethylation450 BeadChip and identified four genome-wide significant differentially methylated regions (DMRs) using a bump hunting approach and a permutation-based multiple testing correction method. We replicated 3/4 DMRs identified in our genome-wide screen in a different set of samples and across different brain regions. The DMRs identified in this study represent suggestive evidence for commonly altered methylation sites in ASD and provide several promising new candidate genes.Molecular Psychiatry advance online publication, 3 September 2013; doi:10.1038/mp.2013.114.
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5. Mathersul D, McDonald S, Rushby JA. {{Automatic facial responses to briefly presented emotional stimuli in autism spectrum disorder}}. {Biological psychology}. 2013 Aug 30.
Emotion processing, including automatic facial mimicry, plays an important role in social reciprocity. Disruptions in these processes have implications for individuals with impaired social functioning, such as autism spectrum disorders (ASDs). Past research has demonstrated that ASDs are impaired in the recognition of briefly presented emotions and display atypical mimicry of emotions presented for protracted duration. Mimicry (electromyography; EMG) of briefly presented emotions was investigated in adults with ASDs. Concurrent measures of skin conductance and cardiac responses were used as markers of orientation and stimulus detection, respectively. A backward masking task was employed whereby the emotional face (happy, angry) was presented for 30ms followed by a neutral face « mask ». An implicit comparison task required rapid gender identification. The ASD group failed to differentiate by valence in their EMG (zygomaticus, corrugator) and demonstrated atypical pre- and post-stimulus arousal. These findings may provide a potential mechanism for marked deficits in social reciprocity.
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6. Orellana LM, Martinez-Sanchis S, Silvestre FJ. {{Training Adults and Children with an Autism Spectrum Disorder to be Compliant with a Clinical Dental Assessment Using a TEACCH-Based Approach}}. {J Autism Dev Disord}. 2013 Sep 4.
The specific neuropsychological and sensory profile found in persons with autism spectrum disorders complicate dental procedures and as a result of this, most are treated under general anesthesia or unnecessary sedation. The main goal of the present study was to evaluate the effectiveness of a short treatment and education of autistic and related communication-handicapped children-based intervention program (five sessions) to facilitate a 10-component oral assessment in children (n = 38, aged 4-9 years) and adults (n = 34, aged 19-41) with autism spectrum disorder (with or without associated intellectual disability). The assessment ranges from entering into the examination room to the evaluation of the dental occlusion. There were statistically significant differences in the number of components reached and in compliance before and after the training program.
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7. Toma C, Torrico B, Hervas A, Valdes-Mas R, Tristan-Noguero A, Padillo V, Maristany M, Salgado M, Arenas C, Puente XS, Bayes M, Cormand B. {{Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations}}. {Molecular psychiatry}. 2013 Sep 3.
Autism is a severe neurodevelopmental disorder, the aetiology of which remains mainly unknown. Family and twin studies provide strong evidence that genetic factors have a major role in the aetiology of this disease. Recently, whole exome sequencing (WES) efforts have focused mainly on rare de novo variants in singleton families. Although these studies have provided pioneering insights, de novo variants probably explain only a small proportion of the autism risk variance. In this study, we performed exome sequencing of 10 autism multiplex families with the aim of investigating the role of rare variants that are coinherited in the affected sibs. The pool of variants selected in our study is enriched with genes involved in neuronal functions or previously reported in psychiatric disorders, as shown by Gene Ontology analysis and by browsing the Neurocarta database. Our data suggest that rare truncating heterozygous variants have a predominant role in the aetiology of autism. Using a multiple linear regression model, we found that the burden of truncating mutations correlates with a lower non-verbal intelligence quotient (NVIQ). Also, the number of truncating mutations that were transmitted to the affected sibs was significantly higher (twofold) than those not transmitted. Protein-protein interaction analysis performed with our list of mutated genes revealed that the postsynaptic YWHAZ is the most interconnected node of the network. Among the genes found disrupted in our study, there is evidence suggesting that YWHAZ and also the X-linked DRP2 may be considered as novel autism candidate genes.Molecular Psychiatry advance online publication, 3 September 2013; doi:10.1038/mp.2013.106.
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8. Wood A. {{Prenatal exposure to sodium valproate is associated with increased risk of childhood autism and autistic spectrum disorder}}. {Evidence-based nursing}. 2013 Sep 2.
