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      Self-referential and social cognition in a case of autism and agenesis of the corpus callosum

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          Abstract

          Background

          While models of autism spectrum conditions (ASC) are emerging at the genetic level of analysis, clear models at higher levels of analysis, such as neuroanatomy, are lacking. Here we examine agenesis of the corpus callosum (AgCC) as a model at the level of neuroanatomy that may be relevant for understanding self-referential and social-cognitive difficulties in ASC.

          Methods

          We examined performance on a wide array of tests in self-referential and social-cognitive domains in a patient with both AgCC and a diagnosis of ASC. Tests included a depth-of-processing memory paradigm with self-referential and social-cognitive manipulations, self-report measures of self-consciousness, alexithymia, and empathy, as well as performance measures of first-person pronoun usage and mentalizing ability. The performance of the AgCC patient was compared to a group of individuals with ASC but without AgCC and with neurotypical controls. These comparison groups come from a prior study where group differences were apparent across many measures. We used bootstrapping to assess whether the AgCC patient exhibited scores that were within or outside the 95% bias-corrected and accelerated bootstrap confidence intervals observed in both comparison groups.

          Results

          Within the depth-of-processing memory paradigm, the AgCC patient showed decreased memory sensitivity that was more extreme than both comparison groups across all conditions. The patient’s most pronounced difficulty on this task emerged in the social-cognitive domain related to information-processing about other people. The patient was similar to the ASC group in benefiting less from self-referential processing compared to the control group. Across a variety of other self-referential (i.e. alexithymia, private self-consciousness) and social-cognitive measures (i.e. self-reported imaginative and perspective-taking subscales of empathy, mentalizing), the AgCC patient also showed more extreme scores than those observed for both of the comparison groups. However, the AgCC patient scored within the range observed in the comparison groups on measures of first-person pronoun usage and self-reported affective empathy subscales.

          Conclusions

          We conclude that AgCC co-occurring with a diagnosis of ASC may be a relevant model at the level of neuroanatomy for understanding mechanisms involved in self-referential and high-level social-cognitive difficulties in ASC.

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          Most cited references66

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          A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells.

          Autism spectrum disorders (ASD) are complex neurodevelopmental diseases in which different combinations of genetic mutations may contribute to the phenotype. Using Rett syndrome (RTT) as an ASD genetic model, we developed a culture system using induced pluripotent stem cells (iPSCs) from RTT patients' fibroblasts. RTT patients' iPSCs are able to undergo X-inactivation and generate functional neurons. Neurons derived from RTT-iPSCs had fewer synapses, reduced spine density, smaller soma size, altered calcium signaling and electrophysiological defects when compared to controls. Our data uncovered early alterations in developing human RTT neurons. Finally, we used RTT neurons to test the effects of drugs in rescuing synaptic defects. Our data provide evidence of an unexplored developmental window, before disease onset, in RTT syndrome where potential therapies could be successfully employed. Our model recapitulates early stages of a human neurodevelopmental disease and represents a promising cellular tool for drug screening, diagnosis and personalized treatment. Copyright © 2010 Elsevier Inc. All rights reserved.
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            The autistic neuron: troubled translation?

            Autism is a complex genetic disorder, but single-gene disorders with a high prevalence of autism offer insight into its pathogenesis. Recent evidence suggests that some molecular defects in autism may interfere with the mechanisms of synaptic protein synthesis. We propose that aberrant synaptic protein synthesis may represent one possible pathway leading to autistic phenotypes, including cognitive impairment and savant abilities.
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              Language use of depressed and depression-vulnerable college students

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                Author and article information

                Journal
                Mol Autism
                Mol Autism
                Molecular Autism
                BioMed Central
                2040-2392
                2012
                21 November 2012
                : 3
                : 14
                Affiliations
                [1 ]Autism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18B Trumpington Road, Cambridge CB2 8AH, UK
                [2 ]Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Whiteknights RG6 6AL, UK
                Article
                2040-2392-3-14
                10.1186/2040-2392-3-14
                3522057
                23171505
                2152337c-a301-4728-a6fc-de15c27271ee
                Copyright ©2012 Lombardo et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 July 2012
                : 30 October 2012
                Categories
                Research

                Neurosciences
                self,autism,mentalizing,agenesis of the corpus callosum,theory of mind,social cognition
                Neurosciences
                self, autism, mentalizing, agenesis of the corpus callosum, theory of mind, social cognition

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