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Endophenotypes in Autism Spectrum Disorders

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Comprehensive Guide to Autism

Abstract

Autism spectrum disorder (ASD) is a complex disease with onset during early childhood and typically a lifelong course. Genetic liability plays a prominent role in ASD, as siblings of affected individuals display on average 25-fold higher autism risk rates compared to the general population. However, genetic contributions fit in most cases with complex, “multiple-hit,” oligogenic/polygenic models encompassing several loci and also gene-environment interactions. Furthermore, ASD should be viewed as the extreme end of a set of continuous dimensions pertaining to the realms of human socialization, language development, and behavior, rather than as a “black or white” medical condition. This complexity spurs interest into the heuristic potential of “endophenotypes” in ASD, as originally applied by Gottesman and Shields (Br J Psychiatry 122:15–30, 1973) to the realm of psychiatry. Endophenotypes can be defined as familial, heritable, and quantitative traits associated with a complex disease. Occupying an intermediate position between genotype and behavior, these traits offer the potential to bridge the gap between complex disease phenotypes, such as autism, and the underlying genetic mechanisms. The most reliable endophenotypes in ASD can be grouped into seven categories: biochemical, morphological, hormonal, immunological, neurophysiological/neuroanatomical, neuropsychological, and behavioral. Their use holds promise to foster advances not only toward more reliable genotype-phenotype correlations in autism research but also in dissecting clinical subgroups of ASD patients with relatively homogeneous pathophysiological underpinnings, aiding clinicians in early diagnosis once incorporated into broader biomarker panels, and predicting developmental trajectories and treatment response.

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Authors and Affiliations

  1. Unit of Child and Adolescent Psychiatry, University “Campus Bio-Medico”, Via Alvaro del Portillo 21, Rome, Italy

    Antonio Maria Persico

  2. Laboratory of Molecular Psychiatry and Neurogenetics, University “Campus Bio-Medico”, Rome, Italy

    Roberto Sacco

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  1. Antonio Maria Persico
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  2. Roberto Sacco
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Correspondence to Antonio Maria Persico .

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Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, Faculty of Science & Technology, London, United Kingdom

    Vinood B. Patel

  2. Nutritional Sciences Division and Genomics Centre, King's College London, London, United Kingdom

    Victor R. Preedy

  3. Faculty of Society and Health, Buckinghamshire New University, Middlesex, United Kingdom

    Colin R. Martin

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Persico, A.M., Sacco, R. (2014). Endophenotypes in Autism Spectrum Disorders. In: Patel, V., Preedy, V., Martin, C. (eds) Comprehensive Guide to Autism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4788-7_1

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  • DOI: https://doi.org/10.1007/978-1-4614-4788-7_1

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