Autism Genetics: Strategies, Challenges, and Opportunities

Brian J. O'Roak1,2 and Matthew W. State1,2,3

1Department of Genetics; 2Program on Neurogenetics; 3Child Study Center, Yale University School of Medicine, New Haven, Connecticut


While it has long been appreciated that genes contribute to pervasive developmental disorders, the specific risks underlying autism spectrum disorders (ASD) have only recently begun to be clarified. In this article, we address what is known about the genetic underpinnings of these syndromes, consider the obstacles facing gene discovery in the immediate future, and evaluate the most widely used methods employed to address these issues. We review the current literature, highlighting exciting recent findings that implicate both rare and common genetic variation in the genesis of autism. Finally we describe key technological advances that are transforming all areas of human genetics and medicine and consider both the opportunities as well as the challenges for autism research posed by these rapid changes. © 2008 INSAR/Wiley Periodicals, Inc.

Article Citation: Autism Res 2008, 1: 4–17. DOI: 10.1002/aur.3

The Potential Role for Emergence in Autism

George M. Anderson

Child Study Center, Yale University School of Medicine, 230 South Frontage Rd., New Haven, Connecticut


Most research on autistic behavior has considered autism as a homogenous category. However, the increasingly apparent genetic, neurobiological and behavioral complexities are prompting an approach that examines different behaviors and aspects one at a time. There is accumulating evidence for viewing autism-related behaviors as separable and fractionable, and often occurring in isolation in family members and the general population. Thus, examination of component behaviors in autism appears to offer a fruitful simplifying approach. On the other hand, some of the most common and characteristic phenomena observed in individuals diagnosed with autism do not run in their families. These novel, or “emergent”, phenomena may arise in the individual from interacting co-occurring traits or from the interaction of underlying genetic and biological factors. Consideration of the role of emergence in autistic behavior and related phenomena should complement the dimensional approach and might help illuminate the components and complexities of autism. © 2008 INSAR/Wiley Periodicals, Inc.

Article Citation: Autism Res 2008, 1: 18–30. DOI: 10.1002/aur.2

Children With Autism Demonstrate Circumscribed Attention During Passive Viewing of Complex Social and Nonsocial Picture Arrays

Noah J. Sasson1, Lauren M. Turner-Brown1, Tia N. Holtzclaw1, Kristen S.L. Lam1, and James W. Bodfish1,2

1Neurodevelopmental Disorders Research Center, University of North Carolina, Chapel Hill, North Carolina; 2Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina


Repetitive behaviors are a defining feature of autism and can include “circumscribed interests”, which involve a tendency to focus on a very specific interest (e.g. trains, schedules, planets, dinosaurs). We wondered if a tendency to have very specific interests might lead children with autism to explore pictures differently.We tested children with and without autism while they looked at arrays of pictures that were made up of both social (e.g. a person smiling) and nonsocial (e.g. a train or a table) pictures. We used eye-tracking technology that measured (a) how many pictures were explored, (b) how long each picture was explored, and (c) in how much detail a picture was explored. We found that children with autism explored fewer pictures overall because they spent more time viewing a smaller selection of pictures. They also looked at more details within the pictures they chose to view. This pattern was especially true for object pictures that are known to be of high interest to children with autism, suggesting that certain types of objects are more likely to “capture and trap” attention in children with autism. This task may help us better understand how people with autism experience the visual world. It may also be useful in studies of the early development of autism, as it is a task that could be used with infants. © 2008 INSAR/Wiley Periodicals, Inc.

Article Citation: Autism Res 2008, 1: 31–42. DOI: 10.1002/aur.4

Face and Object Processing in Autism Spectrum Disorders

Simon Wallace1, Michael Coleman2, and Anthony Bailey1

1Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK; 2Department of Human Communication Science, University College London, London, UK


The strong interest in faces shown by typically developing individuals is reflected in superior performance on tests of discriminating pictures of faces compared with objects. This advanced ability in face processing is achieved using special perceptual strategies to represent the properties of the face, also known as “configural processing”. The aim of this study was to explore whether the deficits in face processing shown by individuals with autism spectrum disorder (ASD) are due to impaired configural processing in the presence of intact feature processing. Twenty-six adults with ASD were matched with 26 adults without ASD on measures of verbal and non-verbal ability. In 2 computerised tests participants were asked to decide whether pairs of face or object pictures were the same or different. On the first test, pictures of faces and cars were presented for 40, 70 or 100msec. Only configural information could be accessed at 40msec durations; whereas configural and featural information could be accessed at 100msec. On the second test, participants were asked to judge whether pairs of faces or houses had been altered in terms of their configural or featural properties. Adults with ASD were less accurate than typically developing adults on all tests of face processing, but the two groups performed equally well at object processing. The main face processing difficulty of adults with ASD was in how they processed feature and configural information together. Interestingly, not all adults with ASD showed unusual patterns of face processing and future studies should establish why this is. © 2008 INSAR/Wiley Periodicals, Inc.

Article Citation: Autism Res 2008, 1: 43–51. DOI: 10.1002/aur.7

Cortical Patterns of Category-Selective Activation for Faces, Places and Objects in Adults with Autism

Kate Humphreys1, Uri Hasson2, Galia Avidan1, Nancy Minshew3, and Marlene Behrmann1

1Carnegie Mellon University, Pittsburgh, Pennsylvania; 2Center for Neural Science, New York University, New York; 3University of Pittsburgh, Pittsburgh, Pennsylvania


We know that people with autism appear to sometimes “see things differently”, for example they tend to focus more on details than on images as a whole, and may have difficulties recognizing faces. We wanted to know how this atypical visual processing is reflected in the way the brain is organized. To find out, we showed people with autism pictures and movies of faces, places and objects while they were in a brain scanner, and looked to see whether their patterns of brain activation were different from those of typically developing individuals of the same age. While there were pronounced differences between the groups when they looked at faces, this was not the case for places or objects. We conclude that there are no gross differences in the way brains of people with autism are organized for processing places or objects, but there are for faces. We think that this observation may be related to the fact that face processing becomes adult-like much later in development than processing for places or objects. © 2008 INSAR/Wiley Periodicals, Inc.

Article Citation: Autism Res 2008, 1: 52–63. DOI: 10.1002/aur.1