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    2 Comments for this article
    Is Preference for Geometry a Valid Early Sign of Autism Spectrum Disorder?
    Terje Falck-Ytter, Ph.D | Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND),
    The article by Pierce et al1 published online on Archives’ website on September 6 (2010) reports a promising new early detection method for Autism Spectrum Disorder (ASD). The investigators showed a short movie that contained social scenes on one side and screen saver animations on the other side to toddlers with ASD, typically developing toddlers and mentally delayed (non-autistic) toddlers. Using a non-invasive eye- tracking technique, they found that preference for the screen saver side was higher in ASD than in both control groups. Screen saver preference was highly predictive of an ASD diagnosis. Most interesting was the suggestion that two previously unrecognized sub-groups of ASD toddlers can be identified from their gaze preference/eye-movement signatures.
    Unfortunately, the applied methods leave room for many alternative interpretations regarding the underlying cause of the observed screen saver preference. Pierce et al conclude that a preference for geometrical patterns is a risk factor for ASD. Generally, in order to explain why a group of subjects look at one particular side of the screen in a preferential looking study, one has to either make sure that the two sides differ only with respect to the stimulus dimension of interest, or include a number of control experiments that exclude rival explanations.
    Firstly, the social scenes in the movie included biological motion, while the screen savers contained non-biological motion. Thus, the preference for the screen savers could reflect a preference for non- biological (e.g. linear, constant velocity) motion (for a recent and relevant study of toddlers with ASD, see2). Secondly, the “geometric responders” (p E5) could be simply “social avoiders”3,4, who would look away from the social side of the screen irrespective of the content on the other side. The authors do partly consider these alternatives (p E7), but not a as a serious threat to the validity of their main conclusion.
    Later on in their article, Pierce and colleagues state that “the present study provides strong evidence that infants at risk for ASD begin life with an unusual preference for geometric repetition” (p E8). The authors do not specify whether they refer to spatial or temporal repetition, although they implicitly indicate the latter (p E1). Regarding temporal repetition, it is not altogether clear to what degree it was a prominent feature in the screen savers, each of which lasted on average only 2.14 seconds and were apparently not repeated. In any case, if repetition is a significant factor, it leaves the role of the format (geometrical patterns) uncertain. That is, the ASD group might have looked at repetitive events even if they were embedded in social, non- geometrical, scenes. Other confounds include, but are not restricted to, differences in low-level visual properties such as amount of motion, color or luminance.
    In summary, we applaud the authors for having invented a promising new early detection tool for ASD. At the same time we think it is premature to conclude that infants at risk for ASD begin life with an unusual preference for geometric patterns.
    1. Pierce K, Conant D, Hazin R, Stoner R, Desmond J. Preference for Geometric Patterns Early in Life As a Risk Factor for Autism. [Published online ahead of print Septermber 6, 2010] Arch Gen Psychiatry. doi:10.1001/archgenpsychiatry.2010.113
    2. Klin A, Lin DJ, Gorrindo P, Ramsay G, Jones W. Two-year-olds with autism orient to non-social contingencies rather than biological motion. Nature. 2009;459(7244):257-261.
    3. Kliemann D, Dziobek I, Hatri A, Steimke R, Heekeren HR. Atypical Reflexive Gaze Patterns on Emotional Faces in Autism Spectrum Disorders. J Neuroscience. 2010;30(37):12281-12287.
    4. Dalton KM, Nacewicz BM, Johnstone T, et al. Gaze fixation and the neural circuitry of face processing in autism. Nat Neurosci. 2005;8(4):519 -526.

    Conflict of Interest: None declared
    Assessing performance of novel autism screening approaches
    Craig Newschaffer, PhD | Drexel University School of Public Health
    I read with great interest the report by Pierce et al.1 in January’s issue of Archives. The preferential looking paradigm described is clearly innovative and the potential for future application in autism detection and diagnosis is quite exciting. However, as an epidemiologist, I wanted to take a moment to comment on the emphasis the authors place on their estimated positive predictive value (PPV) of 100%. Positive predictive value refers to the proportion of test positives that are confirmed with the condition of interest. It is perhaps the most important single metric of screening or diagnostic test performance. However, PPV is dependent on test sensitivity and specificity as well as the prevalence of the condition in the population being tested. In the study sample, the optimal cutpoint of 69% time fixed on geometric patterns yielded 100% specificity (0/51 from figure 2) and 32% sensitivity (12/37 from figure 2). The 100% PPV emphasized by the authors is therefore entirely a function of the 100% specificity seen at this cutpoint in their sample. The sample comprised just 51 typically developing children and it is quite likely, given sampling error, that specificity in reality is not perfect. Further, because of PPV’s dependence on condition prevalence, the estimate reported probably does not apply to populations of most interest to clinicians. The case-control design used here essentially creates a “population” with 42% autism prevalence – a function purely of the number of cases and controls included in the study sample. If one wanted to contemplate the potential performance of the preferential looking test in the general population of toddlers where ASD prevalence might be only 1%, the PPV would most likely be markedly lower. For example, if the true specificity is 99% (not 100%, but still outstanding), with sensitivity at 32%, the PPV would be just 25% - implying that only 1 of 4 toddlers in the general population that test positive on the preferential looking test will have ASD. If the test were applied to a population already known to be at higher risk for ASD (say those referred to an ASD specialty clinic for evaluation), assuming the same sensitivity and specificity, PPV would then be much stronger. For example, in a clinic-referred toddler sample where 60% really had ASD, 98% of those testing positive on the preferential looking test would be true cases. But, in this scenario, the test sensitivity of 32% would be a real concern as two thirds of true cases would be missed.
    The preferential looking paradigm described by Pierce et al.1 is undoubtedly worth further exploration but clinicians interested in early detection and diagnosis of ASDs need to remain aware of the complexity of assessing test performance and not place too much emphasis on any single performance measure derived from a single sample type.
    1. Pierce K, Conant D, Hazin R, Stoner R, Desmond J. Preference for geometric patterns early in life as a risk factor for autism. Arch Gen Psychiatry 2011; 68(1): 101-109.
    The PPVs of 25% and 98% calculated via Bayes’ theorem: [Sensitivity x Prevalence] / [(Sensitivity x Prevalence) + (1-Specificity) x (1 – Prevalence)]

    Conflict of Interest: None declared
    Original Article
    January 3, 2011

    Preference for Geometric Patterns Early in Life as a Risk Factor for Autism

    Author Affiliations

    Author Affiliations: Department of Neurosciences (Drs Pierce and Stoner) and Autism Center of Excellence (Drs Pierce and Stoner, Mr Conant, and Mss Hazin and Desmond), University of California, San Diego.

    Arch Gen Psychiatry. 2011;68(1):101-109. doi:10.1001/archgenpsychiatry.2010.113

    It is undeniable that early treatment can have a significant positive impact on the long-term outcome for children with an autism spectrum disorder (ASD).1-3 Early treatment, however, generally relies on the age at which a diagnosis can be made, thus pushing early identification research into a category of high public health priority. Unfortunately, easily implemented methods for facilitating early identification remain to be found.

    Eye tracking technology holds promise as an objective method for characterizing the early features of autism because it can be implemented with individuals of virtually any age or functioning level. Historically, the bulk of eye tracking studies have been conducted with older children, adolescents, and adults with autism.4-10 In one of the first studies on this topic, Klin and colleagues10 showed that when watching a socially intense movie, adults with autism predominantly looked at the mouth region of the actors whereas typical subjects looked at the eye region. Bringing this effort into the childhood years, Jones and colleagues11 later showed that even 2-year-olds with autism spent more time fixating on the mouth region than the eyes during face viewing. They raised the provocative possibility that how social images are visually examined could be an early warning sign for autism.