International Child Development Resource Center




fMRI STUDY OF DIFFERENCES IN NEURAL ACTIVATION DURING EYE GAZE DISCRIMINATION IN AUTISM. C. D. Ashwin, S. Baron-Cohen, E. T. Bullmore Autism Research Centre, Departments of Experimental Psychology and Psychiatry, University of Cambridge, Cambridge, UK CB2 3EB

Autism is a psychiatric condition emerging in childhood characterised by severe social deficits. Among the most striking social characteristics of autism is abnormal eye gaze behaviour, although the neural mechanisms underlying the abnormal eye gaze behaviour is currently unknown. Information has only recently begun to emerge about the neural mechanisms underlying eye gaze discrimination in the normal population. Recent neuroimaging findings during eye gaze perception allow for hypothesis driven investigations about how eye gaze processing may be different in people with autism. The aim of the present study was to use functional mri to investigate neural differences between people with and without high functioning autism (HFA) or Asperger (AS) Syndrome during an eye gaze discrimination task. The study involved pictures of faces with eyes looking in various directions. Subjects made a choice about which direction the eyes in the pictures were looking towards. The normal control group showed significant activations in areas of the brain implicated in eye gaze perception, including the temporal and prefrontal cortices. The group with HFA/AS activated these areas to a significantly lesser degree. The results provide in vivo evidence for a neural deficit in eye gaze perception in autism.

RELATIONS BETWEEN SOCIAL IMPAIRMENTS AND EEG MEASURES IN CHILDREN WITH HIGH FUNCTIONING AUTISM. C.P. Burnette, S.K. Sutton, A.E. Vaughan, J. Meyer, D. Charak, M. Yale, P. Mundy.* University of Miami, Department of Psychology, Miami, FL 33124

Children with High Functioning Autism (HFA) display social impairments, including core social-cognitive deficits and deficits related to comorbid symptoms of anxiety and dysphoria. These domains of impairment may be associated with different but related measures of neurodevelopment. Social-cognitive deficits in autism may be linked to evidence of decreased activity in frontal medial brain systems, especially left frontal medial activity. Alternatively, comorbid symptoms of dysphoria may be associated with hemispheric asymmetry, especially greater right than left activity. These hypotheses were explored in a resting EEG study of 23 children with HFA and 20 controls to determine if the groups differed on frontal activity and asymmetry measures. Data were also collected on theory of mind (ToM) measures, as well as self-report measures of dysphoria and interpersonal relations. Results indicated that the groups significantly differed on measures of ToM, anxiety, interpersonal relations, and EEG asymmetry measures. A measure of left frontal-parietal coherence was associated with ToM performance in the control (r = -.61, p < ..01), but not the HFA sample. In addition, hemispheric asymmetry indicative of more right but less left frontal activity was associated with self-reports of social anxiety and general anxiety in the controls (rs = -.48 nd -.50). However, the opposite pattern was displayed in the HFA children, as more left and relatively less right activation was related to self-reports of social anxiety, general anxiety, and problems in interpersonal relations (rs = 42 to ..56, ps < .05). These results suggest that different neurobehavioral organizational patterns may be associated with social-cognition and self-report of dysphoria and social relations in HFA children versus control children. The implications of these data for understanding the social-disturbances in children with HFA will be discussed.

PLAY INTERACTIONS BETWEEN CHILDREN WITH AUTISM AND THEIR SIBLINGS. H. De-Levie, A. Rozga, M. Siller, A. Plato and M. Sigman*. Department of Psychology, UCLA, Los Angeles, CA 90024.

Sibling interactions play a pivotal role in the development of a child’s social skills. Yet, very little is known about the nature of social interaction between children with autism and their siblings. A previous study found that, when children with autism interacted with their siblings, the siblings made most of the initiations of the social encounters. In the current study, 20 young children with autism (CA = 58 months; LA = 25 months) were videotaped in their home during play interactions with their typically developing siblings (CA = 5.8 years). Tapes were coded for the onset/ offset of episodes of shared attention between the siblings. In addition, each episode was categorized as resulting from a join or an initiation by either the child with autism, the sibling, or due to their mother’s involvement. The results indicated that children with autism initiated less than one percent of the shared encounters whereas siblings initiated about 22% of the shared encounters. Furthermore, it was found that 44% of the shared encounters were joined by the siblings in comparison to 24% by the child with autism. Finally, our results showed that the type of interaction predicted the duration of the shared encounter. That is, those interactions that commenced with the sibling joining the ongoing activity produced the longest episodes of shared engagement. This study sheds light on how interventions might promote play interaction between children with autism and their siblings.

DO TODDLERS WITH AUTISM RECOGNIZE DISGUST IN THE FACE? A STUDY OF SOCIAL REFERENCING Richard Griffin1, Jacqueline Hill1, Simon Baron-Cohen1, & Mark Johnson2 1 Autism Research Centre, Departments of Experimental Psychology and Psychiatry, University of Cambridge, UK 2 Centre for Brain and Cognitive Development, Birkbeck College, London, UK

Research with typically developing children indicates that by at least 14 months of age, and possibly earlier, children understand that emotional expressions (facial and vocal) refer to specific targets and will modify their behavior as a function of another individual’s emotional expression (social referencing). We report a series of experiments designed to test whether toddlers with autism are able to understand that emotional expressions may have specific referents or targets. The results suggest that toddlers with autism do not interpret emotional expression as referential in nature, nor do they reliably use emotional expressions as a source of information to guide their own actions. These findings are discussed in terms of dyadic (two-way) and triadic (three-way) theories of autistic dysfunction and their relation to theory of mind.

EMPATHISING AND SYSTEMISING IN ADULTS WITH AND WITHOUT ASPERGER SYNDROME. J. Lawson, S. Baron-Cohen* S. Wheelwright. University of Cambridge, Departments of Experimental Psychology and Psychiatry, Downing Site, Cambridge, CB2 3EB.

Empathising and systemising are cognitive abilities developed from within the folk psychology-folk physics model of autism. An experiment was devised to compare these abilities between adults with and without autism spectrum conditions. Three groups of participants (matched on IQ and age) took part in the study: males with Asperger syndrome (n= 18); normallmales (n=44); and normal females, (n=45). Each participant completed a task that involved empathising and a task that involved systemising. On the empathising task, normal females scored significantly higher than normal males, who in turn scored higher than the males with Asperger syndrome. Conversely, on the systemizing task, normal females scored significantly lower than both of the male groups; the male groups did not differ significantly from each other on this task. These results support the idea that autism spectrum conditions involve a deficit in empathising co-existing with a normal level of systemising ability. The results are also in line with the extreme male brain theory that places autism spectrum conditions at an extreme point along a continuum of cognitive styles for the normal population.

EARLY COMMUNICATIVE AND SOCIAL RECIPROCITY BEHAVIORS AMONG CHILDREN WITH AUTISTIC SPECTRUM DISORDERS, WITH AND WITHOUT WORD LOSS. A.G. Lomangino, A. Fish, J. Cooper, P. Kim, and C. Lord*. University of Michigan Autism and Communication Disorders Center, Ann Arbor, MI, 48109.

Recent studies of autism and regression have focused on obtaining profiles of children’s development and losses (Goldberg et al., 2001; Dawson, Osterling, Meltzoff, & Kuhl, 2000). Word loss provides a marked indicator of regression reported by parents of children with autistic spectrum disorders. We examined parent report data on children’s early communicative and symbolic skills for 116 children participating in a multi-site study organized by the Collaborative Programs for Excellence in Autism (CPEA). All subjects had previously received best estimate diagnoses of autistic spectrum disorders following evaluations that included the ADI-R, ADOS, and verbal and non-verbal psychometric testing. Subjects who experienced loss of spontaneous word use, as indicated by parental responses from the ADI-R, were identified. Children in this Word Loss group were matched to subjects without reported word loss with respect to age, gender, maternal education, and race. Subjects’ mothers participated in a telephone interview that included items from the MacArthur CDI Words and Gestures assessment. Descriptive data are reported regarding children’s communicative behavior, social reciprocity, and representational skills at 24 and 36 months of age in the Word Loss and Non-Word Loss groups. Reported behaviors reveal differences in the associations between gesture use and vocabulary, comprehension, and play behavior for the two groups and shifts in the associations over time. For example, controlling for vocabulary, the Word Loss group shows stronger associations between gesture use and play. The findings are examined with respect to the developmental course of regression and the associations between gesture use and other forms of communicative and representational behavior.


High-functioning individuals with autism spectrum disorders (ASD) frequently suffer from comorbid emotional disorders and externalizing behaviors. Little, though, is known about the nature and development of these features. They may be part of the clinical syndrome of ASD and related to pathognomic neurodevelopmental characteristics such as social-cognitive or executive function deficits. Alternatively, comorbidity may reflect a secondary and more general tier of pathology that arises in response to negative feedback triggered, in part, by their social skill deficits. If this is the case, comorbidity in ASD may be expected to be associated with more general processes, such as social attributions. In this study, a group of high-functioning children with ASD, all previously diagnosed with AS, were compared with both learning disabled and normally developing children of similar age and intellectual ability on neurodevelopmental measures (executive function, social-cognition, and emotional processing), social information-processing measures, and internalizing and externalizing symptoms. Results indicated that children with high-functioning ASD exhibited both core neurodevelopmental deficits and elevated symptoms of emotional and behavioral disturbance relative to matched peers. Among participants with ASD, though, comorbidity was not related to core dimensions of autistic pathology, but was instead related to social attributional tendencies. Although children with ASD display social-cognitive deficits they also engage in social attributions which may be especially important to consider in the understanding and treatment of comoribid pathology among children affected by ASD.

DO INDIVIDUALS WITH AUTISTIC SPECTRUM DISORDER (ASD) ATTRIBUTE NEGATIVE VALENCE FACIAL EXPRESSION’S (NVFE’S) “NORMALLY”? J. Piggot, 1 D. Mobbs, 1 H. Kwon, 1 V. Menon, 1 S. Bookheimer 2 and A. L. Reiss1. .Dept. of Psych. & Beh. Sci. 1, Stanford Univ., CA, 94305. Brain Mapping Center 2, Univ. of California, LA. Sponsor: M.I.N.D Institute*

Emotional attribution involves perceptual, emotional and linguistic processing and has been reported as impaired in ASD. This fMRI study investigates the attribution of NVFE’s in ASD. Fusiform, amygdala and prefrontal areas were chosen a priori as regions of interest (ROI). 14 ASD (9-17 y; IQ-112) and 10 control (10-18 y; IQ-114) males undertook an emotional match (EM), emotional label (EL) and control task. Using a 3T GE Signa scanner with T2* weighted gradient (ESPS-TR 2s) 28 axial slices (4mm skip 0.5mm) parallel to the AC-PC axis were acquired and a high resolution T1 weighted 3D SPGR. There was no significant difference in accuracy, response time or ROI activation between ASD and controls in the EL task and the controls in the EM task. The ASD group was slower in the EM than the EL task (t (12) = -3.64; p = 0.03), and slower than controls in the EM task (F (1, 21) = 11.07; p = 0.003). ASD had less fusiform activation in the EM than in the EL task (F (1, 22) = 3.20; p = 0.08) and than controls (F (13) = 5.38; p =0.003) in the EM task. The ASD and control group in the EL task and the control group in the EM task used similar processing strategies. In the EM task the ASD group used an alternative perceptual strategy. Possible explanations include; decreased propensity to attribute emotions, reduced global processing of facial percepts, and difficulty with the perceptual demand of the EM task. We conclude that the ASD group has reduced expertise in perceptual processing in emotional attribution.


Participants’ computer-mediated communication was explored with a program called Bubble Dialogue (Gray et al., 1991) in which the users type text into speech bubbles. Two scenarios, based on Happé (1994), were adapted to investigate understanding of figure of speech and sarcasm, and a third developed by ourselves looked at responses to inappropriate requests (lending money and disclosing home address on a first meeting). Dialogue transcripts were assessed by 62 raters who were blind to the clinical diagnoses (Asperger, Tourette, normal). Hierarchal linear modelling revealed that rated understanding of a figure of speech, and social behaviour was predicted mainly by verbal ability but also by clinical diagnosis. Additionally, the Tourette comparison group showed better understanding of a figure speech and more socially appropriate behaviour than the Asperger group. However, differences between these groups were entirely attributable to individual differences in executive ability. In contrast, understanding of sarcasm was not predicted either by verbal ability, executive ability or clinical diagnosis. This suggests that different types of non-literal speech may not be comparable and not suitable for use as equivalent tests of mentalising. This study hints of the strengths of using computer role play as a more ecologically valid test than “paper and pencil” methods. Moreover, using blind ratings gives a greater consensus of linguistic and social ability, and nested data statistics enables more specified analyses.

MIMETIC RESPONSES TO FACIAL EXPRESSIONS OF EMOTION IN AUTISM. A. Reichmann-Decker, D.N. McIntosh*, P. Winkielman, & J.L. Wilbarger. Emotion & Cognition Lab, Dept. of Psychology, Univ. of Denver, Denver, CO 80208.

Individuals with autism are often characterized by their deficits in complex emotional functioning, specifically in areas such as emotional responsiveness, empathy, and contagion. Complex emotional functioning is grounded in core affective processes that support the quick extraction of the affective valence and the immediate use of this information in automatic behavior. This study examined core affective processes by measuring quick, automatic mimicry to emotional facial expressions in individuals with autism. Atypical mimetic responses are likely to reflect deficits in core affective processes. Participants included 7 adults with an autistic spectrum disorder and 7 typical adults. Participants were shown 8 angry and 8 happy expressions. Participants’ facial activity was recorded over the zygomaticus major and corrugator regions by electromyography (EMG). The responses were analyzed for changes in average activity in the 500 ms interval following the presentation of facial expression compared to 1000 ms prestimulus activity. Both typical adults and adults with autism showed the expected pattern of responses. That is, average activity over the zygomaticus region was greater after the presentation of happy, as opposed to angry faces, whereas activity over the corrugator region was greater after the presentation of angry, as opposed to happy faces. The findings suggest that individuals with autism may demonstrate typical automatic mimicry of emotional facial expressions. The data are preliminary, based on a small N, and should be interpreted with caution.

INCREASING JOINT ATTENTION IN CHILDREN WITH AUTISM USING PARENT EDUCATION Marie Rocha and Laura Schreibman* University of California, San Diego, La Jolla, CA 92093

Previous research has demonstrated that parent-implemented autism intervention can effectively remediate deficits in social skills (Koegel, Bimbela and Schreibman, 1996). Specific to children with autism are deficits in intiating and responding to joint attention initiations. The present study was designed to examine a parent implemented (rather than therapist implemented) intervention targeting joint attention behaviors in children with autism. In the current study, parents were trained to increase their joint attention bids and use naturalistic behavior modification techniques to reinforce appropriate responding. This research suggests that parents of children with autism can be effectively trained to employ joint attention training techniques in laboratory settings and this training can be linked to increases in target behaviors. Additionally, results from generalization probes suggest individual differences in generalizing joint attention training to the natural environment. Although only responding was targeted, increased joint attention initiations were also observed. Results are discussed in terms of treatment implications and future investigations.

BEHAVIORAL REENACTMENT IN AUTISM: LEARNING THROUGH IMITATION. C.Shulman* and B. Haas-Porter, The Hebrew University of Jerusalem, The Department of Psychology Jerusalem Israel, 91905.

The reenactment of intended acts was employed in an attempt to investigate the manner in which children with autism understand intended goals. Their ability to repeat actions not fully executed was the basis for analyzing the comprehension of the intention behind the action rather than their repetition of the actual act as it was performed. Using this paradigm, the capabilities of understanding intention in children with autism and those with mental retardation, matched for chronological and mental ages, and typically developing children, matched for mental age, were compared. The results revealed that children with autism imitated accompanying social behavior when they repeated an action more than the children in the other two groups. This may be a window to understanding which social cues are salient for children with autism as they attempt to understand another’s intention. The results are discussed in terms of the developmental constructs inherent in imitation and its use as a basis for intervention with children with autism.

CHANGES IN SOCIAL-COMMUNICATION SKILLS FROM AGE 2 TO 3 IN CHILDREN WITH AUTISM. L. Turner, S. Pozdol, & W. Stone. Vanderbilt Univ. Medical Center, Nashville, TN 37232.

The purpose of this study was to examine the course of development of early social and communication skills in children with autism over a one year period. Toward this end, 30 children with a diagnosis of autism received evaluations of cognitive, language, and social-communicative skills at ages 2 and 3. The Screening Tool for Autism in Two-Year-Olds (STAT) was used to measure social-communication skills at both time points. The STAT provides a standard context for observing play, requesting, directing attention, and imitation behaviors. In addition to a screening cutoff score, individual scores for each domain are available. Within-group comparisons revealed higher (i.e., improved) scores at age 3 than at age 2 for all domains, with the greatest improvements observed for imitation and play. The fewest gains over this time period were observed for directing attention. Contrary to expectation, improvement in these social-communicative skills was not associated with children’s level of cognitive or language development at age 2, or with the amount of intervention that children received between age 2 and age 3. Changes in play correlated significantly with changes in expressive language, while changes in directing attention correlated with changes in DQ. Results suggest that: 1) play and imitation skills may be more amenable to improvement than communication skills over this time period; and 2) differential patterns of association may exist between social-communication domains and other aspects of development. Implications for understanding the developmental course of autism and for designing early intervention programs will be discussed.



Tulving’s systems theory of memory proposes that the operation of the episodic memory system is accompanied by a characteristic subjective experience of ‘autonoetic conscious awareness’, which involves mental time travel and a re-living of the previously experienced episode. This awareness contrasts with ‘noetic’ awareness, which results from the operation of the semantic memory system. These states of conscious awareness can be measured by asking participants to rate whether or not they ‘remember’ having seen a studied word in a recognition memory test or whether they ‘know’ it was there without specific recollection of the episode. Although Bowler, Gardiner and Grice (2000) have shown a small butsignificant impairment of autonoetic awareness in adults with Asperger’s syndrome, the question remains as to whether such awareness in Asperger individuals is quantitatively or qualitatively different from that of controls. Two experiments will be presented in which manipulations that have been demonstrated to affect remembering and knowing differentially in typical populations are used on a sample of adults with Asperger’s syndrome. The results suggest that the remembering seen in such individuals, although reduced in quantity, is qualitatively similar to that seen in typical individuals

EFFECT OF LOOMING MOTION ON LEARNING IN CHILDREN WITH AUTISM. L. Moskowitz, J. Juska, J. O’Grady & B. Gordon. Johns Hopkins Medical Institutions, Baltimore, MD 21287.

Attention is a major impediment to learning in individuals with autism. Stimulus movement – particularly when it is towards the individual – is known to be a very effective method of engaging attention, in animals as well as humans, but little if anything has been studied of its effects in individuals with autism. We have been investigating which methods of presenting moving stimuli, for which subjects, might be most useful in stimulating attention and teaching individuals with autism. One example has been a low-functioning, nonverbal 12-year-old male. Presentation apparatus was a board with openings, through which projected a movable wooden dowel. In the matching task, pictures of animals were attached to the board, and the picture to be matched was on the movable dowel. Depending upon the condition, this picture either remained static or was manually propelled towards the subject. Task performance was manually recorded, as well as videotaped for confirmation. This particular subject showed evidence of increased attention to the moving stimuli, both in terms of his behavioral attitude (posture and directed gaze) and in his greater learning. His initial learning during the matching task was greater in the moving condition than the static one (64% vs 18%, z = 5.10, p = ..001). Other subjects as well as other methods of presentation, including computer video, are currently being tested and results will be presented. Given the strong indications in the literature for the importance of motion, and this preliminary result, moving stimuli should be considered as a method of enhancing the attention and learning of at least some individuals with autism.

FAMILIARITY-BASED RESPONDING IN AUTISM. J. O’Grady, L. Moskowitz, J. Juska, B. Gordon. Johns Hopkins Medical Institutions, Baltimore, MD.

Material learned by individuals with autism often seems particularly fragile.Items that have seemingly been well-learned may disappear from the individual’;s repertoire (“item attrition”). Here we report further results from an extensive single-case study of a low-functioning nonverbal 14 year old male (O’Grady, Boser & Gordon, IMFAR, 2001), which suggest that familiarity-based responding may be a major cause of apparent item “attrition.” Performance on 8 computerized auditory-to-picture matching tasks was examined. Item attrition was strictly defined as a fall-off in performance across different sessions (from >=80% correct to P2.2.4

The present study examined the relationship between strategy use and memory abilities in autism through an analysis of performance on the California Verbal Learning Test (Delis et al., 1987). Forty-one adults with high-functioning autism and 41 normal controls were matched on age and Verbal IQ. Both simple and semantic strategy use were examined. Simple strategy use was tested by comparing primacy and recency recall. The autism group recalled fewer primacy than recency words, while the control group showed the opposite pattern of performance (p < .006). These findings suggest that individuals with autism rely heavily on rote memory rather than utilizing more developmentally advanced strategies, such as rehearsal. Semantic strategy use was examined with quantitative analyses of interference and intrusion errors on recall trials. Compared to controls, the autism group showed typical levels of proactive interference (PI), but minimal release from PI (p < ..003). Further analyses divided the non-shared category into novel words and broadly-related category words (p < ..001). These findings suggest that individuals with autism encode words into categories, but that their category boundaries may be more distributed. Analyses of intrusions examined whether semantic categories could be utilized effectively to augment recall. Adults with autism made more semantic intrusions during recall trials (p < .02). In addition, although semantic cuing improved correct recall in the autism group, it also resulted in elevated levels of semantic intrusions (p < .02). Overall, these results suggest that individuals with autism have more difficulty utilizing simple and semantic strategies to improve verbal recall. These findings have important implications for the treatment and education of individuals with autism.

PRESERVED PROCEDURAL LEARNING IN AUTISM L.S. Simo, N.J. Minshew , S. Steele, D. Fingerhut, and J.A. Sweeney*. Center for Cognitive Medicine, University of Illinois at Chicago, Chicago, IL 60612 & Center for Autism Research, University of Pittsburgh, Pittsburgh, PA 15213

Procedural learning is the process of learning automatic sequences of behavior that are initiated quickly and precisely with minimal cognitive effort. It is believed to be accomplished through well-delineated frontostriatal and frontocerebellar loops. This process has been studied with the predictive saccade paradigm in several psychiatric and neurologic disorders. In this task, subjects track a visual target jumping back and forth between two fixed positions at a constant rate (1500 ms in this study). After a few trials, saccades become synchronized with target jumps, and reaction times drop as subjects begin to prepare and initiate responses prior to the actual appearance of the next target. We studied the performance on this task of 59 autistic individuals (ADOS and ADI diagnoses; ages 8 to 52) and an individually matched group (age and IQ) of 59 healthy subjects. All participants had an IQ greater than 75. Our results show that reaction times dropped dramatically over the first 5 trials in which the task was performed in both healthy and autistic individuals. This finding indicated that autistic individuals can develop anticipatory responses within the context of a procedural learning paradigm as effectively as healthy individuals. In addition, after the initial learning, autistic patients displayed more anticipatory responses and shorter reaction times than healthy individuals (F(1,116) = 5.98, p P2.2.6
VALIDITY OF THE NONVERBAL LEARNING DISABILITIES MODEL FOR ASPERGER SYNDROME G. Wallace, A. Wagner, L. Kenworthy, T. Ahluvalia, L. Gilotty, L. Sirian, K. Towbin Children’s National Medical Center, Washington, DC 20010

Previous research implicates the nonverbal learning disabilities model (NVLD) as a way to differentiate Asperger Syndrome (AS) from High-Functioning Autism (HFA). However, scant evidence exists to corroborate this hypothesis. Utilizing strict DSM-IV criteria to define groups, it is hypothesized that the NVLD model, particularly those functional subdomains that discriminated groups in previous studies, will not differentiate AS from HFA. The subjects were 34 HFA and 30 AS patients consecutively evaluated in a neuropsychology service. Through a review of charts, two independent and experienced clinicians confirmed diagnoses. Subjects with FSIQ P2.2.7
IMPAIRED MEMORY FOR FACES AND SOCIAL SCENES IN AUTISM: CLINICAL IMPLICATIONS OF MEMORY DYSFUNCTION. D.L. Williams, N.J. Minshew* and G. Goldstein. Univ. of Pittsburgh, Sch. Of Med., Pittsburgh, PA 15213.

A clinical memory test, the Wechsler Memory Scale-III (WMS-III), was used to study the auditory and visual memory of 29 high functioning adults with autism and 34 group-matched normal controls. The material ranged in complexity but the visual stimuli were substantially more complex than the verbal. The individuals with autism performed as well as the controls on immediate and delayed memory for word pairs and stories and on a verbal working memory task. The autism group was impaired on immediate and delayed recall of faces and of family scenes and had impaired spatial working memory. The integrity of verbal working memory and impaired spatial working memory is consistent with the findings of other studies and may reflect the greater computational demands of the spatial task. Most importantly, the deficits in memory for faces and common social scenes demonstrate the contribution of memory dysfunction in autism to deficits in real life function.


WORKING MEMORY IN HIGH-FUNCTIONING PERVASIVE DEVELOPMENTAL DISORDERS. T. Ahluvalia, L. Kenworthy, A. Wagner, G. Wallace, L. Gilotty, L. Syrian, K. Towbin. Children’s National Medical Center, Psychology Dept, 111 Michigan Ave. NW, Washington, DC 20010.

Executive dysfunction has been proposed as a central cognitive deficit in autism. Working memory, an aspect of executive functioning, has received little attention in this literature. We hypothesized working memory deficits in both HFA and AS, but that the two groups would be equivalent on working memory measures. Participants consisted of HFA (N=29) and AS (N=29) patients consecutively evaluated in a neuropsychology service. Diagnoses were confirmed by independent chart review by two experienced clinicians using DSM-IV criteria. Groups matched on age (range = 6-16 years; HFA M=10.9; AS M=10.0), PIQ (M =98.7, SD=15.1), and gender (28 HFA males, 27 AS males). All subjects had FSIQ>70. Subjects completed the WISC-III and Children’s Memory Scale Dot Locations (Dots) subtest. Parent and teacher BRIEFs (Behavior Rating Inventory of Executive Function) were completed. The findings were mixed: In the combined AS and HFA groups, there was a significant difference between Digit Span and the Verbal Comprehension Index of the WISC-III (t=-2.8, p=.007), indicating a relative weakness on a subtest sensitive to working memory. Also, the Working Memory subscales of the parent (t=8.8, p=.00) and teacher(t=6.2, p=.00) BRIEFs were significantly impaired relative to the normative sample. However, in the combined AS and HFA groups, there was no significant difference between Dots and the Perceptual Organization Index. The HFA and AS groups were not significantly different on any of the working memory measures used. Overall, the results suggest the need for further investigation of verbal versus visual working memory in HFA and AS.

USE OF CONTEXT IN WORKING MEMORY IN AUTISM. K. Boser, V. Smrcka, S. Stark, H. Haarmann, & B. Gordon. Johns Hopkins Univ. Sch. of Med., Baltimore, MD 21287; Univ. of Maryland, College Park, MD 20742.

We investigated whether children with autism use contextual cues to integrate information in working memory. To study this hypothesis, five children with autism received storage-plus-processing tasks (complex span), and storage-only tasks (simple span), varying in integration difficulty. The complex counting span task displayed target shapes canonically (as on a dice), distributed but not repeating across displays or distributed repeating. Processing load of the last display was either low or high, showing 3-5 or 6-8 targets respectively. In a word span task, semantic coherence was either absent (unrelated words), present but implicit (related words), or present and made explicit by cueing. Additional tasks included complex sentence, addition, and letter span and simple digit and letter span. Addition and counting were reliably longer than sentence and complex letter spans, whereas digit and simple letter span were equivalent, possibly due to better verbal ability for number words in this population. Word recall improved in either the cued or semantic conditions relative to the unrelated condition. In counting span tasks, subjects recalled more, showed decreased rates (time to count each square) and were less affected by increased processing load in canonical than distributed displays. Rate and recall improved for distributed displays that repeated the same layout across trials, indicating attention to pattern. Individual differences in processing ability will be discussed. The effects of layout on counting recall and semantic cueing on word recall support the hypothesis that integration of information in autism is aided by cues.

INHIBITORY CONTROL IN AUTISM SPECTRUM DISORDERS: HYPER-PROCESSING OF COLOUR VERSUS NORMAL INHIBITION OF LOCATION. J.A. Brian*, S.P. Tipper, B. Weaver, and S.E. Bryson. Autism Research Unit, Hospital for Sick Children, and York University, Toronto, ON., Canada.

In this report, we describe a study of inhibitory mechanisms of control in autism spectrum disorders. A negative priming (NP) task was used to engage two issues. First, related work has shown that inhibition of distractor identity is normal in autism. We examined inhibition of distractor spatial location, and observed that it is also within normal limits in autism. The second issue concerned the selectivity of inhibition. In non-clinical participants inhibition is selectively directed to the properties of the distractor that compete for the control of action. We discovered that such selective inhibition also appears to be normal in autism. Finally, we unexpectedly discovered that the irrelevant perceptual feature of colour produced a facilitation effect in autism, which has not been observed previously in typical controls. This latter result implicates more fluent, but presumably less adaptive, perceptual processes in autism. Indeed, hyper-attention to stimulus features in autism might help to explain the well-documented phenomenon of “stimulus over-selectivity”, wherein the children learn in overly specific ways and have difficulty generalizing across similar stimulus conditions.

OVERLAPPING ADHD SYMPTOMS IN AUTISM: RELATIONSHIP TO EXECUTIVE FUNCTIONING. L.McGrath, R.Joseph, O.Tadevosyan, S.Folstein, H.Tager-Flusberg*. Boston U. Med. School, Boston, MA 02118.

Executive function (EF) deficits are characteristic of several developmental disorders, including ADHD, the symptoms of which can co-occur with autism. However, few studies have examined the effects of these co-occurring symptoms on executive functions in autism, making it unclear whether some autistic EF deficits may be associated with co-occurring ADHD. The purpose of this study was to examine the relationship of ADHD symptoms in autism to executive functioning. 49 children with autism aged 4-14 years were administered a battery of EF tasks: Day-Night Stroop, NEPSY Knock-Tap, Word & Block Span – Forward & Backward, and NEPSY Tower. All children met criteria for autism on the Autism Diagnostic Interview (ADI-R). Of the 49 participants, 22 met syndromal or subsyndromal criteria for ADHD on a modified version of the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Correlational analyses revealed significant associations between ADHD symptomatology and performance on Day-Night Stroop and the two backward span tasks. Separate hierarchical regression analyses were conducted to determine whether behaviors associated with autism or ADHD were better predictors of performance on these 3 tasks. Age and IQ were controlled for in the first step. In the second step, current scores for the social, communication, and repetitive behaviors domains of the ADI-R, and total K-SADS ADHD score were entered stepwise. Results showed that ADHD was the better predictor of EF performance on all 3 tasks. These findings suggest that ADHD symptomatology may be a more powerful predictor than autistic symptomatology of some aspects of executive dysfunction in children with autism.

DEVELOPMENTAL IMPAIRMENT OF PREFRONTAL FUNCTION IN AUTISM. S. Steele, N.J. Minshew, B. Luna and J.A. Sweeney*. Center for Cognitive Medicine, University of Illinois at Chicago, Chicago, IL 60612 & Center for Autism Research, University of Pittsburgh, Pittsburgh, PA 15213

Studies have shown that individuals with autism have difficulties with tasks sensitive to prefrontal functioning. Some data suggest that autistic individuals show a reduced developmental improvement in executive cognitive abilities through late childhood and early adolescence. One method of studying prefrontal functions is through the use of eye movement paradigms that have been validated in non-human primates and human functional imaging studies. Recently, we used an antisaccade task to demonstrate that autistic participants were impaired in their ability to voluntarily suppress context-inappropriate responses. The aim of this study was to replicate our previous finding, and to examine this deficit from late childhood through mid-life. Participants included 59 subjects with autism meeting ADOS and ADI criteria (age8) and 110 healthy individuals (age 9) matched on age and full scale IQ. All participants had an IQ greater than 75. During the antisaccade task, subjects were instructed to first fixate on a central target and then look in the opposite direction from a peripheral target presented unpredictably to the left or the right of center fixation. In addition to replicating previous findings of impaired performance on the antisaccade task in autism, our results indicate that autistic participants did not significantly improve as a function of age as did healthy subjects; older autistic particippants made a similar number of errors as the younger autistic participants. Autistic individuals show a markedly reduced ability to acquire executive skills subserved by prefrontal cortex during late childhood and adolescence relative to the substantial developmental improvement in this cognitive domain observed in healthy individuals. This developmental/maturational disturbance persists into adult life.

PURSUIT EYE MOVEMENT DEFICITS IN AUTISM. Y. Takarae, N. J. Minshew, B. Luna, C. M. Krisky, and J. A. Sweeney*. Center for Cognitive Medicine, University of Illinois at Chicago, Chicago, IL 60612 and Center for Autism Research, University of Pittsburgh, PA

Oculomotor studies in autism provide novel strategies for evaluating the functional integrity of multiple brain areas. The relevant neural systems have been well studied via lesion and single-cell recording studies as well as human neuroimaging studies. Visual pursuit depends on the integrity of a distributed network that includes the “dorsal” visual system that performs visual motion analysis and its projections to dorsal parietal cortex, frontal eye fields and brainstem motor areas via pontine nuclei and the cerebellum. Thus, visual pursuit requires dynamic integration of sensory input, an analysis of pursuit error, and predictions about target motion with high spatial and temporal precision that needs to be translated into motor commands. Hence, visual pursuit requires a high degree of information transfer across multiple brain areas. We compared visual pursuit of 60 high-functioning autistic individuals and 94 IQ, age, and gender matched healthy participants using pure ramp, step ramp and oscillating target tasks. Autistic individuals had comparable pursuit latency to healthy individuals, but demonstrated slower sustained pursuit when tracking both oscillating and ramp targets. Additionally, initial “open loop” pursuit was slower in autistic individuals when targets were presented in the right hemifield. Because pursuit eye movements place high demands on coordination of sensory, cognitive and motor processes subserved by a widely distributed brain systems, these findings indicate that insufficient capacity in the autism brain to meet the demands of the pursuit tasks by dynamically coordinating information processing. The behavioral deficits observed in this study are consistent with disturbance in a distributed network whose key structures, such as frontal cortex and the cerebellum, have been reported to be abnormal in autism.


PROTEOMIC APPROACH REVEALED GLYOXALASE I AS A CANDIDATE GENE FOR AUTISM M. Barua, M.A. Junaid, P.S. Pullarkat and R.K. Pullarkat New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 Our laboratory has been studying autism, the highly heterogeneous purportedly oligogenic disability, by screening for protein abnormalities in autopsied brain tissues using a proteomic approach. Analyses of brain gray matter proteins showed absence of a 22 kDa protein with a pI of 5.0 in four out of seven autism subjects. Proteolytic digestion with trypsin of the protein gel plug in controls followed by peptide mass fingerprint analysis led to its identification as glyoxalase I (EC All the four autism brains showed appearance of a new protein with the same molecular mass but a pI of about 4.9 suggesting a shift in the net charge. Such charge shifts are generally attributable to phosphorylation/ dephosphorylation status of proteins that regulate their biological functions. Glyoxalase I is a Zn2+-containing cytosolic metallotransferase that is expressed very early during embroygenesis. Glyoxalase I catalyzes glutathione-dependent detoxification of alpha-ketoaldehydes (methylglyoxal) to harmless alpha-hydroxy thioesters (lactoylglutathione) that are further metabolized. In four autism brain samples, the glyoxalase I activity is significantly lower when compared with normal controls. These data suggest that glyoxalase I may be one of the candidate genes for autism.

FREQUENCY OF FRAGILE X IN MULTIPLEX AUTISM: TESTING AGRE FAMILIES. W.T. Brown*, S.L. Nolin, C.S. Dobkin, G.S. Houck, A. Glicksman, X.D. Ding, A.D. Gargano, L. Crawford, N. Gitcho, S.J. Spence, D.H. Geschwind. Dept Human Genetics, NYS Inst Basic Research, Staten Island, NY 10314.

Autism has high heritability. Several genetic syndromes have been associated with it, including fragile X. The Autism Genetic Resource Exchange (AGRE) is a publicly available resource of well characterized multiplex families for genetic studies of autism. AGRE families were recruited without regard to prior testing but known neurogenetic syndromes were excluded. To better characterize this resource, we conducted fragile X DNA analysis (Brown 1993) on one proband in each of 480 AGRE families, with follow-up family studies when indicated. Testing revealed 6 families to be positive for fragile X. Review of 326 available medical records showed 114 (35%) had prior negative genetic testing. Thus, the prevalence of fragile X among the approximately 312 previously untested AGRE families was ~ 1.9%. Previous prevalence studies of fragile X in autistic samples have reported frequencies ranging from 0 to 16%; with a mean of around 4%; (Feinstein 1998). The variations may be due to sample sizes, ascertainment differences or differing methodologies. Our 1.9% is similar to a report of 1.6% among 123 unrelated autistic individuals (Bailey 1993), but lower than the 13% we found on an earlier multicenter study of 183 individuals (Brown 1986). A growing awareness of fragile X syndrome may have increased the probability of prior fragile X screening in multiplex autism families. This would have excluded their AGRE inclusion. The observed frequency of 1.9% is similar to the overall mean of 4% in other studies and indicates a significant association of fragile X and autism.

THE MONOAMINE OXIDASE A UVNTR POLYMORPHISM IS ASSOCIATED WITH BOTH IQ AND SYMPTOM SEVERITY IN YOUNG MALES WITH AUTISM SPECTRUM DISORDER: A LONGITUDINAL STUDY Ira L. Cohen, Xudong Liu, Chris Schutz, Bradley N. White, Edmund C. Jenkins, W. Ted Brown, Jeanette J.A. Holden NYS Institute for Basic Research in Developmental Disabilities, Departments of Psychology, Cytogenetics and Molecular Genetics, Staten Island, NY 10314; Department of Psychiatry2 and Physiology, Queen’s University and Cytogenetics & DNA Research Laboratory, Ongwanada,Kingston, Ontario K7M 8A6, Canada and Department of Biology3, Trent University, Peterborough, Ontario, K9J 7B8 Canada.

A functional polymorphism (the upstream variable number tandem repeat region or uVNTR) in the monoamine oxidase A (MAOA) promoter region has been found to be associated with behavioral abnormalities as well as increased serotonergic responsivity. This same region has also been found to be associated with IQ in people with autism spectrum disorder (ASD). In the present study, we examined the relation between MAOA-uVNTR alleles, which have been correlated with high versus low transcription of this gene, and the phenotypic expression of autism spectrum disorder in 32 males less than seven years of age and in 27 of these cases at one-year follow-up. Children with the low activity allele had both lower IQ and more severe autistic behavior than children with the high activity allele. Behaviors associated with autism were a better predictor of genotype than were various IQ measures. Children with the low activity allele showed a worsening in IQ at one-year follow-up but no change in the severity of their autistic behavior or diagnosis. Children with the longer repeat allele were more likely to be classified as falling in the more mildly affected autism spectrum based on DSM-IV, ADI-R or ADOS-G criteria. Therefore, the short repeat allele may serve as a molecular marker for more severe forms of ASD and may account for the presence of hyperserotonemia in some people with autism.

THE SEROTONIN TRANSPORTER : ASSOCIATION IN THE IRISH POPULATION. J Conroy, M Gill, L Gallagher. Neuropsychiatric Lab, Dept. of Genetics, University of Dublin, Trinity College, College Green, Dublin 2, Ireland.

The role of the serotonin transporter gene (5-HTT) in autism has been widely investigated. Two polymorphisms, an insertion in the promoter region and a 12 repeat allele in a variable nucleotide tandem repeat (VNTR) in intron 2, drive higher expression of the 5-HTT gene. Four studies have shown nominally significant transmission disequilibrium of the 5-HTT gene in autism, while 3 studies have reported no linkage disequilibrium. This study investigated the role of 5-HTT in the genetically homogeneous Irish population. 84 families were genotyped for the 5-HTT promoter and VNTR variants, and 78 families were genotyped for a variant in the 3′ untranslated region (3’UTR) of the gene. Transmission disequilibrium testing (TDT) and haplotype based haplotype relative risk (HHRR) analysis were undertaken. . A trend towards preferential transmission of the short promoter (i.e. deletion) allele wasobserved although this did not reach statistical significance (P=0.0987). Neither TDT nor HHRR testing revealed any significant association with the VNTR or 3’UTR polymorphisms. Further SNPs have been identified and several of these are the subject of ongoing investigations in our sample. These include three SNPs in intron 1A (T-C, T-C and T-A), one in exon 1B (A-C), and one in intron 2(G-A). These SNPs were reported as showing some evidence of association with autism (Kim et al, 2002). The results of association studies of these SNPs in our Irish sample will also be reported.

NORMAL METHYLATION PATTER AT THE 5′ SNPRN LOCUS IN PATIENTS FROM THE SOUTH CAROLINA AUTISM PROJECT. S. A. Copeland-Yates, R. J. Schroer, C. Skinner and R. C. Michaelis*. J. C. Self Research Institue, Greenwood Genetic Center, Greenwood, SC 29646.

The discovery that a number of patients with autism have duplications of the maternally derived 15q11-q13 region has prompted the suggestion that an overdose of an imprinted gene(s) expressed solely from the maternally derived chromosome 15 may be the critical etiological factor in these cases. In addition, mutations in the methyl-DNA binding protein 2 (MECP2) have been shown to be responsible for Rett syndrome, one of the autism spectrum disorders. Differential methylation is a hallmark of imprinted genes, and mutations in methyl-DNA binding protein such as MECP2 may disrupt the regulation of activity in imprinting genes. Using both Southern blot and methylation-specific PCR analyses, we determined the degree of methylation at one CG locus in the 5′ end of the SNPRN gene in lymphocyte DNA from 200 patients from the South Carolina Autism Project, as well as in brain samples from seven patients with autism and 2 controls. All samples tested showed a methylation pattern similar to controls. Further experiments will focus on testing the degree of methylation at two NotI sites in the 5′ end of UBE3A, as well as other sites in the imprinted gene cluster in 15q11-q13.

A POPULATION-BASED STUDY OF AUTISM AMONG TWINS IN CALIFORNIA. LA Croen*, JK Grether, J Hallmayer. Kaiser Permanente, Division of Research, Oakland, California 94612.

Data from family and twin studies provide strong support for the notion that genetics play a major role in the etiology of autism. However, results from the few population-based twin studies carried out to date have been inconclusive with regard to the true concordance rate of autism in monozygotic and dizygotic twins. Steffenburg et al (1989) studied 22 twin pairs and reported autism concordance rates of 90% in MZ twins and 0% in DZ twins. Bailey et al (1995) studied 44 twin pairs, and found concordance rates of 73% in MZ twins and 0% in DZ twins. The authors identified children with autistic disorder born in California during 1987-1994 from the electronic records of the Department of Developmental Services, the State agency that provides services to approximately 80% of all children with autism in the state. Of the 4,590,333 live births delivered in this time period, a total of 5,042 children with autism were identified, of which 173 were twins. The percent of twins in the autism sample was 3.4%, which was higher than the percent of twins in the overall birth population in the state for this time period, which was 2.1%, RR=1.6, 95% C.I. 1.4-1.9. The 173 twins with autism represented 137 twin pairs, of which 97 were discordant and 36 concordant for autism. Among the concordant pairs, 24 were male:male, 5 female:female, and 7 male:female. Using Weinberg’s rule, we estimate that autism concordance ranges from 58%-88% among MZ twins, and 14%-36% among DZ twins. These data suggest that heritability estimates from previous studies may have overestimated the role of genetics and underestimated the role of environmental factors in the etiology of autism.

PRELIMINARY REPORT OF A TWIN STUDY OF AUTISM SPECTRUM DISORDER. H. H. Goldsmith, M. A. Gernsbacher, N. C. Miller, & E. A. Sauer, Waisman Center & Department of Psychology, University of Wisconsin, Madison, WI 53706.

Inferences about the degree of genetic influence on autism depend crucially on the risk to siblings relative to population base rates and the differential concordance of monozygotic (MZ) versus dizygotic (DZ) cotwins. Such studies affect the plausibility of various linkage and association approaches. Changing diagnostic practices lead to differences in population base rates and in twin proband identification and thus require new studies. We report preliminary results from a population based twin sample, using statewide birth records from Wisconsin. The project is continuing to enroll twins, confirm zygosity and clinical diagnoses, and assess phenotypes more broadly. Currently, 32 pairs of twins born from 1992 to 1999 have been identified. Interestingly, females account for only 11% of the cases, which is about half the expected frequency. Zygosity remains to be confirmed for one-third of the pairs. The general pattern of concordance was similar to the earlier British and Scandinavian studies. Of 14 known dizygotic pairs (half opposite-sex), only one pair was concordant, and in this pair, one of the cotwins was currently classified only as “suspected PDD.” Only two of the MZ pairs were discordant; in one case the cotwin was clearly within normal range, and in the other, the cotwin had a mild speech disorder but clearly not autism. This latter pair happened to have been enrolled from birth in an intensive longitudinal study, in which their behavioral development was prospectively documented with multiple methods, including standardized, videotaped assessments of emotional and social development.

A DESMIN-RELATED PROTEIN AS A BIOMARKER FOR AUTISM M.A. Junaid, P.S. Pullarkat and R.K. Pullarkat New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314.

Autism is now well recognized as an oligogenic heritable disability with an estimated involvement of more than 10 genes. Positional cloning approaches in several laboratories have revealed genetic loci at various chromosomal locations, however, no definitive gene has yet been identified. Applying a proteomic approach, we have found a defect in the expression of alpha-B-crystallin in autopsied brain samples from two autism individuals. Alpha-B-crystallin is the major protein in human eye lens conferring the refractive property, and is a heat shock protein functioning as a molecular chaperone that is expressed in other tissues under various stress conditions. Mutations in alpha-B-crystallin gene results in accumulation of an intermediate filament protein called desmin and is responsible for desmin-related myopathies. Although western blot analyses with desmin antibody failed to detect desmin in the brain, an abnormal storage of a 28 kDa protein was detected in 3 out of 7 autism brain tissues. Storage of a similar protein at a level of over 3-fold was also observed in cultured lymphoblastoid cells in 5 out of 8 autism patients, and slightly altered proteins were observed in their parents. Using this antibody, it may be possible to identify a major subclass of autism patients. Such an approach will provide a reliable biomarker and a relatively non-invasive method for the early detection of autism. Efforts are underway to isolate and characterize the desmin-related protein in the autism brain samples.

PHENOTYPIC SIMILARITY OBSERVED WITHIN TWO TRICENTRIC IDIC(15) MARKER CHROMOSOMES S.Mann1, D.Liu1, N.Dorrani1, M.Sigman2 and C.Schanen*3. 1Dept Human Genetics and 2Neuropsyciatric Institute, UCLA,Los Angeles, CA 90095 3Nemours Research, A.I.duPont Hospital, Wilmington, DE 19803 Autism is frequently noted in cases of maternally derived idic(15) supernumerary chromosomes. These bisatellited, pseudodicentric marker chromosomes arise by recombination through common breakpoints leading to duplication of similar segments of DNA in most probands. As part of our larger study of autism in chromosome 15q duplications, we identified two unique probands with extremely large idic(15) markers. Cytogenetic analyses indicate that both marker chromosomes are tricentric, containing multiple copies of the proximal long arm including the Prader Willi/Angelman critical region. Both markers are maternally derived and include chromatin from both maternal homologues. The probands were clinically assessed for abnormalities commonly associated with idic(15) including measures of cognition, language, play and specific testing for autism (ADI-R and ADOS-G). Both children have intractable early onset seizures, profound hypotonia and facial dysmorphisms (epicanthal folds, unfolded ears, low nasal bridge and upturned nose). They are severely cognitively impaired (mental ages of 7m and 5m at ages 61m and 101m respectively) and display gross and fine motor delays. Both had limited functional play and no imaginative play. Social and language deficits were present in both although the severity of the mental retardation precludes diagnosis of autism (both were considered to have PDD-NOS). These probands represent the most severe end of the spectrum of phenotypes associated with segmental aneuploidy for chromosome 15q11-q13.

SNP ANALYSIS IN THE GABRB3 REGION OF CHROMOSOME 15 SHOWS LINKAGE BUT NO ASSOCIATION USING ORDERED SUBSET ANALYSIS M.M.Menold1, Y.Shao1, S.J.Kim1, C.M.Wolpert1, S.L.Donnelly1, S.A.Ravan2, R.K.Abramson2, H.H.Wright2, G.R.DeLong1, M.L.Cuccaro1, M.A.Pericak-Vance1, J.R.Gilbert1*. 1Duke Center for Human Genetics, Durham, NC 27710 and 2WS Hall Psychiatric Institute, USC, Columbia, SC 29208

Autistic disorder (AutD) is a complex neurodevelopmental disorder with a strong genetic component. While numerous susceptibility genes probably exist for AutD, it has been difficult to detect them, since each gene is presumed to contribute just a small part to the etiology of the disease. Gene identification is made even more complicated by the clinical heterogeneity present in data sets. Ordered subset analysis (OSA) is a method that can be used to identify a particular set of families that are contributing to linkage or association at a given locus. Using this technique, Shao et al. demonstrated significantly increased LOD scores in the region of the GABRB3 gene by using a factor derived from repetitive behaviors and stereotyped patterns as the covariate for OSA. Using the 23 families that were identified by OSA as being a homogeneous subset of the AutD data set, we analyzed 9 single nucleotide polymorphisms (SNPs) within the GABRB3 gene and in the region beyond the 3′ end of the gene. Eight of the nine SNPs showed positive linkage with a peak LOD score of 1.673 for SNP GABRB3-3PR1. Association analysis was not significant for any of the markers using either the Pedigree Disequilibrium Test (PDT) or Transmit. While this result further supports evidence for an AutD susceptibility gene in the GABRB3 region of chromosome 15, AutD does not appear to be associated with a specific SNP haplotype, and may instead be due to multiple mutation events in this region.

ABSENCE OF MECP2 MUTATIONS IN PATIENTS FROM THE SOUTH CAROLINA AUTISM PROJECT. F. Lobo-Menendez, K. Sossey-Alaoui, J. M. Bell, S. A. Copeland-Yates, S. M. Plank, S. O. Sanford, C. Skinner, R. J. Simensen, R. J. Schroer and R. C. Michaelis*. J. C. Self Research Institute, Greenwood Genetic Center, Greenwood, SC 29646

The methyl-CpG binding protein 2 (MeCP2) gene has recently been identified as the gene responsible for Rett syndrome, one of the autism spectrum disorders. Most female patients with MeCP2 mutations exhibit the classical features of Rett syndrome (RS), including autistic behaviors. Most male patients with MeCP2 mutations exhibit moderate to severe developmental delay/mental retardation. Ninety-nine patients from the South Carolina Autism Project (SCAP) were screened for MeCP2 mutations, including all 41 female patients from whom DNA samples were available plus the 58 male patients with the lowest scores on standard IQ tests and/or the Vineland Adaptive Behavior Scale. No pathogenic mutations were observed in these patients. One patient had the C582T variant, previously reported in the unaffected father of an RS patient. Two other patients had novel single nucleotide polymorphisms in the 3′ UTR of the gene, G1470A and C1516G. These variants were seen in 12/82 and 1/178 phenotypically normal male controls, respectively. The findings from this and other studies suggest that mutations in the coding sequence of the MeCP2 gene are not a significant etiological factor in autism.

MUTATION SCREENING OF METHYL-CpG BINDING PROTEIN FAMILY GENES IN JAPANESE AUTISM AND RETT SYNDROME PATIENTS Masato Mori, Li Hong, Takanori Yamagata, Mariko Y. Momoi Department of Pediatrics, Jichi Medical School, Tochigi, Japan

MeCP2 mutations were found in patients of Rett syndrome, autism and non-specific mental retardation. MeCP2 is a member of Methyl-CpG binding protein family that inactivates DNA by DNA methylation. Transcription silencing by DNA methylation is an important process on brain development. MeCP2, MBD1, MBD2, MBD3 and MBD4 comprise a nuclear protein family sharing the Methyl-CpG binding domain (MBD) and related to transcriptional repression, the MBD family genes except of MBD4 have expression in brain. Thus this MBD family genes candidate for autism and other developmental disorders, we analyzed these genes in autism patients and Rett syndrome. In 5 Rett syndrome patients, three missense mutations and a nonsense mutation were found in MeCP2. A novel nonsense mutation was detected a girl with atypical Rett syndrome, she had only autistic feature before stereotyping movements were developed. And the other atypical Rett syndrome patient was a boy had G232A mutation. That mutation was reported as polymorphism, but it seemed that there were some relations between his clinical features and the mutation. In 53 Japanese autism patients, diagnosed according to DSM-4, all exons of each gene were amplified by PCR and mutation was screened by DHPLC, and finally confirmed by direct sequencing. A missense mutation was founded and several polymorphisms were detected in each gene. Although our findings could not confirm these family genes were responsible for the etiology in the majority of autism, the functional implication of the MBD1 missense mutation and the potential association of the high-polymorphic gene variants with autism need to be studied further.

CO-MORBIDITY OF COHEN SYNDROME AND AUTISTIC SPECTRUM DISORDER. T. Owley and J. Salt. University of Chicago, Chicago, IL 60637.

This single case study describes the co-morbidity of Cohen Syndrome and PDD-NOS in a 17-year-old woman. Cohen Syndrome is a rare connective tissue disorder, linked to chromosome 8q22. Cohen Syndrome is characterized by mental retardation; visual anomalies such as strabismus, myopia, and chorioretinal dystrophy; childhood hypotonia and dysmorphic features such as a short philtrum, prominent upper central incisors and microcephaly. It has been suggested in the literature that individuals with Cohen Syndrome display some characteristics of Autistic Spectrum Disorders. To date this association has only been suggested by parental questionnaire study (Howlin, 2001) without objective individual assessment. The current multi-disciplinary assessment utilized standardized diagnostic measures including the ADI-R, ADOS, standardized assessment measures such as the Vineland Adaptive Behavior Scales, Mullen Scales of Early Learning, Ravens Matrices, & Peabody Picture Vocabulary Test, as well as a comprehensive psychiatric evaluation. Diagnostic and intellectual functioning measures are discussed. Results are strongly indicative of a co-morbidity of PDD and Cohen Syndrome. The case is discussed in relation to the clinical diagnosis, and the genetics of Autistic Spectrum Disorders.

NO ASSOCIATION BETWEEN THE APOE GENE AND AUTISTIC DISORDER. KL Raiford (1), Y Shao (1), IC Allen (1), MM Menold (1), ML Cuccaro(1), JR Gilbert(1), HH Wright (2), RA Abramson (2), G Worley (1), JM Vance (1), MA Pericak-Vance(1)*. (1) Center for Human Genetics, Duke University Medical Center, Durham, NC; (2) University of South Carolina, Columbia, SC.

Autistic Disorder (AutD) is a neurodevelopmental disorder characterized by stereotypic and repetitive behavior and interests, together with social and communicative deficiencies. Peak linkage/association scores on several genomic screens indicate the presence of an autistic disorder susceptibility locus on chromosome 19p13.2 _ q13.4. The apolipoprotein E (APOE) gene on chromosome 19 encodes for a protein, apoE, whose different isoforms (-E2, -E3, -E4) influence neuronal growth, participates in lipid transport and metabolism, repair, growth, and maintenance of axons and myelin during neuronal development. The APOE gene competes with the reelin gene for VLDL/APOER2 receptor binding. A previous report found evidence for an association between AutD and the reelin gene. In addition, it has been suggested that the APOE-2 allele has a protective effect against infertility and miscarriage in AutD families. Based on these data we examined APOE as a candidate gene in AutD. We tested for genetic association using family-based association methods in a data set of 163 multiplex Duke and AGRE AutD families (2 or more AutD affecteds per family) and 159 singleton Duke AutD families (1 AutD affected per family). We also tested APOE promoter SNPs 113cg, 219gt, 427ct, 491at, and 5361ct. We saw no significant evidence that AutD is associated with the APOE gene (PDT p=0.93; TRANSMIT p=0.45) or the APOE promoter SNPs.


Determining the genetic basis of autism has been the focus of multiple international research efforts. As a result of this progress, we identified a need to educate the public about research findings and their potential clinical application. Previously we reported the results of a pilot survey mailed to families participating in our collaborative autism research projects. These families all had children diagnosed with autism or related disorders. Based on the pilot data an educational website,, was developed for families to inform them about the genetic basis of autism. Since the pilot data were generated from a small number of families participating in autism genetics research, we hypothesized that a larger, non-research oriented population would yield different results. Therefore, an online version of the survey was made available on the web site, which was launched in February of 2002. Since then, more than 9500 people have visited the website, and 433 surveys have been submitted. Similar to our pilot population, 387 (89%) of the respondents have a family member with autism, with the majority (81%) having an affected child. However, in contrast to the pilot study sample, a majority of the respondents (93%) indicated that they are not currently participating in research. When asked about possible causes of autism, 85% of respondents identified genetic factors, while 31% cited vaccinations and 33% cited other environmental factors (despite the lack of medical evidence for the latter). Although 24% of respondents correctly identified the recurrence risk for autism among siblings, 38% percent of respondents grossly overestimated the risk and 32% were unsure. Most respondents favored genetic testing to confirm a diagnosis of autism (92%) and genetic testing for prenatal diagnosis of autism (75%). Most respondents (97%) indicated an interest in learning more about the genetic basis of autism. Of note, 70% of respondents indicated that learning about the genetic basis of autism would reduce their anxiety, and could potentially help them with family planning. In summary, the responses obtained from this follow-up survey were remarkably similar to those obtained from our pilot survey. This suggests that a need and desire for education regarding the genetics of autism is not limited to families participating in genetic research. Additionally, our data indicate that web-based tools are an effective method to reach families, for whom obtaining up-to-date knowledge might otherwise be difficult for logistical and financial reasons.

ANALYSIS OF GENETIC RISK FACTORS FOR AUTISTIC DISORDER ON REELIN GENE Yujun Shao, Jonathan Haines *, E. Martin , Kimberly Raiford ,Huiling Li, G.R. DeLong, Holli Hutcheson*, Jim Sutcliffe*, M.L. Cucarro, Susan Folstein**, J.R. Gilbert, M.A. Pericak-Vance, Department of Medicine, Duke University Medical Center, Durham, NC * Program in Human Genetics, Vanderbilt University Medical Ctr, Nashville, TN ** Department of Psychiatry, Tufts University / New England Medical Center, Boston, MA

Several genomic screening efforts have indicated the presence of an autistic disorder (AutD) susceptibility locus within the distal long arm of human Chromosome 7. Reelin is a signaling protein that plays a pivotal part in the migration of several neuronal cell types and in the development of neural connections. Recent reports suggest that Reelin gene at 7q22 influences genetic risk in AutD. We tested for genetic association of several RELN variants including a combination of seven SNPs and a 5’UTR repeat in 234 families collected by our group and 86 AGRE families. Five of these RELN variants were also genotyped on 72 Vanderbilt/Tufts families. Family-based association analysis such as PDT and TRANSMIT were used to test transmission of single-locus markers and multilocus marker haplotypes. The most significant association was detected on exon 44 (PDT p-value = 0.003) and the 5’UTR repeat (PDT p-value = 0.03) from this combined dataset. The two-locus haplotype with these two polymorphisms was over-represented in the affecteds (TRANSMIT p< 0.001). Our analysis confirmed the RELN gene as a potential major contributor to genetic risk in AutD.

RELATIONSHIP BETWEEN GENOTYPE AND PHENOTYPIC CHARACTERISTICS OF AUTISM SPECTRUM DISORDERS. Stodgell1, C.,* S.L. Hyman1, S.E. Bryson2. Univ. of Rochester School of Medicine, Rochester1, New York, and Dalhousie University-IWK Health Centre2, Halifax, Nova Scotia.

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with deficits in socialization & communication &, limited interests and preoccupations. Their prevalence is estimated to be 6/1,000 births. This study examined the relationship between the genotypes of candidate genes (e.g., HOXA1, HOXB1 & RELN, WNT2) and the phenotype of ASDs. We tested the hypothesis that outcome on subscores of the Autism Diagnostic Interview (ADI) would be predicted by the genotype of specific candidate genes. DNA was extracted from leukocytes isolated from peripheral blood. Probands were genotyped for each candidate genes. ADI data was examined for probands with differing allelic variants. For example, summary scores evaluating communication indicated that probands with a AG or GG HOXA1genotype scored worse than probands with the AA genotype (p P2.4.18
SSP TYPING OF HLA ALLELES FROM AMPLIFIED BLOOD SPOT DNA FROM SUBJECTS WITH AUTISM. Torres AR 1, Nield A 1, Zhong X, & Ward D 2. 1 Center for Persons with Disabilities, Utah State University, Logan, Utah USA, 2 Department of Genetics, Yale University, New Haven, CT, USA

We have recently linked the HLA-DRB1-04 allele to subjects with autism spectrum disorder (AR Torres, 2002). An important extension of this work is to HLA type DNA from archival blood spots taken from newborn infants who later are diagnosed with autism. Minimizing the amount of sample used for DNA analysis is critical as the spots are valuable for many types of analysis. Generally, a DNA amplification step will be required as very small amounts of DNA are obtained from such blood spots. Here we describe our approach for typing of class I and class II alleles from samples with limited DNA using a new DNA amplification system, designated Multiple Displacement Amplification (MDA). MDA differs from other amplification methods, such as degenerate-oligonucleotide- primer PCR (DOP-PCR) or primer-extension preamplification (PEP), in that human genomic DNA can be amplified extensively (10,000-100,000 fold) without signifPOSTER SESSION 2 TOPIC 5: SENSORY & MOTOR 2

CORTICAL SOUND PROCESSING IN CHILDREN WITH AUTISM: AGE DEPENDENCE OF THE AUDITORY M100.N.M. Gage1, B. Siegel2, and T.P.L.Roberts1, 1Biomagnetic Imaging Lab & 2Pervasive Developmental Disorders Clinic, University of California, San Francisco, CA 94143

In healthy adults, the auditory evoked M100 occurs ~100 ms post stimulus onset and localizes to auditory cortex. In healthy children, the M100 latency peak (and electric counterpart, N1) is prolonged, typically 30-70 ms later than adults. A recent MEG study provided evidence that M100 latency varies inversely with age, with longer latencies for younger children and shorter, more adult-like latencies for older children and teens. Although the neural mechanisms underlying this latency shift are not known, it has been suggested that they may relate to myelination processes that occur during development. Here we investigate M100 age dependence in normally developing children and children with a diagnosis of autism. We presented 1 kHz tones and recorded auditory evoked responses in 20 controls (12 male, M = 13.5 yrs, SD 1.7), and 20 male children with autism (M = 11.4 yrs, SD 2.0). Results: Control – M100 varied inversely with age in both the left (LH: r = .40;) and right (RH: r = .53) hemispheres. Slopes of a regression line indicated stronger age dependence in RH: LH 615-989 ms years, RH 1020-1346 ms years. Autism – both LH and RH showed 1/age dependence (LH: r = ..58; RH: r = .38). Regression line slopes indicated a weaker dependence in autism, particularly in RH where the slope did not statistically differ from zero: LH 340-415 ms years, RH 220-316 ms years. Results provide evidence for M100 age dependence in healthy children. The lack of strong age dependence in autism may indicate a different maturation path in auditory cortical development in this group.

THE NATURE OF SENSORY REACTIVITY IN AUTISM. C.A. Saulnier, M. Liss, & D. Fein*. University of Connecticut, Storrs, CT 06066.

Using the Sensory Survey, a 103-item scale measuring overreactivity, underreactivity and stimulus seeking behavior, abnormal reactivity to sensory stimuli has been shown to be common in autism but not in typical individuals. The Sensory Survey was administered to 222 parents of individuals with Pervasive Developmental Disorders (PDDs) ranging in age from 2 to 23 and 195 parents of typical individuals ranging in age from 2 to 13. Parents were also administered the Vineland Adaptive Behavior Scales. The Sensory Survey has high reliability for both groups; Cronbach’s alphas for the total scale were .94 and .95, respectively. MANOVA results indicated that individuals with Autistic Disorder demonstrated significantly more overreactivity, undereactivity and seeking behavior than typical individuals and individuals with PDD-NOS [F(3,410)=864.9, p P2.5.3
OBSERVATIONAL LEARNING OF MOTOR SEQUENCES IN AUTISM. I.M. Smith. Dalhousie University, Halifax, NS Canada B3J 3G9.

An observational learning paradigm was used to investigate what factors affect the performance of children with autism, compared with developmentally-matched controls, as they learned a movement sequence. Children watched a video model perform a 5-step series of simple arm movements. Recognition (placing photographs of the 5 postures in order) and reproduction (performing the movements) were tested separately over repeated trials. Half of each group was able to view their own performance (Visual Feedback condition) whereas half could not (No Visual Feedback). On the final eneralization trial, the same movement series was presented on from a different visual perspective. Coders rated the accuracy of children’s copying of the modeled postures and transitions between postures from videotape. Preliminary data demonstrate that children with autism attended well to the video demonstrations. Consistent with earlier findings, children with autism did not have difficulty putting pictures of the elements of a series in correct order, attaining the same level of performance as typical controls by the 3rd trial. However, the ability of children with autism to reproduce the series of movements showed characteristic performance deficits, relative to controls. As previously reported (Smith & Bryson, 1998), the difficulty appeared to lie not in the sequencing of individual movements, but in processing the spatial transformations required to reproduce another’s movements with one’s own body. Children with autism appeared to have particular difficulty accurately producing a familiar series of movements after observing the same series from a novel perspective.

INTERACTIONAL SYNCHRONY IN PERSONS WITH ASD D. Tremain Interactional Syncrhony Studies, Inc., Ft. Wayne, IN 46815 USA

This study was an attempt to replicate the work of Dr. William S. Condon, Boston University (retired) using video and computer technology rather than sound film. Dr. Condon discovered a person’s subconscious body movements syncrhonize with the sounds they hear, and especially speech. He further discovered that persons with autism had a delayed and bilateral asymetry in their body responses to sound. The delay and bilateral asymetry (Condon’s Autism Anomaly) was measurable and constant over time. The data analysis involves frame-by-frame examination of VHS video, as captured by a computer, comparing word boundaries with the subjects’ body movement boundaries (start, stop, change direction). This gives a time-frame resolution of approximately 1/30 second (compared to Dr. Condon’s sound film 1/24 second). The study examined two children with ASD’s, and found the delayed and bilateral asymetry that Dr. Condon described in both subjects. Further research is planned that will attempt to establish Condon’s Autism Anomaly as an accurate, objective indicator of the presence or absense of ASD, as well as the potential of being able to objectively and accurately categorize ASD’s.

SPEECH SOUND CHRONOLOGY IN NON-VERBAL AND MINIMALLY VERBAL CHILDREN WITH AUTISM. L.M. Tully, J.P. McCleery, & L. Schreibman. Autism Research Laboratory, University of California – San Diego, La Jolla, CA 92039.

Previous research examining phonological development in children with autism has focused on verbal children. The present study is an evaluation of speech sound chronology in non-verbal and minimally verbal children with autism age 2 to 6 years. Phoneme-initial consonant production was evaluated using naturalistic observation during play followed by discrete attempts to elicit imitation of sounds. Results indicate that some non-verbal and minimally verbal children with autism present with normal but delayed acquisition of speech sounds, whereas others exhibit atypical speech sound chronology. Discussion focuses on implications for the assessment and treatment of speech skills in children with autism.

FREQUENCY SELECTIVITY AND ASPERGER’S SYNDROME E.J. Weisblatt and J. I. Alcántara Depts.of Psychiatry and Experimental Psychology, University of Cambridge, UK.

A commonly reported problem in autism is difficulty understanding speech in background noise. Alcántara et al. (2002) measured speech reception thresholds (SRTs) of high-functioning individuals with autism (HFA) or Asperger’s syndrome (AS) and found them to be significantly worse than those of age-/IQ-matched controls, especially for background sounds that contained temporal and spectral dips. The aim of this study was to measure auditory frequency selectivity for subjects with HFA/AS to determine whether abnormal peripheral processing explains the observed difficulties in speech-in-noise perception. The auditory filter shapes of 8 normal-hearing high-functioning individuals with HFA/AS were measured using a masking paradigm. The masker was a fixed-level noise whose spectrum had a notch centred at the signal frequency of 2 kHz. The threshold of the signal was determined for a series of notch widths. The function relating signal threshold and notch width was used to calculate the equivalent rectangular bandwidth (ERB) of the auditory filter. The ERB is a measure of the range of frequencies passed by the filter. The smaller the value, the sharper the filter,and the better the frequency selectivity. The mean ERB of the HFA/AS subjects was 354 Hz, larger than the 308 Hz measured in normal-hearing individuals by Moore (1987). Thus, the frequency selectivity of the HFA/AS participants was worse than normal. A decrease in frequency selectivity causes greater masking by noise, as the wider auditory filters pass more noise along with the signal. The decrease in frequency selectivity might account for the increased SRTs for HFA/AS individuals and the reported speech perception problems in noisy environments.


SCREENING, OBSERVATION, INTERVIEW: PSYCHOMETRIC PROPERTIES OF THREE SCALES FOR AUTISM Sven Bölte & Fritz Poustka Department of Child and Adolescent Psychiatry, J.W.G.-University Frankfurt/M., Germany

The clinical diagnosis of autism according to ICD-10 and DSM-IV is one of the most reliable ones in child psychiatry. Taking into account the research on the fundamentals, comorbidity and outcome of the disorder, a considerable etiologic, concurrent and prognostic validity of the diagnosis can also be assumed. Various psychometric scales have been developed to further improve the fidelity of the diagnostic ascertainment in autism. In general, it seems reasonable to have questionnaires for screening as well as standardised observation scales and parental interviews for ensuring diagnosis at one’s disposal. The Autism Screening Questionnaire (ASQ), the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and the Autism Diagnostic Diagnostic Interview-Revised (ADI-R) are frequently used instruments for this purpose in autism. In this study, we present reliability and validity data on the German forms of these scales, that corroborate their utility for use in clinical practice and research.


The purpose of this study was to examine the diagnostic validity of the ADOS in young children, particularly in cases where there is some symptom overlap, such as fragile X syndrome and children with significant developmental delays. Subjects were 106 children ranging in age from 12-50 months (mean = 31 months) and comprising six groups (autism, n =29; fragile X syndrome with autism, n = 10; fragile X syndrome without autism, n= 13; other developmental delay, n = 13; Down’s Syndrome, n =19; and typically-developing children; n=22). Overall mental ages ranged from 8-42 months. ADOS scores were compared with clinical diagnoses formulated by experienced clinicians (based upon 10 + hours of observation and interviews). Results supported the diagnostic validity of the autism cut-off scores on the ADOS. Sensitivity was excellent: none of the children with a clinical diagnosis of autism failed to be identified by the ADOS (97% met autism cut-off, 3% met spectrum cut-off). Specificity of the autism cut-off was also excellent. Only one child in the non-autism groups (2%) met the autism cut-off. More false positives (32% of the children with developmental delays) were noted for the spectrum cut-off. Children who were over-identified by the spectrum cut-off tended to be lower functioning developmentally, F(1,62) = 12.96, p P2.6.3
AGREEMENT AMONG FOUR DIAGNOSTIC INSTRUMENTS FOR PDD IN 2-YEAR-OLDS. J. Kleinman, P. Dixon, M. Barton, J. Green, S. Allen, D. Robins, and D. Fein*. Department of Psychology, University of Connecticut, Storrs, CT 06269.

The diagnosis of autism spectrum disorders has special problems in very young children, although early diagnosis is essential in obtaining needed early intervention. It has been suggested that while deficits in social interaction and communication apply to toddlers with Pervasive Developmental Disorders, perseverative behaviors and maintenance of sameness may not; therefore they may meet criteria for PDD-NOS but not for autism. Four diagnostic instruments were applied to a group of 18-30 month old children (mean age = 27 months) identified as high risk for PDD by failing a screening with The Modified Checklist for Autism in Toddlers (M-CHAT; Robins, Fein, Barton, & Green, 2001). These diagnostic procedures included the Autism Diagnostic Observation Schedule (ADOS; Lord, et al., 2001), Autism Diagnostic Interview-Revised (ADI-R; Lord, Rutter, & LeCouteur, 1995), Childhood Autism Rating Scale (CARS; Schopler, et al., 1980), and clinical judgment based on DSM-IV criteria. Results suggest good diagnostic agreement among 3 of the measures (ADOS, CARS, and clinical judgment, p .33), often under-diagnosing children. Two possible reasons for this finding are that the 3 instruments with high agreement are based on observation while the ADI-R is a parent interview. Furthermore, the ADI-R only scores children as autistic or not autistic, necessitating perseverative behavior or maintenance of sameness, while the other instruments allow more latitude in diagnosing autism or PDD. The ADI-R might be more useful with toddlers with an algorithm for diagnosing PDD-NOS.


Design: Interviews of parents identified the skills and behaviors reported changed with secretin therapy. Content validity was determined with cognitive testing and expert panel review. Two cross-sectional mail surveys identified scales, tested their reliability, construct and criterion validity. A longitudinal mail survey assessed test-retest reliability Subjects: Parents of children diagnosed with Autism, Autistic Disorder, Pervasive Developmental Disorder/Not Otherwise Specified (PDD/NOS) or Aspergers Syndrome. Interview participants (n=10) were referred by a local physician. Study participants (n=61) were recruited from the practices of general and developmental pediatricians. Measures: The questionnaire contained 97 items assessing functional skills and behaviors, and 38 items on sociodemographic characteristics, co-existing medical conditions, medications, and parental mental status. Results: The respondents (n =61) were mainly white (90%), female (93%), >high school education (82%) and more “distressed”. The children were males (82%), diagnosed with PDD/NOS (61%), their mean age was 8.6 years, and 36% were in preschool/kindergarten. The Cronbach’s alpha for the six scales ranged from 0.78 (Receptive Language) to 0.90 (Expressive Language). The of the total score was 0.88. The relationships between scale scores and subgroups supported construct validity. Four scales showed acceptable test-retest reliability (correlation coefficients >0.70) and inter-rater correlations. The difference of the mean teachers and parents score was significant for the Expressive Language Scale (95% C.I. 2.69 to 4.35)

CORRELATION OF THE ADI-R RECIPROCAL SOCIAL INTERACTION WITH THE VABS. SA Ravan, R.K. Abramson,* K.M. Wieduwilt, K.A. Decena, H.H. Wright, and M.L. Cuccaro. Dept. Neuropsych & Behav. Sci., Univ. South Carolina Sch. Med., Columbia, SC 29203

Qualitative impairments in Reciprocal Social Interactions (RSI) are part of the Autism Diagnostic Interview (ADI-R) diagnostic algorithm for Autistic Disorder (AD). The Vineland Adaptive Behavior Scales, survey form, (VABS) an age related measure that assesses personal/social sufficiency in handicapped/nonhandicapped persons, provides adaptive levels and age equivalents. The VABS gives a composite score(VABS-CS) and 4 subdomain scores: Socialization(VABS-S), Communication(VABS-C), Daily Living(VABS-DL), and Motor Skills(VABS-MS). Both the ADI-R and VABS measure social interaction. This study examines the correlation between the RSI and RSI subdomains of the ADI-R with the VAB-CS and subdomain scores. The ADI-R and the VABS were administered to parents of AD children participating in the Duke/USC genetic study of AD. Age adjusted supplemental norms for AD were used to calculate VABS-CS and subdomain scores. The sample (n=122) of AD individuals was 73.8% male, 26.2% female, 73.8% white, 26.2% other race, with mean age 101.4 ± 52.5 months. Significant negative Pearson correlation coefficients were present for the VABS-CS with the RSI algorithm score, r = -.319, p=.001; the VABS-S with the RSI algorithm score, r = -.296, p=0.011); the VABS-C with the RSI algorithm score, r = -.242, p=0.11); and the VABS-DL with the RSI algorithm score, r = -.218, p=0.022). None of the RSI subdomain scores were significant. The highest r values were for the VABS-CS, r = -.454, p=.000), VABS-S, r = -.469, p=.000), VABS-C, r = -.333, p=.000) and VABS-DL, r = -.472, p=.000) with the sum of the 28 items of the ADI-R RSI algorithm score. The sum of ADI-R RSI nonalgorithm items also resulted in significant negative correlations with r values for the VABS-DL > the VABS-CS > the VABS-S > the VABS-C. ANOVA gave significant race by VABS, sex by VABS effects. Thus, the VABS is significantly correlated with the ADI-R RSI algorithm and unexpected VABS race and sex effects were present in this sample.

VALIDITY STUDY OF THE SOCIAL COMMUNICATION QUESTIONNAIRE IN YOUNG CHILDREN E. Hanson,* N. Sullivan, J. Ware, C. Lord, A. Thurm Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115

There have been a number of diagnostic measures developed for autism, including the Autism Diagnostic Interview-Revised (ADI-R; Lord et al, 1994) and several screening instruments. Recently, the Social Communication Questionnaire (SCQ) was developed from previously validated ADI-R criteria, as a screener to be completed by the primary caregiver. The SCQ was developed to have unambiguous and non-technical wording, it focuses on observable behavior, and it focuses on qualitative deviance rather than developmental delay or impairment. A recent study evaluating the SCQ’s discriminative validity in children over 5 found that it was an effective screening questionnaire, as it discriminated PDD from non-PDD diagnosis at all IQ levels. The current study evaluated the reliability and validity of the SCQ by piloting the questionnaire on a sample of children aged 2-4.6 years referred for Pervasive Developmental Disorders, and a control group of children referred for other developmental disabilities. Preliminary results indicate adequate sensitivity and specificity for this age group in differentiating children with autism from those not on the autism spectrum. Factor analysis will indicate whether similar factor structures will emerge as in the older sample, and ROC curve analysis will verify sensitivity and specificity findings.


TENSE ERROR PATTERNS IN CHILDREN WITH AUTISM AND CHILDREN WITH SLI. K. Condouris, L. Evancie and H. Tager-Flusberg*.Lab of Developmental Cognitive Neuroscience, Boston University School of Medicine, Boston, MA 02118

Recent studies using standard and experimental measures have established that there is a subgroup of children with autism that presents with the same grammar deficit seen in children with Specific Language Impairment (SLI): omission of tense morphemes in obligatory contexts. This impaired ability to use tense is an important clinical marker of SLI. The current study further investigated the extent to which this grammar deficit overlaps in the two diagnostic groups by comparing the tense use error patterns in the spontaneous speech of age and language matched children with autism and SLI. Our participants were 21 children with autism aged 4 years to 12 years who were language impaired; 13 language and age matched children with SLI; and 9 age matched children with autism without language impairment. Language samples were collected from a parent-child 30 minute conversation and from examiner-child interactions during the ADOS. These samples were transcribed and coded for grammatical tense morphemes and control morphemes unrelated to tense. None of the groups were impaired on the control morphemes. In contrast, the autistic language-impaired (ALI) and SLI groups were impaired on the third person singular tense morpheme. These results suggest a similar pattern of protracted tense development in some children with autism and in children with SLI. Considering the evidence of genetic overlap between these two diagnostic groups, omission of tense morphemes as a clinical marker of SLI and ALI has significant implications for diagnostic subgroups within autism, neurobiological patterns and genotype/phenotype relationships.

MEMORY FOR NARRATIVES IN CHILDREN WITH AUTISM SPECTRUM DISORDERS. J.J. Diehl, L. Bennetto, and E.C. Young. Univ. of Rochester, Depts. of Clinical & Social Psychology, & Surgery, Rochester, NY 14627.

Narratives are an increasingly popular way to study pragmatic language deficits in children with autism spectrum disorders (ASDs). Narratives also provide researchers an opportunity to examine aspects of memory in ASDs. Previous research on narrative production has found few differences between children with ASDs and controls on measures of morphosyntax, cohesion, and narrative evaluation. The current study focused on memory for narratives, and in particular how information is changed, added, or excluded from story retellings. Subjects included 17 high-functioning children with ASDs and 17 typical controls matched on age, gender, verbal IQ, and receptive/expressive language abilities as measured by the CELF-3. Narratives were collected by using the Strong Narrative Assessment Procedure (SNAP). The study revealed no differences in overall story parameters or story length. However, children with ASDs were somewhat more likely to intrude new information in the story. In particular, they were significantly more likely to make bizarre or idiosyncratic intrusions in their retellings. In contrast, children with ASDs were significantly less likely to include emotions, remembered or inferred, in their narratives. Correlational analyses showed that, for the autism group only, sentence memory scores from the Stanford-Binet were strongly related to the number of basic story components retold (r = ..63), and negatively correlated with the amount of additional information included in the story (r = -.49). These data suggest that children with ASDs rely more heavily on verbal memory when retelling stories than do controls, even when matched on language ability. These data is consistent with other evidence from the SNAP that children with ASDs have difficulty answering questions that require inferences to be made about the story.

VERBAL FLUENCY IN AUTISM AND LANGUAGE IMPAIRMENT. L. Evancie, K. Condouris, L. McGrath, R. Joseph, & H. Tager-Flusberg*. Lab of Developmental Cognitive Neuroscience, Boston U. Sch. of Med., Boston, MA 02118

Verbal fluency (VF) involves skills relating to working memory, lexical store and organization, processing speed, and output strategies. Studies of VF in autism have produced conflicting results. This study seeks to characterize VF abilities with relation to other language and cognitive skills in a large sample of children with autism. 50 children with autism and 40 language-impaired children were matched on age and NVIQ. Semantic and phonemic fluency were assessed with the NEPSY. Participants were also given standardized measures of language, vocabulary, and executive functions. There were no verbal fluency differences between groups, indicating an absence of autism-specific impairment in these children. There were no group differences in the prototypicality or frequency of exemplars produced. In the autism group, semantic frequency scores on VF were significantly correlated with vocabulary, and errors on the VF task were correlated with EF. Only in the language-impaired group was VF performance correlated with general language level. Similar group profiles with respect to output, frequency and prototypicality indicate that the lexicons of children with autism are not disorganized or comprised of bizarre exemplars compared to language-impaired controls. Use of clustering in the autism group suggested that they used semantic organizing strategies to generate novel responses. A negative association between error rate and EF indicated that weakness in set maintenance and inhibition may contribute to VF errors in autism.

PERSONAL AND FICTIONAL NARRATIVE PRODUCTIONS IN HIGH-FUNCTIONING AUTISTIC CHILDREN. S. Goldman* City Univ. of New York, Graduate Center, NY 10016; Albert Einstein College of Medicine, Kennedy Center, New York, NY, 10461; M. Dunn, Albert Einstein College of Medicine, Kennedy Center, New York, NY, 10461; K. Nelson, City Univ. of New York, Graduate Center, NY 10016

The purpose of this study is to assess the relationships between autism and the acquisition of narrative skills and their implications in the elaboration of personal memories. Participants included 14 high-functioning verbal autistic children (ages 9 to 3 years), 12 normally developing children, and 12 language-impaired children, matched for chronological age and non-verbal IQ. For all children, verbal and non-verbal profiles were defined using subtests from the Stanford Binet Intelligence Scale, the Clinical Evaluation of Language Fundamentals, the Wide Range Assessment of Memory, and the Peabody Picture Vocabulary Test. Fictional and personal narratives about personal past experiences (e.g., trips, birthday) were collected and transcribed. Each parent was interviewed about their children’s social behavior, conversational practices, and interest about the past. Psychological assessment confirmed formulation impairment in both autistic and language-impaired children and showed no deficits in verbal story memory in either group. In all children, quantitative analyses were performed across three narrative tasks, (1) story retelling, (2) story telling, (3) personal past events. Results showed no difference among the three groups in narrative length nor in the use of: cognitive and affective mental states, evaluation devices and temporal and causal markers. In contrast, autistic children exhibited lower scores for global narrative markers (e.g., coherence) and deficits in generating high points and goal-oriented stories. We conclude that the discrepancy within the narrative profile of autistic children between the quantitative linguistic measures and the overall narrative scores from story grammar analysis is reflective of their communication and social deficits as well as their lack of co-constructed conversation and spontaneous desire to share experiences.


We report here some preliminary results using Asperger and normal adolescents as script writers for a multimedia social skills intervention program. The multimedia system is based on a threelayer media model. The topmost layer is a series of videos exploring common pragmatic features of communication. Each video dramatises a social scenario, e.g. initiating with the opposite sex, asking for help, etc. Both groups of adolescents received the same set of ten social scenario templates and were asked to suggest dialogue for the central (Asperger) character. The participants were asked to write from three perspectives (1) as the character (2) as ‘yourself’ and (3) as a ‘friend of the character’. Both groups showed internal consistency in their thematic responses. However in ‘awkward’ scenarios – asked to loan bus fare by a stranger or being offered a Discman for sale by a stranger – the Asperger group produced more mature cautious responses on first reading than the other group. Upon discussing their responses in a workshop, it was clear that (a) they did not seek to identify nonverbal cues in other characters (egocentric perspective) and (b) while they could write assertive dialogue for the Asperger character, they were unable to produce the same dialogue when asked to ‘be’ that character in (2) above. These results confirm and extend other research that language usage in AS can give the illusion of ‘shrewdness’. We tease out the implications for our multimedia research.

USING THE ADOS-G TO PROBE FOR EXPRESSION OF MENTAL STATES IN HIGH-FUNCTIONING CHILDREN WITH AN AUTISTIC SPECTRUM DISORDER A. M. Udcoff, F. M. Ploog, and I. L. Cohen. New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314.

The purpose of the present study was to examine the responses of children with high functioning ASD (mean age (SD) = 6.06 (5.58)) to probes about mental states. A certified psychologist used the ADI-R, ADOS-G, and PDD Behavior Inventory, parent and teacher versions, to diagnose all subjects. A research assistant used the Griffiths Mental Development Scales to obtain IQ scores (mean (SD) = 95.96 (8.18)). The investigators chose a task from the ADOS-G (module 3) that required a child to tell a story from pictures. If the child failed to spontaneously address the mental states of the characters, the examiner prompted the child with questions such as “what is this person thinking?” Administrations of the ADOS-G were videotaped and later reviewed by two observers. The observers rated the quality of subject’s responsses to probes for two specifi pictures. Responses were classified into three categories: action, mental state, and other. Results show that children diagnosed with ASD are more likely to answer questions about facial expressions with action words rather than mental state words. However, many responses were unrelated to the probe. The results of this study support previous research that children with ASD have problems expressing an association between facial expressions and thoughts (Tager-Flusberg, 1992; Happè, 1994). Further, this research looked at how information obtained through the ADOS-G could be used to expand the rating system to include a rating on the quality of how children convey mental states, not just whether the child comments on mental states. Thus, the quality of a child’s comprehension and expression of mental states could be a factor for a diagnosis of ASD on the ADOS-G (module 3).

VERBAL DATABASE SUPERIORITY IN ASPERGER’S DISORDER. A.Wagner, L. Kenworthy*, G. Wallace, L. Gilotty, T. Ahluvalia, L. Sirian, K. Towbin. Children’s National Medical Center, Washington, DC 20016.

The distinction between Asperger’s Disorder (AD) and High Functioning Autism (HFA) is controversial. DSM-IV criteria emphasize intact early language in AD. Many argue that AD is differentiated from HFA only by higher verbal intelligence and is simply a “higher” form of high-functioning autism. We hypothesize that children with AD are not able to translate their excellent verbal databases into functional communicative capacities. Two experienced clinicians reviewed charts of 33 HFA and 29 AD patients who had been consecutively evaluated in a neuropsychology service to confirm autism diagnoses (DSM-IV criteria used). Groups matched on age (range = 6-17 years; HFA M=10.9; AD M=10.0), PIQ (HFA M=95.2; AD M=99.8) and gender (30 HFA males, 26 AD males). All patients had FSIQ> 70. As part of their evaluation, the groups completed a range of language related measures. The AD group was significantly superior to the HFA group on measures of verbal knowledge and rote verbal memory, including the WISC-III Verbal Comprehension Index (p POSTER SESSION 2 TOPIC 8: EPIDEMIOLOGY

THE CO-OCCURRENCE OF AUTISTIC SPECTRUM DISORDERS AND MOEBIUS SYNDROME: DATA FROM THE ADI-R AND ADOS. B. McConnell, I. Drmic, W. Roberts, & S.E. Bryson*. The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8

We provide data on the association between autistic spectrum disorders (ASDs) and Moebius syndrome (MoS). MoS is characterized by paralysis of cranial nerves VI and VII, resulting in an inability to make lateral eye movements and to move the muscles involved in facial expression. Twenty-two children with MoS aged 3-12 years were assessed using the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R). Cognition and language were also assessed. Findings indicate that eight (36.4%) of the children with MoS met diagnostic criteria for an ASD. Of the 8 cases, 5 (62.5%) had autism and 3 (37.5%) had Asperger syndrome; 2 additional children were identified as borderline ASD cases, and 2 others had clinically significant autistic features. Among the group with MoS and ASD (n=8), IQs ranged from cognitively impaired to high average (x = 87; SD= 25). Our findings are consistent with previous reports implicating a high co-occurrence rate between autism and MoS. We extend previous research by showing that ASDs and MoS co-occur in children with varying levels of intelligence, including those with average or above average IQs. Our findings also indicate that the spectrum of autism and lesser variants is represented in MoS: some children are classically autistic, others parallel the prototype of Asperger syndrome, and still others show varying degrees of some but not the full criteria for either. Discussion focuses on the embryological implications of the overlap between ASDs and MoS.

SURVEILLANCE OF AUTISM: CAN SCHOOL DATA BE USED FOR SURVEILLANCE OF AUTISM SPECTRUM DISORDERS? R. Nonkin Avchen,* T. Karapurkar, & N. Doernberg, Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, 4770 Buford Hwy, NE, Mailstop F-15, Atlanta, GA 30340

Objectives The Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP) is one of the few large, population-based surveillance programs monitoring ASD in the United States. This paper evaluates the type of special education eligibility categories for children identified as having ASD by MADDSP in order to determine the feasibility of using autism eligibility categories for complete ascertainment of children with ASD. Methods For the study year 1996, MADDSP identified 987 children 3 110 year old that met the case definition for ASD. MADDSP relies on an exhaustive review of records to identify children with an ASD. Potential case records are abstracted at multiple sources (e.g., schools, hospitals, and clinics), which are likely to maintain evaluation or treatment records for children with ASD. Experts review the abstracted data and determine case status in accordance with the DSM-IV criteria for autism and other pervasive developmental disorders. Results Thirty-seven percent of MADDSP ASD cases had a primary school eligibility code of autism, while 54% had some other primary school eligibility code, and 9% had no eligibility code. Other eligibility codes for MADDSP cases were specific developmental delay (35%), speech and language disorders (15%), and behavior disorders (12%). Demographic and other child characteristics were similar between children with an autism eligibility code and those that had another eligibility code. Conclusions Reliance on a school eligibility category of autism is likely to under-represent prevalence estimates for ASD. The question remains as to whether a special education eligibility category of autism could be used as a percent sample to estimate prevalence rates.

RISING AUTISM PREVALENCE RATES: A 12-YEAR REGIONAL TREND ANALYSIS IN TEXAS R. F. Palmer, S. Blanchard, A.Everett, C. R. Jaén, V. James, University of Texas Health Science Center San Antonio, Dept of Family and Community Medicine, San Antonio, Texas 78229-3900

OBJECTIVE: To investigate the pattern of change in the regional distribution of autism rates over time and investigate socioeconomic correlates of this rate of change. METHODS: Administrative data from the Texas Education Agency (TEA) from 1989 to 2001 were analyzed (n = 4,071,433 public school students ages 5 – 18 years). Autism rates were obtained by calculating the ratio of total number of autistic children to the total enrolled by year and school district. County rates calculated and mapped by linking districts using Graphic Information System software. Property wealth from the TEA was also obtained to derive correlations between school district wealth and autism rates by community type (urban, suburban, rural) over time. RESULTS: Consistent with prior reports, there was an overall exponential increase in autism rates over the12-year period. There were marked differences in rates by region, community type, and wealth distribution. While statewide rates were between 0 to 5 per 10,000 in 1989, by 2001 rates ranged from an average 8.5 per 10,000 to 22.4 per 10,000 by region. Large urban areas experiencing the highest 10-year population growth and with highest levels of wealth demonstrated the highest growth rates. CONCLUSIONS: Because rates were derived from administrative data that do not include all cases of autism, they are conservative estimates and most likely underestimate the true prevalence rates. Regional variation might be explained by area differences in resources such as the availability of diagnostic and/or treatment facilities or to differential environmental exposures. It would be useful for future investigations to understand if other states follow a similar regional distribution pattern.

CHARACTERISTICS OF CHILDREN IDENTIFIED WITH AUTISM IN ATLANTA WITH AND WITHOUT A PREVIOUS AUTISM DIAGNOSIS. Tanya Karapurkar, Catherine Rice*, Cornelia Taylor, and Diana Schendel. National Center on Birth Defects and Developmental Disabilities, CDC, Atlanta, GA 30341

Children with autism in Atlanta 3 to 10 years old in 1996 were identified by CDC’s Metropolitan Atlanta Developmental Disabilities Surveillance Project (MADDSP). Although all of children with autism met the DSM-IV criteria for an autism spectrum disorder (ASD; autistic disorder, PDD-NOS, or Asperger’s Disorder) based on systematic screening, abstraction, and review of evaluation reports in school records, not all children had a previous clinical ASD diagnosis prior to identification by MADDSP. In order to assess differences in the characteristics of children with and without a previous ASD diagnosis, we conducted a case-control study examining sociodemographic and diagnostic classification variables among the study groups. There were 467 children born in the five-county metropolitan Atlanta area between 1986 and 1993 with evaluation records from school sources and behavioral features consistent with MADDSP’s DSM-IV based classification of autism. Cases were further divided into children who did, and who did not, have a previous diagnosis of ASD recorded in the child’s evaluation records reviewed by MADDSP. Controls were Atlanta-born children without known developmental disabilities, randomly selected from birth certificates and frequency matched to case children by year of birth. Sociodemographic variables included: age group; child’s sex; median family income; birth multiplicity; parity; and mother’s age, education, and race. Diagnostic variables included presence of a co-existing cognitive impairment, other diagnoses, classification for special education services, and presence of associated features (e.g., attention problems, aggression, etc.). Based on multivariate analyses, we found that the likelihood of a child with autism having a previous ASD diagnosis prior to identification by MADDSP was related to specific sociodemographic factors (e.g., higher family income) and the presence of a co-existing cognitive impairment. Information on the children’s other previous clinical diagnoses and the special education classifications provides additional information on how children not previously identified with autism are classified.

NUMBERS AND RATES OF AUTISM-ASSOCIATED HOSPITLAIZTIONS IN THE US FROM 1988 THROUGH 1999. W Thompson, F DeStefano, C Hoffman, M Blank, E Weintraub, D Shay. Centers for Disease Control and Prevention, Atlanta, GA, 30333.

We examined a nationally representative weighted sample of hospital discharge records from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample. Age-specific primary and secondary hospital discharge diagnoses coded as ICD-9 299.0 were examined from 1988 through 1999. US Census Bureau population estimates were used to estimate hospitalization rates. Between 1988 and 1999, the total number of autism-related hospitalizations increased from 941 to 7,304. In the age groups 0 – 9 years, 10-19 years, and > 20 years, the number of autism hospitalizations per year increased from 280 to 2,955, from 330 to 2151, and from 331 to 2199, respectively. The average annual hospitalization rates for the three age groups were 3.3, 2.5, and 0.6 per 100,000 persons, respectively. There were significant increases in annual hospitalization rates over time for all three age groups. On average, 85% of the autism diagnoses were recorded as secondary diagnoses. Among hospital discharges coded with autism as a secondary diagnosis, the most frequent primary diagnoses were general symptoms (ICD-9 780), epilepsy (ICD-9 345), and disturbance of conduct not elsewhere classified (ICD-9 312). During 1988-1999, hospitalizations related to autism increased substantially in all age groups, including adults over 20 years of age. Most research suggests that factors influencing the development of autism originate from the prenatal or infancy periods. The increased coding of autism as a hospital discharge diagnosis in all age groups suggests that increased awareness and recognition of autism may be contributing to the increasing trends in service utilization for autism.

DIAGNOSTIC CHARACTERISTICS OF A POPULATION-BASED SAMPLE OF VERY YOUNG CHILDREN WITH AUTISTIC SPECTRUM DISORDERS. Van Daalen, E., Willemsen-Swinkels, S.H.N., Dietz C., van Engeland, H. & Buitelaar, J.K. Dept of Child and Adolescent Psychiatry and Rudolf Magnus Institute for Neurosciences, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. [email protected]

Background: The detection and diagnosis of autistic spectrum disorders (ASD) at very early age is hampered by the lack of knowledge about diagnostic procedures, criteria and algorithms of ASD below age 2 year. Aim: To examine (1) the presence of DSM-IV criteria for autistic disorder in children with ASD below age 2 year and (2) the relationship between clinical and ADOS diagnosis. Method: Children with ASD below age 2 year are identified via an ongoing population screening of about 30,000 children at age 14 months and thoroughly assessed using ADOS-G, Vineland, and clinical observation. Results: Sofar, 16 children with ASD below 2 year have been identified. In November 2002, the results will be reported of a larger sample of approximately 20 children with ASD below 2 year.

BEHAVIORAL STABILITY IN CHILDREN WITH HIGH FUNCTIONING AUTISM. C.P. Burnette, D. Charak, A.E. Vaughan, J. Meyer, M. Yale, D. Thorp, P. Mundy.* University of Miami, Department of Psychology, Miami, FL 33124

High functioning children with autism (HFA) frequently suffer from symptoms of comorbid psychopathology. Little is known, however, about the nature, development, and stability of these symptoms. This issue was addressed in an 18-month longitudinal study of 23 children with HFA between 8 and 13 years of age. Children completed cognitive and social-cognitive measures, as well as self-report scales of dysphoria and social competence. The Behavioral Assessment Scale for Children (BASC) revealed significant individual stability on negative Attitude to School (r = .84, p < .001), Atypicality (unusual thoughts and perceptions; r = .47, p < 05), Locus of Control (r = .65, p < 001), Social Stress (r = .48, p < 05), Anxiety (r = .47, p < .05), and Depression (r = .68, p < .001). Self-report of positive social behaviors, such as Relations with Parents (r = .50, p < .03), and Self Reliance (r = .54, p < .02), were also stable. Social-cognitive and cognitive indices at Time 1 predicted self reported social behavior at Time 2. Theory of Mind scores, as well as Performance IQ, especially Block Design predicted self-reports of Interpersonal Relations and Self Reliance (r = .40 to .65, p < .05). Lower Verbal IQ and Block Design scores at Time 1 were related to higher self-report Social Stress at Time 2 (r = .60, p < ..01 respectively). Similarly, lower Verbal IQ at Time 1 was related to self-report Depression at Time 2 (r = ..43, p < .065). Time 1 self-report of Interpersonal Relations predicted self-reports of positive Relations with Parents, Self_Esteem, and Self Reliance at Time 2 (r = .56 to .64, p < .02). These results suggest that HFA children display numerous stable individual differences in their emotional and behavior status, some of which are linked to their cognitive and social cognitive abilities. The implications of these results for understanding the nature and treatment of HFA children will be discussed.

AN EXAMINATION OF REPETITIVE BEHAVIORS IN AUTISM AND OBSESSIVE-COMPULSIVE DISORDER: BRAIN AND BEHAVIORAL SIMILARITIES. J. M. Winter and L. Schreibman. Autism Research Laboratory, University of California, San Diego, Department of Psychology, La Jolla, CA 92093-0109.

It is proposed that the repetitive and ritualistic behaviors, or “obsessions” and “compulsions,” of individuals with autism and individuals with obsessive-compulsive disorder (OCD) are not distinct aspects of the two syndromes, but instead are phenomenologically similar and part of an overlapping class of behaviors. This presentation will provide a review of data that suggests that the brain regions responsible for the development of pathological repetitive behaviors in both disordered populations are the basal ganglia (caudate nucleus) and frontal lobe. Evidence from psychopharmacology, including response to pharmacotherapy, also contributes to the idea of an overlap in neuropathology in autism and OCD, especially the efficacy of selective serotonin reuptake inhibitors (SSRIs) in ameliorating the obsessive-compulsive and repetitive and ritualistic behaviors in both autism and OCD. Data are also cited that support the notion that the behavioral function of repetitive behaviors in typical development, OCD, and autism may be similar in early development, but over time these actions become a less salient component of the behavioral repertoire (typical development) or come to serve a different function for these two disordered populations. Taken together, these studies exploring the links between repetitive behaviors and the brain provide evidence of a similar biobehavioral model in place in both autism and obsessive-compulsive disorder.