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Research Projects Listing
| Projects of the Autism Research Network have resulted in the following scientific articles.
Where available, links to full articles or places to find full articles are provided.
Use the options below to narrow your search, then choose an underlined column heading to sort your results. |
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Title:
Outcome classification of preschool children with autism spectrum disorders using MRI brain measures
Author:
Akshoomoff, N., Lord, C., Lincoln, A., Courchesne, R., Carper, R., Townsend, J., Sourchesne, E.
Journal/Book:
Journal of the American Academy of Child & Adolescent Psychiatry
Volume/Press:
43(3)
Page(s):
349-357
Date:
2004
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OBJECTIVE: To test the hypothesis that a combination of magnetic resonance imaging (MRI) brain measures obtained during early childhood distinguish children with autism spectrum disorders (ASD) from typically developing children and is associated with functional outcome. METHOD: Quantitative MRI technology was used to measure gray and white matter volumes (cerebrum and cerebellum), total brain volume, and the area of the cerebellar vermis in 52 boys with a provisional diagnosis of autism (aged 1.9-5.2 years) and 15 typically developing young children (aged 1.7-5.2 years). Diagnostic confirmation and cognitive outcome data were obtained after the children reached 5 years of age. RESULTS: A discriminant function analysis of the MRI brain measures correctly classified 95.8% of the ASD cases and 92.3% of the control cases. This set of variables also correctly classified 85% of the ASD cases as lower functioning and 68% of the ASD cases as higher functioning. CONCLUSIONS: These results indicate that variability in cerebellar and cerebral size is correlated with diagnostic and functional outcome in very young children with ASD.
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| Link to full article. |
| CPEA |
Title:
Effects of age on brain volume and head circumference in autism
Author:
Aylward, E. H.; Minshew, N. J.; Field, K.; Sparks, B. F.; Singh, N.
Journal/Book:
Neurology
Volume/Press:
59(2)
Page(s):
175-183
Date:
2002
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OBJECTIVE: To determine whether brain volume, as assessed on MRI scans, differs between individuals with autism and control subjects, and whether such differences are affected by age. BACKGROUND: Previous studies have found increased brain weight, head circumference, and MRI brain volume in children with autism. However, studies of brain size in adults with autism have yielded conflicting results. The authors hypothesize that enlargement of the brain may be a feature of brain development during early childhood in autism that normalizes with maturational processes. METHODS: The authors measured total brain volumes from 1.5-mm coronal MRI scans in 67 non-mentally retarded children and adults with autism and 83 healthy community volunteers, ranging in age from 8 to 46 years. Head circumference was also measured. Groups did not differ on age, sex, verbal IQ, or socioeconomic status. RESULTS: Brain volumes were significantly larger for children with autism 12 years old and younger compared with normally developing children, when controlling for height. Brain volumes for individuals older than age 12 did not differ between the autism and control groups. Head circumference was increased in both younger and older groups of subjects with autism, suggesting that those subjects older than age 12 had increased brain volumes as children. CONCLUSIONS: Brain development in autism follows an abnormal pattern, with accelerated growth in early life that results in brain enlargement in childhood. Brain volume in adolescents and adults with autism is, however, normal, and appears to be due to a slight decrease in brain volume for these individuals at the same time that normal children are experiencing a slight increase.
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| Link to full article. |
| CPEA |
Title:
Comparison of the effects of damage to the perirhinal and parahippocampal cortex on transverse patterning and location memory in rhesus macaques
Author:
Alvarado, M., Bachevalier, J.
Journal/Book:
Journal of Neuroscience
Volume/Press:
25(6)
Page(s):
1599-1609
Date:
2005
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Monkeys with damage to the parahippocampal (TH/TF) or perirhinal (PRh) cortex were tested on two sets of the transverse patterning (TP) problem (A+/B-, B+/C-, C+/A- and D+/E-, E+/F-, F+/D-) and delayed nonmatching-to-location paradigm (DNML), with delays ranging from 10 to 600 s. Damage to either area impaired acquisition and performance of TP but not of linear discriminations (e.g., A>B>C>X). Damage to areas TH/TF impaired performance of the DNML at all delays but only affected memory for objects at the longest delay, as measured by a delayed nonmatching-to-sample task (DNMS) (Nemanic et al., 2004). Damage to the PRh impaired performance of the DNMS but not of the DNML. The results present a dissociation in object and place memory for these two cortical regions and suggest a role for each in the cortical circuitry supporting configural/relational memory.
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| Link to full article. |
| CPEA |
Title:
Selective neurotoxic damage to the hippocampal formation impairs acquisition and performance of the transverse patterning task and location memory in rhesus macaques
Author:
Alvarado, M., Bachevalier, J.
Journal/Book:
Hippocampus
Volume/Press:
15(1)
Page(s):
118-131
Date:
2005
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Monkeys with neurotoxic (ibotenic acid) damage to the hippocampal formation and unoperated controls were trained on two sets of transverse patterning problems (A+/B-, B+/C-, C+/A-, and D+/E-, E+/F-, F+/D-) and a delayed nonmatching-to-location paradigm (DNML) with delays of 10s, 30s, 120s, and 600s. Hippocampal lesions produced a size- and area-dependent impairment on transverse patterning. Damage largely limited to the right hippocampus in one subject had no effect on performance on the task. Of the remaining four subjects, two with hippocampal damage greater than 40% bilaterally were unable to solve the two transverse patterning sets, but could solve the linear set of discriminations (A+/B-, B+/C-, C+/X-). The two remaining operated animals were impaired in acquisition of both sets, but were eventually able to solve one of the two transverse patterning discrimination sets. All five operated monkeys were impaired relative to normal controls on DNML, but not on the standard delayed nonmatching-to-sample (DNMS) version with trial-unique objects. The results confirm our previous findings (Alvarado et al., Hippocampus 12:421-433, 2002) using aspiration lesions of the hippocampal formation and strengthen the view that the hippocampal formation is critical for object and spatial relational memory. |
| Link to full article. |
| CPEA |
Title:
The Teratology of Autism
Author:
Arndt T., Stodgell C.J., Rodier P.M.
Journal/Book:
International Journal of Developmental Neuroscience
Volume/Press:
Page(s):
189-199
Date:
2005
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Autism spectrum disorders affect behaviors that emerge at ages when typically developing children become increasingly social and communicative, but many lines of evidence suggest that the underlying alterations in the brain occur long before the period when symptoms become obvious. Studies of the behavior of children in the first year of life demonstrate that symptoms are often detectable in the first 6 months. The environmental factors known to increase the risk of autism have critical periods of action during embryogenesis. Minor malformations that occur frequently in people with autism are known to arise in the same stages of development. Anomalies reported from histological studies of the brain are consistent with an early alteration of development. Congenital syndromes with high rates of autism include somatic that originate early in the first trimester. In addition, it is possible to duplicate a number of anatomic and behavioral features characteristic of human cases by exposing rat embryos to a teratogenic dose of valproic acid at the time of neural tube closure.
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| Link to full article. |
| CPEA |
Title:
Assessment in multisite randomized clinical trials of patients with autistic disorder: the Autism RUPP Network. Research Units on Pediatric Psychopharmacology
Author:
Arnold, L.E., Aman, M.G., Martin, A., Collier-Crespin, A., Vitiello, B., Tierney, E., Asarnow, R., Bell-Bradshaw, F., Freeman, B.J., Gates-Ulanet, P., Klin, A., McCracken, J.T., McDougle, C.J., McGough, J.J., Posey, D.J., Scahill, L., Swiezy, N.B., Ritz, L., Volkmar, F.
Journal/Book:
Journal of Autism and Developmental Disorders
Volume/Press:
30(2)
Page(s):
99-111
Date:
2000
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Assessment of autistic disorder (autism) symptoms, primary and secondary, poses more challenging problems than ordinarily found in multisite randomized clinical trial (RCT) assessments. For example, subjects may be uncommunicative and extremely heterogeneous in problem presentation, and current pharmacological treatments are not likely to alter most core features of autism. The Autism Research Units on Pediatric Psychopharmacology (RUPP Autism Network) resolved some of these problems during the design of a risperidone RCT in children/adolescents. The inappropriateness of the usual anchors for a Clinical Global Impression of Severity (CGI-S) was resolved by defining uncomplicated autism without secondary symptoms as a CGI-S of 3, mildly ill. The communication problems, compromising use of the patient as an informant, were addressed by several strategies, including careful questioning of care providers, rating scales, laboratory tests, and physical exams. The broad subject heterogeneity requires outcome measures sensitive to individual change over a wide spectrum of treatment response and side effects. The problems of neuropsychologically testing nonverbal, lower functioning, sometimes noncompliant subjects requires careful instrument selection/adaptation and flexible administration techniques. The problems of assessing low-end IQs, neglected by most standardized test developers, was resolved by an algorithm of test hierarchy. Scarcity of other autism-adapted cognitive and neuropsychological tests and lack of standardization required development of a new, specially adapted battery. Reliability on the Autism Diagnostic Interview (currently the most valid diagnostic instrument) and other clinician instruments required extensive cross-site training (in-person, videotape, and teleconference sessions). Definition of a treatment responder required focus on individually relevant target symptoms, synthesis of possible modest improvements in many domains, and acceptance of attainable though imperfect goals. The assessment strategy developed is implemented in a RCT of risperidone (McDougle et al., 2000) for which the design and other methodological challenges are described elsewhere (Scahill et al., 2000). Some of these problems and solutions are partially shared with RCTs of other treatments and other disorders.
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| Link to full article. |
| CPEA |
Title:
Functional MRI of autistic individuals during face perception task
Author:
Aylward, E. H., Dawson, G., Meltzoff, A., Panagiotides, H., Steury, K., McPartland, J.
Journal/Book:
Journal of Neuropsychiatry and Clinical Neurosciences
Volume/Press:
Page(s):
173-176
Date:
2000
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| CPEA |
Title:
Effects of age on brain volume and head circumference in autism
Author:
Aylward, E. H., Minshew, N. J., Field, K., Sparks, B. F., Singh, N.
Journal/Book:
Neurology
Volume/Press:
Page(s):
175-183
Date:
2002
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OBJECTIVE: To determine whether brain volume, as assessed on MRI scans, differs between individuals with autism and control subjects, and whether such differences are affected by age. BACKGROUND: Previous studies have found increased brain weight, head circumference, and MRI brain volume in children with autism. However, studies of brain size in adults with autism have yielded conflicting results. The authors hypothesize that enlargement of the brain may be a feature of brain development during early childhood in autism that normalizes with maturational processes. METHODS: The authors measured total brain volumes from 1.5-mm coronal MRI scans in 67 non-mentally retarded children and adults with autism and 83 healthy community volunteers, ranging in age from 8 to 46 years. Head circumference was also measured. Groups did not differ on age, sex, verbal IQ, or socioeconomic status. RESULTS: Brain volumes were significantly larger for children with autism 12 years old and younger compared with normally developing children, when controlling for height. Brain volumes for individuals older than age 12 did not differ between the autism and control groups. Head circumference was increased in both younger and older groups of subjects with autism, suggesting that those subjects older than age 12 had increased brain volumes as children. CONCLUSIONS: Brain development in autism follows an abnormal pattern, with accelerated growth in early life that results in brain enlargement in childhood. Brain volume in adolescents and adults with autism is, however, normal, and appears to be due to a slight decrease in brain volume for these individuals at the same time that normal children are experiencing a slight increase.
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| Link to full article. |
| CPEA |
Title:
Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene
Author:
Bacchelli, E., Blasi, F., Biondolillo, M., Lamb, J.A., Bonora, E., Barnby, G., Parr, J., Beyer, K.S., Klauck, S.M., Poustka, A., Bailey, A.J., Monaco, A.P., Maestrini, E., (IMGSAC).
Journal/Book:
Molecular Psychiatry
Volume/Press:
8(11)
Page(s):
916-924
Date:
2003
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The results from several genome scans indicate that chromosome 2q21-q33 is likely to contain an autism susceptibility locus. We studied the potential contribution of nine positional and functional candidate genes: TBR-1; GAD1; DLX1; DLX2; cAMP-GEFII; CHN1; ATF2; HOXD1 and NEUROD1. Screening these genes for DNA variants and association analysis using intragenic single nucleotide polymorphisms did not provide evidence for a major role in the aetiology of autism. Four rare nonsynonymous variants were identified, however, in the cAMP-GEFII gene. These variants were present in five families, where they segregate with the autistic phenotype, and were not observed in control individuals. The significance of these variants is unclear, as their low frequency in IMGSAC families does not account for the relatively strong linkage signal at the 2q locus. Further studies are needed to clarify the contribution of cAMP-GEFII gene variants to autism susceptibility.
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| Link to full article. |
| CPEA |
Title:
Early medial temporal dysfunction and autism
Author:
Bachevalier, J., Loveland, K.
Journal/Book:
In: D. Cicchetti and E.F. Walker (eds) Neurodevelopmental mechanisms in the genesis and epigenesis of psychopathology
Volume/Press:
Cambridge University Press
Page(s):
215-238
Date:
2003
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| CPEA |
Title:
The orbitofrontal-amygdala circuit and self-regulation of social-emotional behavior in autism
Author:
Bachevalier, J., Loveland, K.
Journal/Book:
Neuroscience and Biobehavioral Reviews
Volume/Press:
Page(s):
Date:
In press, E-Published: 2005
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Individuals with an autistic spectrum disorder are impaired not only in understanding others' mental states, but also in self-regulation of social-emotional behavior. Therefore, a model of the brain in autism must encompass not only those brain systems that subserve social-cognitive and emotional functioning, but also those that subserve the self-regulation of behavior in response to a changing social environment. We present evidence to support the hypothesis that developmental dysfunction of the orbitofrontal-amygdala circuit of the brain is a critical factor in the development of autism and that some of the characteristic deficits of persons with autism in socio-emotional cognition and behavioral self-regulation are related to early dysfunction of different components of this circuit. A secondary hypothesis posits that the degree of intellectual impairment present in individuals with autism is directly related to the integrity of the dorsolateral prefrontal-hippocampal circuit of the brain. Together, these hypotheses have the potential to help explain the neurodevelopmental basis of some of the primary manifestations of autism as well as the heterogeneity of outcomes.
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| CPEA |
Title:
Author:
Baron-Cohen, S., Tager-Flusberg, H., Cohen, D. J. (Eds.)
Journal/Book:
Understanding Other Minds: Perspectives from Developmental Cognitive Neuroscience. Second Edition
Volume/Press:
Oxford: Oxford University Press.
Page(s):
Date:
2000
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Title:
Special issue on Asperger syndrome: euroscience perspectives
Author:
Baron-Cohen, S., Klin, A.
Journal/Book:
Brain and Cognition
Volume/Press:
Page(s):
Date:
In press
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Title:
Special issue on Asperger syndrome: euroscience perspectives
Author:
Baron-Cohen, S., Klin, A.
Journal/Book:
Brain and Cognition
Volume/Press:
Page(s):
Date:
In press
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Title:
How commonly are known medical conditions associated with autism?
Author:
Barton, M., Volkmar, F. R.
Journal/Book:
Journal of Autism and Developmental Disorders
Volume/Press:
Page(s):
273-278
Date:
1998
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Recent research has yielded increasing support for neurobiologic theories of autism. A number of family and twin studies support the role of genetics and have led to wide acceptance of autism as an organically based disorder. Controversy persists, however, over the role of congenital medical conditions in the etiology of autism. Two rather divergent views have emerged. One, advocated by Gillberg and colleagues, proposes that up to 30% of cases of autism are associated with a known medical condition. On the other hand, research by Rutter and colleagues suggests the incidence may be closer to 10%. In this retrospective study records on 211 subjects with autism and other developmental disorders are reviewed to determine the prevalence of associated medical conditions and its variability related to the system used to diagnose autism. Results suggest the prevalence of medical conditions with suspected etiologic relationship with autism varies between 10 and 15%, depending on the diagnostic system employed. Further variability in prevalence rates results from a less strict definition of "medical condition" and yields rates between 25 and 37%. Disparate findings in previous research may stem from variability in both diagnostic system employed and which medical conditions are considered significant in the etiology of autism.
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| Link to full article. |
| CPEA |
Title:
Configural processing in autism and its relationship to face processing
Author:
Behrmann M., Avidan G., Leonard G., Kimchi R., Luna B., Humphreys K., Minshew NJ.
Journal/Book:
Neuropsychologia
Volume/Press:
44(1)
Page(s):
110-129
Date:
2006
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Studies of the perceptual performance of individuals with autism have focused, to a large extent, on two domains of visual behavior, one associated with face processing and the other associated with global or holistic processing. Whether autistic individuals differ from neurotypical individuals in these domains is debatable and, moreover, the relationship between the behaviors in these two domains remains unclear. We first compared the face processing ability of 14 adult individuals with autism with that of neurotypical controls and showed that the autistic individuals were slowed in their speed of face discrimination. We then showed that the two groups differed in their ability to derive the global whole in two different tasks, one using hierarchical compound letters and the other using a microgenetic primed matching task with geometric shapes, with the autistic group showing a bias in favor of local information. A significant correlation was also observed between performance on the face task and the configural tasks. We then confirmed the prediction that the ability to derive the global whole is not only critical for faces but also for other objects as well, as the autistic individuals performed more slowly than the control group in discriminating between objects. Taken together, the results suggest that the bias for local processing seen in autistic individuals might have an adverse impact on their ability to process faces and objects. |
| Link to full article. |
| CPEA |
Title:
Autism as a disorder of neural information processing: directions for research and targets for therapy
Author:
Belmonte, M., Cook, E., Anderson, G., Rubenstein, J., Greenough, W., Beckel-Mitchener, A., Courchesne, E., Boulanger, L., Powell, S., Levitt, P.R., Perry, E.K., Jiang, Y-h., DeLorey, T., Tierney, E.
Journal/Book:
Molecular Psychiatry
Volume/Press:
Page(s):
Date:
In press
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| CPEA |
Title:
Executive functioning in normal and abnormal development
Author:
Bennetto, L., Pennington, B.F.
Journal/Book:
In: S. Segalowitz & I. Rapin (Eds.), Handbook of Neuropsychology, 2nd edition
Volume/Press:
Volume 8, Part II: Child Neuropsychology, Amsterdam: Elsevier.
Page(s):
785-802
Date:
2003
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| CPEA |
Title:
Executive functioning in normal and abnormal development
Author:
Bennetto, L., Pennington, B.F.
Journal/Book:
In: S. Segalowitz & I. Rapin (Eds.), Handbook of Neuropsychology, 2nd edition
Volume/Press:
Volume 8, Part II: Child Neuropsychology, Amsterdam: Elsevier.
Page(s):
785-802
Date:
2003
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Title:
Fear potentiated startle in high functioning individuals with autism
Author:
Bernier, R. Dawson G., Panagiotides, H.
Journal/Book:
Journal of Autism and Developmental Disorders
Volume/Press:
Page(s):
Date:
In press
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| CPEA |
Title:
Fear potentiated startle in high functioning individuals with autism
Author:
Bernier, R. Dawson G., Panagiotides, H.
Journal/Book:
Journal of Autism and Developmental Disorders
Volume/Press:
Page(s):
Date:
In press
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Title:
Understanding impairments in social engagement in autism
Author:
Bernier, R., Webb, S., Dawson, G.
Journal/Book:
In: P. Marshall & N. Fox (Eds) The Development of Social Engagement: Neurobiological Perspectives
Volume/Press:
Oxford University Press
Page(s):
Date:
In press
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Title:
Understanding impairments in social engagement in autism
Author:
Bernier, R., Webb, S., Dawson, G.
Journal/Book:
In: P. Marshall & N. Fox (Eds) The Development of Social Engagement: Neurobiological Perspectives
Volume/Press:
Oxford University Press
Page(s):
Date:
In press
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| CPEA |
Title:
Mutation analysis of the coding sequence of the MECP2 gene in infantile autism
Author:
Beyer, K.S., Blasi, F., Bacchelli, E., Klauck, S.M., Maestrini, E., Poustka, A., International Molecular Genetic Study of Autism Consortium (IMGSAC)
Journal/Book:
Human Genetics
Volume/Press:
Page(s):
305-309
Date:
2002
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Mutations in the coding region of the methyl-CpG-binding protein 2 ( MECP2) gene cause Rett syndrome and have also been reported in a number of X-linked mental retardation syndromes. Furthermore, such mutations have recently been described in a few autistic patients. In this study, a large sample of individuals with autism was screened in order to elucidate systematically whether specific mutations in MECP2 play a role in autism. The mutation analysis of the coding sequence of the gene was performed by denaturing high-pressure liquid chromatography and direct sequencing. Taken together, 14 sequence variants were identified in 152 autistic patients from 134 German families and 50 unrelated patients from the International Molecular Genetic Study of Autism Consortium affected relative-pair sample. Eleven of these variants were excluded for having an aetiological role as they were either silent mutations, did not cosegregate with autism in the pedigrees of the patients or represented known polymorphisms. The relevance of the three remaining mutations towards the aetiology of autism could not be ruled out, although they were not localised within functional domains of MeCP2 and may be rare polymorphisms. Taking into account the large size of our sample, we conclude that mutations in the coding region of MECP2 do not play a major role in autism susceptibility. Therefore, infantile autism and Rett syndrome probably represent two distinct entities at the molecular genetic level.
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| CPEA |
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