International Meeting for Autism Research (IMFAR)
May 5-7, 2005
Boston, Massachusetts

Polymorphisms in the gene for ?2 adrenergic receptor and risk for autism in the AGRE cohort
K. Cheslack-Postava, M.D. Fallin, D. Avramopoulos, S.L. Connors, A.W. Zimmerman, C.G. Eberhart and C.J. Newschaffer

The ?2 adrenoreceptor (B2AR) is part of the catecholamine system, with variants at two polymorphic sites, rs1042713 (codon 16) and rs1042714 (codon 27), conferring increased activity.  Over-stimulation of this receptor may alter brain development, and has been linked to autism in non-identical twins (IMFAR poster 2002).  Study Objectives: Determine whether the presence of Gly16 or Glu27 alleles in the B2AR gene is associated with diagnosis of autism in the Autism Genetic Resource Exchange (AGRE) population.  Methods: The study population included 609 autism case-parent trios from 358 families.  Genotyping was done using TaqMan assasys by design (ABI).  Association between autism and genotypes at each polymorphic site was tested using allelic and genotype-based TDT.  Results: There was a statistically significant increased GRR of 1.66 for the Glu/Glu homozygote at codon 27 that was not sensitive to designation of probands.  HBAT results were consistent with the direction of observed association, but did not reach a level of statistical significance.  There was no significant association with genotype at codon 16.  Conclusions: The Glu27 allele in the B2AR gene may confer increased risk of autism.  The possibility of interaction with stress during pregnancy will also be examined.

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Objective: To determine if the birth date distribution for individuals with autism spectrum disorders (ASDs) differs from that for the general population.  This information might suggest a relationship between infectious or environmental exposures and ASDs.  Methods: Two ASD case groups were studied: 630 single-birth cases ascertained at one medical center and 161 cases from multiple birth ascertained by AGRE.  All cases were born between 1983 and 2002.  Expected birth date distributions came from Maryland vital statistics for 1983-2002.  The Rayleigh test was carried out to examine distribution uniformity of birth date by gender and ASD subtype, and regression analysis was used to estimate the ratio of AD births observed in a given month to those expected based on the Maryland population standard, adjusting for birth cohort effect (5-year groups).  Results: Birth dates of multiple-birht autism cases were non uniformly distributed throughout the calendar year (p<.05).  The observed number of births in March was 4.3 times greater than expected (95% confidence interval (CI): 1.23, 15.2) for female singleton ASD cases after controlling for birth cohort effect.  On the other hand, the observed number of December births was 87% less than expected (95% CI: 0% to 98%) for male multibirth cases.  Conclusions: Birth date distributions that differ from population expectation suggest a role for prenatal infections or other environmental exposures.  The fact that these patterns appear to differ by gender and singleton vs. multiple-birth pregnancy may also be etiologically significant.  Possible contributions of parental autoimmune and psychiatric disorders will be discussed.

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A study of behaviors associated with fever in children with autism/PDD
A.W. Zimmerman, L. Curran, S. Crawford, and C.J. Newschaffer

Clinician and parent reports suggest that behavior improvements involving communcation, attention and social interaction in children with Autism/PDD may be associated with fever.  Objective: To investigate behaviors during and after febrile episodes.  Methods: Behaviors of 60 children (30 matched fever-control pairs) with Autism/PDD, ages 2-17 years, were assessed by parent completion of the Aberrant Behavior Checklist (ABC).  For children with fevers, the ABC was completed at three sequential time points: 1) During a fever (body temperature >=100.4 F); 2) When the fever was gone and the child was feeling better; and 3) Once the child was fever-free for seven days.  Upon receipt of fever data, an age-, sex- and verbal skills-matched control was selected from the list of enrolled children who had not yet submitted fever data and were fever-free at the time.  For each control participant, a parent completed the ABC on three sequential days spaced according to the reported schedule of the febrile child.  Results: Comparisons of mean ABC scores (two way repeated measures ANOVA) showed behavior improvements during fevers on the subscales of Irritability (p=0.016), Stereotypy (p=0.006), Hyperactivity (p=0.001), and Inappropriate Speech (p=0.003).  Per expectation, ABC Lethargy subscale scores were worse during fevers (p=0.002).  In this limited sample, however, factors associated with the underlying attendant illnesses (e.g., symptoms) and parent expectations of behavior changes may have influenced the findings.  Conclusions: Fever may positively affect brain function through an underlying mechanism important to this group of disorders, possibly involving intracellular signaling abnormalities.  Additional research is warranted.

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Investigating Developmental DElays Study: comparison of SCQ and PDDST
C.J. Newschaffer, L-C. Lee, A.B. David and N.L. Lee

Objective: To compare the effectiveness of the Social Communication Questionnaire (SCQ) and the Pervasive Developmental Disorders Screening Test (PDDST) in identifying autism spectrum disorder (ASD) among children age 3-5 years receiving special education services.  Methods: A brief, self-administered questionnaire consisting of demographic questions and the SCQ and PDDST was mailed to all parents of children age 3-5 years receiving special education services through the Howard County School District in Maryland  (n=740).  In the preliminary findings shown here, autism special education classification determined case status.  Clinical assessments using the ADOS and ADI-R will ultimately validate administrative classifications and any results available from these at the time of the meeting will be presented.  Results: Thirty-five percent (n=258) returned completed surveys, and 15% of these (n=38) scored positive for ASD on either the SCQ (score >15) or PDDST (score >13). When compared to the parent's self-report of the child having a special education classification of autism, the sensitivity and specificity of the SCQ was 55.2% and 90.8%, respectively, with a positive predictive value (PPV) of 43.2% and a negative predictive value (NPV) of 94.1%. The sensitivity and specificity of the PDDST when compared to an autism special education classification were 20.7% and 98.7%, respectively (PPV 66.7% and NPV 90.8%).  Results were silimar for both SCQ and PDDST when compared to the parent's self-report of the child having a previous diagnosis of ASD.  Conclusion: Sensitivity of these two brief screening tools appears limited and, while specificity is higher, even in this special education population with enriched autism prevalence, positive predictive value is still fairly low.

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