Reports on autism and parental age have yielded conflicting results on whether mothers, fathers, or both, contribute to increased risk. We analyzed restricted strata of parental age in a 10-year California birth cohort to determine the independent or dependent effect from each parent. Autism cases from California Department of Developmental Services records were linked to State birth files (1990-1999). Only singleton births with complete data on parental age and education were included (n=4,947,935, cases=12,159). In multivariate logistic regression models, advancing maternal age increased risk for autism monotonically regardless of the paternal age. Compared with mothers 25-29 years of age, the adjusted odds ratio (aOR) for mothers 40+ years was 1.51 (95% CI: 1.35-1.70), or compared with mothers <25 years of age, aOR=1.77 (95% CI, 1.56-2.00). In contrast, autism risk was associated with advancing paternal age primarily among mothers <30: aOR=1.59 (95% CI, 1.37-1.85) comparing fathers 40+ vs. 25-29 years of age. However, among mothers >30, the aOR was 1.13 (95% CI, 1.01-1.27) for fathers 40+ vs. 25-29 years of age, almost identical to the aOR for fathers <25 years. Based on the first examination of heterogeneity in parental age effects, it appears that women's risk for delivering a child who develops autism increases throughout their reproductive years whereas father's age confers increased risk for autism when mothers are <30, but has little effect when mothers are past age 30. We also calculated that the recent trend towards delayed childbearing contributed approximately a 4.6% increase in autism diagnoses in California over the decade.
The purpose of this study was to determine the effectiveness of a 10 week water exercise swimming program (WESP) on the aquatic skills and social behaviors of 16 boys with autism spectrum disorders (ASDs). In the first 10 week phase (phase I), eight children (group A) received the WESP while eight children (group B) did not. A second 10 week phase (phase II) immediately followed, with the treatments reversed. Both groups continued their regular treatment/ activity throughout the study. Improvements were seen in aquatic skills for both groups subsequent to the WESP. Following phase I, significant social improvements were seen in group A. Following phase II, social improvements were seen for group B, whereas group A merely maintained the improvements they attained through the implementation of the WESP during phase I. Results indicate that the WESP improved aquatic skills in the participants, and holds potential for social improvements.
One of the most noticeable problems in autism involves the social use of language such as metaphor and metonymy, both of which are very common in daily language use. The present study is the first to investigate the development of metaphor and metonymy comprehension in autism. Eleven children with autism were compared to 17 typically developing children in a metaphor-metonymy comprehension task. Cross-sectional trajectory analyses were used to compare the development of metaphor and metonymy comprehension using a child-friendly story picture task. Trajectories were constructed linking task performance either to chronological age or to measures of mental age. Children with autism showed an impaired metaphor comprehension in relation to both chronological and mental age, whereas performance on metonymy was delayed and in line with their receptive vocabulary. Our results suggest that understanding of metaphors and metonyms are severely affected at all ages examined in the current study.
The aim of the study was to examine the temporal characteristics of information processing in individuals with high-functioning autism and Asperger’s disorder using a rapid serial visual presentation paradigm. The results clearly showed that such people demonstrate an attentional blink of similar magnitude to comparison groups. This supports the proposition that the social processing difficulties experienced by these individuals are not underpinned by a basic temporal-cognitive processing deficit, which is consistent with Minshew’s complex information processing theory. This is the second study to show that automatic inhibitory processes are intact in both autism and Asperger’s disorder, which appears to distinguish these disorders from some other frontostriatal disorders. The finding that individuals with autism were generally poorer than the comparison group at detecting black Xs, while being as good in responding to white letters, was accounted for in the context of a potential dual-task processing difficulty or visual search superiority.
The effectiveness of three local authority early teaching interventions for children with autism spectrum disorders (ASDs) was studied. Thirty-three children (2:6 to 4:0 years old) received one of three early teaching interventions: a 1:1 home-based programme, and two different forms of special nursery placement. Measures from the Psycho-Educational Profile, British Abilities Scale, and Vineland Adaptive Behavior Scales were taken over a 10 month period. The study showed moderate effect sizes for improvements in all scales for children attending a generalized special nursery placement, and for those attending a special nursery placement solely for children with ASDs. Children receiving a home-based 1:1 programme with similar intervention hours showed moderate effect sizes for the PEP and BAS but not for the VABS. These data show that special nursery placements can offer benefits to children with ASDs, especially in the area of adaptive behavioural functioning.
Motivated by auditory and speech deficits in autism spectrum disorders (ASD), the frequency dependence of superior temporal gyrus (STG) 50 msec (M50) and 100 msec (M100) neuromagnetic auditory evoked field responses in children with ASD and typically developing controls were evaluated. Whole-cortex magnetoencephalography (MEG) was obtained from 17 typically developing children and 25 children with ASD. Subjects were presented tones with frequencies of 200, 300, 500, and 1,000 Hz, and left and right STG M50 and M100 STG activity was examined. No M50 latency or amplitude Group differences were observed. In the right hemisphere, a Group×Frequency ANOVA on M100 latency produced a main effect for Group (P=0.01), with an average M100 latency delay of 11 msec in children with ASD. In addition, only in the control group was the expected association of earlier M100 latencies in older than younger children observed. Group latency differences remained significant when hierarchical regression analyses partialed out M100 variance associated with age, IQ, and language ability (all P-values <0.05). Examining the right-hemisphere 500 Hz condition (where the largest latency differences were observed), a sensitivity of 75%, a specificity of 81%, and a positive predictive value (PPV) of 86% was obtained at a threshold of 116 msec. The M100 latency delay indicates disruption of encoding simple sensory information. Given similar findings in language impaired and nonlanguage impaired ASD subjects, a right-hemisphere M100 latency delay appears to be an electrophysiological endophenotype for autism.
Prenatal environmental exposures are among the risk factors being explored for associations with autism. We applied a new procedure combining multiple scan cluster detection tests to identify geographically defined areas of increased autism incidence. This procedure can serve as a first hypothesis-generating step aimed at localized environmental exposures, but would not be useful for assessing widely distributed exposures, such as household products, nor for exposures from nonpoint sources, such as traffic.Geocoded mothers' residences on 2,453,717 California birth records, 1996-2000, were analyzed including 9,900 autism cases recorded in the California Department of Developmental Services (DDS) database through February 2006 which were matched to their corresponding birth records. We analyzed each of the 21 DDS Regional Center (RC) catchment areas separately because of the wide variation in diagnostic practices. Ten clusters of increased autism risk were identified in eight RC regions, and one Potential Cluster in each of two other RC regions.After determination of clusters, multiple mixed Poisson regression models were fit to assess differences in known demographic autism risk factors between the births within and outside areas of elevated autism incidence, independent of case status.Adjusted for other covariates, the majority of areas of autism clustering were characterized by high parental education, e.g. relative risks >4 for college-graduate vs. nonhigh-school graduate parents. This geographic association possibly occurs because RCs do not actively conduct case finding and parents with lower education are, for various reasons, less likely to successfully seek services.
Autism spectrum disorders (ASDs) are a phenotypically and etiologically heterogeneous set of disorders that include obsessive-compulsive behaviors (OCB) that partially overlap with symptoms associated with obsessive-compulsive disorder (OCD). The OCB seen in ASD vary depending on the individual's mental and chronological age as well as the etiology of their ASD. Although progress has been made in the measurement of the OCB associated with ASD, more work is needed including the potential identification of heritable endophenotypes. Likewise, important progress toward the understanding of genetic influences in ASD has been made by greater refinement of relevant phenotypes using a broad range of study designs, including twin and family-genetic studies, parametric and nonparametric linkage analyses, as well as candidate gene studies and the study of rare genetic variants. These genetic analyses could lead to the refinement of the OCB phenotypes as larger samples are studied and specific associations are replicated. Like ASD, OCB are likely to prove to be multidimensional and polygenic. Some of the vulnerability genes may prove to be generalist genes influencing the phenotypic expression of both ASD and OCD while others will be specific to subcomponents of the ASD phenotype. In order to discover molecular and genetic mechanisms, collaborative approaches need to generate shared samples, resources, novel genomic technologies, as well as more refined phenotypes and innovative statistical approaches. There is a growing need to identify the range of molecular pathways involved in OCB related to ASD in order to develop novel treatment interventions.
We recently reported an autistic proband and affected sibling with maternally inherited microduplications within the 15q13.1 and 15q13.3 regions that contain a total of 4 genes. The amyloid precursor protein-binding protein A2 (APBA2) gene is located within the 15q13.1 duplication and encodes a neuronal adaptor protein essential to synaptic transmission that interacts directly with NRXN1 at the presynaptic membrane. We interpreted this as evidence for a putative role of APBA2 in autism as larger maternal duplications of 15q11-q13 are the most common known cause of autism. We therefore resequenced 512 subjects with autism spectrum disorder (ASD) and 463 controls, and identified 7 novel nonsynonymous coding variants in ASD subjects compared with 4 in controls. Five of the seven variants in the ASD group were predicted to affect protein function, alter residues conserved across 18 species, or both. All of the variants for which parental DNA was available were inherited. We also found two different nonsynonymous variants in two siblings with autism: (1) a paternally inherited heterozygous 6 bp deletion and (2) a maternally inherited heterozygous missense mutation, the latter also found in a single control. These results indicate compound heterozygous mutations of APBA2 in this autism sibship. The co-occurrence of two nonsynonymous mutations in both affected siblings in a single family, each transmitted from a different unaffected parent, suggest a role for APBA2 mutations in rare individuals with ASD.
Objective: To determine the effect of serotonin transporter polymorphism promoter region (5-HTTPLR) genotypic variation (low, intermediate, and high expression groups) on response to escitalopram treatment of children and adolescents with autism spectrum disorders (ASDs). Method: The study used a forced titration, open label design, with genotype blind until study completion. Participants were children and adolescents aged 4-17 years of age with a confirmed ASD (autistic disorder, Asperger's disorder, or pervasive developmental disorder, not otherwise specified). Results: There was an interaction between genotype group and time on the Aberrant Behavior Checklist (ABC) Irritability Subscale (primary outcome variable) (linear maximum marginal likelihood estimation=-4.84, Z=-2.89, SE=1.67, P=0.004). Examination of baseline to last visit revealed that a genotype grouping based on a previous study of platelet 5-HT uptake revealed less response in the genotype group that had S/S genotype for 5-HTTLPR and did not have a diplotype in intron 1 previously shown to be associated with increased platelet 5-HT uptake. Conclusion: This genotype-blind, prospective pharmacogenetic study found the group of subjects with associated with the lowest platelet 5-HT uptake from previous study had the smallest reduction in ABC-Irritability scores after open label treatment with escitalopram. Replication is necessary to confirm these findings.
Objective: The present study compared three separate Child Symptom Inventory-4 (CSI-4) scoring algorithms for differentiating children with autism spectrum disorder (ASD) from youngsters with attention-deficit/hyperactivity disorder (ADHD). Method: Parents/teachers completed the CSI-4, a DSM-IV-referenced rating scale, for 6 to 12-year-old clinical referrals with ASD (N=186) and ADHD (N=251). Algorithms were based on either all CSI-4 items (forward logistic regressions) or the 12 DSM-IV symptoms of pervasive developmental disorder (PDD) included in the CSI-4. Results: ROC analyses indicated generally good to excellent values for area under the curve, sensitivity, specificity, and positive predictive power. Algorithms for parent ratings were superior to teacher ratings. The algorithm based solely on PDD symptoms evidenced the greatest generalizability. Conclusion: Although algorithms generated from regression analyses produced greater clinical utility for specific samples, the PDD-based algorithm resulted in greater stability across samples.
