Autism Spectrum Disorder Factors Research Articles

Identification of risk factors for autism spectrum disorders in tuberous sclerosis complex

The purpose of this study was to assess the prevalence of and to identify epidemiologic, genetic, electrophysiologic, and neuroanatomic risk factors for autism spectrum disorders (ASD) in a cohort of patients with tuberous sclerosis complex (TSC). A total of 103 patients with TSC were evaluated for ASD. A retrospective review of patients' records was performed, including mutational analysis. EEG reports were analyzed for the presence of ictal and interictal epileptiform features. Brain MRI scans were evaluated for TSC neuropathology, including tuber burden. Of the 103 patients with TSC, 40%were diagnosed with an ASD. On univariate analysis, patients with ASD were less likely to have mutations in the TSC1 gene. Patients with ASD also had an earlier age at seizure onset and more frequent seizures. On EEG, those with ASD had a significantly greater amount of interictal epileptiform features in the left temporal lobe only. On MRI, there were no differences in the regional distribution of tuber burden, although those with TSC2 and ASD had a higher prevalence of cyst-like tubers. The development of ASD in TSC is not well understood. Given our findings, ASD may be associated with persistent seizure activity early in development in particular brain regions, such as those responsible for social perception and communication in the left temporal lobe. The presence of cyst-like tubers on MRI could provide a structural basis or marker for ASD pathology in TSC, although studies assessing their effect on cortical function are needed.

Common genetic variation in the GAD1 gene and the entire family of DLX homeobox genes and autism spectrum disorders

Biological and positional evidence supports the involvement of the GAD1 and distal-less homeobox genes (DLXs) in the etiology of autism. We investigated 42 single nucleotide polymorphisms in these genes as risk factors for autism spectrum disorders (ASD) in a large family-based association study of 715 nuclear families. No single marker showed significant association after correction for multiple testing. A rare haplotype in the DLX1 promoter was associated with ASD (P-value = 0.001). Given the importance of rare variants to the etiology of autism revealed in recent studies, the observed rare haplotype may be relevant to future investigations. Our observations, when taken together with previous findings, suggest that common genetic variation in the GAD1 and DLX genes is unlikely to play a critical role in ASD susceptibility.

Advances in Our Understanding of Genetic Risk Factors for Autism Spectrum Disorders

Advances in Our Understanding of Genetic Risk Factors for Autism Spectrum Disorders

Prenatal, Perinatal, and Neonatal Factors Associated With Autism Spectrum Disorders

To investigate prenatal, perinatal, and neonatal risk factors for autism spectrum disorders by using participants identified through broad ascertainment and reliable classification methods. The targeted population was 8-year-old children born in 1994 and residing in 1 of the 3 most populous counties in Utah who were identified as having an autism spectrum disorder on the basis of methodology used by the 2002 Autism and Developmental Disabilities Monitoring Network. Of those identified, 132 children (115 boys, 17 girls) had birth certificate records available. Each child was matched by gender and birth year to 100 controls (11 500 boys, 1700 girls) from the birth certificate database in a nested case-control design. Birth certificate records of participants and controls were surveyed for 23 potentially pathologic prenatal, perinatal, and neonatal factors. The prenatal factors that occurred significantly more frequently among children with autism spectrum disorders were advanced maternal age and parity. Increased duration of education among mothers of children with autism spectrum disorders was small but statistically significant. Significant perinatal factors were breech presentation and primary cesarean delivery. When corrected for breech presentation, a known indication for cesarean delivery, the association between primary cesarean delivery and autism spectrum disorders was eliminated. There were no significant associations found between autism spectrum disorders and neonatal factors. In the absence of other complications suggesting fetal distress, the association between breech presentation and autism spectrum disorders in this study suggests a shared etiology rather than causal relationship. Additional investigation focused on both genetic and environmental factors that link these autism spectrum disorder risk factors individually or collectively is needed.

ToF-SIMS cluster ion imaging of hippocampal CA1 pyramidal rat neurons

Recent studies have demonstrated the power of time-of-flight secondary ion mass spectrometry (ToF-SIMS) cluster ion imaging to characterize biological structures, such as that of the rat central nervous system. A large number of the studies to date have been carried out on the “structural scale” imaging several mm 2 using mounted thin sections. In this work, we present our ToF-SIMS cluster ion imaging results on hippocampal rat brain neurons, at the cellular and sub-cellular levels. As a part of an ongoing investigation to examine gut linked metabolic factors in autism spectrum disorders using a novel rat model, we have observed a possible variation in hippocampal Cornu ammonis 1 (CA1) pyramidal neuron geometry in thin, paraformaldehyde fixed brain sections. However, the fixation process alters the tissue matrix such that much biochemical information appears to be lost. In an effort to preserve as much as possible this original information, we have established a protocol using unfixed thin brain sections, along with low dose, 500 eV Cs + pre-sputtering that allows imaging down to the sub-cellular scale with minimal sample preparation.

Perinatal and maternal risk factors for autism spectrum disorders in New South Wales, Australia

This study was commenced in 1999 with the aim of examining risk factors for autism using established population-based data for comparison. Cases were ascertained using active surveillance and compared with birth data. Four risk factors were found to be significantly associated with autism using binary logistic regression analysis; being male [adjusted odds ratio (OR) 4.7, 95% confidence interval (CI) 3.2-7.0], being born prematurely (adjusted OR 2.2, 95% CI 1.5-3.5), having maternal age >/=35 years (adjusted OR 1.7, 95% CI 1.2-2.4) and having a mother born outside Australia (adjusted OR 1.4, 95% CI 1.0-1.9). For analysis completed for pregnancies, rather than live births, multiple birth was also a significant risk factor for one or more children of the pregnancy to be affected by autism (adjusted OR 2.5, 95% CI 1.1-5.5). There was a statistically significant trend towards increasing risk with increasing risk factor 'dose' for gestational age (P = 0.019), multiple birth (P = 0.016) and maternal age (P < 0.001). For mother's country of birth the group with the highest risk were children of mother's born in south-east or north-east Asia. There was a non-significant trend towards a higher proportion of children with developmental disability having risk factors. Replication of risk factors from previous studies and a significant risk factor 'dose' effect add to growing evidence that maternal and perinatal factors are low magnitude risk factors for autism. The association between developmental disability and autism risk factors warrants further examination.

Prenatal exposure to antiepileptic drugs—risk factor for autism spectrum disorder

Prenatal exposure to antiepileptic drugs—risk factor for autism spectrum disorder

Identifying environmental contributions to autism: Provocative clues and false leads

The potential role of environmental factors in autism spectrum disorders (ASD) is an area of emerging interest within the public and scientific communities. The high degree of heritability of ASD suggests that environmental influences are likely to operate through their interaction with genetic susceptibility during vulnerable periods of development. Evaluation of the plausibility of specific neurotoxicants as etiological agents in ASD should be guided by toxicological principles, including dose-effect dependency and pharmacokinetic parameters. Clinical and epidemiological investigations require the use of sufficiently powered study designs with appropriate control groups and unbiased case ascertainment and exposure assessment. Although much of the existing data that have been used to implicate environmental agents in ASD are limited by methodological shortcomings, a number of efforts are underway that will allow more rigorous evaluation of the role of environmental exposures in the etiology and/or phenotypic expression of the disorder. Surveillance systems are now in place that will provide reliable prevalence estimates going forward in time. Anticipated discoveries in genetics, brain pathology, and the molecular/cellular basis of functional impairment in ASD are likely to provide new opportunities to explore environmental aspects of this disorder.

Heritable and nonheritable risk factors for autism spectrum disorders.

Autism spectrum disorders (ASDs) are developmental disabilities where language development is absent or delayed, rote or repetitive behaviors typically emerge, and nonverbal communication, imagination, and social interactions are profoundly hindered (1). The severity of impairment in each of these dimensions can be quite variable, as can individual cognitive functioning (2). However, even higher-functioning persons with ASD are confronted with significant lifelong challenges. The first clinical descriptions of ASD were offered almost simultaneously by psychiatrist Leo Kanner and pediatrician Hans Asperger in the early 1940s. In his original paper, Kanner remarked on “the children’s aloneness from the beginning of life” (3, p. 250), implying that the constellation of behaviors that he observed was the result of pathology he believed to be present at birth. Despite this, because few autistic offspring had autistic parents, no obvious chromosomal anomalies were consistently found among autistic children, and the sibling recurrence rate was erroneously thought to be low (first estimated at only around 2 percent), geneticists initially doubted a role for heredity in ASD etiology (4). It was the publication of the first twin study on autistic disorder (5) that stimulated a stark change in the conventional wisdom. Findings of substantive differences in monozygotic-dizygotic twin concordance in the original and subsequent twin studies, coupled with higher estimates of sibling recurrence from studies conducted in the 1980s, indicated strongly that liability to ASD was heritable. Unfortunately, the subsequent two decades of genetic studies have failed to reveal a satisfactorily complete picture of ASD etiology.