Conventional wisdom among pediatricians has been that children with attention-deficit hyperactivity disorder (ADHD) who receive their diagnosis and are managed in the primary care setting have fewer ...comorbid psychiatric disorders and milder impairments than those seen in psychiatric clinics. The authors sought to determine whether comorbidity and clinical correlates of ADHD differ among children in these two settings.
A case-control study design was used. Participants were 522 children and adolescents of both sexes, six to 18 years of age, with (N=280) and without (N=242) ADHD. Participants were drawn from pediatric and psychiatric clinics in a tertiary care hospital and a health maintenance organization in a large metropolitan area. Assessments were conducted with standardized measures of psychiatric, cognitive, social, academic, and family function.
The number, type, clusters, and age at onset of ADHD symptoms were nearly identical for youths at pediatric and psychiatric ascertainment sources. Regardless of source, participants with ADHD were significantly more likely than controls to have a higher prevalence of mood disorders, other disruptive behavior, anxiety disorders, and substance use disorders. Significant impairments of intellectual, academic, interpersonal, and family functioning did not differ between ascertainment sources.
Children with ADHD from both psychiatric and pediatric practices have prototypical symptoms of the disorder; high levels of comorbidity with mood, anxiety, and disruptive behavior disorders; and impairments in cognitive, interpersonal, and academic function that do not differ by ascertainment source. These findings suggest that children cared for in pediatric practice have similar levels of comorbidity and dysfunction as psychiatrically referred youth.
A fundamental goal in genomics is the discovery of genetic variation that contributes to disease states or to differential drug responses. Single nucleotide polymorphism (SNP) detection has been the ...focus of much attention in the study of genetic variation over the last decade. These SNPs typically occur at a frequency greater than 1% in the human genome. Recently, low‐frequency alleles are also being increasingly recognized as critical to obtain an improved understanding of the correlation between genetic variation and disease. Although many methods have been reported for the discovery and scoring of SNPs, sensitive, automated, and cost‐effective methods and platforms for the discovery of low‐frequency alleles are not yet readily available. We describe here an automated multicapillary instrument for high‐throughput detection of low‐frequency alleles from pooled samples using constant denaturant capillary electrophoresis. The instrument features high optical sensitivity (1×10–12 M fluorescein detection limit), precise and stable temperature control (± 0.01°C), and automation for sample delivery, injection, matrix replacement, and fraction collection. The capillary array is divided into six groups of four capillaries, each of which can be independently set at any temperature ranging from room temperature to 90°C. The key performance characteristics of the instrument are reported.
DNA variants underlying the inheritance of risk for common diseases are expected to have a wide range of population allele frequencies. The detection and scoring of the rare alleles (at frequencies ...of <0.01) presents significant practical problems, including the requirement for large sample sizes and the limitations inherent in current methodologies for allele discrimination. In the present report, we have applied mutational spectrometry based on constant denaturing capillary electrophoresis (CDCE) to DNA pools from large populations in order to improve the prospects of testing the role of rare variants in common diseases on a large scale. We conducted a pilot study of the cytotoxic T lymphocyte-associated antigen-4 gene (CTLA4) in type 1 diabetes (T1D). A total of 1228 bp, comprising 98% of the CTLA4 coding sequence, all adjacent intronic mRNA splice sites, and a 3' UTR sequence were scanned for unknown point mutations in pools of genomic DNA from a control population of 10,464 young American adults and two T1D populations, one American (1799 individuals) and one from the United Kingdom (2102 individuals). The data suggest that it is unlikely that rare variants in the scanned regions of CTLA4 represent a significant proportion of T1D risk and illustrate that CDCE-based mutational spectrometry of DNA pools offers a feasible and cost-effective means of testing the role of rare variants in susceptibility to common diseases.
