The relationships between improvements in daytime sleepiness, fatigue and depression and psychomotor vigilance task testing with CPAP use in patients with obstructive sleep apnea.

OBJECTIVE: The purpose of this study was to determine if the subjective improvements in daytime sleepiness, fatigue and depression experienced by patients with obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) therapy predict an objective improvement in vigilance, and whether patients with mild-to-moderate OSA differ from patients with severe OSA in this regard. METHODS: A total of 182 patients underwent psychomotor vigilance task (PVT) testing and measurements of subjective daytime sleepiness, fatigue and depression at baseline and after a minimum of one month of adherent CPAP use at an adequate pressure. RESULTS: Patients with both mild-to-moderate (n = 92) and severe (n = 90) OSA experienced improvements in subjective daytime sleepiness, fatigue and depression, but objective improvement in vigilance was only seen in patients with severe OSA. In patients with severe OSA, while a correlation was found between improvements in daytime sleepiness and some PVT parameters, changes in subjective daytime sleepiness, fatigue and depression scores were not predictive of objective improvement in vigilance while controlling for all these subjective symptoms and for age, gender, body mass index, apnea-hypopnea index/respiratory event index and total sleep time/total recording time with pulse oximetry below 90%. CONCLUSIONS: We found no predictive relationship between subjective improvements in daytime sleepiness, fatigue and depression and objective vigilance with CPAP use in patients with OSA. These results suggest that subjective complaints of daytime impairment and objective measures of vigilance in patients with OSA should be assessed separately while evaluating the efficacy of CPAP therapy on daytime functioning.

Brief report: the impact of subcortical band heterotopia and associated complications on the neuropsychological functioning of a 13-year-old child.

Motor impairment in children with Asperger syndrome (AS) or high functioning autism (HFA) has been reported previously. This study presents results of a quantitative assessment of neuromotor skills in 14-22 year old HFA/AS. Sixteen HFA/AS and 16 IQ-matched controls were assessed by the Zurich Neuromotor Assessment (ZNA). The HFA/AS group showed strongest impairments of dynamic balance skills and diadochokinesis. Motor abilities were associated with degree of social withdrawal in the full sample and severity of current autistic symptoms in the HFA/AS group. Similar motor patterns as in younger children were found in the older adolescents. The association of autistic symptoms with motor performance points towards an essential role of motor impairment in autism spectrum disorders.

Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism.

BACKGROUND: Certain loci on the human genome, such as glutathione S-transferase M1 (GSTM1), do not permit heterozygotes to be reliably determined by commonly used methods. Association of such a locus with a disease is therefore generally tested with a case-control design. When subjects have already been ascertained in a case-parent design however, the question arises as to whether the data can still be used to test disease association at such a locus. RESULTS: A likelihood ratio test was constructed that can be used with a case-parents design but has somewhat less power than a Pearson's chi-squared test that uses a case-control design. The test is illustrated on a novel dataset showing a genotype relative risk near 2 for the homozygous GSTM1 deletion genotype and autism. CONCLUSION: Although the case-control design will remain the mainstay for a locus with a deletion, the likelihood ratio test will be useful for such a locus analyzed as part of a larger case-parent study design. The likelihood ratio test has the advantage that it can incorporate complete and incomplete case-parent trios as well as independent cases and controls. Both analyses support (p = 0.046 for the proposed test, p = 0.028 for the case-control analysis) an association of the homozygous GSTM1 deletion genotype with autism.

New 19 bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR): a risk factor for spina bifida acting in mothers during pregnancy?

Up to 72% of spina bifida cystica (SB) is preventable by maternal periconceptual folic acid supplementation. The C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene and some other functional polymorphisms are risk factors for SB in some populations. However, despite extensive study, the genetic risk factors for SB are incompletely understood. Polymorphic alleles that diminish bioavailability of reduced folate in the mother during pregnancy could contribute to SB in her fetus, acting in the mother as teratogenic alleles. We recently discovered a polymorphic 19 bp deletion allele (frequency 0.45) within intron-1 of dihydrofolate reductase (DHFR) that is a good candidate for such a genetic factor. Since there is precedence for intron-1 regulatory elements and the deletion allele removes a potential Sp1 transcription factor binding site, we hypothesized that the deletion allele could be functional and act in SB mothers to increase the risk of SB in her fetus. We found that homozygosity for this deletion allele was significantly more frequent in SB mothers, but not in SB fathers or patients, compared with controls and was associated with a significantly increased odds ratio (OR) (2.035) of being an SB mother compared with other genotypes. Genotype distribution obeyed the constraints of Hardy-Weinberg equilibrium in controls, SB patients and fathers, but not in SB mothers. If confirmed, these findings could lead to improved forms of folate supplementation for pregnancy. About half of dietary folates and all of folic acid supplements must be reduced by DHFR to be available for mother and fetus. Reduced folates could be preferable for supplements during pregnancy to prevent SB.