Cognitive outcome of offspring from dexamethasone-treated pregnancies at risk for congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

OBJECTIVES: To test whether dexamethasone (DEX) treatment in pregnancies at risk for congenital adrenal hyperplasia (CAH) impairs cognitive functioning in the offspring. DESIGN: Observational follow-up of prenatally DEX-exposed offspring and controls. METHODS: Study 1 included 140 children aged 512 years: 67 DEX-exposed (long-term: eight CAH girls) and 73 unexposed (with 15 CAH girls). Study 2 included 20 participants aged 11-24 years: seven DEX-exposed (long-term: one CAH woman) and 13 unexposed (with four CAH women). Neuropsychological testing was done in hospital settings or at patients' homes. Data analysis aimed at maximizing detection of the effects of DEX exposure. RESULTS: The vast majority of group comparisons were not marginally or conventionally significant. The few significant findings on short-term prenatal DEX exposure suggested more positive than adverse outcomes. By contrast, few significant findings in females with CAH and long-term DEX exposure indicated slower mental processing than in controls on several neuropsychological variables, although partial correlations of DEX exposure duration with cognitive outcome did not corroborate this association. CONCLUSIONS: Although our studies do not replicate a previously reported adverse effect of short-term prenatal DEX exposure on working memory, our findings on cognitive function in CAH girls with long-term DEX exposure contribute to concerns about potentially adverse cognitive after effects of such exposure. Yet, our studies are not definitive, and replications in larger samples are required.

Correlates of intellectual ability with morphology of the hippocampus and amygdala in healthy adults.

Several prior imaging studies of healthy adults have correlated volumes of the hippocampus and amygdala with measures of general intelligence (IQ), with variable results. In this study, we assessed correlations between volumes of the hippocampus and amygdala and full-scale IQ scores (FSIQ) using a method of image analysis that permits detailed regional mapping of this correlation throughout the surface contour of these brain structures. We delineated the hippocampus and amygdala in high-resolution magnetic resonance images of the brain from 34 healthy individuals. We then correlated FSIQ with overall volumes and with the surface morphologies of each of these structures. Hippocampus volumes correlated significantly and inversely with FSIQ independently of gender, age, socioeconomic status, and whole brain volume. Left and right hippocampus volumes correlated respectively with verbal and performance IQ subscales. Higher IQs were significantly associated with large inward deformations of the surface of the anterior hippocampus bilaterally. These findings suggest that a smaller anterior hippocampus contributes to an increased efficiency of neural processing that subserves overall intelligence.

Mitochondrial DNA abnormalities and autistic spectrum disorders.

OBJECTIVES: To further characterize mtDNA defects associated with autistic features, especially the A3243G mtDNA mutation and mtDNA depletion.Study design Five patients with autistic spectrum disorders and family histories of mitochondrial DNA diseases were studied. We performed mtDNA analysis in all patients and magnetic resonance spectroscopy in three. RESULTS: Three patients manifested isolated autistic spectrum features and two had additional neurologic symptoms. Two patients harbored the A3243G mutation. In two others, the A3243G mutation was not found in accessible tissues but was present in tissues from their mothers. The fifth patient had 72% mtDNA depletion in skeletal muscle. CONCLUSIONS: Autistic spectrum disorders with or without additional neurologic features can be early presentations of the A3243G mtDNA mutation and can be a prominent clinical manifestation of mtDNA depletion. Mitochondrial dysfunction should be considered in patients who have autistic features and associated neurologic findings or who have evidence of maternal inheritance.