Familial influences on sustained attention and inhibition in preschoolers

Background: In this study several aspects of attention were studied in 237 nearly 6-year-old twin pairs. Specifically, the ability to sustain attention and inhibition were investigated using a computerized test battery (Amsterdam Neuropsychological Tasks). Furthermore, the Teacher's Report Form (TRF) was filled out by the teacher of the child and the attention subscale of this questionnaire was analyzed. Methods: The variance in performance on the different tasks of the test battery and the score on the attention scale of the TRF were decomposed into a contribution of the additive effects of many genes (A), environmental effects that are shared by twins (C) and unique environmental influences not shared by twins (E) by using data from MZ and DZ twins. Results: The genetic model fitting results showed an effect of A and E for the attention scale of the TRF, and for some of the inhibition and sustained attention measures. For most of the attention variables, however, it was not possible to decide between a model with A and E or a model with C and E. Time-on-task effects on reaction time or number of errors and the delay after making an error did not show familial resemblances. A remarkable finding was that the heritability of the attention scale of the TRF was found to be higher than the heritability of indices that can be considered to be more direct measures of attention, such as mean tempo in the sustained attention task and response speed in the Go-NoGo task. Conclusion: In preschoolers, familial resemblances on sustained attention and inhibition were observed. © Association for Child Psychology and Psychiatry, 2004

AAV vector-mediated reversal of hypoglycemia in canine and murine glycogen storage disease type Ia

Glycogen storage disease type Ia (GSD-Ia) profoundly impairs glucose release by the liver due to glucose-6-phosphatase (G6Pase) deficiency. An adeno-associated virus (AAV) containing a small human G6Pase transgene was pseudotyped with AAV8 (AAV2/8) to optimize liver tropism. Survival was prolonged in 2-week-old G6Pase (-/-) mice by 600-fold fewer AAV2/8 vector particles (vp), in comparison to previous experiments involving this model (2 x 10(9) vp; 3 x 10(11) vp/kg). When the vector was pseudotyped with AAV1, survival was prolonged only at a higher dose (3 x 10(13) vp/kg). The AAV2/8 vector uniquely prevented hypoglycemia during fasting and fully corrected liver G6Pase deficiency in GSD-Ia mice and dogs. The AAV2/8 vector has prolonged survival in three GSD-Ia dogs to >11 months, which validated this strategy in the large animal model for GSD-Ia. Urinary biomarkers, including lactate and 3-hydroxybutyrate, were corrected by G6Pase expression solely in the liver. Glycogen accumulation in the liver was reduced almost to the normal level in vector-treated GSD-Ia mice and dogs, as was the hepatocyte growth factor (HGF) in GSD-Ia mice. These preclinical data demonstrated the efficacy of correcting hepatic G6Pase deficiency, and support the further preclinical development of AAV vector-mediated gene therapy for GSD-Ia