Prefrontal and occipital asymmetry and volume in boys with autism spectrum disorder.

OBJECTIVE: To examine prefrontal and occipital asymmetry (brain torque) in boys with autism spectrum disorder (ASD) and controls. A secondary aim was to study age-related changes in gray and white matter volume. BACKGROUND: Several studies have found atypical early cortical development in ASD. Atypical brain torque, defined as a greater-than-normal left prefrontal and right occipital asymmetry, has been found in some studies of children and adults with ASD. This configuration may be an early neural marker of ASD risk. METHODS: We studied 24 right-handed boys with ASD and 27 typically developing right-handed boys, 7 to 15 years old, obtaining neuropsychological profiles and measuring prefrontal and occipital volumes on magnetic resonance images. RESULTS: Most participants had the expected rightward prefrontal and leftward occipital asymmetry, with no group differences in direction or degree of asymmetry. We found a trend toward larger prefrontal volume in the ASD group than in the controls. The controls also had a trend toward differences in age associations, correlating with total and left prefrontal white matter volumes. CONCLUSIONS: Our findings suggest that atypical brain torque may not be a neural signature of ASD, although our sample was limited to high-functioning, right-handed boys. Our results provide support for aberrant cortical development in ASD, continuing into adolescence, with prefrontal regions being disproportionally affected.

Control elements in the neighboring ATPase gene influence spatiotemporal expression of the human agouti-related protein.

The agouti-related protein (AgRP) is an orexigenic peptide that plays a significant role in the regulation of energy balance. It is expressed in the hypothalamus, the adrenal glands, and the testis, but sequences determining its spatial and temporal expression have not been identified. Using an elaborate in vitro screening approach, we show here that two adjacent enhancers inside the first intron of the neighboring (1.4 kb downstream) ATPase gene (ATP6V0D1) modulate the human AgRP promoter with profound spatiotemporal variation despite their diminutive sizes (221 and 231 nt). In transgenic mice, the proximal enhancer displayed specificity for the testis, tail, and ears, and the distal one for the testis, front feet, bone, heart, muscle, brain, spinal cord, and tongue, while dietary fat and overnight fasting had differential effects on enhancer activities. AgRP in the testis was localized to pachytene spermatocytes and in the tongue to epithelial cells. Comparative sequence analysis showed that the AgRP-ATP6V0D1 intergenic region is two times longer in humans than in mice and that the two enhancers are conserved in the rhesus monkey genome but not in the mouse genome. These data show that spatiotemporal expression of the human AgRP gene is influenced by diversified primate-specific intronic sequences in its neighboring ATP6V0D1 gene.