Chromosome 22q11 deletion and brain tissue composition

We thank Eliez & Blasey (2001) for their kind comments about our paper (van Amelsvoort et al, 2001). However, we disagree that our paper implied that Eliez et al (2000) reported relatively smaller frontal lobe volumes and would like to draw their attention to the following. Normal brain maturation is accompanied by a reduction in cortical grey matter volume and an increase in white matter volume. Myelination typically progresses from posterior to anterior brain regions and occurs relatively late in frontal regions (where it continues into adulthood). Also, the maturational process from adolescence into adulthood is associated with a net volume reduction in frontal regions (Giedd et al, 1999; Sowell et al, 1999), and not a volume increase as Eliez & Blasey (2001) suggest. Consequently, we interpreted the relatively larger frontal lobe volumes found by Eliezet al (2000) in children and adolescents with velo-cardio-facial syndrome (VCFS) as compared with controls as possibly being caused by a relative delay in onset of ‘maturational’ grey matter reduction in VCFS. Our finding of a regional increase in volume of frontal grey matter and decrease in frontal white matter, in the absence of a difference in total frontal lobe (grey and white matter) volume, supports this interpretation and suggests that subtle differences in tissue composition occur which may reflect a delay in maturational processes (van Amelsvoortet al, 2001). Moreover, white matter abnormalities have been reported in VCFS and abnormal myelination could partially explain the abnormal, or delayed, maturational process. Future studies using longitudinal designs across this age span, and newer techniques such as diffusion tensor imaging, should be able to address this issue.