Abstract
BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11DS), the most common microdeletion in humans, is associated with multiple medical features, almost universal cognitive deficits, and a high risk of schizophrenia. The metabolic basis of the psychological/psychiatric features is not well understood. Volumetric brain imaging studies have shown that gray matter abnormalities in the dorsolateral prefrontal cortex (DLPFC), an area that is believed to be integral for higher neurocognition, as well as being involved in schizophrenia, are associated with the psychological manifestations. However, studies have not characterized any possible metabolite alterations within the DLPFC of children with 22q11DS and their correlations with the psychological findings. METHODS: We conducted a short echo time, single-voxel, in vivo proton spectroscopy study involving children with 22q11DS (n = 26) and matched control subjects (n = 23). RESULTS: Absolute N-acetylaspartate (NAA) levels from the DLPFC were significantly elevated in children with 22q11DS compared with control subjects and the elevations were associated with poor global functioning and higher rates of comorbid attention-deficit/hyperactivity disorder. Children with 22q11DS had a lack of an age-associated decrease in NAA levels, a trend seen in the control subjects. However, the results did not remain statistically significant after corrections for multiple comparisons were made. CONCLUSIONS: These findings represent the first report of proton spectroscopy in children with 22q11DS. The elevated DLPFC NAA levels and the lack of decreasing trends in NAA with age in the 22q11DS group relative to control subjects suggest an alteration in cortical development. Also, such neuronal dysmaturation is associated with psychopathology in children with 22q11DS.