Evidence of developmental alterations in cortical and subcortical regions of children with attention-deficit/hyperactivity disorder: a multivoxel in vivo phosphorus 31 spectroscopy study.

CONTEXT: There is mounting evidence of neurodevelopmental alterations implicating the prefrontal cortex (PFC) and basal ganglia in children with attention-deficit/hyperactivity disorder (ADHD). The brain undergoes substantive structural and functional changes with a differential timing between brain regions during development from childhood to adolescence. In vivo phosphorus 31 magnetic resonance spectroscopy ((31)P MRS) is a noninvasive neuroimaging approach that is sensitive in assessing developmental changes of overproducing/pruning of synapses.

OBJECTIVE

To provide support for a developmental mechanism targeting a bottom-up dysfunction of the basal ganglia impairing the fine-tuning of prefrontal functions in ADHD.

DESIGN

Cross-sectional study.

SETTING

Pittsburgh, Pennsylvania, and the surrounding areas.

PARTICIPANTS

Thirty-one psychostimulant-naive children with ADHD (mean [SD] age, 8.1 [1.2] years; range, 6.1-10.0 years) and 36 healthy control subjects (mean [SD] age, 8.1 [1.3] years; range, 6.1-10.4 years).

MAIN OUTCOME MEASURE: Membrane phospholipid (MPL) precursor levels (ie, phosphomonoesters that are anabolic metabolites of MPL) were assessed in the PFC and basal ganglia as well as in 4 other brain regions using in vivo (31)P MRS.

RESULTS

Lower bilateral MPL precursor levels in the basal ganglia and higher MPL precursor levels in the inferior parietal region (primarily right side) were noted in the children with ADHD as compared with healthy control children. There was a group x age interaction in the PFC and inferior parietal region, with relatively older psychostimulant-naive children with ADHD showing significantly lower PFC and higher inferior parietal MPL precursor levels. No differences between groups were noted in the superior temporal, posterior white matter, or occipital regions.

CONCLUSION

Though based on cross-sectional data, these results are suggestive of possible progressive, nonlinear, and sequential alterations implicating a bottom-up developmental dysfunction in parts of the cortico-striato-thalamo-cortical network in ADHD.