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A Multivoxel In Vivo Phosphorus 31 Spectroscopy Study

Jeffrey A. Stanley, PhD; Heidi Kipp, MEd; Erika Greisenegger, MS; Frank P. MacMaster, PhD; K. Panchalingam, PhD; Matcheri S. Keshavan, MD; Oscar G. Bukstein, MD; Jay W. Pettegrew, PhD

Arch Gen Psychiatry. 2008;65(12):1419-1428.

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 (³¹P 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 ³¹P 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.

Author Affiliations: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan (Drs Stanley, MacMaster, and Keshavan); and Department of Psychiatry, University of Pittsburgh School of Medicine (Drs Panchalingam, Bukstein, and Pettegrew), and Western Psychiatric Institute and Clinic (Mss Kipp and Greisenegger), Pittsburgh, Pennsylvania.

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