The neurodevelopmental disorder, attention deficit hyperactive disorder (ADHD), is one of the most prevalent childhood behavioral disorders, affecting approximately 3% to 9% of the population. ADHD is first diagnosed in children with symptoms of inattention, hyperactivity and impulsivity. Numerous genetic, neuroimaging, molecular and neurochemical studies have provided a greater understanding of the neuropathophysiology of ADHD; however, there are many unanswered questions about ADHD. In vivo phosphorus magnetic resonance spectroscopy (31P MRS) is a noninvasive technique that can directly assess the metabolism of membrane phospholipids (MPL) and high-energy phosphates in multiple, localized brain regions. Preliminary results show significant alterations in MPL metabolism and high-energy phosphate utilization in regions associated with the neural networks of attention [prefrontal (PF), basal ganglia and superior temporal] of children and adolescents with ADHD compared to controls. When compared to normal neurodevelopmental data, these alterations appear to deviate from the naturally occuring changes. Additionally, MPL metabolites correlated with sustained attention performance in the PF and inferior parietal of both ADHD and control subjects. In all, these biochemical alterations in ADHD provide evidence of a deficit in regions responsible for the function of attention that are due to underdeveloped neuronal processes and synapses. It is, however, unclear if these alterations have a non-progressive behavior and as a result also would be present at a relatively earlier stage of illness prior to medication treatment. Therefore, the purpose of this study is to assess cross-sectionally in vivo 31P metabolite differences from 7 different brain regions between 32 medication-naive children with ADHD and 32 healthy age- and gender-matched controls, using a multi-voxel acquisition schemes. MRI structural measurements of total grey and white matter volumes and of key structures also will be obtained. Additionally, metabolite levels for each right and left brain region of interest will be correlated with percent grey and white matter and cerebral spinal fluid in the same region and with the structural measurements. While one would not expect new treatments to emerge directly from this study's findings, the increased molecular/biochemical knowledge of ADHD will anchor future efforts to develop specific somatic treatments for ADHD.
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