title: Analysis of brain metabolism by proton magnetic resonance spectroscopy (1H-MRS) in attention-deficit/hyperactivity disorder suggests a generalized differential ontogenic pattern from controls.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder of childhood. Preliminary studies with proton magnetic resonance spectroscopy ((1)H-MRS) of the brain have reported differences in brain metabolite concentration-to-Cr ratios between individuals with ADHD and unaffected controls in several frontal brain regions including anterior cingulate cortex. Using multivoxel (1)H-MRS, we compared 14 individuals affected with ADHD to 20 individuals without ADHD from the same genetic isolate. After controlling by sex, age, and multiple testing, we found significant differences at the right posterior cingulate of the Glx/Cr ratio density distribution function between ADHD cases and controls (P < 0.05). Furthermore, we found several interactions of metabolite concentration-to-Cr ratio, age, and ADHD status: Ins/Cr and Glx/Cr ratios at the left posterior cingulate, and NAA/Cr at the splenius, right posterior cingulate, and at the left posterior cingulate. We also found a differential metabolite ratio interaction between ADHD cases and controls for Ins/Cr and NAA/Cr at the right striatum. These results show that: (1) NAA/Cr, Glx/Cr, and Ins/Cr ratios, as reported in other studies, exhibit significant differences between ADHD cases and controls; (2) differences of these metabolite ratios between ADHD cases and controls evolve in specific and recognizable patterns throughout age, a finding that replicates previous results obtained by structural MRI, where is demonstrated that brain ontogeny follows a different program in ADHD cases and controls; (3) Ins/Cr and NAA/Cr ratios, at the right striatum, interact in a differential way between ADHD cases and controls. As a whole, these results replicate previous 1H-MRS findings and add new intriguing differential metabolic and ontogeny patterns between ADHD cases and controls that warrant further pursue.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3717, USA.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Arcos-Burgos
authors.forename: Ana C
authors.initials: AC
authors.lastname: Londoño
authors.forename: David A
authors.initials: DA
authors.lastname: Pineda
authors.forename: Francisco
authors.initials: F
authors.lastname: Lopera
authors.forename: Juan David
authors.initials: JD
authors.lastname: Palacio
authors.forename: Andres
authors.initials: A
authors.lastname: Arbelaez
authors.forename: Maria T
authors.initials: MT
authors.lastname: Acosta
authors.forename: Jorge I
authors.initials: JI
authors.lastname: Vélez
authors.forename: Francisco Xavier
authors.initials: FX
authors.lastname: Castellanos
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
mesh_terms: D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods / Q000706:statistics & numerical data*; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D011522:Protons; D018709:Statistics, Nonparametric
chemical_list: D011522:Protons; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline