title: Low N-acetyl-aspartate and high choline in the anterior cingulum of recently abstinent methamphetamine-dependent subjects: a preliminary proton MRS study. Magnetic resonance spectroscopy.
abstract: Studies based on animal models report that methamphetamine (MA) abuse diminishes dopamine (DA) and serotonin innervation in frontal brain regions. In this in vivo human study, we used proton magnetic resonance spectroscopy (MRS), which yields measures of N-acetyl-aspartate (NAA), a marker of living neurons, to examine frontal brain regions possibly affected by methamphetamine dependence (MD). We tested the hypothesis that MD subjects would exhibit abnormally low levels of NAA, referenced to creatine (Cr), in anterior cingulate gray matter. We further hypothesized that the primary visual cortex, which receives relatively less DA innervation than the frontal brain regions, would show normal NAA/Cr ratios in MD subjects. Subjects included nine MD men (mean+/-standard deviation (S.D.)=32.5+/-6.4 years) and nine age-matched control men (mean+/-S.D.=32.7+/-6.8 years). The MD subjects were MA-free for 4-13 weeks. Proton MRS metabolites were expressed as ratios of creatine; the absolute values of which did not distinguish controls and MD subjects. With regard to metabolite ratios, the MD men had significantly lower NAA/Cr in the cingulum (mean+/-standard error (S.E.): control=1.46+/-0.03; MD=1.30+/-0.03; Mann-Whitney P=0.01) but not in the visual cortex (mean+/-S.E.: control=1.64+/-0.06; MD=1.69+/-11; Mann-Whitney P=0.52) relative to controls. These results provide evidence for NAA/Cr deficit that is selective to the anterior cingulum, at least with respect to visual cortex, in MD subjects. The neuronal compromise that these changes reflect may contribute to the attentional deficits and dampened reward system in MD.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of California, Davis, CA, USA. tenordahl@ucdavis.edu
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Nordahl
authors.forename: Ruth
authors.initials: R
authors.lastname: Salo
authors.forename: Kate
authors.initials: K
authors.lastname: Possin
authors.forename: David R
authors.initials: DR
authors.lastname: Gibson
authors.forename: Neil
authors.initials: N
authors.lastname: Flynn
authors.forename: Martin
authors.initials: M
authors.lastname: Leamon
authors.forename: Gantt P
authors.initials: GP
authors.lastname: Galloway
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Spielman
authors.forename: Elfar
authors.initials: E
authors.lastname: Adalsteinsson
authors.forename: Edith V
authors.initials: EV
authors.lastname: Sullivan
mesh_terms: D000328:Adult; D000367:Age Factors; D019969:Amphetamine-Related Disorders / Q000503:physiopathology / Q000534:rehabilitation*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014793:Visual Cortex / Q000187:drug effects / Q000503:physiopathology
chemical_list: D001224:Aspartic Acid; D012701:Serotonin; D008694:Methamphetamine; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline; D004298:Dopamine