title: Additive effects of HIV and chronic methamphetamine use on brain metabolite abnormalities.
abstract: OBJECTIVE
  Proton magnetic resonance spectroscopy (1H-MRS) showed decreased neuronal marker N-acetylaspartate and increased glial marker myo-inositol in subjects with chronic methamphetamine use and in subjects infected with HIV. The authors sought to determine whether HIV and a history of chronic methamphetamine use might have additive or interactive effects on brain metabolite abnormalities.
  
  
  METHODS
  1H-MRS was performed in 68 HIV-positive subjects (24 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 2,167 g [SD=2,788] and last use a mean of 4.9 months earlier [SD=6.0]; 44 with no history of drug abuse) and 75 HIV-negative subjects (36 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 8,241 g [SD=16,850] and last use a mean of 6.3 months earlier [SD=7.8]; 39 with no history of drug abuse). Concentrations of N-acetylaspartate, creatine, choline, and myo-inositol were measured in the frontal cortex, frontal white matter, and basal ganglia.
  
  
  RESULTS
  HIV-negative subjects with a history of chronic methamphetamine use showed lower concentrations of the neuronal marker N-acetylaspartate in the frontal white matter and basal ganglia and higher concentrations of choline compounds and the glial marker myo-inositol in the frontal cortex, relative to subjects with no history of drug abuse. HIV-positive status was associated with lower concentrations of N-acetylaspartate and creatine in the frontal cortex and higher concentrations of myo-inositol in the white matter, compared with HIV-negative status. Compared to the mean concentrations of metabolites in HIV-negative subjects with no history of drug abuse, the mean concentrations in subjects with HIV and chronic methamphetamine use showed additive effects on N-acetylaspartate in all three regions (-9% in the basal ganglia, -7% in the frontal white matter, and -6% in the frontal gray matter), on creatine in the basal ganglia (-7%), and on myo-inositol in the frontal white matter (+11%).
  
  
  CONCLUSIONS
  The combined effects of HIV and chronic methamphetamine use were consistent with an additive model, suggesting additional neuronal injury and glial activation due to the comorbid conditions.
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii, 1356 Lusitana St., 7th Floor, Honolulu, HI 96813, USA. LChang@hawaii.edu
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.forename: Thomas
authors.initials: T
authors.lastname: Ernst
authors.forename: Oliver
authors.initials: O
authors.lastname: Speck
authors.forename: Charles S
authors.initials: CS
authors.lastname: Grob
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000453:epidemiology / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D001479:Basal Ganglia / Q000737:chemistry; D001921:Brain / Q000378:metabolism*; D001927:Brain Diseases / Q000175:diagnosis* / Q000378:metabolism; D002794:Choline / Q000032:analysis; D002908:Chronic Disease; D015897:Comorbidity; D003401:Creatine / Q000032:analysis; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D007294:Inositol / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy / Q000706:statistics & numerical data*; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*
chemical_list: D001224:Aspartic Acid; D008694:Methamphetamine; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline