title: Polysubstance and alcohol dependence: unique abnormalities of magnetic resonance-derived brain metabolite levels.
abstract: BACKGROUND
  Although comorbid substance misuse is common in alcohol dependence, and polysubstance abusers (PSU) represent the largest group of individuals seeking treatment for drug abuse today, we know little about potential brain abnormalities in this population. Brain magnetic resonance spectroscopy studies of mono-substance use disorders (e.g., alcohol or cocaine) reveal abnormal levels of cortical metabolites (reflecting neuronal integrity, cell membrane turnover/synthesis, cellular bioenergetics, gliosis) and altered concentrations of glutamate and γ-aminobutyric acid (GABA). The concurrent misuse of several substances may have unique and different effects on brain biology and function compared to any mono-substance misuse.
  
  
  METHODS
  High field brain magnetic resonance spectroscopy at 4 T and neurocognitive testing were performed at one month of abstinence in 40 alcohol dependent individuals (ALC), 28 alcohol dependent PSU and 16 drug-free controls. Absolute metabolite concentrations were calculated in anterior cingulate (ACC), parieto-occipital (POC) and dorso-lateral prefrontal cortices (DLPFC).
  
  
  RESULTS
  Compared to ALC, PSU demonstrated significant metabolic abnormalities in the DLPFC and strong trends to lower GABA in the ACC. Metabolite levels in ALC and light drinking controls were statistically equivalent. Within PSU, lower DLPFC GABA levels are related to greater cocaine consumption. Several cortical metabolite concentrations were associated with cognitive performance.
  
  
  CONCLUSIONS
  While metabolite concentrations in ALC at one month of abstinence were largely normal, PSU showed persistent and functionally significant metabolic abnormalities, primarily in the DLPFC. Our results point to specific metabolic deficits as biomarkers in polysubstance misuse and as targets for pharmacological and behavioral PSU-specific treatment.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco and Center for Imaging of Neurodegenerative Diseases, Veterans Administration Medical Center San Francisco, CA 94121, USA. christoph.abe@gmail.com
authors.forename: Christoph
authors.initials: C
authors.lastname: Abé
authors.forename: Anderson
authors.initials: A
authors.lastname: Mon
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Durazzo
authors.forename: David L
authors.initials: DL
authors.lastname: Pennington
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Schmidt
authors.forename: Dieter J
authors.initials: DJ
authors.lastname: Meyerhoff
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000175:diagnosis / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D016320:Substance Abuse Treatment Centers / Q000379:methods; D019966:Substance-Related Disorders / Q000175:diagnosis* / Q000378:metabolism*