title: Elevated Glutamate Levels in the Left Dorsolateral Prefrontal Cortex Are Associated with Higher Cravings for Alcohol.
abstract: Quantifying craving longitudinally during the course of withdrawal, early abstinence, and relapse is essential for optimal management of alcohol use disorder (AUD). In an effort to identify biological correlates of craving, we used proton magnetic resonance spectroscopy (1H-MRS) to investigate the correlation between craving and glutamate levels in the left dorsolateral prefrontal cortex (LDLPFC) of patients with AUD.
  
  
  
  Participants underwent 1H-MRS of the LDLPFC with 2-dimensional J-resolved (2DJ) averaged PRESS. MRS data were processed with LCModel and cerebrospinal fluid (CSF)-corrected to generate metabolite concentrations. The Penn Alcohol Craving Scale (PACS) and the 30-day time line follow-back (TLFB 30) were used to quantify craving for alcohol and drinking patterns, respectively.
  
  
  
  There was a statistically significant positive correlation between CSF-corrected glutamate ([Glu]) levels and PACS scores (n = 14; p = 0.005). When PACS scores were dichotomized (< or ≥median = 16), [Glu] levels were significantly higher in the high- versus low-craving group (p = 0.007). In addition, there was a significant negative correlation between CSF-corrected N-acetyl aspartic acid ([NAA]) levels and mean number of drinks per drinking day in the past month (n = 13; TLFB 30; p = 0.012). When mean TLFB 30 was dichotomized (< or ≥median = 7.86), [NAA] levels were significantly lower in subjects that consumed more alcoholic beverages. There was no significant correlation between [Glu] and [NAA] levels with other measures of drinking behavior and or depression symptom severity.
  
  
  
  While limited by small sample size, these data suggest that glutamate levels in LDLPFC are associated with alcohol craving intensity in patients with AUD. Further study with larger sample size is needed to replicate this finding and evaluate the merits of glutamate spectroscopy as a biological correlate of alcohol craving intensity and a guide to treatment interventions.
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, Minnesota.|Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota.|Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hinton
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Karpyak
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, Minnesota.|Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Biernacka
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Gunderson
authors.affiliation: Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Geske
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Feeder
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, Minnesota.|Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota.|Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, Minnesota.|Department of Radiology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: John D
authors.initials: JD
authors.lastname: Port
mesh_terms: D000328:Adult; D064829:Alcohol Abstinence / Q000639:trends; D000428:Alcohol Drinking / Q000378:metabolism*; D019973:Alcohol-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy; D066249:Craving / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D016320:Substance Abuse Treatment Centers / Q000639:trends
chemical_list: D018698:Glutamic Acid
keywords: Alcohol Craving; Alcohol Dependence; Dorsolateral Prefrontal Cortex; Glutamate; Magnetic Resonance Spectroscopy