Elevated Glutamate Levels in the Left Dorsolateral Prefrontal Cortex Are Associated with Higher Cravings for Alcohol

Mark A Frye, David J. Hinton, Victor M Karpyak, Joanna M Biernacka, Lee J. Gunderson, Jennifer Geske, Scott E. Feeder, Doo Sup Choi, John D Port

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)1609-1616
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume40
Issue number8
DOIs
StatePublished - Aug 1 2016

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Prefrontal Cortex
Glutamic Acid
Alcohols
Cerebrospinal fluid
Aspartic Acid
Cerebrospinal Fluid
Sample Size
Magnetic resonance spectroscopy
Craving
Drinking Behavior
Alcoholic Beverages
Metabolites
Alcohol Drinking
Drinking
Spectrum Analysis
Nuclear magnetic resonance
Spectroscopy
Depression
Recurrence

Keywords

  • Alcohol Craving
  • Alcohol Dependence
  • Dorsolateral Prefrontal Cortex
  • Glutamate
  • Magnetic Resonance Spectroscopy

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Elevated Glutamate Levels in the Left Dorsolateral Prefrontal Cortex Are Associated with Higher Cravings for Alcohol. / Frye, Mark A; Hinton, David J.; Karpyak, Victor M; Biernacka, Joanna M; Gunderson, Lee J.; Geske, Jennifer; Feeder, Scott E.; Choi, Doo Sup; Port, John D.

In: Alcoholism: Clinical and Experimental Research, Vol. 40, No. 8, 01.08.2016, p. 1609-1616.

Research output: Contribution to journalArticle

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abstract = "Background: 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. Methods: 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. Results: 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. Conclusions: 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.",
keywords = "Alcohol Craving, Alcohol Dependence, Dorsolateral Prefrontal Cortex, Glutamate, Magnetic Resonance Spectroscopy",
author = "Frye, {Mark A} and Hinton, {David J.} and Karpyak, {Victor M} and Biernacka, {Joanna M} and Gunderson, {Lee J.} and Jennifer Geske and Feeder, {Scott E.} and Choi, {Doo Sup} and Port, {John D}",
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T1 - Elevated Glutamate Levels in the Left Dorsolateral Prefrontal Cortex Are Associated with Higher Cravings for Alcohol

AU - Frye, Mark A

AU - Hinton, David J.

AU - Karpyak, Victor M

AU - Biernacka, Joanna M

AU - Gunderson, Lee J.

AU - Geske, Jennifer

AU - Feeder, Scott E.

AU - Choi, Doo Sup

AU - Port, John D

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N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

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KW - Alcohol Dependence

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KW - Glutamate

KW - Magnetic Resonance Spectroscopy

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