AUTHOR=Morley Kirsten C. , Lagopoulos Jim , Logge Warren , Chitty Kate , Baillie Andrew , Haber Paul S. 

TITLE=Neurometabolite Levels in Alcohol Use Disorder Patients During Baclofen Treatment and Prediction of Relapse to Heavy Drinking

JOURNAL=Frontiers in Psychiatry

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2018.00412

DOI=10.3389/fpsyt.2018.00412

ISSN=1664-0640

ABSTRACT=<p><bold>Background and Aims:</bold> Baclofen, a GABA<sub>B</sub> agonist, is used as a treatment for alcohol dependence. We aimed to examine brain metabolites following administration of baclofen or placebo in alcohol dependent individuals enrolled in a randomized placebo-controlled trial.</p><p><bold>Methods:</bold> Participants included 31 alcohol dependent individuals (recent drinking: <italic>N</italic> = 16; and abstinent: <italic>N</italic> = 15) who had received daily baclofen (BAC 30–75 mg = 20) or placebo (PL = 11) for at least 2 weeks (average 17 days). Using <italic>in vivo</italic> proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS), spectra from the right parietal lobe were analyzed to obtain measures of GABA, Glutamate (Glu), Glutathione (GSH) and N-Acetyl Apartate (NAA) 120 min following administration of PL or BAC.</p><p><bold>Results:</bold> When weighting alcohol dependent participants according to recent alcohol consumption (within 24 h), there were significant differences between BAC and PL on parietal concentrations of GSH (<italic>p</italic> &lt; 0.01) and NAA (<italic>p</italic> &lt; 0.05). Multiple linear regression revealed a significant predictive effect of GSH on heavy drinking days at 12 weeks follow-up (Model: <italic>F</italic> = 14.28, <italic>R</italic><sup>2</sup> = 0.85; GSH: <italic>B</italic> = −1.22, <italic>p</italic> = 0.01) and also percentage days abstinent at 12 weeks follow-up (Model: <italic>F</italic> = 6.50, <italic>R</italic><sup>2</sup> = 0.72; GSH: <italic>B</italic> = 0.99, <italic>p</italic> = 0.06).</p><p><bold>Conclusion:</bold> Our data provide preliminary evidence that the effect of baclofen may be mediated by increased parietal concentrations of the antioxidant GSH and NAA in recently drinking alcohol dependent patients. GSH/Cr levels were also predictive of improved drinking outcomes in the trial and suggests a role for neural oxidative stress in alcohol use disorder.</p>