title: A preliminary examination of cortical neurotransmitter levels associated with heavy drinking in posttraumatic stress disorder.
abstract: Posttraumatic stress disorder (PTSD) patients have low cortical concentrations of γ-aminobutyric acid (GABA) and elevated glutamate (Glu) as measured by proton magnetic resonance spectroscopy ((1)H MRS). Alcohol use disorder (AUD) is highly comorbid with PTSD, but the neurobiological underpinnings are largely unknown. We wanted to determine if PTSD patients with AUD have normalized cortical GABA and Glu levels in addition to metabolite alterations common to AUD. We compared brain metabolite concentrations in 10 PTSD patients with comorbid AUD (PAUD) with concentrtations in 28 PTSD patients without AUD and in 20 trauma-exposed controls (CON) without PTSD symptoms. We measured concentrations of GABA, Glu, N-acetylaspartate (NAA), creatine- (Cr) and choline-containing metabolites (Cho), and myo-Inositol (mI) in three cortical brain regions using (1)H MRS and correlated them with measures of neurocognition, insomnia, PTSD symptoms, and drinking severity. In contrast to PTSD, PAUD exhibited normal GABA and Glu concentrations in the parieto-occipital and temporal cortices, respectively, but lower Glu and trends toward higher GABA levels in the anterior cingulate cortex (ACC). Temporal NAA and Cho as well as mI in the ACC were lower in PAUD than in both PTSD and CON. Within PAUD, more cortical GABA and Glu correlated with better neurocognition. Heavy drinking in PTSD is associated with partially neutralized neurotransmitter imbalance, but also with neuronal injury commonly observed in AUD.
authors.affiliation: Addiction Research Program, Veterans Affairs Medical Center, San Francisco, CA, USA; Northern California Institute for Research and Education, San Francisco, CA, USA. Electronic address: david.pennington2@va.gov.
authors.forename: David Louis
authors.initials: DL
authors.lastname: Pennington
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christoph
authors.initials: C
authors.lastname: Abé
authors.affiliation: Addiction Research Program, Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, CA, USA; Northern California Institute for Research and Education, San Francisco, CA, USA.
authors.forename: Steven Laszlo
authors.initials: SL
authors.lastname: Batki
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA; Northern California Institute for Research and Education, San Francisco, CA, USA.
authors.forename: Dieter Johannes
authors.initials: DJ
authors.lastname: Meyerhoff
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D001224:Aspartic Acid / Q000031:analogs & derivatives; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D002794:Choline / Q000378:metabolism; D015897:Comorbidity; D003401:Creatine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D013313:Stress Disorders, Post-Traumatic / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline
keywords: Alcohol dependence; Brain metabolite concentrations; GABA; Magnetic resonance spectroscopy; Neuronal injury; PTSD