Ulrich Frischknecht1, Derik Hermann1, Nuran Tunc-Skarka2, Guo-Ying Wang2, Markus Sack2, Julia van Eijk2, Traute Demirakca2, Claudia Falfan-Melgoza3, Bertram Krumm4, Sandra Dieter5, Rainer Spanagel5, Falk Kiefer1, Karl F Mann1, Wolfgang H Sommer1,5, Gabriele Ende2, Wolfgang Weber-Fahr3. 1. Department of Addictive Behavior and Addiction Medicine , Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 2. Department of Neuroimaging , Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 3. Research Group for Translational Imaging , Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 4. Department of Biostatistics , Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 5. Institute of Psychopharmacology , Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Abstract
BACKGROUND: Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal-associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats. METHODS: Alcohol-dependent patients (N = 39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence. MRI and MRS data of healthy controls (N = 34) were acquired once. Our thorough quality criteria resulted in N = 15 available spectra from the first and of N = 21 from the second measurement in patients, and of N = 19 from healthy controls. In a translational approach, chronic intermittent ethanol-exposed rats and respective controls (8/group) underwent 5 MRS measurements covering baseline, intoxication, 12 and 60 hours of withdrawal, and 3 weeks of abstinence. RESULTS: In both species, higher levels of markers of glutamatergic metabolism were associated with lower gray matter volumes in the hippocampus in early abstinence. Trends of reduced N-acetylaspartate levels during intoxication persisted in patients with severe alcohol withdrawal symptoms over 2 weeks of abstinence. We observed a higher ratio of glutamate to glutamine during alcohol withdrawal in our animal model. CONCLUSIONS: Due to limited statistical power, we regard the results as preliminary and discuss them in the framework of the hypothesis of withdrawal-induced hyperglutamatergic neurotoxicity, alcohol-induced neural changes, and training-associated effects of abstinence on hippocampal tissue integrity.
BACKGROUND: Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal-associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats. METHODS:Alcohol-dependent patients (N = 39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence. MRI and MRS data of healthy controls (N = 34) were acquired once. Our thorough quality criteria resulted in N = 15 available spectra from the first and of N = 21 from the second measurement in patients, and of N = 19 from healthy controls. In a translational approach, chronic intermittent ethanol-exposed rats and respective controls (8/group) underwent 5 MRS measurements covering baseline, intoxication, 12 and 60 hours of withdrawal, and 3 weeks of abstinence. RESULTS: In both species, higher levels of markers of glutamatergic metabolism were associated with lower gray matter volumes in the hippocampus in early abstinence. Trends of reduced N-acetylaspartate levels during intoxication persisted in patients with severe alcohol withdrawal symptoms over 2 weeks of abstinence. We observed a higher ratio of glutamate to glutamine during alcohol withdrawal in our animal model. CONCLUSIONS: Due to limited statistical power, we regard the results as preliminary and discuss them in the framework of the hypothesis of withdrawal-induced hyperglutamatergic neurotoxicity, alcohol-induced neural changes, and training-associated effects of abstinence on hippocampal tissue integrity.
Authors: Jenny Ceccarini; Gil Leurquin-Sterk; Cleo Lina Crunelle; Bart de Laat; Guy Bormans; Hendrik Peuskens; Koen Van Laere Journal: J Nucl Med Date: 2019-09-03 Impact factor: 10.057
Authors: Corinde E Wiers; Samantha I Cunningham; Dardo G Tomasi; Thomas Ernst; Linda Chang; Ehsan Shokri-Kojori; Gene-Jack Wang; Nora D Volkow Journal: Psychiatry Res Neuroimaging Date: 2020-09-10 Impact factor: 2.493