Hippocampus Volume Loss Due to Chronic Heavy Drinking Thomas P. Beresford, David B. Arciniegas, Julie Alfers, Lori Clapp, Brandon Martin, Yiping Du Dengfeng Liu, Dinggang Shen, and Christos Davatzikos Objective: No clear consensus exists regarding the effect of sustained, heavy drinking on hippo- campal volume. Our prior work hypothesized significantly lowered total hippocampus volumes in heavy chronically drinking alcohol-dependent (AD) subjects compared with light-drinking nonde- pendent control subjects matched for age and gender. Method: Using a series of applicable exclusion criteria culled from previous published studies, we measured hippocampal volumes from MRI scan data acquired on a 3T scanner and subjected those data to automated volume analysis blind to the drinking history. Results: Comparison with AD test (n 5 8) and non-AD control (n 5 8) subjects found significant lessening in total ( p 5 0.020) and left ( p 5 0.010) hippocampal volumes with a near-significant differ- ence on the right ( p 5 0.051). Linear regression demonstrated that neither total brain volume nor intracranial volume affected the hippocampus measures. Conclusions: These data support the view that heavy drinking exerts a unique and selectively injurious effect on the hippocampus. Further study in larger samples must verify this in a search for possible mechanisms of injury. Key Words: Hippocampus, Alcohol Drinking, Volume Loss, MRI Scan. T HE EFFECT OF sustained, heavy drinking on hippocampal volume is a subject of continued contro- versy. Although some reports in the literature point to a volumetric reduction in alcohol-dependent (AD) patients (Bleich et al., 2003a; Sullivan et al., 1995), others are less con- clusive (Agartz et al., 1999). Some have argued that lack of precise sample definition has generated this confusion, citing inclusion of subjects with histories of withdrawal seizures (Sullivan et al., 1996), for example. Others have disputed such claims (Bleich et al., 2003b). With development project funding, we began a prospect- ive study of the hippocampal volume in chronically drinking AD subjects. To assess volume comparisons at baseline, we analyzed new data from heavy-drinking AD test and light-drinking control cases. Early data from convenience samples of heavy drinking and control sub- jects (Beresford et al., 1999) led us to hypothesize that the mean total hippocampus volume (THV) in the AD sub- jects would be significantly smaller than the mean THV in the non-AD control subjects. Our specific aim was to rep- licate the findings of the prior study but in prospectively gathered sample groups utilizing more stringent exclusion and inclusion criteria. METHOD This project received prior approvals from our university institu- tional review board (IRB) as well as from the Research and Development Committee of our Department of Veterans Affairs (DVA) facility where the study was conducted. All subjects were voluntary and signed preapproved consent-for-study documents, consistent with IRB policy. Inclusion/Exclusion Both test (AD) and control subjects were adult male veterans who were eligible for care in the DVA system and were recruited in response to posted flyers advertising the study. Our research design matched AD test and non-AD control subjects for age, gender, and ethnicity. Alcohol-dependent heavy drinkers qualified for study if they met all of the following criteria: (1) Chronic heavy drinking: drank 5 or more standard drinks daily for at least 3 days weekly, and 3 weeks monthly for at least 9 months of the previous year, established through Time Line Follow Back interview (Sobell et al., 1979); (2) Recent heavy drinking: consumed 5 or more standard drinks daily on at least 3 days weekly for the past 30 days, established through TLFB; (3) AD diagnosis: fulfilled DSM-IV criteria for AD as established through the Structured Clinical Interview for DSM-IV Axis I From the Mental Health Service, Department of Veterans Affairs Medical Center, University of Colorado School of Medicine, Denver, Colorado (TPB); the Department of Psychiatry, University of Colorado School of Medicine, Denver, Colorado (TPB, DBA, JA, LC, BM, YD); the Department of Neurology, University of Colorado School of Medicine, Denver, Colorado (DBA); the Depart- ment of Radiology, University of Colorado School of Medicine, Denver, Colorado (YD); and the Department of Radiology, University of Penn- sylvania, Philadelphia, Pennsylvania (DL, DS, CD). Received for publication May 12, 2006; accepted July 28, 2006. This work was supported by Grant R21-AA14010 from the National Institute on Alcohol Abuse and Alcoholism. Reprint requests: Thomas P. Beresford, MD, Denver VA Medical Center (116), 1055 Clermont Street, Denver, CO 80220; Fax: 303-315- 5641; E-mail: thomas.beresford@uchsc.edu Copyright r 2006 by the Research Society on Alcoholism. No claim to original US government works. DOI: 10.1111/j.1530-0277.2006.00223.x Alcohol Clin Exp Res, Vol 30, No 11, 2006: pp 1866–1870 1866 ALCOHOLISM:CLINICAL AND EXPERIMENTAL RESEARCH Vol. 30, No. 11 November 2006