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Original Investigation |

Plasticity of Hippocampal Subfield Volume Cornu Ammonis 2+3 Over the Course of Withdrawal in Patients With Alcohol Dependence

Simone Kühn, PhD1; Katrin Charlet, PhD2; Florian Schubert, PhD3; Falk Kiefer, MD4; Peter Zimmermann, MD5; Andreas Heinz, PhD2; Jürgen Gallinat, PhD2,6
[+] Author Affiliations
1Max Planck Institute for Human Development, Center for Lifespan Psychology, Berlin, Germany
2Charité University Medicine, St Hedwig-Krankenhaus, Clinic for Psychiatry and Psychotherapy, Berlin, Germany
3Physikalisch-Technische Bundesanstalt, Berlin, Germany
4Central Institute of Mental Health, Department of Addictive Behavior and Addiction Medicine, Mannheim, Germany
5Psychotrauma Center of the German Military, Bundeswehrkrankenhaus, Berlin, Germany
6University Clinic Hamburg-Eppendorf, Clinic and Policlinic for Psychiatry and Psychotherapy, Hamburg, Germany
JAMA Psychiatry. 2014;71(7):806-811. doi:10.1001/jamapsychiatry.2014.352.
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Importance  Research focusing on plasticity has shown adult neurogenesis in hippocampal subfields. Chronic alcoholism is associated with decreased plasticity and reduced whole hippocampal volume that could contribute to neuropsychiatric characteristics and outcome of the disease.

Objective  To investigate the effect of alcohol abstinence on neuronal plasticity measured as longitudinal volume change in distinct hippocampal subfields.

Design, Setting, and Participants  We acquired high-resolution structural images of 42 patients addicted to alcohol and 32 healthy control participants. Patients and control participants were both scanned twice, once after withdrawal and 2 weeks later.

Main Outcomes and Measures  Volumes of hippocampal subfields cornu ammonis (CA) 2+3, CA4+dentate gyrus, and subiculum were determined with a user-independent segmentation method.

Results  We found plasticity effects in bilateral CA2+3 in patients addicted to alcohol. Compared with healthy control participants, patients had lower CA2+3 volume at pretest (t31 = −0.73, P = .47) and showed a significant normalization of gray matter volume 2 weeks later. Pretest CA2+3 (t31 = −3.93, P < .001) volume was negatively associated with years of regular alcohol consumption (r42 = −0.32, P < .05) and more severe alcohol-withdrawal symptoms (r38 = −0.35, P < .05). Patients with stronger withdrawal symptoms displayed the largest volume increase of CA2+3 (r38 = 0.55, P < .001).

Conclusions and Relevance  The observed normalization of the bilateral hippocampal CA2+3 volume deficit matches animal data, showing a strong increase of hippocampal neurogenesis after cessation of alcohol consumption, and fits the reported increase of patients’ cognitive function within a few months of alcohol abstinence. The role of CA3 in pattern separation and completion is also critical for formation of hallucinations, which constitute a severe symptom of the withdrawal syndrome. The study adds further biological arguments from structural brain research to abstain from alcohol.

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Figure 1.
Illustration of the Segmentation and Chances in Bilateral Cornu Ammonis 2+3 Volume

A, Illustration of a cornu ammonis 2+3 segmentation for a patient addicted to alcohol overlayed onto a magnetization-prepared gradient-echo image. B, Bilateral cornu ammonis 2+3 volume change in patients addicted to alcohol and healthy control participants in number of voxels (0.5 mm isotropic).aSignificant post hoc comparisons.

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Figure 2.
Scatterplot of Correlation

The negative correlation between regular alcohol consumption in years and cornu ammonis 2+3 volume at pretest (r42 = −0.32, P < .05).

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