We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
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.
Text Size: A A A
Published online

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.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?


Place holder to copy figure label and caption
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.

Graphic Jump Location
Place holder to copy figure label and caption
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).

Graphic Jump Location




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment


Some tools below are only available to our subscribers or users with an online account.

1 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Alcohol Abuse

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Original Article: A Primer on the Precision and Accuracy of the Clinical Examination