Structural changes in the hippocampus in major depressive disorder: contributions of disease and treatment

Structural changes in the hippocampus in major depressive disorder: contributions of disease and treatment


J Psychiatry Neurosci 2010; 35(5): 337-343

Nikolai V. Malykhin, MD, PhD; Rawle Carter, RPN; Peter Seres, BSc, MScE; Nicholas J. Coupland, MB, ChB

Malykhin, Carter, Coupland — Department of Psychiatry; Malykhin, Seres — Department of Biomedical Engineering; Malykhin — Centre for Neuroscience, University of Alberta, Edmonton, Alta.


Background: Previous magnetic resonance imaging (MRI) studies of patients with major depressive disorder (MDD) have consistently shown bilateral and unilateral reductions in hippocampal volume relative to healthy controls. Recent structural MRI studies have addressed the question of whether changes in the volume of hippocampal subregions may be associated with MDD.

Methods: We used a comprehensive and reliable 3-dimensional tracing protocol that enables delineation of hippocampal subregions (head, body, tail) to study changes in the hippocampus of patients with MDD. We recruited 39 MDD patients (16 medicated, 23 unmedicated) and 34 healthy age- and sexmatched controls. We acquired images using a magnetization-prepared rapid acquisition gradient echo sequence on a 1.5-T scanner with a spatial resolution of 1.5 mm x 0.5 mm x 0.5 mm. We performed volumetric analyses, blinded to diagnosis, using the interactive software package Display. All volumes were adjusted for intracranial volume.

Results: We found a significant reduction in the volume of the hippocampal tail bilaterally, right hippocampal head and right total hippocampus in MDD patients. Medicated MDD patients showed increased
hippocampal body volume compared with both healthy controls and unmedicated patients.

Limitations: This study was cross-sectional. Further prospective studies are needed to determine the direct effect of antidepressant treatment.

Conclusions: Our results suggest that decreased hippocampal tail and hippocampal head volumes could be trait changes, whereas hippocampal body changes may be dependent on treatment. We showed that long-term antidepressant treatment may affect hippocampal volume in patients with MDD.

Submitted Jan. 5, 2010; Revised Apr. 8, 2010; Accepted Apr. 8, 2010.

Acknowledgments: This study was supported by the Canadian Institutes of Health Research (CIHR; MOP 64413). Dr. Malykhin receives support from a CIHR/Wyeth Fellowship, and Drs. Malykhin and Coupland receive support from the Alberta Heritage Foundation for Medical Research. This work was presented in part at the 30th Annual Meeting of Canadian College of Neuropsychopharmacology, Banff, Alta., June 15–18, 2007.

Competing interests: None declared

Contributors: Drs. Malykhin and Coupland contributed to the conception and design of the study and the acquisition, analysis and interpretation of data. Mr. Carter and Mr. Seres contributed to the acquisition of the data. Dr. Malykhin wrote the article, which he and all other authors revised. All authors approved the final version submitted for publication. All authors had full access to all of the data in the study and all analyses.

DOI: 10.1503/jpn.100002

Correspondence to: Dr. N.V. Malykhin, Department of Biomedical Engineering, Faculty of Medicine and Dentistry, University of Alberta, Edmonton AB T6G 2V2;