Abnormal hippocampal activation in patients with extensive history of major depression: an fMRI study

Abnormal hippocampal activation in patients with extensive history of major depression: an fMRI study

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J Psychiatry Neurosci 2012;37(1):28-36

Andrea M.B. Milne, PhD; Glenda M. MacQueen, MD, PhD; Geoffrey B.C. Hall, PhD

Milne, MacQueen, Hall — Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, St. Joseph’s Healthcare Hamilton, Centre for Mountain Health Services, Hamilton, Ont.; MacQueen — Department of Psychiatry,Faculty of Medicine, University of Calgary, Foothills Hospital, Calgary, Alta.


Background: Impairment of recollection memory is consistently reported in patients with major depressive disorder (MDD) and may reflect underlying functional hippocampal changes, particularly in those with extensive histories of illness. We hypothesized that relative to controls, patients with a protracted course of illness would show diminished hippocampal activation on functional magnetic resonance imaging (fMRI) during a recollection memory task.
Methods: Patients who experienced 3 or more previously treated depressive episodes were compared with age- and sex-matched controls. We acquired fMRI data while participants performed a recollection memory process dissociation task.
Results: Using bilateral regions of interest (ROIs) prescribed for the right and left hippocampal/parahippocampal complex, we observed increased activation of the right hippocampal and left parahippocampal gyrus in controls compared with patients with MDD during recollection memory trials. Within-group comparisons revealed heightened engagement of the hippocampal head (R/L) for controls during recollection trials, and greater activation of the hippocampal body/tail (R/L) during the learn-list encoding period in both the MDD and control groups. Recollection memory performance was significantly correlated with changes in blood oxygen level–dependent signal during recollection trials in the ROIs of the right hippocampus and right hippocampal head.
Limitations: This study was limited by the inclusion of patients taking antidepressant medication, raising the possibility that the reported findings were treatment effects.
Conclusion: The findings of decreased recruitment of the right hippocampal and left parahippocampal gyrus in patients with MDD suggest that these regions may be sensitive to the impact of disease burden and repeated episodes of MDD. This attenuated activation may represent stable changes in hippocampal function that occur over the course of illness in patients with MDD. The findings from within-group comparisons show that the group differences in the activation of the right hippocampal head were driven by greater engagement of this region among controls during recollection memory performance. These results also associate recollection performance impairments in patients with MDD with diminished hippocampal engagement.

Submitted Jan. 17, 2011; Revised Mar. 22, May 16, 2011; Accepted May 17, 2011.

Acknowledgments: This research was funded by a Young Investigator Award from the Ontario Mental Health Foundation awarded to G.B.C. Hall.

Competing interests: None declared for A.M.B. Milne. G.M. MacQueen declares that her institute has received grant funding from Astra Zeneca and that she has received consultancy and lecture fees from Astra Zeneca, Lilly, BMS, Pfizer, Lundbeck and Servier, lecture fees from CANMAT and both lecture fees and payment for development of educational presentations from the Canadian Psychiatric Association. G.B.C. Hall declares having received grant support from the Ontario Mental Health Foundation and student travel assistance to present at Human Brain Mapping 2008.

Contributors: G.M. MacQueen and G.B.C. Hall designed the study. A.M.B. Milne and G.B.C. Hall acquired the data. All authors analyzed the data, wrote the article and approved its publication.

DOI: 10.1503/jpn.110004

Correspondence to: Dr. G.B.C. Hall, Department of Psychiatry and Behavioural Neurosciences, McMaster University, F130 Fontbonne Bldg., St. Joseph’s Healthcare Hamilton, 50 Charlton Ave. E, Hamilton ON L8N 4A6; hallg@mcmaster.ca