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

J Psychiatry Neurosci. 2012 Jan;37(1):28-36. doi: 10.1503/jpn.110004.


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 parahippocampalgyrus 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use
  • Case-Control Studies
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / physiopathology*
  • Female
  • Functional Neuroimaging
  • Hippocampus / physiopathology*
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Memory / physiology
  • Middle Aged
  • Neuropsychological Tests
  • Parahippocampal Gyrus / physiopathology


  • Antidepressive Agents