Altered hippocampal function with preserved cognitive performance in treatment-naive major depressive disorder.

The hippocampus is implicated in the pathophysiology of major depressive disorder (MDD), with evidence that morphological changes occur with disease progression. It was hypothesized that treatment-naive patients with depression would show performance deficits in hippocampus-dependent memory trials, with concurrent hippocampal activation deficits on functional magnetic resonance imaging, compared with control participants. Thirteen treatment-naive patients with MDD and 13 control participants completed a hippocampus-dependent memory functional magnetic resonance imaging process-dissociation task. On behavioural measures of habit memory and guessing, there were no significant differences between groups. Functional magnetic resonance imaging analysis indicated that compared with the control group, the MDD group showed increased activation in the parahippocampal gyrus and hippocampus on habit memory and nonitem trials. These alterations in hippocampal functioning with preserved cognitive performance on a test of hippocampus-dependent memory in MDD may be indicative of a compensatory mechanism.

An fMRI study of reward circuitry in patients with minimal or extensive history of major depression.

Functional abnormalities in regions associated with reward processing are apparent in people with depression, but the extent to which disease burden impacts on the processing of reward is unknown. This research examined the neural correlates of reward processing in patients with major depressive disorder and varying degrees of past illness burden. Twenty-nine depressed patients and twenty-five healthy subjects with no lifetime history of psychiatric illness completed the study. Subsets of fourteen patients were presenting for first lifetime treatment of a depressive episode, and fifteen patients had at least three treated episodes of depression. We used functional magnetic resonance imaging to study blood oxygen level-dependent signals during the performance of a contingency reversal reward paradigm. The results identified group differences in the response to punishers bilaterally in the orbitofrontal and medial prefrontal regions. In addition, areas such as the nucleus accumbens, anterior cingulate and ventral prefrontal cortices were activated greatest by controls during reward processing, less by patients early in the course of illness and least by patients with highly recurrent illness-suggesting that these areas are sensitive to the impact of disease burden and repeated episodes of depression. Reward processing in people with depression may be associated with diminished signaling of incentive salience, a reduction in the formation of reward-related associations and heightened sensitivities for negatively valenced stimuli, all of which could contribute to symptoms of depression.

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

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.