Effects of antidepressant treatment on neural correlates of emotional and neutral declarative verbal memory in depression

Abstract

Background: Multiple studies have documented deficits in verbal declarative memory function in depression that improve with resolution of symptoms; imaging studies show deficits in anterior cingulate function in depression, a brain area that mediates memory. No studies to date have examined neural correlates of emotionally valenced declarative memory using affectively negative (sad) verbal material that is clinically relevant to understanding depression. Also no studies have examined the effects of treatment on neural correlates of verbal declarative memory. The purpose of this study was to examine the effects of treatment with antidepressants on verbal declarative memory in patients with depression.

Methods: Subjects with (N=18) and without (N=9) mid-life major depression underwent positron emission tomography (PET) imaging during verbal declarative memory tasks with both neutral paragraph encoding compared to a control condition, and emotional (sad) word pair retrieval compared to a control condition. Imaging was repeated in 13 subjects with depression after treatment with antidepressants.

Results: Patients with untreated depression had a failure of anterior cingulate activation relative to controls during retrieval of emotional word pairs. Antidepressant treatment resulted in increased anterior cingulate function compared to the untreated baseline for both neutral and emotional declarative memory.

Limitations: Limitations include a small sample size and variety of antidepressants used.

Conclusions: These results are consistent with alterations in anterior cingulate function that are reversible with treatment in patients with depression. These findings may have implications for understanding the mechanism of action of antidepressants in the treatment of depression.

Fig. 1

Study design of PET imaging of neural correlates of neutral and emotional declarative memory. Arrows refer to individual PET image acquisitions. There were a total of 8 image acquisitions. Learning of all word pairs took place before or in between scan acquisitions. The first two scans were acquired during retrieval of neutral shallowly encoded word pairs (NEU SHALL), followed by two during retrieval of deeply encoded neutral word pairs (NEU DEEP), two during retrieval of deeply encoded emotional word pairs (EMOT DEEP), and two during deep encoding of a neutral paragraph (NEU PAR).

Fig. 2

Statistical parametric map overlaid on an MRI template of areas of greater increases in blood flow during retrieval of emotional (e.g. “sad–devil”) compared to neutral word pairs in healthy subjects (N=9) compared to patients with depression (N=18). Areas of greater increases in blood flow included the anterior cingulate (p<0.005).

Fig. 3

Statistical parametric map overlaid on an MRI template of areas of greater increases in blood flow during a emotional memory task following treatment with fluoxetine compared to the baseline untreated state in patients with depression (N=13). Areas of greater increases in blood flow (in yellow) included the anterior cingulate (p<0.005). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)