Elsevier

Biological Psychiatry

Volume 59, Issue 9, 1 May 2006, Pages 816-820
Biological Psychiatry

Original article
Antidepressant Drug Treatment Modifies the Neural Processing of Nonconscious Threat Cues

https://doi.org/10.1016/j.biopsych.2005.10.015Get rights and content

Background

The amygdala is believed to play a key role in processing emotionally salient, threat-relevant, events that require further online processing by cortical regions. Emotional disorders such as depression and anxiety have been associated with hyperactivity of the amygdala, but it is unknown whether antidepressant treatment directly affects amygdala responses to emotionally significant information.

Methods

The current study assessed the effects of 7 days administration of the selective serotonin reuptake inhibitor (SSRI), citalopram, on amygdala responses to masked presentations of fearful and happy facial expressions in never-depressed volunteers using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging. A double-blind, between-groups design was used with volunteers randomized to 20 mg/day citalopram versus placebo.

Results

Volunteers receiving citalopram showed decreased amygdala responses to masked presentations of threat compared with those receiving placebo. Citalopram also reduced responses within the hippocampus and medial prefrontal cortex (mPFC) specifically during the fear-relevant stimuli. These neural differences were accompanied by decreased recognition of fearful facial expressions assessed after the scan. By contrast, there was no effect of citalopram on the neural or behavioral response to the happy facial expressions.

Conclusions

These results suggest a direct effect of serotonin potentiation on amygdala response to threat-relevant stimuli in humans. Such effects may be important in the therapeutic actions of antidepressants in depression and anxiety.

Section snippets

Subjects

Twenty-four right-handed healthy volunteers screened for psychiatric history of Axis 1 disorders were included in this study, and all gave informed consent. Ethical approval of this study was provided by the local ethics committee (Oxford Psychiatric Research Ethics Committee, United Kingdom). Volunteers were randomized to receive either 20 mg citalopram or placebo every day for 7 days in a double-blind design, with groups matched in terms of gender (7 female subjects per group), age (24 ± 7

Subjective Ratings

As previously found, 7 days of citalopram treatment in healthy volunteers did not affect ratings of mood, anxiety, or energy on subjective ratings scales (all comparisons with placebo p > .1). However, self-rated hostility perception and behavior on the Buss-Durkee Hostility Inventory was reduced after citalopram treatment compared with placebo [t(22) = 2.5, p = .02].

Amygdala ROI

Volunteers receiving placebo showed a significant bilateral response to fearful facial expressions presented outside of conscious

Discussion

These results indicate a direct and dissociable effect of SSRI administration on the processing of subliminal emotional stimuli within the amygdala, which is not mediated through changes in symptom remission in depression. This suggests a modulatory role for serotonin in the neural processing of threat-relevant stimuli and highlights a potential mechanism by which SSRIs may work in mood and anxiety disorders. In confirmation of previous findings, SSRI administration also reduced the recognition

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