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.
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.
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.
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.
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- Regional dissociations within the hippocampus–memory and anxiety.Neurosci Biobehav Rev. 2004; 28: 273-283
- Cognitive Therapy of Depression. Guildford Press, New York1979
- Normalization of enhanced fear recognition by acute SSRI treatment in subjects with a previous history of depression.Am J Psychiatry. 2004; 161: 166-168
- Attentional biases for negative information in induced and naturally occurring dysphoria.Behav Res Ther. 1997; 35: 911-927
- The selective serotonin reuptake inhibitor citalopram increases fear after acute treatment but reduces fear with chronic treatment.Biol Psychiatry. 2004; 55: 1171-1178
- The amygdala.Mol Psychiatry. 2001; 6: 13-34
- The role of serotonin in panic, anxiety and depression.Int Clin Psychopharmacol. 1998; 13: S1-S5
- Neuroimaging abnormalities in the amygdala in mood disorders.Ann N Y Acad Sci. 2003; 985: 420-444
- Pictures of Facial Affect. Consulting Psychologists Press, Palo Alto, CA1976
- Statistical neuroanatomical models from 305 MRI volumes.in: Proceedings of IEEE-Nuclear Science Symposium and Medical Imaging Conference. Nuclear and Plasma Sciences Society, Piscataway, NJ2001: 1813-1817
- Assessing the significance of focal activations using their spatial extent.Hum Brain Mapp. 1994; 1: 210-220
- Attenuation of the neural response to sad faces in major depression by antidepressant treatment.Arch Gen Psychiatry. 2004; 61: 877-889
- The amygdala modulates prefrontal cortex activity relative to conditioned fear.Nature. 1999; 402: 294-296
- The Neuropsychology of Anxiety. 2nd ed. Oxford University Press, Oxford, UK2000
- Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition.Am J Psychiatry. 2004; 161: 1256-1263
- Clinical utility of the selective serotonin reuptake inhibitors in the spectrum of anxiety.Biol Psychiatry. 1998; 44: 812-824
- Selective alteration of personality and social behavior by serotonergic intervention.Am J Psychiatry. 1998; 155: 373-379
- Amygdala and ventral hippocampus contribute differentially to mechanisms of fear and anxiety.Behav Neurosci. 2004; 118: 63-78
- Electrical stimulation of medial prefrontal cortex reduces conditioned fear in a temporally specific manner.Behav Neurosci. 2004; 118: 389-394
- Selective orienting of attention to masked threat faces in social anxiety.Behav Res Ther. 2002; 40: 1403-1414
- Parallel neural responses in amygdala subregions and sensory cortex during implicit fear conditioning.Neuroimage. 2001; 13: 1044-1052
- Differential extrageniculostriate and amygdala responses to presentation of emotional faces in a cortically blind field.Brain. 2001; 124: 1241-1252
- A neuromodulatory role for the human amygdala in processing emotional facial expressions.Brain. 1998; 121: 47-57
- A differential neural response in the human amygdala to fearful and happy facial expressions.Nature. 1996; 383: 812-815
- Discriminating emotional faces without primary visual cortices involves the right amygdala.Nat Neurosci. 2005; 8: 24-25
- Activation of the left amygdala to a cognitive representation of fear.Nat Neurosci. 2001; 4: 437-441
- Neurobiology of emotion perception I.Biol Psychiatry. 2003; 54: 504-514
- Differential neural responses to overt and covert presentations of facial expressions of fear and disgust.Neuroimage. 2004; 21: 1484-1496
- Neuroimaging studies of amygdala function in anxiety disorders.Ann N Y Acad Sci. 2003; 985: 389-410
- Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment.Biol Psychiatry. 2001; 50: 651-658
- A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder.Arch Gen Psychiatry. 2005; 62: 273-281
- GABAergic antagonists block the inhibitory effects of serotonin in the lateral amygdala.J Neurosci. 1999; 19: RC8
- A preferential increase in the extrastriate response to signals of danger.Neuroimage. 2003; 19: 1317-1328
- Distant influences of amygdala lesion on visual cortical activation during emotional face processing.Nat Neurosci. 2004; 7: 1271-1278
- Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge.J Neurosci. 1998; 18: 411-418
- Functional neuroimaging studies of the amygdala in depression.Semin Clin Neuropsychiatry. 2002; 7: 234-242
- Arousal dissociates amygdala and hippocampal fear responses.Neuroimage. 2001; 14: 1070-1079
- Temporal autocorrelation in univariate linear modeling of FMRI data.Neuroimage. 2001; 14: 1370-1386
Published online: February 06, 2006
Accepted: October 7, 2005
Received in revised form: September 8, 2005
Received: April 21, 2005
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.