Paradoxical effects of short-term antidepressant treatment in fMRI emotional processing models in volunteers with high neuroticism

• Published in: Psychological medicine 2014-01, Vol.44 (2), p.241-252
• Main Authors: Di Simplicio, M., Norbury, R., Reinecke, A., Harmer, C. J.
• Format: Article
• Language: English
• Subjects: Adult; Antidepressant drugs; Antidepressants; Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacology; Anxiety Disorders - chemically induced; Anxiety Disorders - drug therapy; Anxiety Disorders - psychology; Biological and medical sciences; Citalopram - administration & dosage; Citalopram - adverse effects; Citalopram - pharmacology; Discrimination (Psychology) - physiology; Double-Blind Method; Emotions; Facial expressions; Female; Happiness; Humans; Information processing; Magnetic Resonance Imaging; Male; Medical sciences; Models, Psychological; Neurobiology; Neuropharmacology; Neuroses; Neuroticism; NMR; Nuclear magnetic resonance; Original Articles; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Reaction Time; Serotonin reuptake inhibitors; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - adverse effects; Serotonin Uptake Inhibitors - pharmacology; Short term; Treatment Outcome; Volunteers; Young Adult
• ISSN: 0033-2917; 1469-8978
• DOI: 10.1017/S0033291713000731

Short-term antidepressant administration has been reported to decrease amygdala response to threat in healthy volunteers and depressed patients. Neuroticism (N) is a risk factor for depression but has also been associated with slow or incomplete remission with antidepressant drug treatment. Our aim was to investigate early selective serotonin reuptake inhibitor (SSRI) administration neural effects on implicit processing of fearful facial expressions in volunteers with high levels of N. Highly neurotic subjects received 20 mg/day citalopram versus placebo for 7 days in a double-blind, between-groups design. On the last day haemoperfusion and functional magnetic resonance imaging (fMRI) data during a gender discrimination task with fearful and happy faces were acquired. A control group of non-neurotic volunteers was also tested. High-N volunteers had reduced responses to threatening facial expressions across key neural circuits compared to low-N volunteers. SSRI treatment was found to elevate resting perfusion in the right amygdala, increase bilateral amygdalae activation to positive and negative facial expressions and increase activation to fearful versus happy facial expressions in occipital, parietal, temporal and prefrontal cortical areas. These results suggest that 7 days of SSRI administration can increase neural markers of fear reactivity in subjects at the high end of the N dimension and may be related to early increases in anxiety and agitation seen early in treatment. Such processes may be involved in the later therapeutic effects through decreased avoidance and increased learning about social 'threat' cues.