title: Paradoxical effects of short-term antidepressant treatment in fMRI emotional processing models in volunteers with high neuroticism.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: MRC Brain and Cognition Sciences Unit, Cambridge, UK.
authors.forename: M
authors.initials: M
authors.lastname: Di Simplicio
authors.affiliation: University Department of Psychiatry, Warneford Hospital, Oxford, UK.
authors.forename: R
authors.initials: R
authors.lastname: Norbury
authors.affiliation: University Department of Psychiatry, Warneford Hospital, Oxford, UK.
authors.forename: A
authors.initials: A
authors.lastname: Reinecke
authors.affiliation: University Department of Psychiatry, Warneford Hospital, Oxford, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Harmer
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology*; D015283:Citalopram / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006240:Happiness; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008960:Models, Psychological; D000075384:Neuroticism; D011930:Reaction Time; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors