title: Amygdala abnormalities in first-degree relatives of individuals with schizophrenia unmasked by benzodiazepine challenge.
abstract: BACKGROUND
  Impaired emotion processing in schizophrenia predicts broader social dysfunction and has been related to negative symptom severity and amygdala dysfunction. Pharmacological modulation of emotion-processing deficits and related neural abnormalities may provide useful phenotypes for pathophysiological investigation.
  
  
  OBJECTIVE
  We used an acute benzodiazepine challenge to identify and modulate potential emotion-processing abnormalities in 20 unaffected first-degree relatives of individuals with schizophrenia, compared to 25 control subjects without a family history of psychosis.
  
  
  METHODS
  An oral 1 mg dose of the short-acting anxiolytic benzodiazepine alprazolam was administered in a balanced crossover placebo-controlled double-blind design, preceding identical 3 T fMRI sessions approximately 1 week apart. Primary outcomes included fMRI activity in amygdala and related regions during two facial emotion-processing tasks: emotion identification and emotion memory.
  
  
  RESULTS
  Family members exhibited abnormally strong alprazolam-induced reduction in amygdala and hippocampus activation during emotion identification, compared to equal reduction in both groups for the emotion memory task.
  
  
  CONCLUSIONS
  GABAergic modulation with alprazolam produced differential responses in family members vs. controls, perhaps by unmasking underlying amygdalar and/or GABAergic abnormalities. Such pharmacological fMRI paradigms could prove useful for developing drugs targeting specific neural circuits to treat or prevent schizophrenia.
authors: Department of Psychiatry, University of Pennsylvania, 10th Floor Gates Bldg., 3400 Spruce St., Philadelphia, PA 19104, USA. danwolf@upenn.edu
authors: Daniel H
authors: DH
authors: Wolf
authors: Theodore D
authors: TD
authors: Satterthwaite
authors: James
authors: J
authors: Loughead
authors: Amy
authors: A
authors: Pinkham
authors: Eve
authors: E
authors: Overton
authors: Mark A
authors: MA
authors: Elliott
authors: Gersham W
authors: GW
authors: Dent
authors: Mark A
authors: MA
authors: Smith
authors: Ruben C
authors: RC
authors: Gur
authors: Raquel E
authors: RE
authors: Gur
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