title: Effects of seven-day diazepam administration on resting-state functional connectivity in healthy volunteers: a randomized, double-blind study.
abstract: BACKGROUND
  Benzodiazepines, such as diazepam, are anxiolytic-sedative drugs, used for the treatment of several different disorders. The pharmacological mechanism of action of benzodiazepines is well understood; however, it remains unclear which neural networks and systems are involved in translating these neurochemical actions into their therapeutic effects.
  
  
  OBJECTIVE
  The objective of this study was to investigate the effects of 7-day diazepam administration compared to placebo on resting-state functional connectivity in healthy adults independent of any task.
  
  
  METHODS
  Thirty-four healthy participants were randomly assigned to receive either diazepam (N = 17) or placebo (15 mg daily for 7 days) and underwent resting-state functional magnetic resonance acquisition. Model-free data analysis was performed using independent component analysis and dual regression.
  
  
  RESULTS
  Consistent with previous research, 11 resting-state networks were identified. Increased connectivity in response to diazepam administration was found in the medial visual network and middle/inferior temporal network. Diazepam did not cause any decreases in functional connectivity.
  
  
  CONCLUSIONS
  Diazepam administration increases functional connectivity in areas of emotional processing independent of any task. Diazepam also enhanced functional connectivity in the medial visual system, which is a brain region rich in GABAA receptors, and shows high binding of GABAergic drugs. These increases in functional connectivity are characteristic of CNS depressants.
authors.affiliation: University Department of Psychiatry, Warneford Hospital, Oxford, OX3 7JX, UK.
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Pflanz
authors.forename: Abbie
authors.initials: A
authors.lastname: Pringle
authors.forename: Nicola
authors.initials: N
authors.lastname: Filippini
authors.forename: Matthew
authors.initials: M
authors.lastname: Warren
authors.forename: Julia
authors.initials: J
authors.lastname: Gottwald
authors.forename: Phil J
authors.initials: PJ
authors.lastname: Cowen
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Harmer
mesh_terms: D000293:Adolescent; D000328:Adult; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects; D012146:Rest; D014795:Visual Pathways / Q000187:drug effects; D055815:Young Adult
chemical_list: D014151:Anti-Anxiety Agents; D011963:Receptors, GABA-A; D003975:Diazepam