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Effects of seven-day diazepam administration on resting-state functional connectivity in healthy volunteers: a randomized, double-blind study

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Abstract

Rationale

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.

Objectives

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.

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Conflicts of interest

The study has been funded by the Medical Research Council.

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Authors and Affiliations

  1. University Department of Psychiatry, Warneford Hospital, Oxford, OX3 7JX, UK

    C. Patrick Pflanz, Abbie Pringle, Nicola Filippini, Matthew Warren, Julia Gottwald, Phil J. Cowen & Catherine J. Harmer

  2. Functional Magnetic Resonance Imaging of the Brain Centre, University of Oxford, Oxford, OX3 9DU, UK

    Nicola Filippini

Authors
  1. C. Patrick Pflanz
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  2. Abbie Pringle
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  3. Nicola Filippini
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  4. Matthew Warren
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  5. Julia Gottwald
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  6. Phil J. Cowen
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  7. Catherine J. Harmer
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Corresponding author

Correspondence to Catherine J. Harmer.

Additional information

C Patrick Pflanz and Abbie Pringle contributed equally to this work.

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Pflanz, C.P., Pringle, A., Filippini, N. et al. Effects of seven-day diazepam administration on resting-state functional connectivity in healthy volunteers: a randomized, double-blind study. Psychopharmacology 232, 2139–2147 (2015). https://doi.org/10.1007/s00213-014-3844-3

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  • DOI: https://doi.org/10.1007/s00213-014-3844-3

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