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Progesterone selectively increases amygdala reactivity in women

Abstract

The acute neural effects of progesterone are mediated by its neuroactive metabolites allopregnanolone and pregnanolone. These neurosteroids potentiate the inhibitory actions of γ-aminobutyric acid (GABA). Progesterone is known to produce anxiolytic effects in animals, but recent animal studies suggest that pregnanolone increases anxiety after a period of low allopregnanolone concentration. This effect is potentially mediated by the amygdala and related to the negative mood symptoms in humans that are observed during increased allopregnanolone levels. Therefore, we investigated with functional magnetic resonance imaging (MRI) whether a single progesterone administration to healthy young women in their follicular phase modulates the amygdala response to salient, biologically relevant stimuli. The progesterone administration increased the plasma concentrations of progesterone and allopregnanolone to levels that are reached during the luteal phase and early pregnancy. The imaging results show that progesterone selectively increased amygdala reactivity. Furthermore, functional connectivity analyses indicate that progesterone modulated functional coupling of the amygdala with distant brain regions. These results reveal a neural mechanism by which progesterone may mediate adverse effects on anxiety and mood.

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Acknowledgements

This work was supported by an internal grant from the Radboud University Nijmegen Medical Center, an EU structural fund objective 1 program, and the Swedish Research Council project 11198.

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Correspondence to G A van Wingen.

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van Wingen, G., van Broekhoven, F., Verkes, R. et al. Progesterone selectively increases amygdala reactivity in women. Mol Psychiatry 13, 325–333 (2008). https://doi.org/10.1038/sj.mp.4002030

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  • DOI: https://doi.org/10.1038/sj.mp.4002030

Keywords

  • fMRI
  • progesterone
  • allopregnanolone
  • amygdala
  • emotion
  • disinhibition

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