The Neurosteroids Allopregnanolone and DHEA Modulate Neurocircuits implicated in Emotion Regulation and Posttraumatic Stress Disorder.

Abstract

The neurosteroids dehydroepiandrosterone (DHEA) and allopregnanolone are integral components of the stress response and exert positive modulatory effects on emotion in human and animal studies. Though these antidepressant and anxiolytic effects have been well established, little research to date has examined their neural correlates. In particular, brain imaging techniques have not yet been used to assess the impact of neurosteroid administration on emotion regulation neurocircuitry. In a parallel line of research, growing evidence supports that intrinsic connectivity networks involved in emotion regulation are disrupted in anxiety disorders. However, the impact of neurosteroids on these intrinsic connectivity networks is unknown. Thus, the current studies aim to describe the impact of neurosteroids on emotion regulation neurocircuits and amygdala intrinsic connectivity by measuring the effects of neurosteroid administration on the Shifted-Attention Emotional Appraisal Task and on resting-state fMRI. We demonstrate that during emotion regulation, DHEA and allopregnanolone reduce activity in regions associated with generation of negative emotion and enhance activity in regions linked to regulatory processes. Further, we demonstrate that these neurosteroids modulate amygdala intrinsic connectivity in ways that run counter to aberrations observed in posttraumatic stress disorder. Thus, our results provide initial neuroimaging evidence that DHEA and allopregnanolone may be useful as pharmacological interventions for anxiety disorders and invite further investigation into the brain basis of neurosteroid emotion regulatory effects.