The neurosteroids allopregnanolone and dehydroepiandrosterone modulate resting-state amygdala connectivity: Neurosteroids Modulate Amygdala Resting fcMRI
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The neurosteroids allopregnanolone and dehydroepiandrosterone (DHEA) are integral components of the stress response and exert positive modulatory effects on emotion in both human and animal studies. Although these antidepressant and anxiolytic effects have been well established, to date, little research has examined their neural correlates, and no research has been conducted into the effects of neurosteroids on large-scale networks at rest. To investigate the neurosteroid impact on intrinsic connectivity networks, participants were administered 400 mg of pregnenolone (N = 16), 400 mg of DHEA (N = 14), or placebo (N = 15) and underwent 3T fMRI. Resting-state brain connectivity was measured using amygdala as a seed region. When compared with placebo, pregnenolone administration reduced connectivity between amygdala and dorsal medial prefrontal cortex, between amygdala and precuneus, and between amygdala and hippocampus. DHEA reduced connectivity between amygdala and periamygdala and between amygdala and insula. Reductions in amygdala to precuneus connectivity were associated with less self-reported negative affect. These results demonstrate that neurosteroids modulate amygdala functional connectivity during resting state and may be a target for pharmacological intervention. Additionally, allopregnanolone and DHEA may shift the balance between salience network and default network, a finding that could provide insight into the neurocircuitry of anxiety psychopathology.
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A study found that allopregnanolone administration reduced connectivity between the amygdala and parietal cortex, and this reduction correlated with decreased negative affect.
“A different study showed that administration of allopregnanolone reduced connectivity between the amygdala and parietal cortex, which was also correlated with reductions in negative affect (Sripada et al., 2014).”
From Developmental sex differences in resting state functional connectivity of amygdala sub-regions (2015) · cites this paper as Sripada et al., 2014
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- Authors
- Sripada, R. K., Welsh, R. C., Marx, C. E., & Liberzon, I.
- Affiliations
- University of Michigan (US)
- Duke University (US)
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2013-12-02
- Volume
- 35
- Issue
- 7
- Pages
- 3249-3261
- ISSN
- 1065-9471 (ISSN-L)
- PMC
- PMC4739102
- OpenAlex
- W2124282497
- Cited by
- 66
- References
- 112
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 10 · 2014: 5
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Brain Mapping (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institute of Mental Health (R24 MH075999)
- Telemedicine and Advanced Technology Research Center (W81XWH-08-2-0208)
- VA Career Development Transition Award and Veterans Affairs Mid-Atlantic Mental Illness, Research, Education and Clinical Center
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- allopregnanolone, dehydroepiandrosterone, pregnenolone, neurosteroids, resting-state functional connectivity, amygdala, resting-state networks, salience network, default mode network, dorsomedial prefrontal cortex, precuneus, hippocampus, insula, negative affect, anxiety
- MeSH terms
- Adolescent, Adult, Amygdala, Dehydroepiandrosterone, Double-Blind Method, Humans, Image Processing, Computer-Assisted, Functional Laterality, Magnetic Resonance Imaging, Male, Movement, Oxygen, Pregnanolone, Rest, Statistics as Topic, Case-Control Studies, Neurotransmitter Agents, Young Adult
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