The neurosteroids allopregnanolone and dehydroepiandrosterone modulate resting-state amygdala connectivity.
The neurosteroids allopregnanolone and dehydroepiandrosterone modulate resting-state amygdala connectivity.
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DOI：
10.1002/hbm.22399
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发表时间：
2014-07
影响因子：
4.8
通讯作者：
Liberzon I
中科院分区：
文献类型：
--
作者：
Sripada RK;Welsh RC;Marx CE;Liberzon I
神经类固醇四氢孕酮和脱氢表雄酮 (DHEA) 是应激反应的组成部分，在人类和动物研究中对情绪发挥积极的调节作用。尽管这些抗抑郁和抗焦虑作用已得到充分证实，但迄今为止很少有研究检查它们的神经相关性，也没有研究神经类固醇对休息时的大规模网络的影响。为了研究神经类固醇对内在连接网络的影响，参与者服用了 400 毫克孕烯醇酮 (N = 16)、400 毫克 DHEA (N = 14) 或安慰剂 (N = 15)，并接受了 3T fMRI。使用杏仁核作为种子区域来测量静息状态的大脑连接性。与安慰剂相比，孕烯醇酮给药减少了杏仁核和 dmPFC 之间、杏仁核和楔前叶之间以及杏仁核和海马之间的连接。 DHEA 减少了杏仁核和杏仁核周围以及杏仁核和岛叶之间的连接。杏仁核与楔前叶连接的减少与自我报告的负面影响减少有关。这些结果表明，神经类固醇在静息状态下调节杏仁核的功能连接，并且可能是药物干预的目标。此外，四氢孕酮和 DHEA 可能会改变显着网络和默认网络之间的平衡，这一发现可以提供对焦虑精神病理学神经回路的深入了解。
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. Though these antidepressant and anxiolytic effects have been well established, little research to date 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. Compared to placebo, pregnenolone administration reduced connectivity between amygdala and dmPFC, between amygdala and precuneus, and between amygdala and hippocampus. DHEA reduced connectivity between amygdala and peri-amygdala 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.