Enhanced noradrenergic activity by yohimbine and differential fear conditioning in patients with major depression with and without adverse childhood experiences
Enhanced noradrenergic activity by yohimbine and differential fear conditioning in patients with major depression with and without adverse childhood experiences
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育亨宾增强去甲肾上腺素能活性和有或没有不良童年经历的重度抑郁症患者的差异性恐惧调节
DOI：
10.1016/j.pnpbp.2019.109751
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发表时间：
2020
影响因子：
5.6
通讯作者：
Katja Wingenfeld
中科院分区：
文献类型：
--
作者：
Linn K. Kuehl;Christian E. Deuter;Julian Hellmann-Regen;Michael Kaczmarczyk;Christian Otte;Katja Wingenfeld
重度抑郁症（MDD）与生物应激系统的变化有关，包括蓝斑-去甲肾上腺素能系统。累积的证据表明，中枢α 2受体上调，导致MDD患者中枢水平的去甲肾上腺素能活性降低。不良的童年经历（ACE），如身体或性虐待可能有助于这些变化。此外，去甲肾上腺素可以影响认知过程，例如学习和记忆。认知功能障碍是抑郁症的重要症状之一，本研究旨在通过对α 2受体拮抗剂育亨宾和安慰剂进行双盲给药后的差异恐惧条件反射范式，探讨α 2受体失调与抑郁症学习过程的关系。为了系统地研究ACE的作用，我们纳入了四组健康受试者和伴或不伴ACE的MDD患者（MDD−/ACE−：N= 44，MDD−/ACE+：N= 26，MDD+/ACE−：N= 24，MDD+/ACE+：N = 24;未使用抗抑郁药）。总的来说，恐惧反应后育亨宾更高的皮肤电导反应和恐惧增强惊吓反应。虽然我们没有发现显著的MDD效应，但ACE对区分两种条件刺激的能力有显著影响（CS+预测厌恶刺激，CS-预测无），这取决于药物条件。育亨宾后，CS歧视没有ACE的个人，但没有在ACE的个人。对育亨宾反应的差异可能是由ACE患者α 2受体调节异常所致。对威胁和安全信号的辨别能力受损可能会导致ACE后脆弱性增强。
Major depressive disorder (MDD) has been associated with changes in the biological stress systems, including the locus coeruleus-noradrenergic system. Accumulated evidence suggests an upregulation of central alpha2-receptors, leading to decreased noradrenergic activity on a central level in MDD patients. Adverse childhood experiences (ACE) such as physical or sexual abuse might contribute to those changes. Furthermore, noradrenaline can affect cognitive processes, e.g. learning and memory. Cognitive dysfunctions constitute an important symptom of MDD.We aimed to investigate the relationship of alpha2-receptor dysregulation with learning processes in MDD by conducting a differential fear conditioning paradigm after double-blind administration of the alpha2-receptor antagonist yohimbine versus placebo. To investigate the role of ACE systematically, we included four groups of healthy participants and MDD patients with and without ACE (MDD−/ACE−:N= 44, MDD−/ACE+:N= 26, MDD+/ACE−:N= 24, MDD+/ACE+: N = 24; without antidepressant medication).We found increased noradrenergic activity after yohimbine administration across groups as measured by alpha-amylase and blood pressure. Overall, fear responses were higher after yohimbine as indicated by skin conductance responses and fear-potentiated startle responses. While we found no significant MDD effect, ACE had significant impact on the ability to discriminate between both conditioned stimuli (CS+ predicting an aversive stimulus, CS- predicting none), depending on drug condition. After yohimbine, CS discrimination decreased in individuals without ACE, but not in individuals with ACE. Differences in the response to yohimbine might be explained by aberrant alpha2-receptor regulation in individuals with ACE. Impaired discrimination of threat and safety signals might contribute to enhanced vulnerability following ACE.
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影响因子：
4.6
作者：
Grillon, C;Morgan, CA
通讯作者：
Morgan, CA
DOI：
10.1016/0169-328x(93)90189-v
发表时间：
1993-05-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
PLOTSKY, PM;MEANEY, MJ
通讯作者：
MEANEY, MJ
影响因子：
7.4
作者：
Glover, Ebony M.;Phifer, Justine E.;Crain, Daniel F.;Norrholm, Seth D.;Davis, Michael;Bradley, Bekh;Ressler, Kerry J.;Jovanovic, Tanja
通讯作者：
Jovanovic, Tanja
影响因子：
56.9
作者：
MEANEY, MJ;AITKEN, DH;SAPOLSKY, RM
通讯作者：
SAPOLSKY, RM
盐酸育亨宾的自主神经和精神作用
DOI：
--
发表时间：
2004
期刊：
Psychopharmacologia
影响因子：
--
作者：
G. Holmberg;S. Gershon
通讯作者：
S. Gershon