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- W2969553695 endingPage "109751" @default.
- W2969553695 startingPage "109751" @default.
- W2969553695 abstract "Abstract 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." @default.
- W2969553695 created "2019-08-29" @default.
- W2969553695 creator A5012855236 @default.
- W2969553695 creator A5018081371 @default.
- W2969553695 creator A5030243368 @default.
- W2969553695 creator A5043039477 @default.
- W2969553695 creator A5075629890 @default.
- W2969553695 creator A5081170951 @default.
- W2969553695 date "2020-01-01" @default.
- W2969553695 modified "2023-10-03" @default.
- W2969553695 title "Enhanced noradrenergic activity by yohimbine and differential fear conditioning in patients with major depression with and without adverse childhood experiences" @default.
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