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What is the relation between major depressive disorder and amygdala reactivity?

Hao, Y.; Xu, C.; Kweon, H.; Farah, M.

2026-01-01 psychiatry and clinical psychology
10.64898/2025.12.24.25342967 medRxiv
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The present study focuses on the role of amygdala reactivity to negative facial expressions in major depressive disorder (MDD). A number of studies have found amygdala hyperreactivity in depressed patients compared with control subjects. This has been interpreted in terms of a negative depressive bias in attention and memory, given the amygdalas role in attending to and remembering negatively valenced stimuli. However, failure to find amygdala hyperreactivity in depression is not uncommon, and a recent failure to replicate the effect with an extremely well-powered analysis of UK Biobank data led many to conclude that amygdala reactivity plays no role in depression. In the present study, the same UK Biobank sample is used to evaluate an alternative hypothesis about the relation between MDD and amygdala reactivity, namely that people who are vulnerable to MDD, whether or not they are currently depressed, will show elevated amygdala activity. Depression history was used as a proxy for vulnerability and regression analyses assessed the strength of the relation between three MDD history measures and amygdala reactivity. Two of three assessments of depression history showed highly significant relations with amygdala reactivity, the third showing a combination of significant and nonsignificant trends depending on the analysis.

Published in Journal of Affective Disorders (predicted rank #1) · training set

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