Amygdala-Hippocampal Connectivity Changes During Acute Psychosocial Stress: Joint Effect of Early Life Stress and Oxytocin
Open accessAbstract
Previous evidence shows that acute stress changes both amygdala activity and its connectivity with a distributed brain network. Early life stress (ELS), especially emotional abuse (EA), is associated with altered reactivity to psychosocial stress in adulthood and moderates or even reverses the stress-attenuating effect of oxytocin (OXT). The neural underpinnings of the interaction between ELS and OXT remain unclear, though. Therefore, we here investigate the joint effect of ELS and OXT on transient changes in amygdala-centered functional connectivity induced by acute psychosocial stress, using a double-blind, randomized, placebo-controlled, within-subject crossover design. Psychophysiological interaction analysis in the placebo session revealed stress-induced increases in functional connectivity between amygdala and medial prefrontal cortex, posterior cingulate cortex, putamen, caudate and thalamus. Regression analysis showed that EA was positively associated with stress-induced changes in connectivity between amygdala and hippocampus. Moreover, hierarchical linear regression showed that this positive association between EA and stress-induced amygdala-hippocampal connectivity was moderated after the administration of intranasal OXT. Amygdala-hippocampal connectivity in the OXT session correlated negatively with cortisol stress responses. Our findings suggest that altered amygdala-hippocampal functional connectivity during psychosocial stress may have a crucial role in the altered sensitivity to OXT effects in individuals who have experienced EA in their childhood.
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Chronic stress causes alterations in the hippocampus including dendritic atrophy, synaptic spine loss, suppressed neurogenesis, and volumetric reductions, which impair hippocampal-dependent cognitive processes such as memory formation and emotional regulation.
“These alterations include dendritic atrophy, synaptic spine loss, suppressed neurogenesis, and volumetric reductions, which collectively impair hippocampal-dependent cognitive processes such as memory formation and emotional regulation [86,87,88,89,90].”
From Chronic Stress-Associated Depressive Disorders: The Impact of HPA Axis Dysregulation and Neuroinflammation on the Hippocampus—A Mini Review (2025) · cites this paper as [87]
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- Authors
- Fan, Y., Pestke, K., Feeser, M., Aust, S., Pruessner, J. C., Böker, H., Bajbouj, M., & Grimm, S.
- Affiliations
- Stiftung Charité (DE)
- Freie Universität Berlin (DE)
- Montreal Neurological Institute and Hospital (CA)
- University of Zurich (CH)
- Corresponding author
- Fan, Yan
- Venue
- Neuropsychopharmacology
- Published
- 2015-04-29
- Volume
- 40
- Issue
- 12
- Pages
- 2736-2744
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4864649
- OpenAlex
- W2006280192
- Cited by
- 75
- References
- 50
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 9 · 2020: 4 · 2019: 10 · 2018: 4 · 2017: 9 · 2016: 5 · 2015: 4
- FWCI
- 12.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- KOPS (University of Konstanz) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- acute psychosocial stress, early life stress, emotional abuse, oxytocin, functional connectivity, cortisol stress response, medial prefrontal cortex, posterior cingulate cortex, intranasal oxytocin
- MeSH terms
- Adolescent, Adult, Amygdala, Double-Blind Method, Hippocampus, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Neural Pathways, Oxygen, Oxytocin, Psychiatric Status Rating Scales, Retrospective Studies, Stress, Psychological, Linear Models, Cross-Over Studies, Young Adult
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