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Greater amygdala activity and dorsomedial prefrontal–amygdala coupling are associated with enhanced inflammatory responses to stress
Open accessAbstract
Psychological stress is implicated in the etiology of many common chronic diseases and mental health disorders. Recent research suggests that inflammation may be a key biological mediator linking stress and health. Nevertheless, the neurocognitive pathways underlying stress-related increases in inflammatory activity are largely unknown. The present study thus examined associations between neural and inflammatory responses to an acute laboratory-based social stressor. Healthy female participants (n=31) were exposed to a brief episode of stress while they underwent an fMRI scan. Blood samples were taken before and after the stressor, and plasma was assayed for markers of inflammatory activity. Exposure to the stressor was associated with significant increases in feelings of social evaluation and rejection, and with increases in levels of inflammation. Analyses linking the neural and inflammatory data revealed that heightened neural activity in the amygdala in response to the stressor was associated with greater increases in inflammation. Functional connectivity analyses indicated that individuals who showed stronger coupling between the amygdala and the dorsomedial prefrontal cortex (DMPFC) also showed a heightened inflammatory response to the stressor. Interestingly, activity in a different set of neural regions was related to increases in feelings of social rejection. These data show that greater amygdala activity in response to a stressor, as well as tighter coupling between the amygdala and the DMPFC, are associated with greater increases in inflammatory activity. Results from this study begin to identify neural mechanisms that might link stress with increased risk for inflammation-related disorders such as cardiovascular disease and depression.
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“Importantly, these increases in cytokine activity and amygdala responsivity to stress exposure are also associated with greater social disconnection and depressed mood (Muscatell et al, 2015), as well as cognitive disturbance and increased fatigue (Harrison et al, 2009b).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Muscatell et al, 2015
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“This heightened amygdala response to stress is associated with increased IL-6 production (Inagaki et al, 2012;Muscatell et al, 2015).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Muscatell et al, 2015
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“Finally, exposure to a laboratory stressor that increases IL-6 concentrations peripherally was associated with increased functional connectivity between the dorsomedial PFC and the amygdala in a manner that was correlated with IL-6 (Muscatell et al, 2015).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Muscatell et al, 2015
In the citing paper
“peripheral levels of IL-6 were associated with increased activation of the amygdala and increased functional connectivity between the amygdala and dorsomedial prefrontal cortex (dmPFC) in response to negative social feedback (Muscatell et al., 2015).”
From The interplay between stress, inflammation, and emotional attention: relevance for depression (2019) · cites this paper as Muscatell et al., 2015
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Metadata
- Authors
- Muscatell, K. A., Dedovic, K., Slavich, G. M., Jarcho, M. R., Breen, E. C., Bower, J. E., Irwin, M. R., & Eisenberger, N. I.
- Affiliations
- University of California, Los Angeles (US)
- Loras College (US)
- Corresponding author
- Eisenberger, Naomi I.
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 43
- Pages
- 46-53
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC4368432
- OpenAlex
- W1968731032
- Cited by
- 240
- References
- 56
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 12 · 2023: 12 · 2022: 45 · 2021: 19 · 2020: 21 · 2019: 22 · 2018: 18 · 2017: 20 · 2016: 18 · 2015: 9
- FWCI
- 8.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award (NIE)
- UCLA Cousins Center for Psychoneuroimmunology Seed Grant (NIE)
- UCLA Clinical & Translational Science Institute (CTSI) Seed Grant (NIE)
- NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI (UL1TR000124)
- NIA/NIH (AG028748)
- Canadian Institutes of Health Research Post-Doctoral Research Fellowship (KD)
- National Science Foundation Graduate Research Fellowship (KAM)
- NIH Pre-Doctoral Institutional Training Grant (MH015750)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- psychological stress, inflammation, amygdala, dorsomedial prefrontal cortex, social stress, social rejection, social evaluation, plasma inflammatory markers, cardiovascular disease, depression
- MeSH terms
- Adolescent, Amygdala, Emotions, Female, Humans, Inflammation, Magnetic Resonance Imaging, Neural Pathways, Stress, Psychological, Tumor Necrosis Factor-alpha, Biomarkers, Interleukin-6, Prefrontal Cortex, Young Adult
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