Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma?

Danese, Andrea; J Lewis, Stephanie

doi:10.1038/npp.2016.198

Cited by 393Stress Responses and CortisolChild Abuse and TraumaTryptophan and brain disorders

Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma?

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Danese, Andrea, J Lewis, Stephanie·2017·Neuropsychopharmacology

DOI 10.1038/npp.2016.198PMC PMC5143500

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Abstract

The brain and the immune system are not fully formed at birth, but rather continue to mature in response to the postnatal environment. The two-way interaction between the brain and the immune system makes it possible for childhood psychosocial stressors to affect immune system development, which in turn can affect brain development and its long-term functioning. Drawing from experimental animal models and observational human studies, we propose that the psychoneuroimmunology of early-life stress can offer an innovative framework to understand and treat psychopathology linked to childhood trauma. Early-life stress predicts later inflammation, and there are striking analogies between the neurobiological correlates of early-life stress and of inflammation. Furthermore, there are overlapping trans-diagnostic patterns of association of childhood trauma and inflammation with clinical outcomes. These findings suggest new strategies to remediate the effect of childhood trauma before the onset of clinical symptoms, such as anti-inflammatory interventions and potentiation of adaptive immunity. Similar strategies might be used to ameliorate the unfavorable treatment response described in psychiatric patients with a history of childhood trauma.

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Childhood trauma may lead to an increase in HPA axis sensitivity and a heightened response to subsequent stressors.
“childhood trauma may lead to an increase in HPA axis sensitivity and, thus, to a heightened response to subsequent stressors [28, 29].”
From The HPA Axis as Target for Depression (2024) · cites this paper as [28]
The “102 REVIEW” section says childhood trauma is associated with later hyperactive HPA-axis functioning and that childhood maltreatment predicts greater reactivity to subsequent psychosocial challenges. But the responses it describes to those challenges are inflammatory; it does not establish that increased HPA-axis sensitivity causes the heightened response. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Positive ELS/CT history is an independent risk factor for peripheral immune dysregulation and long-term, low-grade inflammatory excess (a pro-inflammatory phenotype) in adulthood.
“There is growing evidence suggesting that positive ELS/CT history is an independent risk factor for peripheral immune dysregulation and long-term, low-grade inflammatory excess (i.e., a pro-inflammatory phenotype) in adulthood (101, 164–172).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [172]
The dysfunctional neuroendocrine interface following ELS/CT may be closely correlated to immunological alterations and related long-term health consequences.
“Given this, the dysfunctional neuroendocrine interface following ELS/CT may be closely correlated to immunological alterations and related long-term health consequences (4, 36, 101, 153, 154, 172, 173)”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [172]

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Authors: Danese, A., & J Lewis, S.
Affiliations: King's College London (GB)
Corresponding author: Danese, Andrea
ORCID: Danese, Andrea
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2016-09-15
Volume: 42
Issue: 1
Pages: 99-114
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/npp.2016.198
PMC: PMC5143500
OpenAlex: W2518751885
Cited by: 393
References: 211
Citations by year: 2026: 43 · 2025: 37 · 2024: 49 · 2023: 47 · 2022: 54 · 2021: 53 · 2020: 40 · 2019: 33 · 2018: 22 · 2017: 13 · 2016: 1 · 2012: 1
FWCI: 2.36
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Research Portal (King's College London) (submittedVersion)
Funders: National Institute for Health and Care Research (ACF-2013-17-004)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: early life stress, childhood trauma, psychoneuroimmunology, neuroimmune interactions, brain development, immune system development, inflammation, psychopathology, anti-inflammatory therapy, adaptive immunity, treatment response
MeSH terms: Adult Survivors of Child Adverse Events, Animals, Mental Disorders, Brain, Humans, Inflammation, Psychoneuroimmunology, Stress, Psychological

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Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma?

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