Persistent depressive symptoms, HPA-axis hyperactivity, and inflammation: the role of cognitive-affective and somatic symptoms
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Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity and inflammation are thought to be prominent in the aetiology of depression. Although meta-analyses have confirmed this relationship, there is considerable variability in the effect sizes across studies. This could be attributed to a differential role of such biological systems in somatic versus cognitive-affective depressive symptoms which remains largely unexplored. Furthermore, most longitudinal research to date has focused on transient rather than persistent depressive symptoms. In the current study, we investigated the associations of hair cortisol and plasma C-reactive protein (CRP) with the longitudinal persistence and dimensions (cognitive-affective versus somatic) of depressive symptoms over a 14-year period using Trait‐State‐Occasion (TSO) structural equation modelling. The data came from a large sample of older adults from the English Longitudinal Study of Ageing. Depressive symptoms were assessed from wave 1 (2002–03) to wave 8 (2016–17). Hair cortisol (N = 4761) and plasma CRP (N = 5784) were measured in wave 6 (2012–13). Covariates included demographic, socioeconomic, lifestyle, chronic disease, and medication data. Our results revealed that higher cortisol and CRP levels were significantly associated with persistent depressive symptoms across the study period. Notably, both biomarkers exhibited stronger relationships with somatic than with cognitive-affective symptoms. The associations with somatic symptoms were also independent of relevant confounding factors. In contrast, their associations with cognitive-affective symptoms were weak after adjustment for all covariates. These distinct associations reveal the importance of considering symptom-specific effects in future studies on pathophysiological mechanisms. Ultimately, this will have the potential to advance the search for biomarkers of depression and facilitate more targeted treatments.
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Increased levels of hair cortisol were predictive of MDD somatic symptoms.
“increased levels of hair cortisol were predictive of MDD somatic symptoms.”
From Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management (2023) · cites this paper as [200]
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- Authors
- Iob, E., Kirschbaum, C., & Steptoe, A.
- Affiliations
- University College London (GB)
- Technische Universität Dresden (DE)
- Corresponding author
- Iob, Eleonora
- Venue
- Molecular Psychiatry
- Published
- 2019-08-21
- Volume
- 25
- Issue
- 5
- Pages
- 1130-1140
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC7192852
- OpenAlex
- W2969829094
- Cited by
- 305
- References
- 68
- Citations by year
- 2026: 47 · 2025: 65 · 2024: 44 · 2023: 37 · 2022: 45 · 2021: 37 · 2020: 29 · 2019: 1
- FWCI
- 18.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- RCUK | Economic and Social Research Council (ES/P000347/1)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- persistent depressive symptoms, HPA axis hyperactivity, inflammation, hair cortisol, C-reactive protein, somatic depressive symptoms, older adults, depression pathophysiology, depression biomarkers, chronic stress
- MeSH terms
- Affect, Aged, C-Reactive Protein, Cognition, Depression, Female, Hair, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Inflammation, Longitudinal Studies, Male
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