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Persistent depressive symptoms, HPA-axis hyperactivity, and inflammation: the role of cognitive-affective and somatic symptoms

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Iob, Eleonora, Kirschbaum, Clemens, Steptoe, Andrew·2020·Molecular Psychiatry

Abstract

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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Fig. 1 Trait-State-Occasion (TSO) model of depressive symptoms. Simplified illustration, eFigure 1 in SI file for full specification model. C = cognitive-affective score. S = somatic score. Squares represent observed variables; circles represent latent factors. The overall factor measures the longitudinal persistence of depressive symptoms. The cognitive-affective and somatic factors correspond to the two symptom-specific dimensions
Fig. 1 Trait-State-Occasion (TSO) model of depressive symptoms. Simplified illustration, eFigure 1 in SI file for full specification model. C = cognitive-affective score. S = somatic score. Squares represent observed variables; circles represent latent factors. The overall factor measures the longitudinal persistence of depressive symptoms. The cognitive-affective and somatic factors correspond to the two symptom-specific dimensionsCC BY · PubMed Central
Fig. 2 Mean scores of somatic and cognitive-affective depressive symptoms at each wave (1–8) by hair cortisol and CRP tertiles. Data source: ELSA, waves 1–8. CRP = C-reactive protein. The trajectories of the mean scores were estimated using a smoothing function with linear regression. The grey bands represent the confidence intervals of the trajectories. The data presented in this graph are for descriptive purposes only and do not relate to the trait-state-occasion models tested in the main analysis
Fig. 2 Mean scores of somatic and cognitive-affective depressive symptoms at each wave (1–8) by hair cortisol and CRP tertiles. Data source: ELSA, waves 1–8. CRP = C-reactive protein. The trajectories of the mean scores were estimated using a smoothing function with linear regression. The grey bands represent the confidence intervals of the trajectories. The data presented in this graph are for descriptive purposes only and do not relate to the trait-state-occasion models tested in the main analysisCC BY · PubMed Central
Fig. 3 Marginal effects of hair cortisol and C-reactive protein on persistent depressive symptoms: overall, cognitive-affective, and somatic factors. Data source: ELSA, waves 1–8. N: Cortisol = 4761, C-reactive protein = 5784. Unstandardised regression coefficients and confidence intervals. Estimator = WLSMV. Unadjusted model = Model 1 (no covariates). Fully adjusted model = Model 3 (adjusted for demographic, socioeconomic, lifestyle, chronic disease, and medication data)
Fig. 3 Marginal effects of hair cortisol and C-reactive protein on persistent depressive symptoms: overall, cognitive-affective, and somatic factors. Data source: ELSA, waves 1–8. N: Cortisol = 4761, C-reactive protein = 5784. Unstandardised regression coefficients and confidence intervals. Estimator = WLSMV. Unadjusted model = Model 1 (no covariates). Fully adjusted model = Model 3 (adjusted for demographic, socioeconomic, lifestyle, chronic disease, and medication data)CC BY · PubMed Central

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Research works printed but not linked: 2

  1. Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1:385–401. · DOI · Paper page
  2. NatCen Social Research. English longitudinal study of ageing (ELSA): user guide to the nurse visit datasets. Waves 2, 4, 6, 8. 2018.

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Metadata

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
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
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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