Associations between IL-6 and trajectories of depressive symptoms across the life course: Evidence from ALSPAC and UK Biobank cohorts

Amelia J Edmondson-Stait; Ella Davyson; Xueyi Shen; Mark James Adams; Golam M Khandaker; Veronique E Miron; Andrew M McIntosh; Stephen M Lawrie; Alex S F Kwong; Heather C Whalley

doi:10.1192/j.eurpsy.2025.7

Associations between IL-6 and trajectories of depressive symptoms across the life course: Evidence from ALSPAC and UK Biobank cohorts

Amelia J Edmondson-Stait^*, Ella Davyson, Xueyi Shen, Mark James Adams, Golam M Khandaker, Veronique E Miron, Andrew M McIntosh, Stephen M Lawrie, Alex S F Kwong, Heather C Whalley

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.

METHODS: We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10-28 years; N = 4,835) and UK Biobank (39-86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8).

RESULTS: Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.

CONCLUSIONS: These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.

Original language	English
Article number	e27
Pages (from-to)	1-54
Number of pages	54
Journal	European Psychiatry
Volume	68
Issue number	1
Early online date	27 Jan 2025
DOIs	https://doi.org/10.1192/j.eurpsy.2025.7
Publication status	Published - 27 Jan 2025

Keywords / Materials (for Non-textual outputs)

ALSPAC
UK Biobank
depression
inflammation
trajectories

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10.1192/j.eurpsy.2025.7

associations-between-il-6-and-trajectories-of-depressive-symptoms-across-the-life-course-evidence-from-alspac-and-uk-biobank-cohortsFinal published version, 1.32 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

1 Finished
2 Active

Identifying modifiable causes and consequences of youth mental health
Kwong, A. (Principal Investigator)
Wellcome Trust (Rcl)
1/01/24 → 31/12/28
Project: Research
Exploiting genomic approaches to identify the environmental basis of depression
McIntosh, A. (Principal Investigator)
Wellcome Trust (Rcl)
1/06/21 → 31/05/27
Project: Research
Translational Neuroscience: Training The Next Generation Of Basic Neuroscientists To Embrace Clinical Research
Ffrench-Constant, C. (Principal Investigator), Deary, I. (Co-investigator), Kind, P. (Co-investigator), Lawrie, S. (Co-investigator), Price, D. (Co-investigator), Shipston, M. (Co-investigator) & Wardlaw, J. (Co-investigator)
UK-based charities
1/09/17 → 31/08/23
Project: Research

Cite this

Edmondson-Stait, A. J., Davyson, E., Shen, X., Adams, M. J., Khandaker, G. M., Miron, V. E., McIntosh, A. M., Lawrie, S. M., Kwong, A. S. F., & Whalley, H. C. (2025). Associations between IL-6 and trajectories of depressive symptoms across the life course: Evidence from ALSPAC and UK Biobank cohorts. European Psychiatry, 68(1), 1-54. Article e27. https://doi.org/10.1192/j.eurpsy.2025.7

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title = "Associations between IL-6 and trajectories of depressive symptoms across the life course: Evidence from ALSPAC and UK Biobank cohorts",

abstract = "BACKGROUND: Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.METHODS: We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10-28 years; N = 4,835) and UK Biobank (39-86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8). RESULTS: Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.CONCLUSIONS: These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.",

keywords = "ALSPAC, UK Biobank, depression, inflammation, trajectories",

author = "Edmondson-Stait, \{Amelia J\} and Ella Davyson and Xueyi Shen and Adams, \{Mark James\} and Khandaker, \{Golam M\} and Miron, \{Veronique E\} and McIntosh, \{Andrew M\} and Lawrie, \{Stephen M\} and Kwong, \{Alex S F\} and Whalley, \{Heather C\}",

year = "2025",

month = jan,

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doi = "10.1192/j.eurpsy.2025.7",

language = "English",

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AU - Davyson, Ella

AU - Shen, Xueyi

AU - Adams, Mark James

AU - Khandaker, Golam M

AU - Miron, Veronique E

AU - McIntosh, Andrew M

AU - Lawrie, Stephen M

AU - Kwong, Alex S F

AU - Whalley, Heather C

PY - 2025/1/27

Y1 - 2025/1/27

N2 - BACKGROUND: Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.METHODS: We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10-28 years; N = 4,835) and UK Biobank (39-86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8). RESULTS: Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.CONCLUSIONS: These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.

AB - BACKGROUND: Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.METHODS: We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10-28 years; N = 4,835) and UK Biobank (39-86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8). RESULTS: Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.CONCLUSIONS: These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.

KW - ALSPAC

KW - UK Biobank

KW - depression

KW - inflammation

KW - trajectories

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M3 - Article

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SN - 0924-9338

VL - 68

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JO - European Psychiatry

JF - European Psychiatry

IS - 1

M1 - e27

ER -

Associations between IL-6 and trajectories of depressive symptoms across the life course: Evidence from ALSPAC and UK Biobank cohorts

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

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Projects

Identifying modifiable causes and consequences of youth mental health

Exploiting genomic approaches to identify the environmental basis of depression

Translational Neuroscience: Training The Next Generation Of Basic Neuroscientists To Embrace Clinical Research

Cite this