Early-life inflammatory markers and subsequent psychotic and depressive episodes between 10 to 28 years of age

Edmondson-Stait, Amelia J.; Shen, Xueyi; Adams, Mark; Barbu, Miruna C.; Jones, Hannah; Miron, Véronique E.; Allardyce, Judith; Boardman, James P.; Lawrie, Stephen M.; McIntosh, Andrew M.; Khandaker, Golam; Kwong, Alex; Whalley, Heather

doi:10.1016/j.bbih.2022.100528

Cited by 7 publications

(5 citation statements)

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“…Previous studies have shown higher IL-6 is associated with depressive symptoms in both a cross-sectional and cross-lag relationship 3, 7, 13, 16, 29, 56 . The study presented in chapter 4 showed IL- 6 was associated with the total number of depressive episodes, representing increased burden of depression in ALSPAC 8 . Cross-sectionally, an inflammatory subgroup of depression has been shown to associate with depression severity 10 .…”

Section: Discussionmentioning

confidence: 97%

“…Additionally, we assessed the differences in markers of socioeconomic status used in ALSPAC and UK Biobank. To ensure consistency with our previous ALSPAC study we used maternal education as a marker of socioeconomic status 8 . However, Townsend deprivation index was used as a marker of socioeconomic status in UK Biobank as no measure of maternal education was available.…”

Section: Methodsmentioning

confidence: 99%

“…Neuroimaging and post-mortem brain studies have shown increased markers of neuroinflammation in individuals with depression compared to controls [4][5][6] . Longitudinal studies have shown increased blood IL-6 levels in childhood associate with depressive and psychotic symptoms in early adulthood [7][8][9] . Increased inflammatory markers have been also shown to associate with worse depressive symptom severity, including in a Mendelian randomisation (MR) study that found a potential causal association of IL-6 with suicidal thoughts 10,11 .…”

Section: Introductionmentioning

confidence: 99%

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

Edmondson-Stait,

Davyson,

Shen

et al. 2024

Preprint

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Peripheral inflammatory markers, including serum IL-6, are associated with depression, but less is known about how these markers associate with depression at different stages of the life-course. We examined associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10-28y;N=4,835) and UK Biobank (39-86y;N=39,613) using multi-level growth curve modelling. Models were adjusted for sex, BMI and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire (SMFQ) in ALSPAC (max timepoints=11) and the Patient Health Questionnaire-2 (PHQ-2) in UK Biobank (max timepoints=8). Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 (ALSPAC, age 16y)). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 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. 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.

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Section: Discussionmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Edmondson-Stait,

Davyson,

Shen

et al. 2024

Preprint

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“…These factors, together with all other significant factors found in this study (cognition, mobility, perceived stress, interpersonal activities, and self-care), only explained 50.8% of the association between tuberculosis and PEs. This association could possibly be further explained by other important factors such as systemic inflammation triggered by the bacterial infection [ 47 ] or anti-tuberculosis medication [ 30 ]. Future studies may seek to identify additional factors.…”

Section: Discussionmentioning

confidence: 99%

Association between tuberculosis and psychotic experiences: Mediating factors and implications for patient care in low- and middle-income countries

Monistrol-Mula,

Felez-Nobrega,

et al. 2024

J Glob Health

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Background Tuberculosis may play a role in the aetiology of psychosis. However, little is known about the association between tuberculosis and psychotic experiences (PEs) or the mediating factors of this association. Methods We analysed cross-sectional data from 48 low- and middle-income countries of the World Health Survey (WHS). Tuberculosis assessment was based on past 12-month symptoms of active tuberculosis. We assessed four types of past 12-month PEs with the Composite International Diagnostic Interview. We performed multivariable multinomial logistic regression and mediation analysis. Results We analysed data on 224 842 individuals aged ≥18 years (mean age = 38.3 years, standard deviation = 16.0; 50.7% women). Tuberculosis was associated with 1.84 (95% confidence interval (CI) = 1.41–2.40), 2.18 (95%CI = 1.58–3.03), and 3.79 (95%CI = 2.88–4.98) times higher odds for 1, 2, and ≥3 PEs, respectively. The mediation analysis showed that the association between tuberculosis and at least one PE is mainly explained by anxiety (31.5%), sleep/energy (27.8%), and pain/discomfort (23.5%). Conclusions Tuberculosis was associated with increased odds of PEs. Factors such as affect, sleep, and pain should be considered in tuberculosis patients to target those who might be particularly vulnerable to PEs, and consequently, to psychotic disorders and other adverse effects of PE.

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“…People with depression exhibit increased concentrations of biomarkers of inflammation, including cytokines such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) [ 11 ]. Early-life increases in the inflammatory biomarker IL-6 can predict the total number of depressive episodes later in life, even when accounting for gender, body mass index, and socioeconomic status [ 12 ]. People living with HIV exhibit chronic inflammation, evidenced by increased cytokine release and monocyte activation and alterations in neurometabolites such as choline (Cho) and myo-inositol (mI), which persist despite antiretroviral therapy (ART) [ 13 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

Multi-modal analysis of inflammation as a potential mediator of depressive symptoms in young people with HIV: The GOLD depression study

Mudra Rakshasa-Loots,

Naidoo,

Hamana

et al. 2024

PLoS ONE

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People living with HIV are at three times greater risk for depressive symptoms. Inflammation is a notable predictor of depression, and people with HIV exhibit chronic inflammation despite antiretroviral therapy. We hypothesised that inflammatory biomarkers may mediate the association between HIV status and depressive symptoms. Participants (N = 60, 53% girls, median [interquartile range (IQR)] age 15.5 [15.0, 16.0] years, 70% living with HIV, of whom 90.5% were virally-suppressed) completed the nine-item Patient Health Questionnaire (PHQ-9). We measured choline and myo-inositol in basal ganglia, midfrontal gray matter, and peritrigonal white matter using magnetic resonance spectroscopy, and 16 inflammatory proteins in blood serum using ELISA and Luminex™ multiplex immunoassays. Using structural equation mediation modelling, we calculated standardised indirect effect estimates with 95% confidence intervals. Median [IQR] total PHQ-9 score was 3 [0, 7]. HIV status was significantly associated with total PHQ-9 score (B = 3.32, p = 0.022). Participants with HIV showed a higher choline-to-creatine ratio in the basal ganglia than those without HIV (β = 0.86, pFDR = 0.035). In blood serum, participants with HIV showed higher monocyte chemoattractant protein-1 (MCP-1, β = 0.59, pFDR = 0.040), higher chitinase-3 like-1 (YKL-40, β = 0.73, pFDR = 0.032), and lower interleukin-1beta (IL-1β, β = -0.67, pFDR = 0.047) than those without HIV. There were no significant associations of any biomarkers with total PHQ-9 score. None of the indirect effects were significant, mediating <13.1% of the association. Findings remained consistent when accounting for age, gender, and time between neuroimaging and PHQ-9 administration. Using a robust analytical approach in a community-based sample, we have shown that participants living with HIV reported greater depressive symptoms than those without HIV, but we did not find that neuroimaging and blood biomarkers of inflammation significantly mediated this association. Further studies with participants experiencing severe depression may help to elucidate the links between HIV, inflammation, and depression.

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Early-life inflammatory markers and subsequent psychotic and depressive episodes between 10 to 28 years of age

Cited by 7 publications

References 58 publications

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

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

Association between tuberculosis and psychotic experiences: Mediating factors and implications for patient care in low- and middle-income countries

Multi-modal analysis of inflammation as a potential mediator of depressive symptoms in young people with HIV: The GOLD depression study

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