Trajectories of Inflammation in Youth and Risk of Mental and Cardiometabolic Disorders in Adulthood

Abstract

Importance: Research suggests that low-grade, nonresolving inflammation may predate adult mental and physical illness. However, evidence to date is largely cross-sectional or focuses on single disorder outcomes.

Objectives: To examine trajectories of inflammation as measured by C-reactive protein (CRP) levels in a large sample of children and adolescents, and to explore associations between different identified trajectories and mental and related cardiometabolic health outcomes in early adulthood.

Design, setting, and participants: In a longitudinal cohort study using data from the large UK-based Avon Longitudinal Study of Parents and Children (ALSPAC), latent class growth analysis (LCGA) was used to explore different trajectories of inflammation, with logistic regression exploring association with mental and physical health outcomes. Participants with measurable CRP data and associated mental and cardiometabolic health outcomes recorded were included in the analysis. Data analysis was performed from May 1, 2023, to March 30, 2024.

Exposures: Inflammation was assessed via CRP levels at ages 9, 15, and 17 years. LCGA was used to identify different trajectories of inflammation.

Main outcomes and measures: Outcomes assessed at age 24 years included psychotic disorders, depressive disorders, anxiety disorders, hypomania, and, as a measure of insulin resistance, Homeostasis Model Assessment (HOMA2) score.

Results: A total of 6556 participants (3303 [50.4%] female) were included. Three classes of inflammation were identified: persistently low CRP levels (reference class, n = 6109); persistently raised CRP levels, peaking at age 9 years (early peak, n = 197); and persistently raised CRP levels, peaking at age 17 years (late peak, n = 250). Participants in the early peak group were associated with a higher risk of psychotic disorder (odds ratio [OR], 4.60; 95% CI, 1.81-11.70; P = .008), a higher risk of severe depression (OR, 4.37; 95% CI, 1.64-11.63; P = .02), and higher HOMA2 scores (β = 0.05; 95% CI, 0.01-0.62, P = .04) compared with participants with persistently low CRP. The late peak group was not associated with any outcomes at age 24 years.

Conclusions and relevance: Low-grade systemic inflammation peaking in midchildhood was associated with specific mental and cardiometabolic disorders in young adulthood. These findings suggest that low-grade persistent inflammation in early life may be an important shared common factor for mental-physical comorbidity and so could be relevant to future efforts of patient stratification and risk profiling.

Figure.. Latent Class Growth Analysis–Derived C-Reactive Protein (CRP) Level Trajectories

CRP level trajectories form across childhood and adolescence. This graph depicts the z scores from the Z-transformed CRP values for each trajectory at each time point from the 3-class model, which had the best model fit. Class 1 represents the largest reference group with the least divergence from the mean with a stable average across time points. Class 2 represents the early peak group, whose CRP levels were persistently higher than those of the reference group but peaked early at age 9 years. Class 3 represents the late peak group, whose CRP levels were persistently higher than those of the reference group but peaked later at age 17 years.