In people with schizophrenia (PwS), inflammation and metabolic issues significantly increase morbidity and mortality. However, our ability to understand inflammatory-metabolic mechanisms in this population has been limited to cross-sectional studies. This study involved 169 PwS and 156 non-psychiatric comparisons (NCs), aged 25-65, observed between 2012 and 2022 with 0 to 5 follow-ups post-baseline. High-sensitivity C-reactive protein (hs-CRP), a marker of inflammation, was measured via a particle-enhanced immuno-turbidimetric assay. Body mass index (BMI) was used as a proxy for metabolic function. The measurement intervals for hs-CRP and BMI ranged between 6 and 48 months. Linear mixed models (LMM) results revealed that at all time points, PwS has a higher hs-CRP (t (316) = 4.73, p < .001) and BMI (t (315) = 4.13, p < .001) than NCs; however, for BMI, this difference decreased over time (t (524) = -5.15, p < .001). To study interrelationships between hs-CRP and BMI, continuous time structural equational modeling (CTSEM) was used, accounting for uneven measurement intervals. CTSEM results showed that both hs-CRP predicted future BMI (Est. = 12.91, 95 % CI [7.70; 17.88]) and BMI predicted future hs-CRP (Est. = 1.54, 95 % CI [1.00; 2.04]), indicating a bidirectional relationship between inflammation and metabolic function. Notably, the influence of hs-CRP on future BMI was more robust than the other lagged relationship (p = .015), especially in PwS (Est. = 2.43, 95 % CI [0.39; 0.97]). Our study highlights the important role of inflammation in metabolic function and offers insights into potential interventions targeting inflammation in PwS.
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