Baseline inflammatory profile is associated with short-term antipsychotic-induced weight gain in first-episode psychosis: results from the OPTiMiSE study.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) is a major clinical concern in schizophrenia spectrum disorders. While inflammatory pathways are implicated, it is unclear whether baseline variation in these processes contributes to individual susceptibility to early weight gain. An antipsychotic quasi-naïve sample of first-episode patients treated with the same antipsychotic is ideal to evaluate this association. METHODS: Data from the OPTiMiSE trial were used, including 208 first-episode psychosis patients treated with amisulpride for four weeks. Baseline plasma inflammatory and immune-related markers were assessed. Outcomes were percentage weight change and clinically significant weight gain (≥7%). Associations were examined using correlation and multivariable regression analyses adjusted for clinical covariates, and sparse principal component analysis (PCA) to identify multivariate proteomic patterns. RESULTS: No individual biomarkers were significantly associated with weight outcomes after multiple testing correction, although several showed nominal associations. A multivariate proteomic profile (sparse PC2) was associated with greater weight gain (β = 0.50, p = 0.017). This profile was characterized by lower baseline levels of multiple markers, including TNF-α, TNF-β, IL-7, IL-12p40, IL-15, IL-16, IL-17, GM-CSF, and IFN-γ, and was more common in individuals with lower positive symptom severity. CONCLUSIONS: A lower baseline inflammatory profile, captured by a sparse principal component, was associated with greater weight gain following antipsychotic initiation. This profile was characterized by relatively lower levels of several predominantly T cell-related immune markers, suggesting that baseline immune-related variation may be associated with individual susceptibility to AIWG.