Immune mediators form stable clusters and associate with dendritic cell functioning and cardiovascular risk in first episode psychosis

BACKGROUND: Previous research suggests a high-inflammation subtype of psychosis, based on different combinations of immune mediators. We examined clustering and longitudinal stability of circulating immune mediators in young adults with first-episode psychosis (FEP) and healthy controls. Because circulating mediators act on immune cells and chronic low-grade inflammation drives atherogenesis from young adulthood, we assessed the profiles' biological and clinical relevance using dendritic-cell transcriptomes and cardiovascular risk markers. METHODS: Discovery and replication cohorts comprised 131 patients (82 male) and 130 controls (58 male), studied at baseline and one-year follow-up. Soluble immune mediators were measured from fasting serum samples using a 38-plex Luminex assay. Given their skewed distribution, mediator levels were converted to ranks. Their clustering and longitudinal stability were investigated using Latent Profile Analysis (LPA) and randomized references. Biological significance was evaluated using clinical data, cardiovascular risk markers, and dendritic-cell phenotypes isolated from simultaneous blood samples. RESULTS: Relative mediator levels were stable over one year. LPA identified three groups with low, medium, and high mediator concentrations. Few individuals shifted groups at follow-up. FEP status was not associated with group membership, but serum low-density lipoprotein (LDL) cholesterol was associated with the "high" group in the discovery sample. Dendritic-cell transcriptomes clustered distinctly according to participants' LPA profiles. CONCLUSION: In both patients and controls, immunological mediators formed distinct profiles with high intraindividual stability. Transcriptomic analysis of dendritic cells suggests these immune profiles have physiological relevance. In the discovery sample, the immunological mediator-profile was associated with higher serum LDL cholesterol.