Differences in the regulation of inflammatory pathways in adolescent- and adult-onset first-episode psychosis.

A precise description of the inflammatory response in first-episode psychosis (FEP) by age of onset does not exist. We explored baseline and 6-month follow-up differences in the pro/anti-inflammatory balance in plasma and peripheral blood mononuclear cells in adolescent-onset FEP (≤ 18 y.o., N = 27) and adult-onset FEP (≥ 25 y.o., N = 43) using non-parametric 1-category ANCOVA, with age group as an independent variable and values of pro- and anti-inflammatory markers at baseline and at follow-up as dependent variables. We used a non-parametric repeated-measures mixed-effects model to explore the baseline/6-month change in pro- and anti-inflammatory markers within adolescent- and adult-onset groups, exploring differential trajectories of change by means of the interaction of time by age-of-onset group. Levels of the nuclear transcription factor (NFκB), a master regulator of the inflammatory and oxido/nitrosative status of cells, were higher in adolescent-onset FEP both at baseline and after 6 months. During follow-up, we found further increases in levels of soluble inflammatory markers (PGE2 and NO2-) only in adolescent-onset FEP. In contrast, in adult-onset FEP, the expression of inducible NO synthase (iNOS), which is also pro-inflammatory, tended to decrease, with no further increase in other pro-inflammatory markers. Significant differences in the direction of change by age-of-onset cohort exist only for NFκB (F = 4.165, df = 2, 70.95, p = 0.019). Our results support the existence of changes in the pro/anti-inflammatory balance in FEP depending on the neurodevelopmental stage at illness onset. These results also suggest that inflammation may be a potential therapeutic target in adolescent-onset FEP.