AbstractBackgroundInflammation is a possible biological mechanism underlying the association between childhood maltreatment and psychosis. Previous investigations on this regard were mainly conducted on chronic schizophrenia and lacked control for confounders. We aim to investigate the role of familial liability, childhood maltreatment and recent stress in determining cytokine abnormalities at the onset of psychosis.MethodsWe recruited 114 first-episode psychosis (FEP) patients, 57 unaffected biological siblings of FEP patients, and 251 community-based controls. Plasma cytokines (IL-1β, IL-6, TNF-α, IFN-γ, IL-4, IL-10 and TGF-β) were measured and differences across the groups analysed after adjusting for potential confounders.ResultsFEP had a higher pro- and anti-inflammatory cytokine profile (IL-1β, IL-6, TNF-α, IL-10 and TGF-β), which was not observed in unaffected siblings. Siblings presented decreased IL-1β when compared with patients and controls. Childhood maltreatment was associated with higher levels of TGF-β in both patients and siblings when compared with controls. Physical childhood abuse was associated with increased levels of TGF-β in FEP patients but with decreased levels in controls. Other childhood maltreatment subtypes or recent stressors did not affect cytokine levels in any of the groups.ConclusionsNormal or reduced cytokines in siblings represent possibly a protective factor and suggest that the identified inflammatory profile in FEP can be a real pathophysiological component of psychosis. Experience of childhood maltreatment may contribute as long-term immune priming for the TGF-β pathway, and increased levels of this cytokine in both patients and siblings exposed to childhood maltreatment point to a possible biological candidate of familial risk for psychosis.