The moderating role of lifetime social engagement on the relationship between C-reactive protein and negative symptoms among young adults at clinical high risk for psychosis.

One potential mechanism that may contribute to the development of negative symptoms is inflammation. Inflammatory markers have been shown to be elevated in Clinical High Risk for Psychosis (CHR-P) individuals and may be associated with negative symptoms. Social engagement in early developmental periods may decrease stress and interact with downstream processes, such as inflammation. Herein, we hypothesized that lifetime social engagement may moderate the association between C-Reactive Protein (CRP), a marker of inflammation, and negative symptoms in CHR-P young adults and healthy controls (HC) such that this association would be significant only among those at CHR-P with lower, but not greater, social engagement. 48 individuals (30 CHR-P and 18 healthy controls; HC) from the North American Prodromal Longitudinal Study (NAPLS)-2 cohort, were included in this analysis. Negative symptoms were assessed using the Scale of Psychosis-risk Symptoms (SOPS), and social engagement was calculated using the Life Events Stress scale. A generalized linear model with robust estimation was used to test the association of CRP, diagnosis, and social engagement (and their interactions) with negative symptoms, adjusting for age, sex, ethnicity, childhood poverty, and depressive symptoms. Simple slopes for the association between negative symptoms and CRP moderated by social engagement were calculated and stratified by CHR-P groups. CHR-P subjects had significantly greater negative symptoms than HC subjects (p < 0.001), though there was no significant difference in CRP values or social engagement. In the generalized linear models of the whole sample, negative symptoms were significantly associated with CRP (β = 1.34, SE = 1.35, 95 %CI -1.31-4.00, p = 0.035) as well as CHR-P (β = 8.16, SE = 1.71, 95 %CI 4.80-11.52, p < 0.001). There was a significant association between negative symptoms and the interaction of CRP-by-social engagement (β = 0.37, SE = 0.56, 95 %CI -0.74-1.47, p = 0.008), but not the interaction of CRP-by-CHR-P or CHR-P-by-social engagement (both p > 0.25). There was a significant association between negative symptoms and the three-way interaction of CRP-by-CHR-P-by-social engagement (β = -5.27, SE = 1.70, 95 %CI -8.60 to -1.94, p = 0.002). Based on the simple slopes analysis, we observed a significant positive association between negative symptoms and CRP amongst the CHR-P group at low (-1SD; p = 0.02) and mean levels of social engagement (p = 0.04) but not in the individuals with high social engagement (+1SD; p = 0.34) or in any of the HC social engagement levels (p all > 0.2). In this sample of CHR-P individuals, there was an association between negative symptoms and the interaction between diagnosis, CRP, and social engagement, adjusting for relevant clinical and demographic covariates. Greater engagement in social activities appeared to buffer the relationship between inflammation, as measured by CRP, and negative symptoms. The data herein suggests that these associations in young individuals at risk for psychosis may be buffered by social engagement, perhaps by limiting stress and its downstream impacts on the brain and behavior.