Goldsmith David R, Yuan Qingyue E, Addington Jean, Bearden Carrie E, Cadenhead Kristin S, Cannon Tyrone D, Carrión Ricardo E, Keshavan Matcheri, Mathalon Daniel H, Perkins Diana O, Stone William S, Tsuang Ming T, Woods Scott W, Walker Elaine F, Ku Benson S
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Brain Behav Immun. 2025 Jul 27;129:890-897. doi: 10.1016/j.bbi.2025.07.023.
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.
一种可能导致阴性症状出现的潜在机制是炎症。炎症标志物在临床高危精神病个体（CHR-P）中已被证明有所升高，并且可能与阴性症状相关。早期发育阶段的社交参与可能会减轻压力，并与诸如炎症等下游过程相互作用。在此，我们假设一生的社交参与可能会调节炎症标志物C反应蛋白（CRP）与CHR-P青年及健康对照（HC）中阴性症状之间的关联，使得这种关联仅在社交参与较低而非较高的CHR-P个体中显著。本分析纳入了北美前驱期纵向研究（NAPLS）-2队列中的48名个体（30名CHR-P个体和18名健康对照；HC）。使用精神病风险症状量表（SOPS）评估阴性症状，并使用生活事件压力量表计算社交参与度。采用具有稳健估计的广义线性模型来检验CRP、诊断和社交参与（及其相互作用）与阴性症状之间的关联，并对年龄、性别、种族、童年贫困和抑郁症状进行了校正。计算了由社交参与调节的阴性症状与CRP之间关联的简单斜率，并按CHR-P组进行分层。CHR-P受试者的阴性症状显著多于HC受试者（p < 0.001），尽管CRP值或社交参与度没有显著差异。在整个样本的广义线性模型中，阴性症状与CRP（β = 1.34，SE = 1.35，95%CI -1.31 - 4.00，p = 0.035）以及CHR-P（β = 8.16，SE = 1.71，95%CI 4.80 - 11.52，p < 0.001）显著相关。阴性症状与CRP×社交参与的相互作用之间存在显著关联（β = 0.37，SE = 0.56，95%CI -0.74 - 1.47，p = 0.008），但与CRP×CHR-P或CHR-P×社交参与的相互作用均无显著关联（p均> 0.25）。阴性症状与CRP×CHR-P×社交参与的三向相互作用之间存在显著关联（β = -5.27，SE = 1.70，95%CI -8.60至-1.94，p = 0.002）。基于简单斜率分析，我们观察到在社交参与度低（-1SD；p = 0.02）和平均水平（p = 0.04）的CHR-P组中，阴性症状与CRP之间存在显著正相关，但在社交参与度高（+1SD；p = 0.34）的个体或任何HC社交参与度水平中均无此关联（p均> 0.2）。在这个CHR-P个体样本中，校正相关临床和人口统计学协变量后，阴性症状与诊断、CRP和社交参与之间的相互作用存在关联。更多地参与社交活动似乎缓冲了以CRP衡量的炎症与阴性症状之间的关系。本文数据表明，精神病风险青年个体中的这些关联可能会被社交参与缓冲，或许是通过限制压力及其对大脑和行为的下游影响。
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