Barker Lauren F, McRae Allan F, Yuen Hok Pan, Henders Anjali K, Wallace Leanne M, Lin Tian, Phassouliotis Christina, Spark Jessica, Kerr Melissa, Byrne Enda M, Amminger G Paul, Nelson Barnaby, Wray Naomi R, McGorry Patrick D
Institute for Molecular Bioscience, The University of Queensland, Saint Lucia, Queensland, Australia.
Orygen, Parkville, Victoria, Australia.
Biol Psychiatry Glob Open Sci. 2025 Jun 3;5(5):100546. doi: 10.1016/j.bpsgos.2025.100546. eCollection 2025 Sep.
White blood cell (WBC) counts, DNA methylation, and gene expression are reported to be associated with psychosis. However, it is not known whether these associations precede the onset of psychosis or whether they are relevant for the stratification of psychosis risk in clinically high-risk individuals. The STEP (Staged Treatment in Early Psychosis) clinical trial evaluated the effectiveness of a sequential intervention strategy for preventing psychosis in a cohort of young people at ultra-high risk (UHR) of psychosis. Participants were assessed for remission of UHR status after up to 6 months of treatment with psychosocial therapy.
Cell-type proportions estimated from whole-blood DNA methylation samples ( = 91) were used to test for associations between WBC proportions at trial baseline and remission of UHR status (31 remitters, 60 nonremitters), including at which step of the trial remission occurred. DNA methylome-wide association and differential expression analyses were conducted to test for associations with remission of UHR status.
Baseline lymphocyte cell proportions (odds ratio [OR], 0.23; 95% CI, 0.07-0.62; = 9.2 × 10) and neutrophil-lymphocyte ratio (OR, 2.9; 95% CI, 1.37-7.46; = .012) were significantly associated with remission status. There were suggestive associations between specific cell types and the timing of remission during the trial; however, these did not survive correction for multiple testing. No methylation probes or differentially expressed genes were associated with remission status when cell-type proportions were included as covariates.
Our results indicate the potential importance of WBCs for further stratification of psychosis risk in UHR individuals and reinforce the importance of routine collection of WBC data for future clinical trials.
据报道，白细胞（WBC）计数、DNA甲基化和基因表达与精神病有关。然而，尚不清楚这些关联是在精神病发作之前出现，还是与临床高危个体的精神病风险分层相关。STEP（早期精神病的分阶段治疗）临床试验评估了一种序贯干预策略对预防一组超高危（UHR）精神病青年人群中精神病的有效性。参与者在接受长达6个月的心理社会治疗后，接受UHR状态缓解情况的评估。
利用从全血DNA甲基化样本（n = 91）估计的细胞类型比例，来测试试验基线时白细胞比例与UHR状态缓解（31名缓解者，60名未缓解者）之间的关联，包括缓解发生在试验的哪个阶段。进行全基因组DNA甲基化关联分析和差异表达分析，以测试与UHR状态缓解的关联。
基线淋巴细胞比例（优势比[OR]，0.23；95%置信区间，0.07 - 0.62；P = 9.2×10⁻³）和中性粒细胞与淋巴细胞比例（OR，2.9；9置信区间，1.37 - 7.46；P = 0.012）与缓解状态显著相关。特定细胞类型与试验期间缓解时间之间存在提示性关联；然而，这些关联在多重检验校正后未通过。当将细胞类型比例作为协变量纳入时，没有甲基化探针或差异表达基因与缓解状态相关。
我们的结果表明白细胞对于进一步分层UHR个体的精神病风险具有潜在重要性，并强调了在未来临床试验中常规收集白细胞数据的重要性。
