Oliver Dominic, Davies Cathy, Zelaya Fernando, Selvaggi Pierluigi, De Micheli Andrea, Catalan Ana, Baldwin Helen, Arribas Maite, Modinos Gemma, Crossley Nicolas A, Allen Paul, Egerton Alice, Jauhar Sameer, Howes Oliver D, McGuire Philip, Fusar-Poli Paolo
Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
Front Psychiatry. 2023 Mar 8;14:1092213. doi: 10.3389/fpsyt.2023.1092213. eCollection 2023.
The impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways.
Data from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects ( = 30 healthy controls [HCs], = 80 APS, = 20 BLIPS and = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at < 0.05.
Whole-brain voxel-wise analyses and Bayesian ROI analyses were also conducted. No significant group differences were found in global [(3,143) = 1,41, = 0.24], bilateral frontal cortex [(3,143) = 1.01, = 0.39], hippocampus [(3,143) = 0.63, = 0.60] or striatum [(3,143) = 0.52, = 0.57] rCBF. Similar null findings were observed in lateralized ROIs ( > 0.05). All results were robust to addition of covariates ( > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses ( > 0.05). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses.
On this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia.
精神病临床高危（CHR-P）结构的影响取决于对结果的准确预测。与有精神病性症状衰减（APS）的个体相比，有短暂有限间歇性精神病性症状（BLIPS）的个体首次发作精神病（FEP）的风险更高。基于神经生物学参数（如静息状态、局部脑血流量（rCBF））的候选生物标志物信息对亚组分层进行补充，可能有助于优化风险评估。基于先前的证据，我们假设与APS个体相比，BLIPS个体在与多巴胺能通路相关的关键区域会表现出rCBF增加。
使用ComBat合并四项研究的数据（以考虑研究间差异），分析150名年龄和性别匹配的受试者（n = 30名健康对照[HC]，n = 80名APS，n = 20名BLIPS，n = 20名FEP）的rCBF。除了对双侧/左侧/右侧额叶皮质、海马体和纹状体进行感兴趣区域（ROI）分析外，还检查了全脑灰质（GM）rCBF。使用一般线性模型评估组间差异：（i）单独评估；（ii）以全脑GM rCBF作为协变量进行评估；（iii）以全脑GM rCBF和吸烟状态作为协变量进行评估。显著性设定为p < 0.05。
还进行了全脑体素水平分析和贝叶斯ROI分析。在全脑（F(3,143) = 1.41，p = 0.24）、双侧额叶皮质（F(3,143) = 1.01，p =
