Arribas Maite, Barnby Joseph M, Patel Rashmi, McCutcheon Robert A, Kornblum Daisy, Shetty Hitesh, Krakowski Kamil, Stahl Daniel, Koutsouleris Nikolaos, McGuire Philip, Fusar-Poli Paolo, Oliver Dominic
Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Social Computation and Cognitive Representation (SoCCR) Lab, Department of Psychology, Royal Holloway, University of London, London, UK.
Mol Psychiatry. 2025 Jan 22. doi: 10.1038/s41380-025-02896-3.
Modelling the prodrome to severe mental disorders (SMD), including unipolar mood disorders (UMD), bipolar mood disorders (BMD) and psychotic disorders (PSY), should consider both the evolution and interactions of symptoms and substance use (prodromal features) over time. Temporal network analysis can detect causal dependence between and within prodromal features by representing prodromal features as nodes, with their connections (edges) indicating the likelihood of one feature preceding the other. In SMD, node centrality could reveal insights into important prodromal features and potential intervention targets. Community analysis can identify commonly occurring feature groups to define SMD at-risk states. This retrospective (2-year) cohort study aimed to develop a global transdiagnostic SMD network of the temporal relationships between prodromal features and to examine within-group differences with sub-networks specific to UMD, BMD and PSY. Electronic health records (EHRs) from South London and Maudsley (SLaM) NHS Foundation Trust were included from 6462 individuals with SMD diagnoses (UMD:2066; BMD:740; PSY:3656). Validated natural language processing algorithms extracted the occurrence of 61 prodromal features every three months from two years to six months before SMD onset. Temporal networks of prodromal features were constructed using generalised vector autoregression panel analysis, adjusting for covariates. Edge weights (partial directed correlation coefficients, z) were reported in autocorrelative, unidirectional and bidirectional relationships. Centrality was calculated as the sum of (non-autoregressive) connections leaving (out-centrality, c) or entering (in-centrality, c) a node. The three sub-networks (UMD, BMD, PSY) were compared using permutation analysis, and community analysis was performed using Spinglass. The SMD network revealed strong autocorrelations (0.04 ≤ z ≤ 0.10), predominantly positive connections, and identified aggression (c = 0.103) and tearfulness (c = 0.134) as the most central features. Sub-networks for UMD, BMD, and PSY showed minimal differences, with 3.5% of edges differing between UMD and PSY, 0.8% between UMD and BMD, and 0.4% between BMD and PSY. Community analysis identified one positive psychotic community (delusional thinking-hallucinations-paranoia) and two behavioural communities (aggression-cannabis use-cocaine use-hostility, aggression-agitation-hostility) as the most common. This study represents the most extensive temporal network analysis conducted on the longitudinal interplay of SMD prodromal features. The findings provide further evidence to support transdiagnostic early detection services across SMD, refine assessments to detect individuals at risk and identify central features as potential intervention targets.
对严重精神障碍(SMD)的前驱期进行建模,包括单相情绪障碍(UMD)、双相情绪障碍(BMD)和精神障碍(PSY),应考虑症状和物质使用(前驱特征)随时间的演变及相互作用。时间网络分析可以通过将前驱特征表示为节点来检测前驱特征之间及内部的因果依赖性,其连接(边)表明一个特征先于另一个特征出现的可能性。在严重精神障碍中,节点中心性可以揭示重要的前驱特征和潜在干预靶点。社区分析可以识别常见的特征组来定义严重精神障碍的风险状态。这项回顾性(2年)队列研究旨在建立一个关于前驱特征之间时间关系的全球跨诊断严重精神障碍网络,并检查特定于单相情绪障碍、双相情绪障碍和精神障碍的子网络在组内的差异。纳入了来自南伦敦和莫兹利国民保健服务基金会信托(SLaM)的6462名被诊断为严重精神障碍的个体的电子健康记录(EHRs)(单相情绪障碍:2066例;双相情绪障碍:740例;精神障碍:3656例)。经过验证的自然语言处理算法从严重精神障碍发病前两年至六个月每三个月提取61种前驱特征的出现情况。使用广义向量自回归面板分析构建前驱特征的时间网络,并对协变量进行调整。报告了自相关、单向和双向关系中的边权重(偏直接相关系数,z)。中心性计算为离开(出中心性,c)或进入(入中心性,c)一个节点的(非自回归)连接的总和。使用置换分析比较三个子网络(单相情绪障碍、双相情绪障碍、精神障碍),并使用Spinglass进行社区分析。严重精神障碍网络显示出强烈的自相关性(0.04≤z≤0.10),主要是正向连接,并确定攻击行为(c = 0.103)和流泪(c = 0.134)为最核心的特征。单相情绪障碍、双相情绪障碍和精神障碍的子网络显示出极小的差异,单相情绪障碍和精神障碍之间有3.5%的边不同,单相情绪障碍和双相情绪障碍之间有0.8%的边不同,双相情绪障碍和精神障碍之间有0.4%的边不同。社区分析确定一个阳性精神病社区(妄想思维 - 幻觉 - 偏执)和两个行为社区(攻击行为 - 大麻使用 - 可卡因使用 - 敌意、攻击行为 - 激动 - 敌意)为最常见的社区。这项研究代表了对严重精神障碍前驱特征的纵向相互作用进行的最广泛的时间网络分析。研究结果为支持跨诊断的严重精神障碍早期检测服务提供了进一步的证据,完善了评估以检测有风险的个体,并确定核心特征作为潜在的干预靶点。