Background and Hypothesis Symptoms that precede a first episode of psychosis (FEP) can ideally be targeted by early intervention services with the aim of preventing or delaying psychosis onset. However, these precursor symptoms emerge in combinations and sequences that do not rest fully within traditional diagnostic categories. To advance our understanding of illness trajectories preceding FEP, we aimed to investigate combinations and temporal associations among precursor symptoms. Study Design Participants were from PEPP-Montréal, a catchment-based early intervention program for FEP. Through semistructured interviews, collateral from relatives, and a review of health and social records, we retrospectively measured the presence or absence of 29 precursor symptoms, including 9 subthreshold psychotic and 20 nonpsychotic symptoms. Sequences of symptoms were derived from the timing of the first precursor symptom relative to the onset of FEP. Study Results The sample included 390 participants (68% men; age range: 14–35 years). Combinations of precursor symptoms most frequently featured depression, anxiety, and substance use. Of 256 possible pairs of initial and subsequent precursor symptoms, many had asymmetrical associations: eg, when the first symptom was suspiciousness, the incidence rate ratio (IRR) of subsequent anxiety was 3.40 (95% confidence interval [CI]: 1.79, 6.46), but when the first symptom was anxiety, the IRR of subsequent suspiciousness was 1.15 (95% CI: 0.77, 1.73). Conclusions A detailed examination of precursor symptoms reveals diverse clinical profiles that cut across diagnostic categories and evolve longitudinally prior to FEP. Their identification may contribute to risk assessments and provide insights into the mechanisms of illness progression.

中文翻译：

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首次精神病发作前先兆症状的组合和时间关联

背景和假设 理想情况下，早期干预服务可以针对首次精神病发作 (FEP) 之前的症状，以预防或延迟精神病发作。然而，这些先兆症状以组合和顺序出现，并不完全属于传统的诊断类别。为了加深我们对 FEP 之前疾病轨迹的理解，我们旨在研究先兆症状之间的组合和时间关联。研究设计参与者来自 PEPP-Montréal，这是一个基于流域的 FEP 早期干预计划。通过半结构化访谈、亲属提供的资料以及对健康和社会记录的审查，我们回顾性地测量了 29 种先兆症状的存在或不存在，其中包括 9 种阈下精神病症状和 20 种非精神病症状。症状序列源自第一个先兆症状相对于 FEP 发作的时间。研究结果 样本包括 390 名参与者（68% 为男性；年龄范围：14-35 岁）。最常见的先兆症状组合是抑郁、焦虑和药物滥用。在 256 对可能的初始和随后的前驱症状中，许多具有不对称关联：例如，当第一个症状是可疑时，随后焦虑的发生率比 (IRR) 为 3.40（95% 置信区间 [CI]：1.79，6.46） ，但当第一个症状是焦虑时，随后怀疑的 IRR 为 1.15 (95% CI: 0.77, 1.73)。结论 对先兆症状的详细检查揭示了不同的临床特征，这些特征跨越诊断类别并在 FEP 之前纵向发展。它们的识别可能有助于风险评估并提供对疾病进展机制的见解。