BACKGROUND A key clinical challenge in the management of individuals at clinical high risk for psychosis (CHR) is that it is difficult to predict their future clinical outcomes. Here, we investigated if the levels of circulating molecular lipids are related to adverse clinical outcomes in this group. METHODS Serum lipidomic analysis was performed in 263 CHR individuals and 51 healthy control subjects, who were then clinically monitored for up to 5 years. Machine learning was used to identify lipid profiles that discriminated between CHR and control subjects, and between subgroups of CHR subjects with distinct clinical outcomes. RESULTS At baseline, compared with control subjects, CHR subjects (independent of outcome) had higher levels of triacylglycerols with a low acyl carbon number and a double bond count, as well as higher levels of lipids in general. CHR subjects who subsequently developed psychosis (n = 50) were distinguished from those that did not (n = 213) on the basis of lipid profile at baseline using a model with an area under the receiver operating curve of 0.81 (95% confidence interval = 0.69-0.93). CHR subjects who became psychotic had lower levels of ether phospholipids than CHR individuals who did not (p < .01). CONCLUSIONS Collectively, these data suggest that lipidomic abnormalities predate the onset of psychosis and that blood lipidomic measures may be useful in predicting which CHR individuals are most likely to develop psychosis.

中文翻译：

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脂质代谢失调先于精神病发作

背景 管理处于临床精神病（CHR）高危个体的一个关键临床挑战是​​难以预测他们未来的临床结果。在这里，我们调查了循环分子脂质的水平是否与该组的不良临床结果相关。方法 对 263 名 CHR 个体和 51 名健康对照受试者进行血清脂质组学分析，然后对他们进行长达 5 年的临床监测。机器学习用于识别区分 CHR 和对照受试者以及具有不同临床结果的 CHR 受试者亚组的血脂谱。结果在基线时，与对照受试者相比，CHR 受试者（独立于结果）具有更高水平的具有低酰基碳数和双键计数的三酰甘油，以及一般较高水平的脂质。使用受试者操作曲线下面积为 0.81 的模型（95% 置信区间 = 0.69-0.93）。与没有精神病的 CHR 个体相比，患有精神病的 CHR 受试者的醚磷脂水平较低 (p < .01)。结论 总的来说，这些数据表明脂质组学异常早于精神病发作，并且血脂组学测量可能有助于预测哪些 CHR 个体最有可能发展为精神病。使用受试者操作曲线下面积为 0.81 的模型（95% 置信区间 = 0.69-0.93）。与没有精神病的 CHR 个体相比，患有精神病的 CHR 受试者的醚磷脂水平较低 (p < .01)。结论 总的来说，这些数据表明脂质组学异常早于精神病发作，并且血脂组学测量可能有助于预测哪些 CHR 个体最有可能发展为精神病。使用受试者操作曲线下面积为 0.81 的模型（95% 置信区间 = 0.69-0.93）。与没有精神病的 CHR 个体相比，患有精神病的 CHR 受试者的醚磷脂水平较低 (p < .01)。结论 总的来说，这些数据表明脂质组学异常早于精神病发作，并且血脂组学测量可能有助于预测哪些 CHR 个体最有可能发展为精神病。