Serretti Alessandro, Baune Bernhard T
Department of Medicine and Surgery, Kore University of Enna, Enna, Italy.
Oasi Research Institute-IRCCS, Troina, Italy.
Neuropsychiatr Dis Treat. 2025 Mar 13;21:547-562. doi: 10.2147/NDT.S514514. eCollection 2025.
Schizophrenia polygenic risk scores (SCZ PRS) have emerged as important tools for modulating factors not only in schizophrenia but also in major psychiatric disorders, such as major depression (MDD) and bipolar disorder (BD). Initially developed to capture the common variant risk for SCZ, accumulating evidence highlights the transdiagnostic impact of SCZ PRS on clinical severity, treatment response, and functional outcomes. This review synthesizes recent findings on the relationship between SCZ PRS and treatment outcomes across SCZ, BD, and MDD. A higher SCZ PRS is associated with poorer treatment outcomes, including treatment resistance or non-remission to antidepressants in MDD, reduced antipsychotic response in SCZ, and diminished lithium efficacy in BD. SCZ PRS is also linked to persistent negative symptoms, cognitive impairments, and long-term illness severity in SCZ. While the effect sizes are generally modest, integration of SCZ PRS with environmental factors, multiomics, and neuroimaging may enhance predictive accuracy. Despite variability in reported associations, the overarching evidence supports a transdiagnostic influence of SCZ PRS on disease trajectories and treatment responses. As a promising component of precision psychiatry, SCZ PRS holds potential for guiding more targeted and effective interventions. Future research should focus on combining SCZ PRS with multimodal approaches to fully realize its clinical utility.
精神分裂症多基因风险评分（SCZ PRS）已成为重要工具，不仅可用于调节精神分裂症中的因素，还可用于调节重度抑郁症（MDD）和双相情感障碍（BD）等主要精神疾病中的因素。SCZ PRS最初是为了捕捉精神分裂症的常见变异风险而开发的，越来越多的证据凸显了其对临床严重程度、治疗反应和功能结局的跨诊断影响。本综述综合了近期关于SCZ PRS与精神分裂症、双相情感障碍和重度抑郁症治疗结局之间关系的研究发现。较高的SCZ PRS与较差的治疗结局相关，包括重度抑郁症对抗抑郁药的治疗抵抗或未缓解、精神分裂症中抗精神病药物反应降低以及双相情感障碍中锂盐疗效降低。SCZ PRS还与精神分裂症中持续的阴性症状、认知障碍和长期疾病严重程度有关。虽然效应大小通常较小，但将SCZ PRS与环境因素、多组学和神经影像学相结合可能会提高预测准确性。尽管报道的关联存在差异，但总体证据支持SCZ PRS对疾病轨迹和治疗反应的跨诊断影响。作为精准精神病学的一个有前景的组成部分，SCZ PRS具有指导更有针对性和有效干预措施的潜力。未来的研究应侧重于将SCZ PRS与多模式方法相结合，以充分实现其临床效用。
