Haram Marit, Jangmo Andreas, Jaholkowski Piotr, Pasman Joëlle, Meijsen Joeri, Shorter John R, Corfield Elizabeth C, Frei Oleksandr, Reichborn-Kjennerud Ted, Buil Alfonso, Lu Yi, Werge Thomas, Sullivan Patrick, Andreassen Ole A, Tesli Martin
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Mol Psychiatry. 2025 Sep 17. doi: 10.1038/s41380-025-03243-2.
Genetic risk could be informative for identifying individuals at risk of depression with severe outcomes. With the novel approach of combined health care registries and self-report measures related to depression, the authors aimed to identify the impact of polygenic risk scores (PRS) for major depression on self report measures and a diagnosis of depression across diagnostic thresholds. The study sample comprised participants from the Norwegian Mother, Father and Child Cohort Study with linked information of depression diagnoses during 2006-2022 from health registries. Linear and logistic models were used to estimate the associations between PRS for major depression and self-reported measures related to depression (Symptom Checklist- 5, Satisfaction With Life Scale, Rosenberg Self-Esteem Scale), and a diagnosis of depression. Analyses were performed in groups stratified by level of depression severity defined by registrations in primary and specialist health care. Among the 105 623 individuals included in the study, mean (SD) age was 33.9 (5.3) and 58.5% were female. The associations between PRS for major depression and Rosenberg Self-Esteem Scale were more prominent in individuals with a history of inpatient status compared to outpatient status (β = 0.095, cluster robust 95% CI 0.029-0.162; P = 0.005) and status of primary care (β = 0.098, cluster robust 95% CI 0.035-0.160; P = 0.002). PRS for major depression were associated with a diagnosis of depression in all groups of depression severity, with highest effect sizes for more severe types (history of inpatient status: OR = 1.85, cluster robust 95% CI 1.75-1.94; P < 0.01). The results provide new knowledge of how PRS for major depression vary with depression severity.
遗传风险有助于识别有严重抑郁症后果风险的个体。通过结合医疗保健登记和与抑郁症相关的自我报告测量的新方法，作者旨在确定重度抑郁症的多基因风险评分（PRS）对自我报告测量以及跨越诊断阈值的抑郁症诊断的影响。研究样本包括来自挪威母婴队列研究的参与者，他们与2006年至2022年期间健康登记处的抑郁症诊断信息相关联。使用线性和逻辑模型来估计重度抑郁症的PRS与与抑郁症相关的自我报告测量（症状清单-5、生活满意度量表、罗森伯格自尊量表）以及抑郁症诊断之间的关联。分析在按初级和专科医疗保健登记定义的抑郁症严重程度分层的组中进行。在纳入研究的105623名个体中，平均（标准差）年龄为33.9（5.3）岁，58.5%为女性。与门诊状态相比，重度抑郁症的PRS与罗森伯格自尊量表之间的关联在有住院史的个体中更为显著（β = 0.095，聚类稳健95%置信区间0.029 - 0.162；P = 0.005）以及初级保健状态（β = 0.098，聚类稳健95%置信区间0.035 - 0.160；P = 0.002）。重度抑郁症的PRS与所有抑郁症严重程度组的抑郁症诊断相关，对于更严重类型的影响最大（住院史：OR = 1.85，聚类稳健95%置信区间1.75 - 1.94；P < 0.01）。结果提供了关于重度抑郁症的PRS如何随抑郁症严重程度变化的新知识。
