The two major subtypes of bipolar disorder (BD), BD-I and BD-II, are distinguished based on the presence of manic or hypomanic episodes. Historically, BD-II was perceived as a less severe form of BD-I. Recent research has challenged this concept of a severity continuum. Studies in large samples of unrelated patients have described clinical and genetic differences between the subtypes. Besides an increased schizophrenia polygenic risk load in BD-I, these studies also observed an increased depression risk load in BD-II patients. The present study assessed whether such clinical and genetic differences are also found in BD patients from multiplex families, which exhibit reduced genetic and environmental heterogeneity. Comparing 252 BD-I and 75 BD-II patients from the Andalusian Bipolar Family (ABiF) study, the clinical course, symptoms during depressive and manic episodes, and psychiatric comorbidities were analyzed. Furthermore, polygenic risk scores (PRS) for BD, schizophrenia, and depression were assessed. BD-I patients not only suffered from more severe symptoms during manic episodes but also more frequently showed incapacity during depressive episodes. A higher BD PRS was significantly associated with suicidal ideation. Moreover, BD-I cases exhibited lower depression PRS. In line with a severity continuum from BD-II to BD-I, our results link BD-I to a more pronounced clinical presentation in both mania and depression and indicate that the polygenic risk load of BD predisposes to more severe disorder characteristics. Nevertheless, our results suggest that the genetic risk burden for depression also shapes disorder presentation and increases the likelihood of BD-II subtype development.

双相情感障碍 (BD) 的两种主要亚型 BD-I 和 BD-II 是根据是否存在躁狂或轻躁狂发作来区分的。从历史上看，BD-II 被认为是 BD-I 的一种不太严重的形式。最近的研究对这种严重程度连续统一体的概念提出了挑战。对不相关患者的大样本研究描述了亚型之间的临床和遗传差异。除了 BD-I 中精神分裂症多基因风险负荷增加外，这些研究还观察到 BD-II 患者的抑郁症风险负荷增加。本研究评估了这种临床和遗传差异是否也存在于来自多重家族的 BD 患者中，这些患者表现出减少的遗传和环境异质性。比较来自安达卢西亚双极家庭 (ABiF) 研究的 252 名 BD-I 和 75 名 BD-II 患者，临床过程，分析了抑郁和躁狂发作期间的症状以及精神合并症。此外，还评估了 BD、精神分裂症和抑郁症的多基因风险评分 (PRS)。BD-I 患者不仅在躁狂发作期间遭受更严重的症状，而且在抑郁发作期间更频繁地表现出无能为力。较高的 BD PRS 与自杀意念显着相关。此外，BD-I 病例表现出较低的抑郁症 PRS。与从 BD-II 到 BD-I 的严重程度连续体一致，我们的结果将 BD-I 与躁狂症和抑郁症中更明显的临床表现联系起来，并表明 BD 的多基因风险负荷倾向于更严重的疾病特征。尽管如此，