Schizophrenia has substantial variation in symptom severity, course of illness, and overall functioning. Earlier age of onset (AOO) is consistently associated with negative outcomes and yet the causes of this association are still unknown. We used a multiplex, extended pedigree design (total N = 771; 636 relatives from 43 multigenerational families with at least 2 relatives diagnosed with schizophrenia and 135 matched controls) to examine among the schizophrenia relatives (N = 103) the relationship between AOO and negative and positive symptom severity, cognition, and community functioning. Most importantly, we assessed whether there are shared genetic effects between AOO and negative symptoms, positive symptoms, cognition, and community functioning. As expected, earlier AOO was significantly correlated with increased severity of negative and positive symptoms and poorer cognition and community functioning among schizophrenia patients. Notably, the genetic correlation between AOO of schizophrenia and negative symptoms was significant (R_g = −1.00, p = .007). Although the genetic correlations between AOO and positive symptoms, cognition, and community functioning were estimated at maximum and in the predicted direction, they were not statistically significant. AOO of schizophrenia itself was modestly heritable, although not significant and negative symptoms, positive symptoms, and cognition were all strongly and significantly heritable. In sum, we replicated prior findings indicating that earlier AOO is associated with increased symptom severity and extended the literature by detecting shared genetic effects between AOO and negative symptoms, suggestive of pleiotropy.

中文翻译：

---

为什么发病年龄可以预测精神分裂症的临床严重程度？多重扩展谱系研究。

精神分裂症在症状严重程度、病程和整体功能方面有很大差异。早期发病年龄 (AOO) 始终与负面结果相关，但这种关联的原因仍然未知。我们使用多重扩展谱系设计（总N = 771；来自 43 个多代家庭的 636 名亲属，其中至少有 2 名亲属被诊断患有精神分裂症和 135 名匹配的对照）来检查精神分裂症亲属（N= 103) AOO 与阴性和阳性症状严重程度、认知和社区功能之间的关系。最重要的是，我们评估了 AOO 与阴性症状、阳性症状、认知和社区功能之间是否存在共同的遗传效应。正如预期的那样，早期 AOO 与精神分裂症患者的阴性和阳性症状严重程度增加以及认知和社区功能较差显着相关。值得注意的是，精神分裂症的 AOO 与阴性症状之间的遗传相关性显着（R _g = -1.00，p= .007)。尽管 AOO 与阳性症状、认知和社区功能之间的遗传相关性在最大和预测方向上被估计，但它们没有统计学意义。精神分裂症的 AOO 本身具有适度遗传性，虽然不显着，阴性症状、阳性症状和认知都具有强烈且显着的遗传性。总之，我们复制了先前的发现，表明早期 AOO 与症状严重程度增加有关，并通过检测 AOO 和阴性症状之间的共同遗传效应来扩展文献，这表明多效性。