Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan.
Department of General Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
Psychol Med. 2023 Jul;53(10):4454-4463. doi: 10.1017/S0033291722001271. Epub 2022 Aug 16.
Individuals with schizophrenia (SCZ) and bipolar disorder (BD) display cognitive impairments, but the impairments in those with SCZ are more prominent, supported by genetic overlap between SCZ and cognitive impairments. However, it remains unclear whether cognitive performances differ between individuals at high and low genetic risks for SCZ or BD.
Using the latest Psychiatric Genomics Consortium (PGC) data, we calculated PGC3 SCZ-, PGC3 BD-, and SCZ BD polygenic risk scores (PRSs) in 173 SCZ patients, 70 unaffected first-degree relatives (FRs) and 196 healthy controls (HCs). Based on combinations of three PRS deciles, individuals in the genetic SCZ, genetic BD and low genetic risk groups were extracted. Cognitive performance was assessed by the Brief Assessment of Cognition in Schizophrenia.
SCZ-, BD-, SCZ BD-PRSs were associated with case-control status ( = 0.020-0.061), and SCZ-PRS was associated with relative-control status ( = 0.023). Furthermore, individuals in the highest decile for SCZ PRSs had elevated BD-PRSs [odds ratio (OR) = 6.33] and SCZ BD-PRSs (OR = 1.86) compared with those in the lowest decile. Of the three genetic risk groups, the low genetic risk group contained more HCs, whereas the genetic BD and SCZ groups contained more SCZ patients ( < 0.05). SCZ patients had widespread cognitive impairments, and FRs had cognitive impairments that were between those of SCZ patients and HCs ( < 0.05). Cognitive differences between HCs in the low genetic risk group and SCZ patients in the genetic BD or genetic SCZ groups were more prominent (Cohen's > -0.20) than those between HCs and SCZ patients in the no genetic risk group. Furthermore, SCZ patients in the genetic SCZ group displayed lower scores in verbal fluency and attention than those in the genetic BD group ( > -0.20).
Our findings suggest that cognitive impairments in SCZ are partially mediated through genetic loadings for SCZ but not BD.
精神分裂症（SCZ）和双相情感障碍（BD）患者存在认知障碍，但 SCZ 患者的认知障碍更为明显，这与 SCZ 和认知障碍之间存在遗传重叠有关。然而，目前尚不清楚 SCZ 或 BD 高遗传风险个体与低遗传风险个体的认知表现是否存在差异。
我们使用最新的精神疾病基因组学联盟（PGC）数据，在 173 名 SCZ 患者、70 名未受影响的一级亲属（FR）和 196 名健康对照（HC）中计算了 PGC3 SCZ、PGC3 BD 和 SCZ BD 多基因风险评分（PRS）。根据三个 PRS 十分位数的组合，提取了遗传 SCZ、遗传 BD 和低遗传风险组的个体。认知表现通过 Brief Assessment of Cognition in Schizophrenia 进行评估。
SCZ、BD、SCZ BD-PRS 与病例对照状态相关（ = 0.020-0.061），SCZ-PRS 与相对对照状态相关（ = 0.023）。此外，与最低 PRS 十分位数相比，SCZ PRS 最高十分位数的个体具有更高的 BD-PRS（比值比（OR）=6.33）和 SCZ BD-PRS（OR=1.86）。在这三个遗传风险组中，低遗传风险组包含更多的 HC，而遗传 BD 和 SCZ 组包含更多的 SCZ 患者（<0.05）。SCZ 患者存在广泛的认知障碍，而 FR 的认知障碍介于 SCZ 患者和 HC 之间（<0.05）。与无遗传风险组相比，低遗传风险组的 HC 与遗传 BD 或遗传 SCZ 组的 SCZ 患者之间的认知差异更为明显（Cohen's >-0.20）。此外，遗传 SCZ 组的 SCZ 患者在言语流畅性和注意力方面的得分低于遗传 BD 组（> -0.20）。
我们的研究结果表明，SCZ 的认知障碍部分是通过 SCZ 而不是 BD 的遗传负荷介导的。
