Objective

Cognitive impairment is an important feature of schizophrenia (SZ) and bipolar disorder (BP) with severity across the two disorders characterized by significant heterogeneity. Youth at family risk for SZ and BP were clustered based on cognitive function and examined in terms of the clinical, genetic, and brain imaging correlates of cluster membership.

Method

One hundred sixty participants, 32 offspring of patients with SZ, 59 offspring of patients with BP and 69 offspring of healthy control parents underwent clinical and cognitive assessments, genotyping and structural MRI. K-means clustering was used to group family risk participants based on cognitive measures. Clusters were compared in terms of cortical and subcortical brain measures as well as polygenic risk scores.

Results

Participants were grouped in 3 clusters with intact, intermediate, and impaired cognitive performance. The intermediate and impaired clusters had lower total brain surface area compared with the intact cluster, with prominent localization in frontal and temporal cortices. No between-cluster differences were identified in cortical thickness and subcortical brain volumes. The impaired cluster also had poorer psychosocial functioning and worse PRS-COG compared with the other 2 clusters and with offspring of healthy control parents, while there was no significant between-cluster difference in terms of PRS-SZ and PRS-BP. PRS-COG predicted psychosocial functioning, yet this effect did not appear to be mediated by an effect of PRS-COG on brain area.

Conclusion

Stratification based on cognition may help to elucidate the biological underpinnings of cognitive heterogeneity across SZ and BP risk.

中文翻译：

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具有精神分裂症和双相情感障碍家庭风险的青少年认知亚型的遗传和结构脑相关性

客观的

认知障碍是精神分裂症 (SZ) 和双相情感障碍 (BP) 的一个重要特征，这两种疾病的严重程度具有显着的异质性。有 SZ 和 BP 家庭风险的青少年根据认知功能进行聚类，并根据聚类成员的临床、遗传和脑成像相关性进行检查。

方法

160 名参与者、SZ 患者的 32 名后代、BP 患者的 59 名后代和健康对照父母的 69 名后代接受了临床和认知评估、基因分型和结构 MRI。K 均值聚类用于根据认知测量对家庭风险参与者进行分组。在皮质和皮质下大脑测量以及多基因风险评分方面比较了簇。

结果

参与者被分为认知表现完整、中等和受损的 3 个集群。与完整的簇相比，中间簇和受损的簇具有较低的总脑表面积，在额叶和颞叶皮质中具有突出的定位。在皮质厚度和皮质下脑容量方面没有发现簇间差异。与其他 2 个集群和健康对照父母的后代相比，受损集群的心理社会功能和 PRS-COG 也更差，而 PRS-SZ 和 PRS-BP 之间没有显着的集群差异。PRS-COG 预测社会心理功能，但这种影响似乎不是由 PRS-COG 对大脑区域的影响所介导的。

结论

基于认知的分层可能有助于阐明跨 SZ 和 BP 风险的认知异质性的生物学基础。