Deng Mengjie, Liu Zhening, Zhang Wen, Wu Zhipeng, Cao Hengyi, Yang Jie, Palaniyappan Lena
Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
National Clinical Research Center for Mental Disorders, Changsha, Hunan, China.
Schizophrenia (Heidelb). 2022 Jun 2;8(1):54. doi: 10.1038/s41537-022-00260-w.
Working memory (WM) deficit in schizophrenia is thought to arise from a widespread neural inefficiency. However, we do not know if this deficit results from the illness-related genetic risk and influence the symptom burden in various domains, especially in patients who have an early onset illness. We used graph theory to examine the topology of the functional connectome in 99 subjects (27 early-onset schizophrenia (EOS), 24 asymptomatic siblings, and 48 healthy subjects) during an n-back task, and calculated their polygenic risk score (PRS) for susceptibility to schizophrenia. Linear regression analysis was used to test associations of the PRS, clinical symptoms, altered connectomic properties, and WM accuracy in EOS. Indices of small-worldness and segregation were elevated in EOS during the WM task compared with the other two groups; these connectomic aberrations correlated with increased PRS and negative symptoms. In patients with higher polygenic risk, WM performance was lower only when both the connectomic aberrations and the burden of negative symptoms were higher. Negative symptoms had a stronger moderating role in this relationship. Our findings suggest that the aberrant connectomic topology is a feature of WM task performance in schizophrenia; this relates to higher polygenic risk score as well as higher burden of negative symptoms. The deleterious effects of polygenic risk on cognition are played out via its effects on the functional connectome, as well as negative symptoms.
精神分裂症的工作记忆（WM）缺陷被认为源于广泛的神经效率低下。然而，我们尚不清楚这种缺陷是否由疾病相关的遗传风险导致，以及是否会影响各个领域的症状负担，尤其是早发性疾病患者。我们使用图论来检查99名受试者（27名早发性精神分裂症（EOS）患者、24名无症状的同胞以及48名健康受试者）在n-back任务期间功能连接组的拓扑结构，并计算他们对精神分裂症易感性的多基因风险评分（PRS）。采用线性回归分析来检验EOS患者中PRS、临床症状、连接组特性改变与WM准确性之间的关联。相比于其他两组，EOS患者在WM任务期间的小世界特性和分离指数升高；这些连接组异常与更高的PRS和阴性症状相关。在多基因风险较高的患者中，只有当连接组异常和阴性症状负担都较高时，WM表现才较低。阴性症状在这种关系中具有更强的调节作用。我们的研究结果表明，异常的连接组拓扑结构是精神分裂症患者WM任务表现的一个特征；这与更高的多基因风险评分以及更高的阴性症状负担有关。多基因风险对认知的有害影响是通过其对功能连接组以及阴性症状的影响来体现的。
