BACKGROUND Emerging evidence suggests disruptions in the wiring organization of the brain's network in schizophrenia (SZ) and bipolar disorder (BD). As the importance of genetic predisposition has been firmly established in these illnesses, children (offspring) of patients constitute an at-risk population. This study examines connectome organization in children at familial high risk for psychosis. METHODS Diffusion-weighted magnetic resonance imaging scans were collected from 127 nonpsychotic offspring 8 to 18 years of age (average age = 13.5 years) of a parent diagnosed with SZ (SZ offspring; n = 28) or BD (BD offspring; N = 60) and community control subjects (n = 39). Resting-state functional magnetic resonance imaging scans were available for 82 subjects. Anatomical and functional brain networks were reconstructed and examined using graph theoretical analysis. RESULTS SZ offspring were found to show connectivity deficits of the brain's central rich club (RC) system relative to both control subjects and BD offspring. The disruption in anatomical RC connectivity in SZ offspring was associated with increased modularity of the functional connectome. In addition, increased coupling between structural and functional connectivity of long-distance connections was observed in both SZ offspring and BD offspring. CONCLUSIONS This study shows lower levels of anatomical RC connectivity in nonpsychotic young offspring of SZ patients. This finding suggests that the brain's anatomical RC system is affected in at-risk youths, reflecting a connectome signature of familial risk for psychotic illness. Moreover, finding no RC deficits in offspring of BD patients suggest a differential effect of genetic predisposition for SZ versus BD on the developmental formation of the connectome.

中文翻译：

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精神分裂症和双相情感障碍患者年轻后代的解剖丰富俱乐部和结构-功能耦合的影响

背景 新出现的证据表明，精神分裂症 (SZ) 和双相情感障碍 (BD) 中大脑网络的布线组织存在中断。由于遗传易感性在这些疾病中的重要性已得到牢固确立，因此患者的儿童（后代）构成了高危人群。这项研究检查了患有家族性精神病高危儿童的连接组组织。方法 扩散加权磁共振成像扫描收集了 127 名 8 至 18 岁（平均年龄 = 13.5 岁）的父母诊断为 SZ（SZ 后代；n = 28）或 BD（BD 后代；N = 60）的非精神病后代) 和社区控制对象 (n = 39)。82 名受试者可进行静息状态功能磁共振成像扫描。使用图论分析重建和检查解剖学和功能性脑网络。结果 发现 SZ 后代与对照受试者和 BD 后代相比，大脑中枢富俱乐部 (RC) 系统的连接缺陷。SZ 后代解剖 RC 连接的中断与功能连接组的模块化增加有关。此外，在 SZ 后代和 BD 后代中都观察到长距离连接的结构和功能连接之间的耦合增加。结论 本研究显示 SZ 患者的非精神病年轻后代的解剖 RC 连接水平较低。这一发现表明，高危青少年的大脑解剖 RC 系统受到影响，反映了精神病家族风险的连接组特征。