Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha 410011, China; Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China; Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China; The China National Clinical Research Center for Mental Health Disorders, Changsha, China.
Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China; Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China; The China National Clinical Research Center for Mental Health Disorders, Changsha, China.
Schizophr Res. 2020 Aug;222:354-361. doi: 10.1016/j.schres.2020.04.033. Epub 2020 Jun 2.
The pattern of decreased prefronto-thalamic connectivity and increased sensorimotor-thalamic connectivity has been consistently documented in schizophrenia. However, whether this thalamo-cortical abnormality pattern is of genetic predisposition remains unknown. The present study for the first time aimed to investigate the common and distinct characteristics of this circuit in schizophrenia patients and their unaffected siblings who share half of the patient's genotype. Totally 293 participants were recruited into this study including 94 patients with schizophrenia, 96 their healthy siblings, and 103 healthy controls scanned using gradient-echo echo-planar imaging at rest. By using a fine-grained atlas of thalamus with 16 sub-regions, we mapped the thalamocortical network in three groups. Decreased thalamo-prefronto-cerebellar connectivity was shared between schizophrenia and their healthy siblings, but increased sensorimotor-thalamic connectivity was only found in schizophrenia. The shared thalamo-prefronto-cerebellar dysconnectivity showed an impressively gradient reduction pattern in patients and siblings comparing to controls: higher in the controls, lower in the patients and intermediate in the siblings. Anatomically, the decreased thalamic connectivity mostly centered on the pre-frontal thalamic subregions locating at the mediodorsal nucleus, while the increased functional connectivity with sensorimotor cortices was only observed in the caudal temporal thalamic subregion anchoring at the dorsal and ventral lateral nuclei. Moreover, both decreased thalamo-prefronto-cerebellar connectivity and increased sensorimotor-thalamic connectivity were related to clinical symptoms in patients. Our findings extend the evidence that the decreased thalamo-prefronto-cerebellar connectivity may be related to the high genetic risk in schizophrenia, while increased sensorimotor-thalamic connectivity potentially represents a neural biomarker for this severe mental disorder.
前额叶-丘脑连接减少和感觉运动-丘脑连接增加的模式在精神分裂症中得到了一致的证实。然而，这种丘脑-皮质异常模式是否具有遗传易感性仍不清楚。本研究首次旨在调查精神分裂症患者及其携带一半患者基因型的未受影响的兄弟姐妹中，这种回路的共同和独特特征。共有 293 名参与者参与了这项研究，包括 94 名精神分裂症患者、96 名健康兄弟姐妹和 103 名健康对照者，他们在静息状态下使用梯度回波 echo-planar 成像进行扫描。通过使用 16 个亚区的精细丘脑图谱，我们在三组中绘制了丘脑皮质网络。精神分裂症患者及其健康兄弟姐妹之间存在丘脑-前额叶-小脑连接减少，而感觉运动-丘脑连接增加仅在精神分裂症患者中发现。与对照组相比，患者和兄弟姐妹之间共享的丘脑-前额叶-小脑连接障碍表现出令人印象深刻的梯度降低模式：对照组较高，患者较低，兄弟姐妹居中。在解剖学上，减少的丘脑连接主要集中在前额叶丘脑亚区，位于中背核，而与感觉运动皮质的增加功能连接仅在位于背侧和腹外侧核的尾状颞叶丘脑亚区观察到。此外，丘脑-前额叶-小脑连接减少和感觉运动-丘脑连接增加均与患者的临床症状相关。我们的发现扩展了证据，表明丘脑-前额叶-小脑连接减少可能与精神分裂症的高遗传风险有关，而感觉运动-丘脑连接增加可能代表这种严重精神障碍的神经生物标志物。
