Ajunwa Chelsea C, Zhang Jiahe, Collin Guusje, Keshavan Matcheri S, Tang Yingying, Zhang Tianhong, Li Huijun, Shenton Martha E, Stone William S, Wang Jijun, Niznikiewicz Margaret, Whitfield-Gabrieli Susan
Department of Psychology, Northeastern University, Boston, MA.
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA.
bioRxiv. 2024 Oct 25:2024.10.25.620271. doi: 10.1101/2024.10.25.620271.
The Clinical High Risk (CHR) stage of psychosis is characterized by subthreshold symptoms of schizophrenia including negative symptoms, dysphoric mood, and functional deterioration. Hyperconnectivity of the default-mode network (DMN) has been observed in early schizophrenia, but the extent to which hyperconnectivity is present in CHR, and the extent to which such hyperconnectivity may underlie transdiagnostic symptoms, is not clear. As part of the Shanghai At-Risk for Psychosis (SHARP) program, resting-state fMRI data were collected from 251 young adults (158 CHR and 93 controls, M = 18.72, SD = 4.68, 129 male). We examined functional connectivity of the DMN by performing a whole-brain seed-to-voxel analysis with the MPFC as the seed. Symptom severity across a number of dimensions, including negative symptoms, positive symptoms, and affective symptoms were assessed. Compared to controls, CHRs exhibited significantly greater functional connectivity (p < 0.001 uncorrected) between the MPFC and 1) other DMN nodes including the posterior cingulate cortex (PCC), and 2) auditory cortices (superior and middle temporal gyri, STG/MTG). Furthermore, these two patterns of hyperconnectivity were differentially associated with distinct symptom clusters. Within CHR, MPFC-PCC connectivity was significantly correlated with anxiety (r= 0.23, p=0.006), while MPFC-STG/MTG connectivity was significantly correlated with negative symptom severity (r=0.26, p=0.001). Secondary analyses using item-level symptom scores confirmed a similar dissociation. These results demonstrate that two dissociable patterns of DMN hyperconnectivity found in the CHR stage may underlie distinct dimensions of symptomatology.
精神病的临床高危（CHR）阶段的特征是存在低于阈值的精神分裂症症状，包括阴性症状、烦躁情绪和功能衰退。在早期精神分裂症中已观察到默认模式网络（DMN）的过度连接，但CHR阶段中过度连接的程度以及这种过度连接可能成为跨诊断症状基础的程度尚不清楚。作为上海精神病高危（SHARP）项目的一部分，我们收集了251名年轻人（158名CHR患者和93名对照，平均年龄M = 18.72，标准差SD = 4.68，男性129名）的静息态功能磁共振成像（fMRI）数据。我们以内侧前额叶皮质（MPFC）为种子，通过全脑种子点到体素分析来检查DMN的功能连接。评估了包括阴性症状、阳性症状和情感症状等多个维度的症状严重程度。与对照组相比，CHR患者在MPFC与1）其他DMN节点（包括后扣带回皮质（PCC））以及2）听觉皮质（颞上回和颞中回，STG/MTG）之间表现出显著更强的功能连接（未校正p < 0.001）。此外，这两种过度连接模式与不同的症状群有不同的关联。在CHR患者中，MPFC - PCC连接与焦虑显著相关（r = 0.23，p = 0.006），而MPFC - STG/MTG连接与阴性症状严重程度显著相关（r = 0.26，p = 0.001）。使用项目级症状评分的二次分析证实了类似的分离。这些结果表明，在CHR阶段发现的两种可分离的DMN过度连接模式可能是不同症状维度的基础。
