Hong Yang , Xiao Chen , Zuo-Bing Chen , Le Li , Xue-Ying Li , Francisco Xavier Castellanos , Tong-Jian Bai , Qi-Jing Bo , Jun Cao , Zhi-Kai Chang , Guan-Mao Chen , Ning-Xuan Chen , Wei Chen , Chang Cheng , Yu-Qi Cheng , Xi-Long Cui , Jia Duan , Yiru Fang , Qi-Yong Gong , Wen-Bin Guo , Zheng-Hua Hou , Lan Hu , Li Kuang , Feng Li , Hui-Xian Li , Kai-Ming Li , Tao Li , Yan-Song Liu , Zhe-Ning Liu , Yi-Cheng Long , Bin Lu , Qing-Hua Luo , Hua-Qing Meng , Daihui Peng , Hai-Tang Qiu , Jiang Qiu , Yue-Di Shen , Yu-Shu Shi , Tian-Mei Si , Yan-Qing Tang , Chuan-Yue Wang , Fei Wang , Kai Wang , Li Wang , Xiang Wang , Ying Wang , Yu-Wei Wang , Xiao-Ping Wu , Xin-Ran Wu , Chun-Ming Xie , Guang-Rong Xie , Hai-Yan Xie , Peng Xie , Xiu-Feng Xu , Jian Yang , Jia-Shu Yao , Shu-Qiao Yao , Ying-Ying Yin , Yong-Gui Yuan , Yu-Feng Zang , Ai-Xia Zhang , Hong Zhang , Ke-Rang Zhang , Lei Zhang , Zhi-Jun Zhang , Jing-Ping Zhao , Rubai Zhou , Yi-Ting Zhou , Jun-Juan Zhu , Zhi-Chen Zhu , Chao-Jie Zou , Xi-Nian Zuo , Chao-Gan Yan <<<

AbstractAberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks. <<<

Linn Sofie Sæther , Thor Ueland , Beathe Haatveit , Luigi Angelo Maglanoc , Attila Szabo , Srdjan Djurovic , Pål Aukrust , Daniel Roelfs , Christine Mohn , Monica Bettina Elkjaer Greenwood Ormerod , Trine Vik Lagerberg , Nils Eiel Steen , Ingrid Melle , Ole Andreas Andreassen , Torill Ueland <<<

AbstractA potential relationship between dysregulation of immune/inflammatory pathways and cognitive impairment has been suggested in severe mental illnesses (SMI), such as schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, multivariate relationships between peripheral inflammatory/immune-related markers and cognitive domains are unclear, and many studies do not account for inter-individual variance in both cognitive functioning and inflammatory/immune status. This study aimed to investigate covariance patterns between inflammatory/immune-related markers and cognitive domains and further elucidate heterogeneity in a large SMI and healthy control (HC) cohort (SZ = 343, BD = 289, HC = 770). We applied canonical correlation analysis (CCA) to identify modes of maximum covariation between a comprehensive selection of cognitive domains and inflammatory/immune markers. We found that poor verbal learning and psychomotor processing speed was associated with higher levels of interleukin-18 system cytokines and beta defensin 2, reflecting enhanced activation of innate immunity, a pattern augmented in SMI compared to HC. Applying hierarchical clustering on covariance patterns identified by the CCA revealed a high cognition—low immune dysregulation subgroup with predominantly HC (24% SZ, 45% BD, 74% HC) and a low cognition—high immune dysregulation subgroup predominantly consisting of SMI patients (76% SZ, 55% BD, 26% HC). These subgroups differed in IQ, years of education, age, CRP, BMI (all groups), level of functioning, symptoms and defined daily dose (DDD) of antipsychotics (SMI cohort). Our findings suggest a link between cognitive impairment and innate immune dysregulation in a subset of individuals with severe mental illness. <<<