来自杂志 Molecular Psychiatry 的文献。
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1.
庞庞
(2025-01-31 20:05):
#paper doi https://doi.org/10.1038/s41380-024-02442-7 Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study作者测试了精神分裂症中的大尺度结构改变是否与正常的结构和功能连接组架构相关,并系统评估了这些网络水平改变的稳健性和普遍性。利用来自26个ENIGMA站点的2439名精神分裂症成年患者和2867名健康对照者的解剖MRI扫描,以及人类连接组计划的正常数据(n = 207),根据两个网络易感性模型评估了精神分裂症的结构改变:(i)中枢易损性模型,检查区域网络中心性与疾病相关改变幅度之间的关联;(ii)病变中心图谱绘制,识别其典型连接模式最接近疾病相关形态改变的区域。
Molecular Psychiatry,
2024-6.
DOI: 10.1038/s41380-024-02442-7
Abstract:
AbstractSchizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations …
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AbstractSchizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia’s alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.
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2.
庞庞
(2023-08-31 23:18):
#Paper Disrupted intrinsic functional brain topology in patients with major depressive disorder DOI：10.1038/s41380-021-01247-2 作者解决了因为样本量过少抑郁症异常脑机制研究不一致的问题，发现，与NC相比，MDD患者的全局和局部效率降低。在节点水平上，MDD患者的特征是感觉运动网络（SMN）、背侧注意网络（DAN）和视觉网络（VN）的节点度降低，默认模式网络（DMN）、SMN、DAN和VN的节点效率降低。
Abstract:
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 …
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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.
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3.
Arwen
(2023-01-31 22:38):
#paper, Inflammation and cognition in severe mental illness: patterns
of covariation and subgroups, https://doi.org/10.1038/s41380-022-01924-w 严重精神疾病(SMI)如精神分裂症(SZ)和双相情感障碍(BD)中免疫/炎症通路失调和认知障碍之间的潜在关系已被提出。然而，外周炎症/免疫相关标记物与认知领域之间的多变量关系尚不清楚，许多研究没有解释认知功能和炎症/免疫状态的个体间差异。本研究旨在研究炎症/免疫相关标记物与认知域之间的协方差模式，并进一步阐明大型SMI和健康对照(HC)队列(SZ=343, BD=289, HC=770)的异质性。应用典型相关分析(CCA)来确定综合选择的认知域和炎症/免疫标记之间的最大共变模式。发现较差的语言学习和精神运动处理速度与较高水平的白细胞介素-18系统细胞因子和β防御素2有关，反映了先天免疫的增强激活，与HC相比，SMI的这种模式有所增强。对CCA确定的协方差模式进行分层聚类，发现以HC为主的高认知-低免疫失调亚组(24% SZ, 45% BD, 74% HC)和以SMI患者为主的低认知-高免疫失调亚组(76% SZ, 55% BD, 26% HC)。这些亚组在智商、受教育年限、年龄、CRP、BMI(所有组)、功能水平、症状和抗精神病药物的限定日剂量(DDD) (SMI队列)方面存在差异。
Abstract:
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 …
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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.
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