Cell type-specific manifestations of cortical thickness heterogeneity in schizophrenia.
Cell type-specific manifestations of cortical thickness heterogeneity in schizophrenia.
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DOI：
10.1038/s41380-022-01460-7
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发表时间：
2022-04
影响因子：
11
通讯作者：
Zalesky, Andrew
中科院分区：
文献类型：
--
作者：
Di Biase, Maria A.;Geaghan, Michael P.;Reay, William R.;Seidlitz, Jakob;Weickert, Cynthia Shannon;Pebay, Alice;Green, Melissa J.;Quide, Yann;Atkins, Joshua R.;Coleman, Michael J.;Bouix, Sylvain;Knyazhanskaya, Evdokiya E.;Lyall, Amanda E.;Pasternak, Ofer;Kubicki, Marek;Rathi, Yogesh;Visco, Andrew;Gaunnac, Megan;Lv, Jinglei;Mesholam-Gately, Raquelle, I;Lewandowski, Kathryn E.;Holt, Daphne J.;Keshavan, Matcheri S.;Pantelis, Christos;Ongur, Dost;Breier, Alan;Cairns, Murray J.;Shenton, Martha E.;Zalesky, Andrew
精神分裂症患者的大脑形态存在显着差异，但人们对这种异质性的细胞和遗传基础知之甚少。在这里，我们试图确定精神分裂症的皮质厚度（CTh）异质性是否与不同神经细胞类型的区域间变异有关，正如从已建立的基因表达数据和个体特异性基因组变异推断的那样。这项研究共有 1849 名参与者，包括发现组（140 例病例和 1267 名对照）和验证组（335 例病例和 185 名对照）。为了表征 CTh 异质性，为 34 个皮质区域建立了标准范围，并测量了每个精神分裂症患者与这些范围的偏差程度。 CTh 偏差可以通过检查的七种神经细胞类型中的五种的区域间基因表达水平来解释：（1）星形胶质细胞； (2)内皮细胞； (3) 少突胶质祖细胞 (OPC)； (4) 兴奋性神经元； (5)抑制性神经元。 CTh 改变与细胞类型转录图谱之间的区域比对区分了广泛的患者亚型，这些亚型根据来自同一个体的基因组数据进行了验证。在主要为神经元/内皮细胞的亚型中（22%的患者），CTh偏差与精神分裂症的多基因风险（sczPRS）是协变的，该风险是根据标记神经元和内皮细胞的基因专门计算的（r = −0.40，p = 0.010）。然而，在以神经胶质细胞/OPC 为主的亚型（43% 的患者）中，CTh 偏差与根据神经胶质细胞和 OPC 相关基因计算的 sczPRS 共变（r = −0.30，p = 0.028）。这种对基因组、转录组和大脑表型数据的多尺度分析可能表明精神分裂症中的 CTh 异质性与细胞类型特定功能的个体间变异有关。分解与皮质细胞类型相关的异质性可以为未来的疾病建模工作确定精神分裂症子集的优先级。
Brain morphology differs markedly between individuals with schizophrenia, but the cellular and genetic basis of this heterogeneity is poorly understood. Here, we sought to determine whether cortical thickness (CTh) heterogeneity in schizophrenia relates to interregional variation in distinct neural cell types, as inferred from established gene expression data and person-specific genomic variation. This study comprised 1849 participants in total, including a discovery (140 cases and 1267 controls) and a validation cohort (335 cases and 185 controls). To characterize CTh heterogeneity, normative ranges were established for 34 cortical regions and the extent of deviation from these ranges was measured for each individual with schizophrenia. CTh deviations were explained by interregional gene expression levels of five out of seven neural cell types examined: (1) astrocytes; (2) endothelial cells; (3) oligodendrocyte progenitor cells (OPCs); (4) excitatory neurons; and (5) inhibitory neurons. Regional alignment between CTh alterations with cell type transcriptional maps distinguished broad patient subtypes, which were validated against genomic data drawn from the same individuals. In a predominantly neuronal/endothelial subtype (22% of patients), CTh deviations covaried with polygenic risk for schizophrenia (sczPRS) calculated specifically from genes marking neuronal and endothelial cells (r = −0.40, p = 0.010). Whereas, in a predominantly glia/OPC subtype (43% of patients), CTh deviations covaried with sczPRS calculated from glia and OPC-linked genes (r = −0.30, p = 0.028). This multi-scale analysis of genomic, transcriptomic, and brain phenotypic data may indicate that CTh heterogeneity in schizophrenia relates to inter-individual variation in cell-type specific functions. Decomposing heterogeneity in relation to cortical cell types enables prioritization of schizophrenia subsets for future disease modeling efforts.
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通过神经影像学基因组学解剖自闭症和精神分裂症。
DOI：
10.1093/brain/awab096
发表时间：
2021-08-17
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Moreau CA;Raznahan A;Bellec P;Chakravarty M;Thompson PM;Jacquemont S
通讯作者：
Jacquemont S
DOI：
10.1176/appi.ajp.2015.14091200
发表时间：
2016-04-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Clementz BA;Sweeney JA;Hamm JP;Ivleva EI;Ethridge LE;Pearlson GD;Keshavan MS;Tamminga CA
通讯作者：
Tamminga CA
精神病生物型中的大脑结构生物标志物：中间表型的双极 - 奇异性网络的发现。
影响因子：
10.6
作者：
Ivleva EI;Clementz BA;Dutcher AM;Arnold SJM;Jeon-Slaughter H;Aslan S;Witte B;Poudyal G;Lu H;Meda SA;Pearlson GD;Sweeney JA;Keshavan MS;Tamminga CA
通讯作者：
Tamminga CA
DOI：
10.1073/pnas.1507125112
发表时间：
2015-06-09
影响因子：
11.1
作者：
Darmanis S;Sloan SA;Zhang Y;Enge M;Caneda C;Shuer LM;Hayden Gephart MG;Barres BA;Quake SR
通讯作者：
Quake SR
影响因子：
4.5
作者：
Hedman, Anna M.;van Haren, Neeltje E. M.;Pol, Hilleke E. Hulshoff
通讯作者：
Pol, Hilleke E. Hulshoff