AbstractUnderstanding the neuroanatomy of schizophrenia remains elusive due to heterogeneous findings across neuroimaging studies. Here we investigated whether patterns of brain atrophy associated with schizophrenia would localize to a common brain network using a coordinate network mapping meta-analysis approach.

摘要由于神经影像学研究的异质性发现，了解精神分裂症的神经解剖学仍然难以捉摸。在这里，我们使用坐标网络映射荟萃分析方法研究了与精神分裂症相关的脑萎缩模式是否会定位于常见的大脑网络。

Utilizing the human connectome as a wiring diagram, we identified a connectivity pattern, a schizophrenia network, uniting heterogeneous results from 90 published studies of atrophy in schizophrenia (total n > 8,000). This network was specific to schizophrenia, differentiating it from atrophy in individuals at high risk for psychosis (n = 3,038), normal aging (n = 4,195), neurodegenerative disorders (n = 3,707) and other psychiatric conditions (n = 3,432).

利用人类连接体作为接线图，我们确定了一种连接模式，一种精神分裂症网络，结合了90项已发表的精神分裂症萎缩研究的异质性结果（总n > 8,000）。 = 3,038），正常衰老（n=4195），神经退行性疾病（n=3707）和其他精神疾病（n = 3,432).

The network was also stable with disease progression and across different clusters of schizophrenia symptoms. Patterns of brain atrophy in schizophrenia were negatively correlated with lesions linked to psychosis-related thought processes in an independent cohort (n = 181). Our results propose a unique, stable, and unified schizophrenia network, addressing a significant portion of the heterogeneity observed in previous atrophy studies..

随着疾病进展和不同的精神分裂症症状群，该网络也保持稳定。 = 181). 我们的研究结果提出了一个独特，稳定和统一的精神分裂症网络，解决了先前萎缩研究中观察到的很大一部分异质性。。

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Fig. 1: Heterogeneity analyses.Fig. 2: Mapping atrophy coordinates in schizophrenia to brain networks.Fig. 3: Mapping atrophy patterns in schizophrenia to a common brain network.Fig. 4: Comparing schizophrenia subgroups: spatial permutation tests (two-sided).Fig. 5: Schizophrenia versus high-risk individuals.Fig.

图1：异质性分析。图2：将精神分裂症中的萎缩坐标映射到大脑网络。图3：将精神分裂症的萎缩模式映射到一个共同的大脑网络。图4：比较精神分裂症亚组：空间排列测试（双面）。图5：精神分裂症与高危人群。图。

6: Lesion-based validation..

6： 基于病变的验证。。

Data availability

数据可用性

All atrophy coordinates used in this work are derived from previously published studies, as referenced in previous meta-analyses23,49,50. The functional connectivity data utilized in this study can be accessed online through the Harvard Dataverse at https://doi.org/10.7910/DVN/ILXIKS. For inquiries related to the Vietnam Head Injury Study, please contact J.

这项工作中使用的所有萎缩坐标均来自先前发表的研究，如先前的荟萃分析23,49,50所述。https://doi.org/10.7910/DVN/ILXIKS.有关越南颅脑损伤研究的询问，请联系J。

Grafman at jgrafman@northwestern.edu. The final schizophrenia network map is available via NeuroVault (https://neurovault.org/images/889224/)..

格拉夫曼atjgrafman@northwestern.edu.最终的精神分裂症网络图可通过NeuroVault获得(https://neurovault.org/images/889224/)。。

Code availability

代码可用性

The processing pipeline for functional connectivity data can be found at https://github.com/bchcohenlab/BIDS_to_CBIG_fMRI_Preproc2016. The statistical analyses were conducted using MATLAB R2022b. MATLAB code for spatial permutation testing can be accessed via Zenodo at https://zenodo.org/records/13851081 (ref.

功能连接数据的处理管道可以在https://github.com/bchcohenlab/BIDS_to_CBIG_fMRI_Preproc2016.使用MATLAB R2022b进行统计分析。空间置换测试的MATLAB代码可以通过Zenodo访问https://zenodo.org/records/13851081（参考。

54)..

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Makhlouf, A. & Siddiqi, S. Heterogenous patterns of brain atrophy in schizophrenia localize to a common brain network. Zenodo https://zenodo.org/records/13851081 (2024).Download referencesAcknowledgmentsWe express our gratitude to the participants who volunteered for the studies analyzed in this paper.

Makhlouf，A。＆Siddiqi，S。精神分裂症脑萎缩的异质模式定位于一个共同的大脑网络。Zenodohttps://zenodo.org/records/13851081（2024年）。下载参考文献致谢我们感谢自愿参与本文分析研究的参与者。

We thank A. Cohen, M. Ferguson, C. Lin, and L. Soussand for their efforts in developing the computational methods used in this study. We also thank P. Flynn and L. Sterina for administrative support. This work was supported by the following sources: Harvard Medical School (Dupont Warren Fellowship Award) and the NIH (grant no.

我们感谢A.Cohen，M.Ferguson，C.Lin和L.Soussand在开发本研究中使用的计算方法方面所做的努力。我们也感谢P.Flynn和L.Sterina的行政支持。这项工作得到了以下来源的支持：哈佛医学院（杜邦沃伦奖学金）和美国国立卫生研究院（批准号：。

R01MH113929) (A.T.M.); Canadian Institutes of Health Research Vanier Scholarship and a University of British Columbia Friedman Award for Scholars in Health (J.L.S.); Harvard Medical School (Dupont Warren Fellowship Award and Livingston Award), Brain and Behavior Research Foundation Young Investigator Grant (no.

R01MH113929）（A.T.M.）；加拿大卫生研究院瓦尼尔奖学金和不列颠哥伦比亚大学弗里德曼健康学者奖（J.L.S.）；哈佛医学院（杜邦沃伦奖学金和利文斯顿奖），大脑与行为研究基金会青年研究员资助（no。

31081), Sidney R. Baer, Jr. Foundation, Baszucki Brain Research Fund, and the NIH (grant nos K23MH129829 and R01MH113929) (J.J.T.); the Nancy Lurie Marks Foundation, the Kaye Family Research Endowment, the Baszucki Brain Research Fund and the NIH (grant nos. R01MH113929, R21MH126271, R56AG069086, R01MH115949, and R01AG060987) (M.D.F.); the NIH (grant nos.

31081），Sidney R.Baer，Jr.基金会，Baszucki大脑研究基金和NIH（批准号K23MH129829和R01MH113929）（J.J.T.）；Nancy Lurie Marks基金会，Kaye家庭研究基金会，Baszucki大脑研究基金和NIH（批准号R01MH113929，R21MH126271，R56AG069086，R01MH115949和R01AG060987）（M.D.F.）；美国国立卫生研究院（批准号：。

K23MH121657, R21MH126271, and R01MH136248), the Brain and Behavior Research Foundation Young Investigator Grant, the Baszucki Brain Research Fund and the Department of Veterans Affairs (grant no. I01CX002293) (S.H.S.).Author informationAuthors and AffiliationsCenter for Brain Circuit Therapeutics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USAAhmed T.

K23MH121657，R21MH126271和R01MH136248），大脑和行为研究基金会青年研究员资助，巴斯祖基大脑研究基金和退伍军人事务部（资助号I01CX002293）（S.H.S.）。作者信息美国马萨诸塞州波士顿哈佛医学院布莱根妇女医院脑回路治疗学作者和附属机构。

Makhlouf, William Drew, Jacob L. Stubbs, Joseph J. Taylor, Michael D. Fox & Shan H. SiddiqiDepartment o.

马克卢夫（Makhlouf）、威廉·德鲁（WilliamDrew）、雅各布·L·斯塔布斯（JacobL.Stubbs）、约瑟夫·J·泰勒（JosephJ.Taylor）、迈克尔·D·福克斯（MichaelD.Fox）和山·H·西迪奇（ShanH.Siddiqi。

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PubMed Google ScholarContributionsA.T.M., D.S., M.D.F., and S.H.S. conceived and designed the study. A.T.M., W.D., J.L.S., M.D.F., and S.H.S. designed the analytical procedures. A.T.M., W.D., J.L.S., J.J.T., and D.L. preprocessed and prepared the data for analysis. A.T.M., W.D., J.L.S., J.J.T., and S.H.S.

PubMed谷歌学术贡献。T、 M.，D.S.，M.D.F。和S.H.S.构思并设计了这项研究。A、 T.M.，W.D.，J.L.S.，M.D.F。和S.H.S.设计了分析程序。A、 T.M.，W.D.，J.L.S.，J.J.T。和D.L.预处理并准备数据进行分析。A、 T.M.，W.D.，J.L.S.，J.J.T。和S.H.S。

performed the neuroimaging and statistical analyses. D.L., J.J.T., J.L.S., and J.G. contributed the data. A.T.M. and S.H.S. wrote the paper, with input from all authors.Corresponding authorCorrespondence to.

。D、 L.，J.J.T.，J.L.S。和J.G.贡献了数据。A、 T.M.和S.H.S.在所有作者的意见下撰写了这篇论文。对应作者对应。

Ahmed T. Makhlouf.Ethics declarations

Ahmed T.Makhlouf。道德宣言

Competing interests

相互竞争的利益

S.H.S. holds intellectual property related to using individualized resting-state network mapping for targeting TMS, filed in 2016, which has not generated royalties and is unrelated to this work. S.H.S. also serves as a scientific consultant for Magnus Medical, has received investigator-initiated research funding from Neuronetics (2019) and Brainsway (2022), received speaking fees from Brainsway (2021) and Otsuka (for PsychU.org, 2021) and holds shares in Brainsway (publicly traded) and Magnus Medical (privately held).

S、 H.S.拥有与使用个性化静息状态网络映射定位TMS相关的知识产权，于2016年提交，尚未产生版税，与这项工作无关。S.H.S.还担任Magnus Medical的科学顾问，从Neuronetics（2019）和Brainsway（2022）获得了研究者发起的研究资金，从Brainsway（2021）和Otsuka（对于PsychU.org，2021）获得了演讲费，并持有Brainsway（公开交易）和Magnus Medical（私人持有）的股份。

M.D.F. is a scientific consultant for Magnus Medical and owns separate intellectual property related to using functional connectivity to target TMS for depression, filed in 2013, which has not generated royalties and is unrelated to this work. The other authors declare no competing interests..

M、 D.F.是Magnus Medical的科学顾问，拥有与使用功能连接治疗抑郁症相关的独立知识产权，于2013年提交，尚未产生版税，与这项工作无关。其他作者声明没有利益冲突。。

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Nature Mental Health thanks Richard Dear, Golia Shafiei, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

自然心理健康感谢Richard Dear，Golia Shafiei和另一位匿名审稿人对这项工作的同行评议做出的贡献。

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a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Reprints and permissionsAbout this articleCite this articleMakhlouf, A.T., Drew, W., Stubbs, J.L.

协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议对本文拥有专有权；本文接受稿件版本的作者自行存档仅受此类出版协议和适用法律的条款管辖。转载和许可本文引用本文Makhlouf，A.T.，Drew，W.，Stubbs，J.L。

et al. Heterogeneous patterns of brain atrophy in schizophrenia localize to a common brain network..

精神分裂症脑萎缩的异质模式定位于一个共同的大脑网络。。

Nat. Mental Health (2024). https://doi.org/10.1038/s44220-024-00348-5Download citationReceived: 12 October 2023Accepted: 07 October 2024Published: 12 December 2024DOI: https://doi.org/10.1038/s44220-024-00348-5Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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