Post-Stroke Depression Is Associated With Shared Neurodevelopmental Risk and Circuit Disruption.
Overview
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China
- Department of Rehabilitation, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
- Center of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Abstract
Introduction: Post‐stroke depression (PSD) affects approximately 30% of stroke survivors and worsens functional outcomes, yet its biological basis remains poorly understood.
Methods: We integrated cross‐disorder genomics, developmental spatial transcriptomics, and causal neuroimaging in 16 PSD patients and 14 matched controls. Polygenic overlap was quantified using MiXeR and conditional FDR (condFDR). Shared risk variants were mapped using genetically informed spatial mapping of cells for complex traits (gsMap) onto the embryonic mouse brain (E16.5). Resting‐state fMRI with group independent component analysis (ICA), functional network connectivity (FNC), and spectral dynamic causal modeling (spDCM) characterised circuit‐level alterations.
Results: Stroke and depression showed robust polygenic overlap (Dice = 0.09). condFDR prioritized five pleiotropic loci implicating HDAC9‐mediated neurovascular inflammation and PITX2‐driven cardio‐cerebral signaling. gsMap revealed enrichment of shared genetic risk in developing cortical regions at E16.5. PSD exhibited selective default mode network (DMN)–sensorimotor network (SMN) decoupling and reduced directed DMN→SMN influence (BPA = –0.12 Hz; Pp > 0.99). Auditory network (AN) outflow to DMN, SMN, and ventral attention network (VAN) was broadly attenuated, and AN→DMN effective connectivity scaled with depressive severity (BPA = –0.19 Hz; Pp > 0.99).
Conclusion: PSD reflects a unified developmental–acquired pathophysiology where latent developmental genetic vulnerability, revealed at E16.5, is unmasked by stroke‐triggered circuit decompensation. HDAC9/
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data Availability Statement
Publicly available GWAS summary statistics were obtained from the consortia repositories detailed in Section 2. The following researcher‐generated materials are available from the corresponding author upon reasonable request: (i) derived neuroimaging measures (e.g., subject‐specific regional BOLD time series); (i) statistical outputs (e.g., PEB parameter estimates and effective connectivity matrices); and (iii) analysis scripts for data preprocessing, spDCM modeling, and statistical inference (implemented in MATLAB/
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 4 keywords, 17 MeSH terms, 4 funders, 58 references.
Cite
This paper
Xu, Z., Zhang, S., Li, J., Wu, J., Ma, J., Ma, Z., Tao, J., Hua, X., & Xu, J. (2026). Post-Stroke Depression Is Associated With Shared Neurodevelopmental Risk and Circuit Disruption. Brain and behavior, 16(5), e71502. https://
BibTeX
@article{xu2026post,
author = {Xu, Zhi‐Jie and Zhang, Su‐Xiang and Li, Ji‐Ling and Wu, Jia‐Jia and Ma, Jie and Ma, Zhen‐Zhen and Tao, Ji‐Ming and Hua, Xu‐Yun and Xu, Jian‐Guang},
title = {{Post-Stroke Depression Is Associated With Shared Neurodevelopmental Risk and Circuit Disruption}},
journal = {Brain and behavior},
year = {2026},
month = may,
volume = {16},
number = {5},
pages = {e71502},
publisher = {Wiley},
issn = {2162-3279},
doi = {10.1002/
url = {https://
pmid = {42178876},
pmcid = {PMC13239996}
}
RIS
TY - JOUR
AU - Xu, Zhi‐Jie
AU - Zhang, Su‐Xiang
AU - Li, Ji‐Ling
AU - Wu, Jia‐Jia
AU - Ma, Jie
AU - Ma, Zhen‐Zhen
AU - Tao, Ji‐Ming
AU - Hua, Xu‐Yun
AU - Xu, Jian‐Guang
TI - Post-Stroke Depression Is Associated With Shared Neurodevelopmental Risk and Circuit Disruption
T2 - Brain and behavior
J2 - Brain Behav
PY - 2026
DA - 2026/
VL - 16
IS - 5
SP - e71502
SN - 2162-3279
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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