Evidence mapPaperPMID 42178876Full record

ArticleBrain and behavior2026

Post-Stroke Depression Is Associated With Shared Neurodevelopmental Risk and Circuit Disruption.

Zhi-Jie Xu, Su-Xiang Zhang, Ji-Ling Li, Jia-Jia Wu, Jie Ma, Zhen-Zhen Ma, Ji-Ming Tao, Xu-Yun Hua, Jian-Guang Xu

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Article in Brain and behavior, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

9 authors.

Zhi-Jie XuSchool of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Su-Xiang ZhangDepartment of Rehabilitation, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Ji-Ling LiDepartment of Rehabilitation, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Jia-Jia WuEngineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China.
Jie MaEngineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China.
Zhen-Zhen MaDepartment of Rehabilitation, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Ji-Ming TaoDepartment of Rehabilitation, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Xu-Yun HuaDepartment of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China.
Jian-Guang XuSchool of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Funding

High-Level Chinese Medicine Key Discipline Construction Project (Integrative Chinese and Western Medicine Clinic) of the National Administration of TCM zyyzdxk-2023065National Natural Science Foundation of China 82172554National Natural Science Foundation of China 82272583National Natural Science Foundation of China 82272589National Natural Science Foundation of China 82302870Shanghai Health Care Commission 2022JC026Shanghai Hospital Development Center Foundation-Shanghai Municipal Hospital Rehabilitation Medicine Specialty Alliance SHDC22023304
6 · The paper itself

Abstract

introductionPost-stroke depression (PSD) affects approximately 30% of stroke survivors and worsens functional outcomes, yet its biological basis remains poorly understood.

methodsWe 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.

resultsStroke 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).

conclusionPSD reflects a unified developmental-acquired pathophysiology where latent developmental genetic vulnerability, revealed at E16.5, is unmasked by stroke-triggered circuit decompensation. HDAC9/PITX2 pathways and AN-DMN circuitry are mechanistically grounded targets for potential biomarker development and circuit-informed interventions.

Indexed as

DepressionNerve NetStrokeAdultAnimalsBrainFemaleGenetic Predisposition to DiseaseHistone DeacetylasesHumansMagnetic Resonance ImagingMaleMiceMiddle AgedMultifactorial InheritanceNeurodevelopmentHDAC9 protein, humanHistone DeacetylasesRepressor Proteinsdefault mode networkneurodevelopmentpost‐stroke depressionshared genetic risk

Identifiers

PMID42178876
PMCPMC13239996

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.