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Retrospective Study
Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Psychiatry. Sep 19, 2026; 16(9): 118381
Published online Sep 19, 2026. doi: 10.5498/wjp.118381
Anatomical specificity of post-stroke depression: Subcortical lesions, age-related patterns, and predictors of treatment response
Ju-Xian Gu, Meng-Jun Zhang, Feng-Rong Li, Xia Wang, Shuai-Shuai Li
Ju-Xian Gu, Meng-Jun Zhang, Feng-Rong Li, Xia Wang, Shuai-Shuai Li, Department of Encephalopathy I, Hejian Branch of Cangzhou Central Hospital, Cangzhou 062450, Hebei Province, China
Co-first authors: Ju-Xian Gu and Meng-Jun Zhang.
Author contributions: Gu JX was responsible for overall study integrity and final approval of the version to be published; Gu JX and Zhang MJ contributed equally to this work, conceived and designed the study, supervised the research process, and drafted the manuscript as co-first authors; Li FR and Wang X were responsible for data acquisition, statistical analysis, and interpretation of clinical data; Li SS contributed to literature review, biomarker data management, and manuscript revision for important intellectual content; all authors have read and approved the final manuscript.
AI contribution statement: No AI tools were used at any stage of manuscript preparation. The authors assume full responsibility for the integrity and scientific validity of this work.
Supported by 2023-2024 Cangzhou Municipal Bureau of Science and Technology, No. 23244102228.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Cangzhou Central Hospital [approval No. 2025-1108-01(z)]. The study protocol complied with the ethical principles outlined in the Declaration of Helsinki and relevant institutional guidelines.
Informed consent statement: Due to the retrospective design, the use of anonymized routinely collected clinical data, and the absence of any intervention beyond standard clinical care, the requirement for written informed consent was waived by the Ethics Committee of Cangzhou Central Hospital.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Data sharing statement: The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. Data are not publicly available due to institutional data protection policies and patient confidentiality requirements.
Corresponding author: Xia Wang, Associate Chief Physician, Department of Encephalopathy I, Hejian Branch of Cangzhou Central Hospital, No. 32 Jingkai Street, Cangzhou 062450, Hebei Province, China. 2099508270@qq.com
Received: January 30, 2026
Revised: February 25, 2026
Accepted: July 15, 2026
Published online: September 19, 2026
Processing time: 205 Days and 22 Hours
Abstract
BACKGROUND

Cerebral infarction is the leading cause of death and disability among adults, with post-stroke depression (PSD) and anxiety affecting 30%-50% of survivors. PSD and anxiety worsens rehabilitation outcomes and increases mortality risk, yet 30%-40% of patients respond inadequately to first-line therapy. Predictors of treatment response remain poorly characterized.

AIM

To investigate the anatomical patterns, clinical characteristics, and predictive factors of PSD, and to examine the influence of infarct location, age, and biomarkers on depressive symptom severity and treatment outcomes.

METHODS

This retrospective study enrolled 256 stroke patients with depression from June 2022 to June 2024. Depression severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD). All patients completed 8 weeks of standardized treatment including antidepressant medication and rehabilitation therapy. Serum biomarkers were measured before and after treatment. Treatment response was defined as ≥ 25% reduction in HAMD scores. Patients were stratified across eight anatomical infarct locations and three age groups for detailed analysis. Univariate and multivariate logistic regression identified independent predictors of treatment response, and receiver operating characteristic curve analysis assessed predictive model performance.

RESULTS

Baseline HAMD scores averaged 24.2 ± 6.0 points, with 77.3% of patients achieving favorable treatment response. Depression severity demonstrated striking anatomical specificity, with subcortical lesions exhibiting significantly higher HAMD scores than cortical lesions. Basal ganglia/internal capsule infarcts showed the highest depression severity, followed by thalamic infarcts. Among cortical regions, frontal lobe infarcts demonstrated the highest scores, while occipital lesions showed the lowest burden. Posterior fossa structures exhibited intermediate depression severity. Multivariate logistic regression identified lower baseline HAMD score, shorter disease duration, and absence of comorbid hypertension as independent predictors of favorable treatment response. The predictive model demonstrated good discriminative ability. There was a moderate positive correlation between age and depression severity, and older patients had significantly higher HAMD scores than younger patients.

CONCLUSION

For the anatomical specificity of PSD, we found that the particularly subcortical lesions involving with the basal ganglia and thalamus are a much higher risk. This anatomical vulnerability indicates that subcortical-frontal mood regulatory circuits likely play a critical role. Depression severity and treatment response progressively increase with age, where greater degrees of baseline symptom severity, longer disease duration, and presence of vascular comorbidites predicted response.

Keywords: Post-stroke depression; Infarct location; Anatomical specificity; Age-related patterns; Treatment response prediction

Core Tip: Post-stroke depression is a heterogeneous clinical condition. Modified Soufeng Decoction could significantly improve the anxiety, depression and recovery of neurological function in patients with cerebral infarction when combined with conventional therapy. Treatment response is conditioned by baseline symptom severity, disease duration and vascular comorbidities, thus reinforcing the necessity of early and tailored intervention.

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