Song HY, Yang Y, Sun XY, Zhang MJ, Wang SG. Serum proprotein convertase subtilisin/kexin type 9 levels correlate with depression severity in post-stroke patients. World J Psychiatry 2026; 16(11): 122026 [DOI: 10.5498/wjp.122026]
Corresponding Author of This Article
Hong-Yan Song, Department of Pharmacy, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou 061000, Hebei Province, China. 963809412@qq.com
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Psychology
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research-article
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Song HY, Yang Y, Sun XY, Zhang MJ, Wang SG. Serum proprotein convertase subtilisin/kexin type 9 levels correlate with depression severity in post-stroke patients. World J Psychiatry 2026; 16(11): 122026 [DOI: 10.5498/wjp.122026]
World J Psychiatry. Nov 19, 2026; 16(11): 122026 Published online Nov 19, 2026. doi: 10.5498/wjp.122026
Serum proprotein convertase subtilisin/kexin type 9 levels correlate with depression severity in post-stroke patients
Hong-Yan Song, Yue Yang, Xiao-Yang Sun, Meng-Jun Zhang, Shu-Gen Wang
Hong-Yan Song, Yue Yang, Shu-Gen Wang, Department of Pharmacy, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
Xiao-Yang Sun, Ethics Committee Office, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
Meng-Jun Zhang, Department One of Neurology, Hejian Branch of Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
Author contributions: Song HY conceived and designed the study; Song HY, Yang Y, and Wang SG collected data and coordinated laboratory procedures; Sun XY oversaw ethical compliance; Zhang MJ provided clinical neurology expertise and contributed to patient follow-up; Song HY drafted the manuscript; and all authors reviewed and approved the final manuscript.
AI contribution statement: The authors declare that no AI tools were used in the preparation of this manuscript, including study design, data collection, data analysis, interpretation of results, manuscript writing, or language editing. The authors assume full responsibility for the integrity, accuracy, originality, and scientific validity of the manuscript and all submitted materials.
Supported by Key Research and Development Program of Cangzhou, No. 23244102156.
Institutional review board statement: The Ethics Committee of Cangzhou Central Hospital reviewed and approved this study (approval No. 2025-114-02). All procedures were conducted in accordance with the Declaration of Helsinki.
Informed consent statement: The Ethics Committee of Cangzhou Central Hospital waived the requirement for written informed consent because this was a retrospective study using de-identified clinical data.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: The datasets generated and analyzed during this study are available from the corresponding author (Hong-Yan Song, 963809412@qq.com) upon reasonable request. No additional data are available.
Corresponding author: Hong-Yan Song, Department of Pharmacy, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou 061000, Hebei Province, China. 963809412@qq.com
Received: April 24, 2026 Revised: June 10, 2026 Accepted: September 10, 2026 Published online: November 19, 2026 Processing time: 197 Days and 23 Hours
Abstract
BACKGROUND
Post-stroke depression (PSD) is a common neuropsychiatric complication affecting an estimated 30%-40% of stroke survivors and adversely affecting rehabilitation and quality of life. Emerging evidence suggests that proprotein convertase subtilisin/kexin type 9 (PCSK9) may be involved in neuroinflammation and mood regulation. Evolocumab, a PCSK9 inhibitor, may have effects beyond lipid lowering when added to statin therapy; however, its association with depressive symptoms in patients with PSD remains unclear.
AIM
To investigate the association between serum PCSK9 levels and depression severity in patients with PSD receiving evolocumab plus statin therapy and to assess the association of this combination with changes in depressive symptoms.
METHODS
This retrospective study included 128 patients with PSD: 64 received evolocumab (140 mg every 2 weeks) plus atorvastatin (20 mg daily), and 64 received atorvastatin alone (20 mg daily). The primary outcomes were serum PCSK9 concentrations and 17-item Hamilton Depression Rating Scale (HAMD-17) scores at baseline and at weeks 4, 8, and 12. Secondary outcomes included Hamilton Anxiety Scale (HAMA) scores, lipid profiles, inflammatory markers [interleukin-6 (IL-6), tumor necrosis factor-α, and high-sensitivity C-reactive protein], and cognitive function assessed using the Montreal Cognitive Assessment (MoCA). Correlation analyses examined associations between PCSK9 concentrations and clinical outcomes.
RESULTS
At week 12, serum PCSK9 levels decreased from 385.6 ± 78.4 ng/mL to 156.3 ± 42.1 ng/mL in the combination-therapy group, compared with 378.2 ± 76.9 ng/mL to 298.5 ± 68.7 ng/mL in the atorvastatin-only group (P < 0.001). HAMD-17 scores decreased from 22.8 ± 4.5 to 10.2 ± 3.1 and from 22.3 ± 4.2 to 14.6 ± 3.8, respectively (P < 0.001 for the between-group comparison at week 12). Serum PCSK9 levels were positively correlated with HAMD-17 scores at week 12 (r = 0.652, P < 0.001). Compared with the atorvastatin-only group, the combination-therapy group had lower week-12 HAMA scores (8.5 ± 2.3 vs 12.1 ± 3.2, P < 0.001) and IL-6 concentrations (3.2 ± 0.8 pg/mL vs 5.1 ± 1.2 pg/mL, P < 0.001), higher MoCA scores (25.8 ± 2.1 vs 23.4 ± 2.6, P = 0.001), and a higher depression treatment response rate (73.4% vs 48.4%, P = 0.003).
CONCLUSION
In this retrospective, evolocumab added to atorvastatin was associated with greater reductions in serum PCSK9 levels and depressive symptom scores than atorvastatin alone. The correlation between PCSK9 concentrations and depression severity suggests that PCSK9 warrants further investigation as a potential biomarker in PSD. Prospective studies are needed to establish whether PCSK9 inhibition improves depressive symptoms.
Core Tip: In this retrospective study of patients with post-stroke depression, the addition of evolocumab to atorvastatin was associated with greater reductions in serum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations and depression scores than atorvastatin alone. Serum PCSK9 concentrations correlated positively with depression severity at week 12 (r = 0.652). The combination-therapy group had a higher treatment response rate (73.4% vs 48.4%, P = 0.003), lower inflammatory marker concentrations, and higher cognitive assessment scores. These findings support further evaluation of PCSK9 as a candidate biomarker and potential treatment target; causal and clinical efficacy claims require prospective confirmation.
