Cardiovascular

Changes in Serum GDF-15 in Relation to the Onset of Post-Stroke Depression After Acute Ischemic Stroke and the Development of a Comprehensive Prediction Model.

TL;DR

Serum GDF-15 is closely associated with PSD onset after AIS, and a comprehensive prediction model integrating GDF-15 with other clinical factors demonstrates high clinical utility for predicting PSD risk.

Key Findings

The PSD group differed significantly from the non-PSD group on multiple demographic and clinical characteristics.

  • 302 patients with AIS were enrolled; 100 developed PSD and 202 did not
  • The PSD group had older age, higher NIHSS scores, and a greater proportion of patients with a family history of psychiatric disorders and frontal lobe infarction (p < 0.05)
  • Left ventricular ejection fraction was lower in the PSD group (p < 0.05)
  • Study was retrospective, conducted at Siyang County Hospital of Traditional Chinese Medicine between January 2023 and October 2025

Multiple serum biomarkers were elevated in PSD patients compared to non-PSD patients.

  • Serum levels of hs-CRP, homocysteine, uric acid, IL-6, NfL, and GDF-15 were all elevated in the PSD group (p < 0.05)
  • These biomarkers were measured at admission
  • Elevated GDF-15 was identified as a key differentiating factor between the two groups

Higher NIHSS scores were identified as an independent risk factor for post-stroke depression.

  • OR = 1.230 (95% CI: 1.045–1.447)
  • p < 0.05
  • NIHSS measures stroke severity at admission
  • Identified via logistic regression analysis

Family history of psychiatric disorders was a strong independent risk factor for PSD.

  • OR = 7.760 (95% CI: 1.709–35.238)
  • p < 0.05
  • This was the largest odds ratio among all independent risk factors identified
  • Identified via logistic regression analysis

Frontal lobe infarction was an independent risk factor for post-stroke depression.

  • OR = 5.275 (95% CI: 1.574–17.678)
  • p < 0.05
  • Identified via logistic regression analysis

Elevated IL-6 levels were an independent risk factor for post-stroke depression.

  • OR = 1.319 (95% CI: 1.089–1.599)
  • p < 0.05
  • Identified via logistic regression analysis

Elevated neurofilament light chain (NfL) levels were an independent risk factor for post-stroke depression.

  • OR = 1.103 (95% CI: 1.018–1.195)
  • p < 0.05
  • Identified via logistic regression analysis

Elevated serum GDF-15 levels were an independent risk factor for post-stroke depression after acute ischemic stroke.

  • OR = 1.021 (95% CI: 1.009–1.033)
  • p < 0.05
  • GDF-15 was measured at admission
  • Identified via logistic regression analysis

A nomogram-based prediction model combining GDF-15 and other clinical factors achieved high discriminatory performance for predicting PSD.

  • Area under the ROC curve (AUC) = 0.863 (95% CI: 0.810–0.885)
  • The model incorporated NIHSS scores, family history of psychiatric disorders, frontal lobe infarction, IL-6, NfL, and GDF-15
  • Model performance was assessed using receiver operating characteristic (ROC) analysis

What This Means

This research suggests that a protein called GDF-15, measured in the blood shortly after a stroke, is linked to the later development of post-stroke depression (PSD) — a common and serious complication affecting stroke survivors. In a study of 302 patients admitted after acute ischemic stroke, 100 (about one-third) went on to develop depression. Patients who developed PSD tended to be older, have more severe strokes, have a family history of psychiatric illness, and have higher blood levels of several inflammatory and neurological markers, including GDF-15, IL-6, and neurofilament light chain (NfL). Using statistical modeling, the researchers identified six independent risk factors for post-stroke depression: stroke severity (measured by NIHSS score), family history of psychiatric disorders, infarction in the frontal lobe of the brain, and elevated levels of IL-6, NfL, and GDF-15. These six factors were combined into a nomogram — a visual clinical prediction tool — that achieved an AUC of 0.863, indicating strong ability to distinguish patients who will develop PSD from those who will not. This research suggests that measuring GDF-15 alongside other clinical information at hospital admission could help clinicians identify stroke patients at high risk of developing depression, potentially enabling earlier monitoring or intervention. The combination of inflammatory markers, neurological injury markers, stroke location, and patient history appears to capture multiple biological pathways involved in post-stroke depression development.

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Citation

Guo C, Liu X, Yun Y, Mi Z. (2026). Changes in Serum GDF-15 in Relation to the Onset of Post-Stroke Depression After Acute Ischemic Stroke and the Development of a Comprehensive Prediction Model.. Actas espanolas de psiquiatria. https://doi.org/10.62641/aep.v54i4.2230