Risk factors and early identification markers for post-ischemic stroke anxiety and depression

Abstract

BACKGROUND

Ischemic stroke is one of the leading global causes of disability and death. Despite advances in modern medical technology that improve acute treatment and rehabilitation measures, post-stroke anxiety and depression (PSD) do not receive sufficient attention.

AIM

To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice.

METHODS

This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024. Based on assessments using the Hamilton Rating Scale for Anxiety (HAMA) and Hamilton Rating Scale for Depression (HAMD) at 2 weeks (± 3 days) post-stroke, patients were classified into the PSD group (HAMA ≥ 7 and/or HAMD ≥ 7) and the non-PSD group (HAMA < 7 and HAMD < 7). Observation indicators included psychological assessment, demographic and clinical characteristics, stroke-related clinical indicators, neuroimaging assessments, and laboratory biomarkers. Multivariate logistic regression analysis was used to identify independent risk factors for PSD, and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers.

RESULTS

Of the 112 patients, 46 (41.1%) were diagnosed with PSD. Multivariate analysis identified five independent risk factors: Female gender [Odds ratio (OR) = 2.32, 95% confidence interval (CI): 1.56-3.45], history of mental disorders prior to stroke (OR = 3.17, 95%CI: 1.89-5.32), infarct location in the frontal lobe or limbic system (OR = 2.86, 95%CI: 1.73-4.71), stroke severity with National Institutes of Health Stroke Scale ≥ 8 at admission (OR = 2.54, 95%CI: 1.62-3.99), and low social support (Social Support Rating Scale < 35, OR = 2.18, 95%CI: 1.42-3.36). Subgroup analysis showed that depression patients more commonly had left hemisphere lesions (68.4% vs 45.2%), while anxiety patients more frequently presented with right hemisphere lesions (59.5% vs 39.5%). The PSD group exhibited larger infarct volumes (8.7 cm³vs 5.3 cm³), more severe white matter hyperintensities, and more pronounced frontal lobe atrophy. Analysis of inflammatory markers showed significantly elevated levels of interleukin-6 (7.8 pg/mL vs 4.5 pg/mL) and tumor necrosis factor-alpha (15.6 pg/mL vs 9.8 pg/mL) in the PSD group, while hypothalamic-pituitary-adrenal axis function assessment revealed higher cortisol levels (386.5 ± 92.3 nmol/L vs 328.7 ± 75.6 nmol/L) and flattened diurnal rhythm in the PSD group.

CONCLUSION

PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry, neuroinflammatory responses, and dysfunction of the hypothalamic-pituitary-adrenal axis.

Keywords: Ischemic stroke; Anxiety and depression; Risk factors; Biomarkers; Brain-derived neurotrophic factor

Core Tip: Post-stroke anxiety and depression are common but underrecognized complications after ischemic stroke, adversely affecting recovery and prognosis. This study integrates demographic, clinical, neuroimaging, inflammatory, and neuroendocrine indicators to identify independent risk factors and early biomarkers for post-stroke anxiety and depression. Female gender, prior mental disorders, frontal-limbic infarcts, severe stroke, and low social support were key predictors. Elevated interleukin-6, tumor necrosis factor-alpha, and cortisol, alongside reduced insulin-like growth factor-1, showed strong diagnostic value, providing a multidimensional framework for early screening and targeted intervention in high-risk patients.