Comprehensive psychological and neurological rehabilitation for post-stroke depression: A retrospective comparative study with biomarker exploration

Abstract

BACKGROUND

Post-stroke depression (PSD) is one of the most common and debilitating neuropsychiatric sequelae after ischemic stroke, with a prevalence of 30%-50%, which significantly hinders neurological recovery, participation in rehabilitation, and long-term quality of life. Although the clinical burden of stroke is high, integrated rehabilitation strategies that effectively combine structured psychological rehabilitation with its neurological counterpart are under-defined. The best combination of interventions and predictors of response to therapies have not yet been systematically characterized.

AIM

To assess clinical effectiveness of a psychological rehabilitation oriented comprehensive intervention program aimed for PSD patients, find out independent predictors effecting treatment response and novel serum biomarkers including neuropeptide Y (NPY) as indicators for rehabilitation outcome of PSD patients, also use validated nomogram prediction model in order to guide personalized clinical decision-making.

METHODS

A retrospective study was performed comprised of 178 patients with confirmed acute cerebral infarction and PSD, that were admitted to Departments of Neurology and Rehabilitation Medicine between September 2020 and March 2024. Patients were assigned to a comprehensive rehabilitation group (CRG) (n = 96) receiving cognitive behavioral therapy (CBT)-centered psychological rehabilitation combined with systematic neurological rehabilitation, or a control group (CG) (n = 82) receiving standard pharmacological treatment and basic physiotherapy. The primary outcome was change in Hamilton Depression Rating Scale-17 (HAMD-17) and remission rate (HAMD-17 < 7) at 12 weeks. Secondary outcomes were the Fugl-Meyer Assessment (FMA), Modified Barthel Index (MBI), Montreal Cognitive Assessment and Stroke-Specific Quality of Life Scale. Single serum biomarkers included NPY, brain-derived neurotrophic factor (BDNF), pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and IL-10], neuroendocrine markers and indices of oxidative stress collected at baseline and 12 weeks. Independent predictors of response to treatment were identified through multivariable logistic regression analysis and a nomogram model was built, internally validated using Bootstrap resampling, and assessed by calibration curves and decision curve analysis.

RESULTS

The CRG showed significantly lower HAMD-17 scores (7.2 ± 3.4 vs 13.8 ± 4.6; P < 0.001) and higher rates of depression remission (67.7% vs 29.3%; P < 0.001) from those in the CG at 12 weeks follow-up visit, respectively. The CRG had significantly higher FMA scores (78.5 ± 14.2 vs 58.3 ± 16.8; P < 0.001) and MBI scores (76.8 ± 13.5 vs 58.6 ± 15.2; P < 0.001). In the multivariable logistic regression analyses, seven independent predictors of therapeutic response were identified: Early initiation of psychological intervention [≤ 2 weeks; odds ratio (OR) = 4.12, 95% confidence interval (CI): 2.28-7.44, P < 0.001]; Baseline serum NPY level ≥ 82.5 pg/mL (OR = 3.38, 95%CI: 1.95-5.86, P < 0.001); Mild-to-moderate depression severity (HAMD-17 < 17; OR = 2.94, 95%CI: 1.68-5.14, P < 0.001); High family involvement (family support questionnaire ≥ 28; OR = 2.65, 95%CI: 1.58-4.44, P < 0.001); Intact cognition (Mini-Mental State Examination ≥ 24; OR = 2.42, 95%CI: 1.45-4.04, P = 0.001); Non-dominant hemisphere lesion (OR = 2.08, 95%CI: 1.22-3.55, P = 0.008); and baseline IL-1β < 8.2 pg/mL (OR = 1.86, 95%CI: 1.10-3.15, P = 0.021). The Bootstrap-validated C-index of the nomogram model was 0.85 (area under the curve = 0.87, 95%CI: 0.81-0.92), sensitivity 80.2%, specificity 83.6%. Post-intervention, CRG displayed significantly higher serum NPY levels (98.6 ± 18.4 pg/mL vs 76.2 ± 15.8 pg/mL), BDNF (22.5 ± 5.2 ng/mL vs 15.2 ± 4.8 ng/mL) and markedly lower IL-1β, IL-6 and TNF-α levels compared with CG (all P < 0.001).

CONCLUSION

CBT-based comprehensive rehabilitation program effectively improves depression and motor functions in patients with PSD. The timing of the intervention, neuroinflammatory state, cognitive reserve and family support, as well as lesion laterality shape treatment response. The serum NPY is a candidate biomarker and the Nomogram, a potential decision-support tool pending external validation before clinical use.

Keywords: Post-stroke depression; Psychological rehabilitation; Cognitive behavioral therapy; Neuropeptide Y; Neurological rehabilitation; Neuroinflammation; Nomogram prediction model

Core Tip: Ischemic stroke can lead to post-stroke depression (PSD), which is an important protective factor for neurological recovery, rehabilitation compliance and patient quality of life. In this retrospective study, we found that a cognitive behavioral therapy-centered comprehensive rehabilitation program integrating psychological with neurological rehabilitation was superior to standard care in terms of depressive symptoms, motor recovery, cognitive function and daily living ability. Baseline serum neuropeptide Y identified as a prospective treatment response biomarker. Earlier intervention, enhanced family engagement, preserved cognition, reduced inflammation and non-dominant hemisphere lesions also predicted better outcomes. An internally validated nomogram might facilitate individualized rehabilitation planning in PSD patients.