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

Table 1 Demographic and clinical characteristics of study participants

Characteristic	PSD group (n = 46)	Non-PSD group (n = 66)	P value
Gender (female)	56.5	39.4	0.003
Age (years)	64.5 ± 12.2	66.3 ± 11.9	0.295
Education level			0.672
Primary school or below	41.3	39.4
Secondary school	39.1	40.9
College or above	19.6	19.7
Marital status (married)	82.6	86.4	0.462
Residence type (urban)	58.7	56.1	0.591
History of mental disorders	17.4	6.1	< 0.001
Social support (SSRS Score)	31.6 ± 7.7	38.8 ± 8.6	< 0.001
Smoking history	28.3	25.8	0.657
Alcohol history	19.6	15.2	0.435
History of hypertension	65.2	62.1	0.723
History of diabetes	26.1	25.8	0.954
History of dyslipidemia	30.4	28.8	0.837
History of atrial fibrillation	13.0	10.6	0.678

PSD: Post-stroke anxiety and depression; SSRS: Social Support Rating Scale.

Table 2 Stroke characteristics and post-stroke anxiety and depression

Stroke characteristic	PSD group (n = 46)	Non-PSD group (n = 66)	P value
NIHSS score at admission	8.2 ± 2.3	5.1 ± 1.8	< 0.001
Stroke location
Frontal lobe infarct	32.0	17.4	0.003
Limbic system infarct (including anterior cingulate cortex and basal ganglia-thalamic regions)	28.1	15.2	0.006
Functional status at 2 weeks post-stroke
mRS score	3.1 ± 0.9	2.0 ± 0.7	< 0.001
BI score	65.0 ± 15.0	80.0 ± 10.0	< 0.001
TOAST classification			0.327
History of stroke recurrence	15.2	9.1	0.345
Time of stroke onset (hours)	4.5 ± 1.2	3.0 ± 0.8	0.023
Systolic blood pressure at stroke onset (mmHg)	160.0 ± 20.0	150.0 ± 15.0	0.047
Blood glucose level at stroke onset (mmol/L)	7.5 ± 1.5	6.8 ± 1.0	0.032

PSD: Post-stroke anxiety and depression; NIHSS: National Institutes of Health Stroke Scale; mRS: Modified Rankin Scale; BI: Barthel Index; TOAST: Trial of Org 10172 in Acute Stroke Treatment Classification.

Table 3 Risk factors for post-stroke anxiety and depression: Multivariate analysis

Risk factor	Odds ratio	95% confidence interval	P value
Female gender	2.32	1.56-3.45	< 0.001
History of mental disorders prior to stroke	3.17	1.89-5.32	< 0.001
Infarct location in the frontal lobe or limbic system	2.86	1.73-4.71	< 0.001
Stroke severity with NIHSS ≥ 8 at admission	2.54	1.62-3.99	< 0.001
Low social support (SSRS score < 35)	2.18	1.42-3.36	0.002
Smoking history	1.45	0.92-2.29	0.110
Alcohol history	1.32	0.81-2.16	0.265
History of hypertension	1.28	0.85-1.93	0.246
History of diabetes	1.54	0.98-2.42	0.062

NIHSS: National Institutes of Health Stroke Scale; SSRS: Social Support Rating Scale.

Table 4 Subgroup analysis: Differences between anxiety and depression

Characteristic	Anxiety only (n = 15)	Depression only (n = 14)	Comorbid anxiety-depression (n = 17)	P value
Left hemisphere lesions	45.2	68.4	58.8	0.037
Right hemisphere lesions	59.5	39.5	47.1	0.044
NIHSS score at admission	6.5 ± 1.5	7.0 ± 2.0	9.5 ± 2.5	0.013
Functional status at 2 weeks post-stroke
mRS score	2.5 ± 0.8	3.0 ± 0.9	3.5 ± 1.0	< 0.001
BI score	75.0 ± 10.0	68.0 ± 12.0	60.0 ± 15.0	< 0.001
Social support score (SSRS)	35.0 ± 5.0	32.0 ± 6.0	30.0 ± 7.0	0.021
Time of stroke onset (hours)	3.5 ± 1.0	4.0 ± 1.2	4.5 ± 1.5	0.034
Systolic blood pressure at stroke onset (mmHg)	155.0 ± 20.0	160.0 ± 22.0	165.0 ± 25.0	0.048
Blood glucose level at stroke onset (mmol/L)	7.0 ± 1.2	7.2 ± 1.3	7.8 ± 1.5	0.039
Education level				0.056
Primary school or below	40.0	50.0	64.7
Secondary school	40.0	35.7	29.4
College or above	20.0	14.3	5.9
Age (years)	63.0 ± 10.0	65.0 ± 11.0	67.0 ± 12.0	0.234

NIHSS: National Institutes of Health Stroke Scale; mRS: Modified Rankin Scale; BI: Barthel Index; SSRS: Social Support Rating Scale.

Table 5 Neuroimaging findings

Neuroimaging feature	PSD group (n = 46)	Non-PSD group (n = 66)	P value
Infarct volume (cm³)	8.7 ± 2.5	5.3 ± 1.8	0.003
White matter hyperintensities (WMH)
Fazekas score (periventricular)	2.0 ± 0.5	1.0 ± 0.3	0.012
Fazekas score (deep white matter)	2.0 ± 0.4	1.0 ± 0.3	0.008
Brain atrophy
Frontal lobe atrophy (%)	25.0 ± 5.0	10.6 ± 3.0	0.017
Global brain atrophy (%)	45.7 ± 7.0	33.3 ± 6.0	0.086
Apparent diffusion coefficient (ADC)	0.82 ± 0.10 × 10-3 mm2/second	0.89 ± 0.12 × 10-3 mm2/second	0.045
Dynamic contrast-enhanced MRI parameters
Wash-in rate (WIR)	50.33 ± 5.0 seconds-1	45.00 ± 4.5 seconds-1	0.038
Time to peak (TTP)	120 ± 10 seconds	110 ± 8 seconds	0.027
Wash-out rate (WOR)	30.00 ± 3.5 seconds-1	25.00 ± 3.0 seconds-1	0.042

PSD: Post-stroke anxiety and depression; WMH: White matter hyperintensities; ADC: Apparent diffusion coefficient; WIR: Wash-in rate; TTP: Time to peak; WOR: Wash-out rate.

Table 6 Inflammatory and neuroendocrine biomarkers

Indicator	PSD group (n = 46)	Non-PSD group (n = 66)	P value
Inflammatory markers
IL-6 (pg/mL)	7.8 ± 1.2	4.5 ± 0.8	< 0.001
TNF-α (pg/mL)	15.6 ± 2.3	9.8 ± 1.5	< 0.001
CRP (mg/L)	12.5 ± 3.4	8.2 ± 2.1	0.002
MCP-1 (pg/mL)	450 ± 60	380 ± 50	0.010
HPA axis function
Morning serum cortisol (nmol/L)	386.5 ± 92.3	328.7 ± 75.6	< 0.001
Diurnal cortisol rhythm (evening decline)	Reduced	Normal	-
ACTH level (pg/mL)	40.5 ± 7.8	35.2 ± 6.5	0.034
Diurnal cortisol variation (%)	25.0 ± 5.0	35.0 ± 6.0	0.001
Cortisol awakening response (nmol/L)	150.0 ± 30.0	180.0 ± 40.0	0.02

PSD: Post-stroke anxiety and depression; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; CRP: C-reactive protein; MCP-1: Monocyte chemoattractant protein-1; HPA: Hypothalamic-pituitary-adrenal; ACTH: Adrenocorticotropic hormone.