High serum levels of 8-OHdG are an independent predictor of post-stroke depression in Chinese stroke survivors

Figures & data

Table 1 Baseline characteristics of the studied sample

Baseline characteristics	PSD (n=70)	No-PSD (n=171)	P-value
Demographic characteristics
Female, %	25 (35.7)	61 (35.7)	0.995
Age (years), median (IQR)	64 (57–71)	64 (56–70)	0.732
Years of education (years), median (IQR)	3 (0–6)	3 (0–6)	0.990
SBP (mmHg), mean ± SD	156.7±20.2	153.3±22.6	0.285
DBP (mmHg), mean ± SD	84.4±12.1	81.0±13.1	0.061
BMI, kg/m^2, mean ± SD	24.5±3.7	24.2±3.0	0.489
Prescribed drugs used chronically prior to the ischemic events
Hypertension medicine use, n (%)	36 (51.4)	95 (55.6)	0.559
Diabetes medicine use, n (%)	10 (14.3)	33 (19.3)	0.356
Lipid-lowering medicine use, n (%)	0	4 (2.3)	0.462
Aspirin or clopidogrel use, n (%)	4 (5.7)	9 (5.3)	1.000
Stroke etiology, n (%)
Atherosclerosis	61 (87.1)	156 (91.2)	0.098
Cardioembolism	4 (5.7)	8 (4.7)
Small vessel occlusion	3 (4.3)	7 (4.1)
Unknown	2 (2.9)	0
Lesion location (%)
Frontal lobe	6 (8.6)	28 (16.4)	0.106
Parietal lobe	1 (1.4)	7 (4.1)
Temporal lobe	1 (1.4)	7 (4.1)
Occipital lobe	3 (4.3)	7 (4.1)
Basal ganglia	24 (34.3)	43 (25.1)
Brainstem	4 (5.7)	21 (12.3)
Cerebellum	5 (7.1)	6 (3.5)
Thalamus	4 (5.7)	19 (11.1)
Other	22 (31.5)	33 (19.3)
Vascular risk factors, n (%)
Hypertension	48 (68.6)	111 (64.9)	0.586
Diabetes mellitus	16 (22.9)	37 (21.6)	0.836
Coronary artery disease	0	8 (4.7)	0.149
Hyperlipidemia	1 (1.4)	11 (6.4)	0.195
Smokers	21 (30.0)	50 (29.2)	0.906
Alcohol consumers	23 (32.9)	64 (37.4)	0.503
Stroke severity, median NIHSS score (IQR)	4 (2–6)	2 (1–3)	<0.001***
NIHSS ≤3	34 (48.5)	130 (76.0)	<0.001***
Cognitive function, median MMSE score (IQR)	19 (15–25)	23 (18–26)	0.018*
BI score, median (IQR)	72.5 (50–100)	95 (60–100)	0.013*
Laboratory parameters
8-OHdG (ng/L), median (IQR)	218.0 (170.6–246.7)	164.8 (121.1–208.0)	<0.001***
CAT (U/L), mean ± SD	64.1±23.9	57.3±20.1	0.025*
FBG (mmol/L), median (IQR)	5.3 (4.3–7.8)	4.8 (4.3–5.9)	0.04*
TG (mmol/L), median (IQR)	4.9 (4.2–5.7)	4.6 (3.9–5.4)	0.158
TC (mmol/L), median (IQR)	1.8 (1.3–2.3)	1.5 (1.2–2.0)	0.231
HDL-C (mmol/L), median (IQR)	1.1 (0.9–1.3)	1.1 (0.9–1.3)	0.492
LDL-C (mmol/L), median (IQR)	2.8 (2.2–3.7)	2.7 (2.1–3.4)	0.400

Notes: Continuous variables are expressed as the mean ± SD or the median (IQR). Categorical values are given as frequencies (percentages). The P-values reflect comparisons between PSD group and non-PSD group.

* <0.05,

*** <0.001, vs PSD group by univariate.

Abbreviations: 8-OHdG, 8-hydroxy-2′-deoxyguanosine; BI, modified Barthel index; BMI, body mass index; CAT, catalase; DBP, diastolic blood pressure; FBG, fasting blood glucose; HDL-C, high-density lipoprotein cholesterol; IQR, interquartile range; LDL-C, low-density lipoprotein cholesterol; MMSE, mini-mental state examination; NIHSS, National Institutes of Health Stroke Scale; PSD, post-stroke depression; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride.

Table 2 Adjusted OR of depression for 8-OHdG levels in stroke patients

Variables	OR (95% CI)	P-value
Age	1.006 (0.965–1.048)	0.779
Sex	0.728 (0.292–1.818)	0.497
NIHSS score	1.288 (1.099–1.511)	0.002**
MMSE score	0.931 (0.870–0.996)	0.038*
BI score	1.002 (0.985–1.020)	0.795
Smokers	1.379 (0.568–3.350)	0.477
Alcohol consumers	0.745 (0.332–1.673)	0.476
CAT	1.007 (0.991–1.024)	0.383
FBG	1.198 (1.020–1.407)	0.027*
Hypertension	1.385 (0.642–2.991)	0.406
Diabetes mellitus	0.566 (0.205–1.559)	0.271
Statins at admission	1.979 (0.139–28.158)	0.614
Vitamin C at admission	0.722 (0.160–3.255)	0.672
8-OHdG level at admission	1.019 (1.012–1.027)	<0.001***
8-OHdG level at admission	7.477 (3.432–16.289)	<0.001***
>200.0 ng/L

Note:

* P<0.05,

** P<0.01,

*** P<0.001.

Abbreviations: 8-OHdG, 8-hydroxy-2′-deoxyguanosine; BI, Barthel index; CAT, catalase; FBG, fasting blood glucose; MMSE, mini-mental state examination; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio.

Figure 1 Serum levels of 8-OHdG and CAT in patients with PSD and those without depression.

Notes: (A) 8-OHdG levels, (B) CAT levels. In the box-and-whisker plots, the horizontal line in the middle of each box indicates the median value; the lower and upper ends of the box represent the 25th and 75th percentiles, respectively, and the peripheral lines extending to the outer fences represent 10th and 90th percentiles. *P<0.05; ***P<0.001 compared with the non-PSD group via Mann–Whitney U test.
Abbreviations: 8-OHdG, 8-hydroxy-2′-deoxyguanosine; CAT, catalase; PSD, post-stroke depression.

Figure 2 Correlation between CAT and 8-OHdG levels in acute stroke patients or PSD patients.

Note: (A) In stroke patients, (B) in PSD patients.
Abbreviations: 8-OHdG, 8-hydroxy-2′-deoxyguanosine; CAT, catalase; PSD, post-stroke depression.

Figure 3 Receiver operator characteristic curve demonstrating sensitivity as a function of 1-specificity for predicting post-stroke depression within 1 month based on the serum 8-OHdG levels in stroke patients.

Abbreviation: 8-OHdG, 8-hydroxy-2′-deoxyguanosine.

Figure S1 Study flow chart.

Abbreviation: PSD, post-stroke depression.

Table S1 Prescribed drugs employed of the studied subjects at admission

Drugs	PSD patients (n=70)	Non-PSD patients (n=171)	P-value
Statins use, n (%)	69 (98.6)	164 (95.9)	0.514
Alprostadil injection, cinepazide maleate injection, or	12 (17.1)	42 (24.6)	0.210
vinpocetine injection
Aspirin or clopidogrel use, n (%)	65 (92.9)	158 (92.4)	0.902
Hypertension medicine use, n (%)	36 (51.4)	79 (46.2)	0.461
Diabetes medicine use, n (%)	19 (27.1)	45 (26.3)	0.895
Butylphthalide use, n (%)	24 (34.3)	68 (39.8)	0.427
Vitamin C injection use, n (%)	4 (5.7)	12 (7.0)	0.933
Mannitol use, n (%)	3 (4.3)	5 (2.9)	0.889
Ginkgo leaf extract and dipyridamole injection use, n (%)	4 (5.7)	10 (5.8)	1.000
Urinary kallidinogenase use, n (%)	1 (1.4)	8 (4.7)	0.424
Folic acid use, n (%)	3 (4.3)	7 (4.1)	1.000

Abbreviation: PSD, post-stroke depression.

Table S2 Serum 8-OHdG and CAT levels according to the severity of stroke and depression

Laboratory variables	A (n=130)	B (n=34)	C (n=41)	D (n=36)	P-value
8-OHdG (ng/L), median (IQR)	163.9 (124.8–211.1)	223.1*** (185.4–258.8)	164.9### (106.7–200.7)	212.9***,a (166.4–239.2)	<0.001***
CAT (U/L), median (IQR)	57.1 (42.9–70.7)	64.6 (45.1–77.6)	56.8 (43.1–69.1)	63.4 (51.2–80.4)	0.150

Notes: Patients were divided into 4 groups according to the severity of stroke and depression. A group: minor stroke (NIHSS ≤3) + depression (−); B group: minor stroke (NIHSS ≤3) + depression (+); C group: moderate-to-severe stroke (NIHSS >4) + depression (−); D group: moderate-to-severe stroke (NIHSS >4) + depression (+). The P-values reflect comparisons of serum 8-OHdG and CAT levels in the 4 groups.

*** P<0.001 compared to A group by univariate analysis;

### P<0.001 compared to B group by univariate analysis;

a P<0.001 compared to C group by univariate analysis.

Abbreviations: 8-OHdG, 8-Hydroxy-2′-deoxyguanosine; CAT, catalase; IQR, interquartile range; NIHSS, National Institutes of Health Stroke Scale.

Table S3 Comparisons of serum 8-OHdG and CAT levels in patients with minor stroke and those with moderate-to-severe stroke

Laboratory variables	NIHSS ≤3 (n=164)	NIHSS >3 (n=77)	P-value
8-OHdG (ng/L), mean ± SD	182.5±60.6	184.1±58.4	0.841
CAT (U/L), mean ± SD	58.8±21.9	60.2±20.4	0.638

Abbreviations: 8-OHdG, 8-Hydroxy-2′-deoxyguanosine; CAT, catalase; NIHSS, National Institutes of Health Stroke Scale.

Table S4 Correlations between oxidative stress markers and NIHSS scores

NIHSS scores	8-OHdG	CAT
NIHSS1	r=−0.03, P=0.642	r=0.041, P=0.523
NHSS2	r=−0.219, P=0.068	r=0.090, P=0.458
NIHSS3	r=−0.086, P=0.265	r=−0.030, P=0.700

Notes: NIHSS1: stroke group. NIHSS2: post-stroke depression group. NIHSS3: non-PSD group.

Abbreviations: 8-OHdG, 8-Hydroxy-2′-deoxyguanosine; CAT, catalase; NIHSS, National Institutes of Health Stroke Scale.