Kynurenine and depressive symptoms in a poststroke population

Figures & data

Table 1 Clinical demographic characteristics by depression tertiles (n=86)

	Mean ± SD or % (low)* n=30	Mean ± SD or % (medium)* n=28	Mean ± SD or % (high)* n=28	χ^2 or F**	P-value^†
Age (years)	67.9±14.3	73.0±13.1	74.6±14.7	1.81	0.17
Sex (male)	56.7	53.6	46.4	0.63	0.73
History of depression	3.3	3.6	14.3	3.42	0.18
Antidepressant use	0	7.1	14.3	4.56	0.10
Living alone	20.0	42.9	28.6	3.64	0.16
Level of education > high school	55.1	40.7	40.7	10.89	0.37
Marital status (married)	56.7	42.9	53.6	12.47	0.13
Employment status (retired)	62.1	82.1	78.6	6.77	0.34
Days since stroke	25.4±35.1	22.9±37.3	20.1±28.6	0.18	0.84
Lesion volume (mm^3) (n=71)	31,107±61,158	17,700±39,967	15,502±14,894	0.86	0.43
CES-D scale	2.7±2.2	11.9±2.7	26.6±9.8
NIHSS	4.2±5.2	5.3±3.9	6.3±5.3	1.29	0.28
MMSE	26.3±4.2	27.2±2.3	26.3±4.4	0.51	0.60
Hypertension	73.3	75.0	96.4	6.22	0.045‡
Antihypertensive medication use	53.3	53.6	75.0	4.04	0.395
Diabetes	26.7	17.9	28.6	1.00	0.61
Hyperlipidemia	66.7	53.6	82.1	5.22	0.07
Cholesterol-lowering medication use	56.7	53.6	78.6	4.86	0.31
Obesity (BMI ≥30)	20.0	25.0	17.9	0.46	0.80
Smoking	33.3	3.6	17.9	8.49	0.014‡
Sum of risk factors§	2.2±1.4	1.8±1.0	2.4±0.9	15.08	0.129

Notes:

* Lowest CES-D scale tertile (0–6), middle tertile (7–16), highest tertile (17–47);

** χ² or F-values and corresponding ^†P-values reflect results of Pearson’s χ² tests with CES-D scale tertiles for categorical variables and ANOVAs between CES-D scale tertiles and continuous variables, respectively;

‡ P-values represent significant (P<0.05) associations between the CES-D scale and clinical/demographic variables;

§ sum of risk factors represents the sum of potential risk factors, including hypertension, diabetes, hyperlipidemia, obesity, or smoking.

Abbreviations: SD, standard deviation; BMI, body mass index; CES-D, Center for Epidemiological Studies Depression; NIHSS, National Institutes of Health Stroke Scale; MMSE, Mini-Mental State Examination; ANOVA, analysis of variance.

Figure 1 Mean serum kynurenine/tryptophan (K/T) ratios in low (0–6), medium (7–16), and high (17–47) Center for Epidemiological Studies Depression (CES-D) scale tertiles (n=86).

Table 2 Immunological assay results*

Immunological markers	Mean ± SD or median (IQR)
KYN (μmol/L)	3.04±1.64
TRP (μmol/L)	43.88±11.82
K/T (μmol/mmol)	73.32±43.22
IL-6 (pg/L)	3.90 (2.29–7.82)
IL-10 (pg/L)	0.20 (0.20–2.07)
IL-18 (pg/L)	251.40 (163.20–348.30)
IL-1β (pg/L)	0.19 (0.12–0.40)
TNF (pg/L)	1.91 (0.09–3.28)
IFNγ (pg/L)	0.61 (0.23–1.00)

Notes:

* n=86 for KYN, TRP, and K/T ratios; n=53 for cytokine assays.

Abbreviations: SD, standard deviation; IQR, interquartile range; KYN, kynurenine; TRP, tryptophan; K/T, KYN/TRP.

Figure 2 Mean serum cytokine/IL-10 ratios in low (0–6), medium (7–16), and high (17–47) Center for Epidemiological Studies Depression (CES-D) scale tertiles; n=53 for each panel.

Notes: (A) Mean serum IL-6/IL-10; (B) mean serum IL-18/IL-10; (C) mean serum IFNγ/IL-10; (D) mean serum TNF/IL-10; (E) mean serum IL-1β/IL-10 ratio in low (0–6), medium (7–16), and high (17–47) CES-D scale tertiles. *P<0.0005; ^†P<0.05.

Table 3 Differences between cytokines and cytokine ratios by CES-D tertiles (n=53)

Cytokines			Immunologic ratios
	F2,46*	P-value†		F2,46*	P-value†
IL-6	3.04	0.06	IL-6/IL-10	0.88	0.42
IL-18	2.12	0.13	IL-18/IL-10	3.30	0.046^‡
TNF	0.34	0.71	TNF/IL-10	0.69	0.51
IFNγ	2.54	0.09	IFNγ/IL-10	4.02	0.025^‡
IL-1β	3.55	0.037^‡	IL-1β/IL-10	4.34	0.019^‡
IL-10	1.83	0.17	–	–	–

Notes:

* F-statistics and corresponding

† P-values (^‡P<0.05) reflect results of independents in analysis-of-covariance models controlling for NIHSS score, age, antidepressant use, and hypertension. Controlling for smoking instead of hypertension showed similar results (for IL-1β, P=0.11; for IL-18/IL-10, P=0.008; for IFNγ/IL-10, P=0.17; for IL-1β/IL-10, P=0.025).

Abbreviations: CES-D, Center for Epidemiological Studies Depression; NIHSS, National Institutes of Health Stroke Scale.