3.1 Sample characteristics
Participants (n=61), ages 18–73, were healthy volunteers (n=31) or were moderately depressed (mean score ± SD: HDRS-17, 20.13 ± 3.40; BDI, 25.87 ± 8.22) patients with a DSM-IV diagnosis of MDD (n=31) seeking evaluation and treatment, with (n=14) or without (n=16) a prior history of suicide attempt. There were no differences between depressed and healthy groups with respect to demographic characteristics, and suicide attempters differed from nonattempters only in having a lower educational level (see ). Of note, depression severity as measured by either clinician rating (HDRS-17) or self-report (BDI) did not distinguish between attempters and nonattempters. Depressed subjects were not on psychotropic medications except for two suicide attempters, who were taking (1) hypericum perforatum and (2) eszoplicone and zolpidem; and one nonattempter who was taking duloxetine.
Demographic characteristics of the study population across diagnostic groups.
3.2 Associations between kynurenine levels and suicide attempt status
There was a significant effect of KYN levels on suicide attempt status across the three groups: MDD attempter, MDD nonattempter, and healthy volunteers (F (2,58) = 4.03, p = 0.023). We tested two a priori planned contrasts and found that mean plasma KYN levels were higher in MDD suicide attempters compared with MDD nonattempters (t (58) = 2.10, p = 0.040), but MDD nonattempters did not differ from healthy volunteers (t (58) = 0.418, p = 0.677) (see ). In binary logistic regression analysis, higher KYN predicted suicide attempt (χ2(1) = 6.354, p = 0.012). Results were unchanged when the three subjects on medications were omitted (data not shown).
Plasma kynurenine levels are elevated in suicide attempters compared with nonattempters or healthy volunteers. Abbreviations: MDD, Major Depressive Disorder; *, p < 0.05.
3.3 Post-hoc analyses of the effects of other clinical and demographic factors on suicide attempt status
KYN levels did not correlate with age, educational level, smoking status, or HDRS-17 or BDI scores, but positively correlated with BMI and TRP in the total sample (see ). Mean KYN levels were higher in males (1.60 ± 0.30 vs. 1.27 ± 0.33 μmol/L, t (59) = 3.95, p < 0.001). When the KYN-associated covariates (BMI, TRP, sex) were included in separate logistic regression models, only KYN was a significant predictor of suicide attempt status in all models (data not shown).
Since neither age nor smoking status correlated significantly with KYN levels (see ), including them in the regression model would have a negligible additive effect on the association between KYN and suicide attempt status. However, both age (Shah, 2011) and smoking status (Hughes, 2008
) have been associated with suicide risk, so we tested for main effects and interactions between each of these variables and KYN, with regard to suicide attempt. In this sample, age was not associated with attempts (Wald statistic
= 0.669, df
= 1, p
= 0.414) and the KYN by age interaction term was not significant (Wald statistic
= 0.464, df
= 1, p
= 0.496). Within depressed individuals, smoking status was not significantly different between attempters and nonattempters (see ). However, when smoking and KYN levels were included in a regression model with all participants, both were associated with attempt (KYN: Wald statistic
= 7.404, df
= 1, p
= 0.007; smoking status: Wald statistic
= 6.6, df
= 1, p
= 0.010). The interaction term was not significant (Wald statistic
= 0.875, df
= 1, p
= 0.350), indicating that KYN levels were associated with suicide attempt in both smokers and non-smokers.
3.4 Relationships between tryptophan and kynurenine
The KYN:TRP ratio estimates the rate of TRP metabolism. When entered as a predictor in a logistic regression model in the entire sample with suicide attempter status as outcome measure, the KYN:TRP ratio showed a strong trend toward predicting suicide attempt (χ2 (1) = 3.70, p = 0.056). Average TRP was higher in suicide attempters than in nonattempters (see ). However, when included as covariate in a logistic regression with KYN as predictor, KYN levels predicted suicide attempt status (Wald statistic = 4.573, df = 1, p = 0.032) but TRP levels did not (Wald statistic = 0.414, df = 1, p = 0.520). Subgroup correlational analyses revealed that TRP correlated positively with KYN in the total sample and in all subgroups except among suicide attempters, where there was a clear lack of association (see ).
3.4 Neopterin levels as an indicator of immune system activation
In correlation analyses, the KYN:TRP ratio correlated positively with neopterin levels, a marker of a cell-mediated immune response, in suicide attempters (rs = 0.55, p = 0.043) but there was only a nonsignificant trend for a positive correlation in depressed nonattempters (rs = 0.44, p = 0.09) and the association was again weaker in the controls (rs = 0.29, p = 0.11).