Peripheral metabolic abnormalities of lipids and amino acids implicated in increased risk of suicidal behavior in major depressive disorder

Suicide is the most serious consequence of major depressive disorder (MDD), yet a vast majority of MDD patients never attempt nor commit suicide. This discrepancy suggests a predisposition to suicidal behavior independent of MDD. However, the molecular basis of this predisposition remains largely unknown, hampering development of specific and targeted treatment of MDD patients at risk for suicide. A proton nuclear magnetic resonance (¹H NMR)-based metabonomic approach was used to capture metabolic perturbations related to suicide predisposition in the context of MDD. ¹H NMR spectra of plasma sampled from drug-naïve depressed suicide attempters (n = 21), non-attempters (n = 35), and healthy controls (n = 35) were recorded and analyzed through a multivariate statistical approach. Multivariate statistical analysis demonstrated that the depressed suicide attempter group was significantly distinguishable from the depressed non-attempter group and controls group. Several key metabolites, including lipids (low-density lipoprotein, very low-density lipoprotein, cholesterol and unsaturated lipid), lipid metabolism-related molecules (glucose, pyruvate and lactate) and amino acids (alanine, glycine and taurine) responsible for discriminating depressed suicide attempters from the nonattempters and controls were identified. This study is the first to indicate that peripheral perturbations in lipid and amino acid metabolism may be implicated in the predisposition to suicide in MDD patients.