The Metabonomics Of Plasma Of Major Depressive Disorder With Suicide Attempts

Background and Objective:About one million suicides and ten million suicide attempts occurworldwide each year. Suicide is not simply a response to stress, butgenerally a complication of a psychiatric disorder. Suicide is the mostserious consequence of major depressive disorder (MDD), yet a vastmajority of MDD patients never attempt nor commit suicide. Thisdiscrepancy suggests a predisposition to suicidal behavior independent ofMDD. However, the molecular basis of this predisposition remainslargely unknown, hampering development of specific and targetedtreatment of MDD patients at risk for suicide.In this study, a proton nuclear magnetic resonance (1H-NMR)-basedmetabonomic approach was used to capture metabolic perturbations relatedto suicide predisposition in the context of MDD. In addition, combining themultiple variable statically methods and OPLS-DA, we identified the keymetabolites that could significantly distinguish suicide from the depressednon-attempter group and controls group combining multivariate statisticalanalysis. Methods:1. Patients：35healthy subjects served as control group．56diagnosedpatients with major depressive disorders who match the selectionconditions served as disease group, including21depressed patients whoattempted suicide, and35depressed non-attempters．2. Sample collection： Fasting blood sample was collected withvacutainer tubes containing the chelating agent ethylene diamine tetraaceticacid (EDTA). The blood sample was centrifuged and divided into aliquotsand then stored at-80℃refrigerator, avoiding freeze–thaw cycles.3. NMR analysis of plasma samples：The NMR technique basedmetabonomic method was established, and the plasma was introduced toNMR. Applying the NMR method, the plasma samples from the healthysubjects, the MDD patients and the MDD patients companied with suicideattempts were collected and detected by the machine. The plasmaendogenous metabolites were identified．4. Data analysis: Through a variety of analysis of statistical analysismethod of analysis produced massive data, following-up the normalization,Through the least squares discriminant analysis (OPLS-DA) to undergosamples classification; According to non-parameter test results, ifp<0.05，significant difference was taken into consideration.Results:1. Through the OPLS-DA analysis, it demonstrated that suicide attempters were completely distinguishable from the healthy controls andnon-attempters.2. Compared with the healthy controls,14metabolites in themetabolic composition of plasma samples from depression with suicideattempts, there are higher levels of low-density lipoprotein (LDL), verylow-density lipoprotein (VLDL), glucose, acetone, and taurine combinedwith lower levels of cholesterol, unsaturated lipid, pyruvate, lactate, acetate,alanine, valine, glycine, and glutamine.3. Compared with the depressive patients (non-suicide attempts),11metabolites in the metabolic composition of plasma samples fromdepression with suicide attempts, there are higher levels of myo-inositol,glucose, pyruvate, alanine, glycine, and taurine combined with lowerlevels of low-density lipoprotein (LDL), very low-density lipoprotein(VLDL), cholesterol, unsaturated lipid, and lactate.4. Comparative analyses of the differential metabolites responsible fordiscriminating suicide attempters from non-attempters were performed.Metabolic disturbances of lipids (LDL, VLDL, cholesterol and unsaturatedlipid), lipid metabolism-related molecules (glucose, pyruvate and lactate),and amino acids (alanine, glycine and taurine) were attributable to thepredisposition to suicidal behavior in MDD patients.Conclusions：In conclusion, through a1HNMR-based metabonomics approach, the current study links peripheral metabolic abnormalities in lipid and aminoacid metabolism to the predisposition to suicide in MDD patients.