Background: Schizophrenia is a chronic, recurrent disease that starts with a first psychotic episode and continues with periods of remission and acute psychosis with impaired interaction with stress. Aims: to allocate the gender differences in relation to distress in the salivary levels of the tryptophan (Trp), kynurenine (KYN) metabolites, cortisol and serotonin in patients with schizophrenia following psychological stress test. Methods: Eighty chronic schizophrenia patients and healthy controls, were subjected to a modified version of the Vienna test. Two saliva samples were gathered before and 10 minutes following stress test. Salivary concentration of cortisol, serotonin, Trp, L. KYN, Kynurenic acid (KYA), quinolinic acid (QUIN) and picolinic acid (PIC) were quantified by liquid chromatography triple quadrupole mass spectrometry. Results: Highly significant rise in the mean salivary post stress test cortisol concentration (P<0.001) and significant decrease in mean salivary PIC (P<0.05) of total schizophrenic patient group. Schizophrenic women showed decreased post stress salivary QUIN:KYA ratio (P<0.001), whereas men with schizophrenia exhibited increased QUIN:KYA (P<0.001) and KYN:Trp (P<0.05) ratios in comparison to their respective control values. Significant positive correlations of the pre-stress salivary PIC and QUIN (r=0.344, P=0.05) with highest sensitivity and specificities displayed by salivary cortisol and L.KYN values. Conclusion: Schizophrenic men showed aberrant response to psychological stress than women as reflected by highest neurotoxic QUIN: KYA index. This neurotoxic index is suggested as a marker for the therapeutic evaluation of the effect of antipsychotic drug on the patient-environment interaction.