Objectives: Volatile organic compounds (VOCs) in the breathing air were found to be altered in schizophrenia patients compared to healthy participants. The aim of this study was to confirm these findings and to examine for the first time whether these VOCs are stable or change in concentration during the early treatment course. Moreover, it was investigated whether there is a correlation of the VOCs with the existing psychopathology of schizophrenia patients, i.e., whether the concentration of masses detected in the breath gas changes when the psychopathology of the participants changes. Methods: The breath of a total of 22 patients with schizophrenia disorder was examined regarding the concentration of VOCs using proton transfer reaction mass spectrometry. The measurements were carried out at baseline and after two weeks at three different time points, the first time immediately after waking up in the morning, after 30 min, and then after 60 min. Furthermore, 22 healthy participants were investigated once as a control group. Results: Using bootstrap mixed model analyses, significant concentration differences were found between schizophrenia patients and healthy control participants (m/z 19, 33, 42, 59, 60, 69, 74, 89, and 93). Moreover, concentration differences were detected between the sexes for masses m/z 42, 45, 57, 69, and 91. Mass m/z 67 and 95 showed significant temporal changes with decreasing concentration during awakening. Significant temporal change over two weeks of treatment could not be detected for any mass. Masses m/z 61, 71, 73, and 79 showed a significant relationship to the respective olanzapine equivalents. The length of hospital stay showed no significant relationship to the masses studied. Conclusion: Breath gas analysis is an easy-to-use method to detect differences in VOCs in the breath of schizophrenia patients with high temporal stability. m/z 60 corresponding to trimethylamine might be of potential interest because of its natural affinity to TAAR receptors, currently a novel therapeutic target under investigation. Overall, breath signatures seemed to stable over time in patients with schizophrenia. In the future, the development of a biomarker could potentially have an impact on the early detection of the disease, treatment, and, thus, patient outcome.

Background: Signatures from the metabolome and microbiome have already been introduced as candidates for diagnostic and treatment support. The aim of this study was to investigate the utility of volatile organic compounds (VOCs) from the breath for detection of schizophrenia and depression. Methods: Patients with a diagnosis of major depressive disorder (MDD) or schizophrenia, as well as healthy controls, were recruited to participate. After being clinically assessed and receiving instruction, each participant independently collected breath samples for subsequent examination by proton transfer–reaction mass spectrometry. Results: The sample consisted of 104 participants: 36 patients with MDD, 34 patients with schizophrenia and 34 healthy controls. Through mixed-model and deep learning analyses, 5 VOCs contained in the participants’ breath samples were detected that significantly differentiated between diagnostic groups and healthy controls, namely VOCs with mass-to-charge ratios ( m / z ) 60, 69, 74, 88 and 90, which had classification accuracy of 76.8% to distinguish participants with MDD from healthy controls, 83.6% to distinguish participants with schizophrenia from healthy controls and 80.9% to distinguish participants with MDD from those with schizophrenia. No significant associations with medication, illness duration, age of onset or time in hospital were detected for these VOCs. Limitations: The sample size did not allow generalization, and confounders such as nutrition and medication need to be tested. Conclusion: This study established promising results for the use of human breath gas for detection of schizophrenia and MDD. Two VOCs, 1 with m / z 60 (identified as trimethylamine) and 1 with m / z 90 (identified as butyric acid) could then be further connected to the interworking of the microbiota–gut–brain axis.