{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T02:34:38Z","timestamp":1792982078674,"version":"4.5.0"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Major depressive disorder (MDD) is one of the most common psychiatric disorders with multifactorial etiologies. Metabolomics has recently emerged as a particularly potential quantitative tool that provides a multi-parametric signature specific to several mechanisms underlying the heterogeneous pathophysiology of MDD. The main purpose of the present study was to investigate possibilities and limitations of breath-based metabolomics, breathomics patterns to discriminate MDD patients from healthy controls (HCs) and identify the altered metabolic pathways in MDD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Breath samples were collected in Tedlar bags at awakening, 30 and 60 min after awakening from 26 patients with MDD and 25 HCs. The non-targeted breathomics analysis was carried out by proton transfer reaction mass spectrometry. The univariate analysis was first performed by T-test to rank potential biomarkers. The metabolomic pathway analysis and hierarchical clustering analysis (HCA) were performed to group the significant metabolites involved in the same metabolic pathways or networks. Moreover, a support vector machine (SVM) predictive model was built to identify the potential metabolites in the altered pathways and clusters. The accuracy of the SVM model was evaluated by receiver operating characteristics (ROC) analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 23 differential exhaled breath metabolites were significantly altered in patients with MDD compared with HCs and mapped in five significant metabolic pathways including aminoacyl-tRNA biosynthesis (<jats:italic>p<\/jats:italic> = 0.0055), branched chain amino acids valine, leucine and isoleucine biosynthesis (<jats:italic>p<\/jats:italic> = 0.0060), glycolysis and gluconeogenesis (<jats:italic>p<\/jats:italic> = 0.0067), nicotinate and nicotinamide metabolism (<jats:italic>p<\/jats:italic> = 0.0213) and pyruvate metabolism (<jats:italic>p<\/jats:italic> = 0.0440). Moreover, the SVM predictive model showed that butylamine (<jats:italic>p<\/jats:italic> = 0.0005, p<jats:sub>FDR<\/jats:sub>=0.0006), 3-methylpyridine (<jats:italic>p<\/jats:italic> = 0.0002, p<jats:sub>FDR<\/jats:sub> = 0.0012), endogenous aliphatic ethanol isotope (<jats:italic>p<\/jats:italic> = 0.0073, p<jats:sub>FDR<\/jats:sub> = 0.0174), valeric acid (<jats:italic>p<\/jats:italic> = 0.005, p<jats:sub>FDR<\/jats:sub> = 0.0162) and isoprene (<jats:italic>p<\/jats:italic> = 0.038, p<jats:sub>FDR<\/jats:sub> = 0.045) were potential metabolites within identified clusters with HCA and altered pathways, and discriminated between patients with MDD and non-depressed ones with high sensitivity (0.88), specificity (0.96) and area under curve of ROC (0.96).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>According to the results of this study, the non-targeted breathomics analysis with high-throughput sensitive analytical technologies coupled to advanced computational tools approaches offer completely new insights into peripheral biochemical changes in MDD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpsyt.2022.1061326","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T14:43:28Z","timestamp":1671029008000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Breathomics profiling of metabolic pathways affected by major depression: Possibilities and limitations"],"prefix":"10.3389","volume":"13","author":[{"given":"Laila","family":"Gbaoui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Fachet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"L\u00fcno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Meyer-Lotz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Frodl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hoeschen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"B1","unstructured":"Depression and Other Common Mental Disorders: Global Health Estimates2017"},{"key":"B2","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.neuropharm.2016.07.002","article-title":"Kynurenine pathway metabolism and the microbiota-gut-brain axis","volume":"112","author":"Kennedy","year":"2016","journal-title":"Neuropharmacology."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nrdp.2016.65","article-title":"Major depressive disorder","volume":"2","author":"Otte","year":"2016","journal-title":"Nat Rev Dis Prim."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fpsyg.2021.641779","article-title":"Pathophysiology of major depression by clinical stages","volume":"12","author":"Menezes Galv\u00e3o","year":"2021","journal-title":"Front Psychol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"002","DOI":"10.1016\/j.jpsychires.2019.08.002","article-title":"Changes in the global burden of depression from 1990 to 2017: findings from the global burden of disease study","volume":"126","author":"Liu","year":"2020","journal-title":"J Psychiatric Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"963","DOI":"10.13031\/trans.56.9922","article-title":"Predicting soil bulk density using advanced pedotransfer functions in an arid environment","volume":"56","author":"Al-Qinna","year":"2013","journal-title":"Transact ASABE."},{"key":"B7","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1038\/mp.2012.33","article-title":"Berk M. The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance and therapeutic implications","volume":"18","author":"Moylan","year":"2013","journal-title":"Mol Psychiatry."},{"key":"B8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.neubiorev.2010.01.010","article-title":"Human hypothalamus-pituitary-adrenal axis responses to acute psychosocial stress in laboratory settings","volume":"35","author":"Foley","year":"2010","journal-title":"Neurosci Biobehav Rev"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2289","DOI":"10.2147\/NDT.S62289","article-title":"The cortisol awakening response and major depression: examining the evidence","volume":"11","author":"Dedovic","year":"2015","journal-title":"Neuropsych Dis Treat"},{"key":"B10","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/nrn3346","article-title":"Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour","volume":"13","author":"Cryan","year":"2012","journal-title":"Nat Rev Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fpsyt.2020.00541","article-title":"Altered composition of gut microbiota in depression: a systematic review","volume":"11","author":"Barandouzi","year":"2020","journal-title":"Front Psychiatry."},{"key":"B12","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3389\/fpsyt.2019.00034","article-title":"Systematic review of gut microbiota and major depression","volume":"10","author":"Cheung","year":"2019","journal-title":"Front Psychiatry."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnins.2017.00493","article-title":"Saia-Cereda, VM, Nascimento, JM, Martins-de-Souza D. The energy metabolism dysfunction in psychiatric disorders postmortem brains","volume":"11","author":"Zuccoli","year":"2017","journal-title":"Focus Prot Evid."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1016\/j.biopha.2021.111869","article-title":"Energy metabolism in major depressive disorder: recent advances from omics technologies and imaging","volume":"3","author":"Gu","year":"2021","journal-title":"Biomed Pharmacotherapy."},{"key":"B15","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.biopsych.2019.08.016","article-title":"Metabolomics profile in depression: a pooled analysis of 230 metabolic markers in 5283 cases with depression and 10,145 controls","volume":"87","author":"Bot","year":"2020","journal-title":"Biol Psychiatry."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1088\/1752-7155\/6\/2\/024001","article-title":"Microbial volatile compounds in health and disease conditions","volume":"6","author":"Thorn","year":"2012","journal-title":"J Breath Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.2147\/NDT.S164134","article-title":"Plasma disturbance of phospholipid metabolism in major depressive disorder by integration of proteomics and metabolomics","volume":"14","author":"Gui","year":"2018","journal-title":"Neuropsychiatr Dis Treat."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-018-0183-x","article-title":"Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters : a targeted metabolomics study","author":"Pan","year":"2018","journal-title":"Translat Psychiatry"},{"key":"B19","doi-asserted-by":"publisher","first-page":"7012","DOI":"10.1101\/2020.02.10.927012","article-title":"alterations in acylcarnitines, amines, lipids inform about mechanism of action of citalopram\/escitalopram in major depression","volume":"3","author":"MahmoudianDehkordi","year":"2020","journal-title":"BioRxiv"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0068283","article-title":"Pharmacometabolomics of response to sertraline and to placebo in major depressive disorder","volume":"8","author":"Zhu","year":"2013","journal-title":"Poss Role Methoxyindole Pathway"},{"key":"B21","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1371\/journal.pone.0160542","article-title":"Branched-chain amino acids as new biomarkers of major depression - a novel neurobiology of mood disorder","volume":"11","author":"Baranyi","year":"2016","journal-title":"PLoS ONE"},{"key":"B22","doi-asserted-by":"publisher","first-page":"371","DOI":"10.4196\/kjpp.2014.18.5.371","article-title":"Alterations of amino acid level in depressed rat brain Korean","volume":"18","author":"Yang","year":"2014","journal-title":"J Physiol Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1743-422X-8-98","article-title":"Exhaled breath condensate sampling is not a new method for detection of respiratory viruses","volume":"8","author":"Houspie","year":"2011","journal-title":"Virol J"},{"key":"B24","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1101\/194985","article-title":"Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community","author":"Yan","year":"2017","journal-title":"Proceed Nat Acad Sci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"33","DOI":"10.4172\/2327-5073.1000151","volume":"3","author":"Sohrabi","year":"2014","journal-title":"Clin Microbiol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1007\/s40846-016-0164-6","article-title":"Significance of exhaled breath test in clinical diagnosis: a special focus on the detection of diabetes mellitus","volume":"36","author":"Das","year":"2016","journal-title":"J Med Biol Eng."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1088\/1752-7155\/4\/2\/026003","article-title":"Volatile biomarkers in the breath of women with breast cancer","volume":"4","author":"Phillips","year":"2010","journal-title":"J Breath Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1046\/j.1524-4741.2003.09309.x","article-title":"Breath test for bca volatile markers of breast cancer in the breath breath test for BCA","volume":"9","author":"Phillips","year":"2003","journal-title":"Breast J."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.aca.2017.09.021","article-title":"Review of recent developments in determining volatile organic compounds in exhaled breath as biomarkers for lung cancer","volume":"996","author":"Zhou","year":"2017","journal-title":"Diag Anal Chimica Acta."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2663","DOI":"10.1002\/ijc.24970","article-title":"Breath gas aldehydes as biomarkers of lung cancer","volume":"126","author":"Fuchs","year":"2010","journal-title":"Int J Cancer."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1038\/bjc.2011.128","article-title":"Diagnosis of head-and-neck cancer from exhaled breath","volume":"104","author":"Hakim","year":"2011","journal-title":"Br J Cancer."},{"key":"B32","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/bjc.2014.361","article-title":"Analysis of exhaled breath for diagnosing head and neck squamous cell carcinoma: a feasibility study","volume":"111","author":"Gruber","year":"2014","journal-title":"Br J Cancer."},{"key":"B33","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1080\/15622975.2022.2040052","article-title":"Volatile organic compounds from exhaled breath in schizophrenia","volume":"3","author":"Jiang","year":"2022","journal-title":"World J Biol Psychiatry"},{"key":"B34","author":"Marion","year":"2002","journal-title":"United States Patent Application Publication"},{"key":"B35","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1136\/jcp.48.5.466","article-title":"Volatile organic compounds in the breath of patients with schizophrenia","volume":"48","author":"Phillips","year":"1995","journal-title":"J Clin Pathol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1513\/AnnalsATS.201504-213OC","article-title":"Exhaled nitric oxide decreases during academic examination stress in asthma","volume":"12","author":"Ritz","year":"2015","journal-title":"Ann Am Thorac Soc."},{"key":"B37","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1002\/ijop.12494","article-title":"Exhaled breath analysis in evaluation of psychological stress: a short literature review","volume":"54","author":"Tonacci","year":"2019","journal-title":"Int J Psychol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.4314\/ajpherd.v17i3.71103","article-title":"A report on the evaluation of a breath workshop for stress management by sport psychology students","volume":"17","author":"Edwards","year":"2011","journal-title":"Af J Physical Health Edu Recreat Dance"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fpsyt.2022.819607","article-title":"Volatile organic compounds from breath differ between patients with major depression and healthy controls","volume":"13","author":"Lueno","year":"2022","journal-title":"Front Psychiatry"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1001\/archpsyc.1961.01710120031004","article-title":"An inventory for measuring depression","volume":"4","author":"Beck","year":"1961","journal-title":"Arch Gen Psychiatry"},{"key":"B41","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","article-title":"A rating scale for depression","volume":"23","author":"Hamilton","year":"1960","journal-title":"J Neurol Neurosurg Psychiat."},{"key":"B42","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1088\/0967-3334\/28\/5\/005","article-title":"An off-line breath sampling and analysis method suitable for large screening studies","volume":"28","author":"Steeghs","year":"2007","journal-title":"Physiol Measur"},{"key":"B43","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1088\/0967-3334\/28\/1\/007","article-title":"The suitability of tedlar bags for breath sampling in medical diagnostic research","volume":"28","author":"Steeghs","year":"2007","journal-title":"Physiol Meas."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1039\/b204712h","article-title":"The Application of proton transfer reaction-mass spectrometry (PTR-MS) to the monitoring and analysis of volatile organic compounds in the atmosphere","volume":"5","author":"Hewitt","year":"2003","journal-title":"J Environ Monitor."},{"key":"B45","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s13361-019-02209-3","article-title":"A library of proton-transfer reactions of H3O+ Ions used for trace gas detection","volume":"3","author":"Pagonis","year":"2019","journal-title":"J Am Soc Mass Spectromet"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-19120-0","article-title":"Missing value imputation approach for mass spectrometry-based metabolomics data","volume":"8","author":"Wei","year":"2018","journal-title":"Sci Rep."},{"key":"B47","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: a flexible statistical power analysis program for the social","volume":"39","author":"Faul","year":"2007","journal-title":"BehavBiomed Sci Behav Res Methods."},{"key":"B48","author":"Nielsen","year":"2019","journal-title":"Hierarchical Clustering"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2342","DOI":"10.1093\/bioinformatics\/btq418","article-title":"MetPA: a web-based metabolomics tool for pathway analysis and visualization","volume":"27","author":"Xia","year":"2011","journal-title":"Bioinformatics."},{"key":"B50","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1093\/bioinformatics\/btg382","article-title":"A global test for groups of genes : testing association with a clinical outcome","volume":"20","author":"Goeman","year":"2004","journal-title":"Bioinformatics"},{"key":"B51","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1093\/bib\/bbl022","article-title":"Graph-based methods for analysing networks in cell biology","volume":"7","author":"Aittokallio","year":"2006","journal-title":"Brief Bioinform"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1038\/nbt1206-1565","article-title":"What is a support vector machine?","volume":"24","author":"Noble","year":"2006","journal-title":"Nat Biotechnol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/0006-3223(92)90039-3","article-title":"Low plasma \u03b3-aminobutyric acid levels in male patients with depression","volume":"32","author":"Petty","year":"1992","journal-title":"Biol Psychiatry."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12950-020-00266-0","article-title":"Tryptophan-kynurenine metabolism: a link between the gut and brain for depression in inflammatory bowel disease","volume":"18","author":"Chen","year":"2021","journal-title":"J Neuroinflammation."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-58806-w","article-title":"Serum metabolic profiles of the tryptophan-kynurenine pathway in the high risk subjects of major depressive disorder","volume":"10","author":"Sakurai","year":"2020","journal-title":"Scient Reports"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jpsychires.2015.02.021","article-title":"Collective unconscious: how gut microbes shape human behavior","volume":"63","author":"Dinan","year":"2015","journal-title":"J Psychiatric Res"},{"key":"B57","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.neurpharm.2016.07.002","article-title":"FKynurenine pathway metabolism and the microbiota-gut-brain axis","volume":"112","author":"Kennedy","year":"2018","journal-title":"Front Microbiol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/s41398-019-0391-z","article-title":"Altered gut metabolome contributes to depression-like behaviors in rats exposed to chronic unpredictable mild stress","volume":"9","author":"Jianguo","year":"2019","journal-title":"TranslatPsychiatry"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1128\/IAI.00862-09","article-title":"Stressor exposure disrupts commensal microbial populations in the intestines and leads to increased colonization by citrobacter rodentium","volume":"78","author":"Bailey","year":"2010","journal-title":"Infect Immun"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fendo.2020.00025","article-title":"The role of short-chain fatty acids from gut microbiota in gut-brain communication","volume":"11","author":"Silva","year":"2020","journal-title":"Front Endocrinol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3402\/mehd.v27.30971","article-title":"Neuromodulatory effects and targets of the SCFAs and gasotransmitters produced by the human symbiotic microbiota","volume":"1","author":"Oleskin","year":"2016"},{"key":"B62","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/s41588-019-0350-x","article-title":"Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases","volume":"51","author":"Sanna","year":"2019","journal-title":"Nat Genetics"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21176356","article-title":"Short-chain fatty acids and their association with signalling pathways in inflammation. Glucose and lipid metabolism","volume":"21","author":"He","year":"2020","journal-title":"Int J Mol Sci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1194\/jlr.R067629","article-title":"Short- and Medium-chain fatty acids in energy metabolism : the cellular perspective","volume":"57","author":"Sch\u00f6nfeld","year":"2016","journal-title":"J Lipid Res"},{"key":"B65","doi-asserted-by":"publisher","first-page":"858","DOI":"10.3390\/nu3100858","article-title":"Regulation of inflammation by short chain fatty acids","volume":"3","author":"Vinolo","year":"2011","journal-title":"Nutrients"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.3390\/nu10121939","article-title":"Faecal short chain fatty acids profile is changed in polish depressive women","volume":"10","author":"Skonieczna-Zydecka","year":"2018","journal-title":"Nutrients"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.2147\/NDT.S186071","article-title":"Metabonomics reveals peripheral and central short- chain fatty acid and amino acid dysfunction in a naturally occurring depressive model of macaques","volume":"5","author":"Deng","year":"2019","journal-title":"Neuropsych Dis Treat"},{"key":"B68","doi-asserted-by":"publisher","first-page":"7225","DOI":"10.1007\/s11906-017-0722-5","article-title":"Microbial short-chain fatty acids and blood pressure regulation","volume":"5","author":"Pluznick","year":"2017","journal-title":"Curr Hypert Reports"},{"key":"B69","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1177\/1535370220979952","article-title":"Analyses of short-chain fatty acids and exhaled breath volatiles in dietary intervention trials for metabolic diseases","volume":"246","author":"Lee","year":"2021","journal-title":"Exp Biol Med."},{"key":"B70","article-title":"We are intechopen, the world's leading publisher of open access books built by scientists, for scientists top 1 %. in","author":"Auguet","year":"2021","journal-title":"Intech"},{"key":"B71","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2016.00047","article-title":"Ethanol production by selected intestinal microorganisms and lactic acid bacteria growing under different nutritional conditions","volume":"7","author":"Elshaghabee","year":"2016","journal-title":"Front Microbiol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1053\/gast.2000.19267","article-title":"Increased gastrointestinal ethanol production in obese mice: implications for fatty liver disease pathogenesis","volume":"119","author":"Cope","year":"2000","journal-title":"Gastroenterology."},{"key":"B73","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1177\/002580240004000304","article-title":"Endogenous ethanol \u2018auto-brewery syndrome' as a drunk-driving defence challenge","volume":"40","author":"Logan","year":"2000","journal-title":"Med Sci Law."},{"key":"B74","doi-asserted-by":"publisher","first-page":"3371","DOI":"10.1128\/IAI.00449-12","article-title":"Candida albicans and bacterial microbiota interactions in the cecum during recolonization following broad-spectrum antibiotic therapy","volume":"80","author":"Mason","year":"2012","journal-title":"Infect Immun."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1007\/s11064-008-9865-8","article-title":"Mitochondrial dysfunction and psychiatric disorders","volume":"34","author":"Rezin","year":"2009","journal-title":"Neurochem Res."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-57566-x","article-title":"Systematic impacts of chronic unpredictable mild stress on metabolomics in rats","volume":"10","author":"Geng","year":"2020","journal-title":"Scientific Reports"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnins.2019.00926","article-title":"Pilot study of metabolomic clusters as state markers of major depression and outcomes to CBT treatment","volume":"13","author":"Bhattacharyya","year":"2019","journal-title":"Front Neurosci"},{"key":"B78","doi-asserted-by":"publisher","first-page":"47","DOI":"10.5713\/ajas.16.0428","article-title":"Blood amino acids profile responding to heat stress in dairy cows","volume":"31","author":"Guo","year":"2018","journal-title":"As Au J Anim Sci."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1373\/clinchem.2016.256909","article-title":"Real-time quantification of amino acids in the exhalome by secondary electrospray ionization-mass spectrometry: a proof-of-principle study","volume":"62","author":"Garc\u00eda-G\u00f3mez","year":"2016","journal-title":"Clin Chem."},{"key":"B80","doi-asserted-by":"publisher","first-page":"8526","DOI":"10.1039\/C6CC03070J","article-title":"Secondary electrospray ionization coupled to high-resolution mass spectrometry reveals tryptophan pathway metabolites in exhaled human breath","volume":"52","author":"Garc\u00eda-G\u00f3mez","year":"2016","journal-title":"Chem Commun."},{"key":"B81","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.bbr.2016.11.035","article-title":"Potential antidepressant and resilience mechanism revealed by metabolomic study on peripheral blood mononuclear cells of stress resilient rats","volume":"320","author":"Li","year":"2016","journal-title":"Behav Brain Res"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S1462399406000068","article-title":"Tryptophan metabolism in the central nervous system: medical implications","volume":"8","author":"Ruddick","year":"2006","journal-title":"Expert Rev Mol Med."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15761\/ICM.1000105","article-title":"Anthranilic acid: a potential biomarker and treatment target for schizophrenia","volume":"4","author":"Oxenkrug","year":"2016","journal-title":"Psychiatry Ment Health."},{"key":"B84","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1620\/tjem.153.79","article-title":"Alteration of tryptophan metabolism in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis","volume":"153","author":"Igari","year":"1987","journal-title":"Tohoku J Exp Med."},{"key":"B85","doi-asserted-by":"publisher","first-page":"365","DOI":"10.15761\/IMM.1000169","article-title":"Elevated anthranilic acid plasma concentrations in type 1 but not type 2 diabetes mellitus","volume":"2","author":"Oxenkrug","year":"2015","journal-title":"HHS Public Access."},{"key":"B86","doi-asserted-by":"publisher","first-page":"E166","DOI":"10.1503\/jpn.190139","article-title":"The role of anthranilic acid in the increase of depressive symptoms and major depressive disorder during treatment for hepatitis c with pegylated interferon-\u03b12a and oral ribavirin","volume":"46","author":"Pawlowski","year":"2021","journal-title":"J Psychiatry Neurosci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1001\/jamapsychiatry.2019.1335","article-title":"Association of schizophrenia risk with disordered niacin metabolism","volume":"76","author":"Periyasamy","year":"2019","journal-title":"Am Med Assoc"},{"key":"B88","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3390\/metabo5010003","article-title":"Breath analysis as a potential and non-invasive frontier in disease diagnosis: an overview","volume":"5","author":"Pereira","year":"2015","journal-title":"Metabolites."},{"key":"B89","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1111\/j.1365-3040.2009.01946.x","article-title":"Isoprene synthesis protects transgenic tobacco plants from oxidative stress","volume":"32","author":"Vickers","year":"2009","journal-title":"Plant Cell and Environment."},{"key":"B90","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1111\/j.1469-8137.2005.01409.x","article-title":"Ozone linked references are available on jstor for this article : phytologist rapid report isoprene decreases the concentration of nitric oxide in leaves exposed to elevated ozone","volume":"166","author":"Velikova","year":"2005","journal-title":"New Phytol"},{"key":"B91","doi-asserted-by":"publisher","first-page":"e112","DOI":"10.1038\/ctg.2015.40","article-title":"Isoprene in the exhaled breath is a novel biomarker for advanced fibrosis in patients with chronic liver disease: a pilot study","volume":"6","author":"Alkhouri","year":"2015","journal-title":"Clin Transl Gastroenterol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"7101","DOI":"10.1088\/1752-7155\/6\/2\/027101","article-title":"Decline of exhaled isoprene in lung cancer patients correlates with immune activation","volume":"6","author":"Fuchs","year":"2012","journal-title":"J Breath Res"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1515\/CCLM.2008.181","article-title":"Breath isoprene - aspects of normal physiology related to age. Gender and cholesterol profile as determined in a proton transfer reaction mass spectrometry study","volume":"46","author":"Kushch","year":"2008","journal-title":"Clin Chem Lab Med."},{"key":"B94","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1152\/jappl.2001.91.2.762","article-title":"Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling","volume":"91","author":"Karl","year":"2001","journal-title":"J Appl Physiol"},{"key":"B95","doi-asserted-by":"publisher","first-page":"7479","DOI":"10.1371\/journal.pone.0097479","article-title":"The potential biomarker panels for identification of major depressive disorder (MDD) patients with and without early life stress (ELS) by metabonomic analysis","volume":"9","author":"Ding","year":"2014","journal-title":"PLoS ONE"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12991-017-0144-4","article-title":"Is low total cholesterol levels associated with suicide attempt in depressive patients?","volume":"3","author":"Messaoud","year":"2017","journal-title":"Ann Gen Psychiatry"},{"key":"B97","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s12160-008-9045-8","article-title":"Cholesterol depression","volume":"36","author":"Shin","year":"2008","journal-title":"Soc Behav Med"},{"key":"B98","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1515\/cclm-2019-0974","article-title":"Applying mass spectrometry-based assays to explore gut microbial metabolism and associations with disease","volume":"58","author":"Heaney","year":"2020","journal-title":"Clin Chem Lab Med."},{"key":"B99","doi-asserted-by":"publisher","first-page":"301","DOI":"10.17179\/excli2020-3239","article-title":"Trimethylamine N-oxide (TMAO) in human health","volume":"20","author":"Gatarek","year":"2021","journal-title":"EXCLI J."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.3390\/nu10101398","article-title":"H, Ram\u00edrez MJ, Milagro FI, Mart\u00ednez JA, Solas M. Implication of trimethylamine N-Oxide (TMAO) in disease: potential biomarker or new therapeutic target","volume":"10","author":"Janeiro","year":"2018","journal-title":"Nutrients"},{"key":"B101","author":"Al-Ani","year":"2015","journal-title":"Analysis of Breath Allows for Non-Invasive Identification and Quantification of Diseases and Metabolic Dysfunction"},{"key":"B102","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1007\/s00217-006-0429-3","article-title":"The ability of biogenic amines and ammonia production by single bacterial cultures","volume":"225","author":"\u00d6zogul","year":"2007","journal-title":"Eu Food Res Technol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1136\/jcp.46.9.861","article-title":"Increased pentane and carbon disulfide in the breath of patients with schizophrenia","volume":"46","author":"Phillips","year":"1993","journal-title":"J Clin Pathol."},{"key":"B104","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1080\/08958370701401418","article-title":"Oxidative stress in smokers and non-smokers","volume":"19","author":"Isik","year":"2007","journal-title":"Inhal Toxicol."}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2022.1061326\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T14:43:35Z","timestamp":1671029015000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2022.1061326\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":104,"alternative-id":["10.3389\/fpsyt.2022.1061326"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2022.1061326","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,14]]},"article-number":"1061326"}}