{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T02:52:34Z","timestamp":1778813554988,"version":"3.51.4"},"reference-count":103,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T00:00:00Z","timestamp":1705449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Treatment of head and neck squamous cell carcinoma (HNSCC) has a detrimental impact on patient quality of life. The rate of recognized distress\/depression among HNSCC patients ranges from 9.8% to 83.8%, and the estimated prevalence of depression among patients receiving radiotherapy is 63%. Shorter overall survival also occurs in preexisting depression or depressive conditions. The present study analyzes the nuclear magnetic resonance (NMR) blood serum metabolic profiles during radio-\/chemoradiotherapy and correlates the detected alterations with pain and\/or distress accumulated with the disease and its treatment. NMR spectra were acquired on a Bruker 400 MHz spectrometer and analyzed using multivariate methods. The results indicate that distress and\/or pain primarily affect the serum lipids and metabolites of energy (glutamine, glucose, lactate, acetate) and one-carbon (glycine, choline, betaine, methanol, threonine, serine, histidine, formate) metabolism. Sparse disturbances in the branched-chain amino acids (BCAA) and in the metabolites involved in protein metabolism (lysine, tyrosine, phenylalanine) are also observed. Depending on the treatment modality\u2014radiotherapy or concurrent chemoradiotherapy\u2014there are some differences in the altered metabolites.<\/jats:p>","DOI":"10.3390\/metabo14010060","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T07:41:28Z","timestamp":1705477288000},"page":"60","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Metabolite Biomarkers of Prolonged and Intensified Pain and Distress in Head and Neck Cancer Patients Undergoing Radio- or Chemoradiotherapy by Means of NMR-Based Metabolomics\u2014A Preliminary Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9460-837X","authenticated-orcid":false,"given":"\u0141ukasz","family":"Boguszewicz","sequence":"first","affiliation":[{"name":"Department of Medical Physics, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicja","family":"Heyda","sequence":"additional","affiliation":[{"name":"1st Radiation and Clinical Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mateusz","family":"Ciszek","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4486-3567","authenticated-orcid":false,"given":"Agata","family":"Biele\u0144","sequence":"additional","affiliation":[{"name":"1st Radiation and Clinical Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Skorupa","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolanta","family":"Mrochem-Kwarciak","sequence":"additional","affiliation":[{"name":"Analytics and Clinical Biochemistry Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Sk\u0142adowski","sequence":"additional","affiliation":[{"name":"1st Radiation and Clinical Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1611-8241","authenticated-orcid":false,"given":"Maria","family":"Sok\u00f3\u0142","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland"},{"name":"1st Radiation and Clinical Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1177\/0194599818783964","article-title":"Pain in Head and Neck Cancer Survivors: Prevalence, Predictors, and Quality-of-Life Impact","volume":"159","author":"Cramer","year":"2018","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/j.ejso.2016.10.026","article-title":"Prevalence, incidence, and risk factors for shoulder and neck dysfunction after neck dissection: A systematic review","volume":"43","author":"Gane","year":"2017","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.oraloncology.2009.03.014","article-title":"Issues of intimacy and sexual dysfunction following major head and neck cancer treatment","volume":"45","author":"Low","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wan Leung, S., Lee, T.F., Chien, C.Y., Chao, P.J., Tsai, W.L., and Fang, F.M. (2011). Health-related quality of life in 640 head and neck cancer survivors after radiotherapy using EORTC QLQ-C30 and QLQ-H&N35 questionnaires. BMC Cancer, 11.","DOI":"10.1186\/1471-2407-11-128"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1177\/0194599818776873","article-title":"Prevalence and Risk Factors of Suicidal Ideation among Patients with Head and Neck Cancer: Longitudinal Study","volume":"159","author":"Henry","year":"2018","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.31557\/APJCP.2022.23.6.1827","article-title":"Psychosocial Distress of Head Neck Cancer (HNC) Patients Receiving Radiotherapy: A Systematic Review","volume":"23","author":"Nayak","year":"2022","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4072","DOI":"10.1002\/cncr.31675","article-title":"Suicide risk among cancer survivors: Head and neck versus other cancers","volume":"124","author":"Simpson","year":"2018","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101295","DOI":"10.1016\/j.eclinm.2022.101295","article-title":"Subsequent risk of suicide among 9,300,812 cancer survivors in US: A population-based cohort study covering 40 years of data","volume":"44","author":"Liu","year":"2022","journal-title":"eClinicalMedicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.radonc.2010.02.005","article-title":"Quality of life as predictor of survival: A prospective study on patients treated with combined surgery and radiotherapy for advanced oral and oropharyngeal cancer","volume":"97","author":"Oskam","year":"2010","journal-title":"Radiother Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1001\/archoto.2009.107","article-title":"The role of pain in head and neck cancer recurrence and survivorship","volume":"135","author":"Scharpf","year":"2009","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1200\/JCO.2007.12.9510","article-title":"Quality of life scores predict survival among patients with head and neck cancer","volume":"26","author":"Ronis","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.1365-2273.1984.tb01493.x","article-title":"Quality of life in treated head and neck cancer patients: A preliminary report","volume":"9","author":"Morton","year":"1984","journal-title":"Clin. Otolaryngol. Allied Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.1002\/hed.26868","article-title":"The prognostic impact of depression or depressive symptoms on patients with head and neck cancer: A systematic review and meta-analysis","volume":"43","author":"Bardash","year":"2021","journal-title":"Head Neck"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1002\/pon.4816","article-title":"Depressive symptoms in relation to overall survival in people with head and neck cancer: A longitudinal cohort study","volume":"27","author":"Jansen","year":"2018","journal-title":"Psychooncology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.5037\/jomr.2012.3101","article-title":"Head and neck cancer pain: Systematic review of prevalence and associated factors","volume":"3","author":"MacFarlane","year":"2012","journal-title":"J. Oral Maxillofac. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1080\/21642850.2022.2033121","article-title":"The role of pain and psychological distress in fatigue: A co-twin and within-person analysis of confounding and causal relations","volume":"10","author":"Andelic","year":"2022","journal-title":"Health Psychol. Behav. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"430","DOI":"10.4161\/cc.6.4.3829","article-title":"The neuroendocrine impact of chronic stress on cancer","volume":"6","author":"Thaker","year":"2007","journal-title":"Cell Cycle"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nri1571","article-title":"Stress-induced immune dysfunction: Implications for health","volume":"5","author":"Glaser","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"eabq7982","DOI":"10.1126\/sciadv.abq7982","article-title":"Psychological distress and eustress in cancer and cancer treatment: Advances and perspectives","volume":"8","author":"Wu","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ting, E.Y., Yang, A.C., and Tsai, S.J. (2020). Role of Interleukin-6 in Depressive Disorder. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062194"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.bbi.2010.12.012","article-title":"Stress hormones increase cell proliferation and regulates interleukin-6 secretion in human oral squamous cell carcinoma cells","volume":"25","author":"Tamae","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.oraloncology.2015.08.007","article-title":"Chronic stress promotes oral cancer growth and angiogenesis with increased circulating catecholamine and glucocorticoid levels in a mouse model","volume":"51","author":"Xie","year":"2015","journal-title":"Oral Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"50","DOI":"10.21053\/ceo.2019.00906","article-title":"Association Between Interleukin-6 and Head and Neck Squamous Cell Carcinoma: A Systematic Review","volume":"14","author":"Uz","year":"2021","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"407","DOI":"10.3322\/caac.21672","article-title":"Addressing distress management challenges: Recommendations from the consensus panel of the American Psychosocial Oncology Society and the Association of Oncology Social Work","volume":"71","author":"Deshields","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Jadoon, N.A., Munir, W., Shahzad, M.A., and Choudhry, Z.S. (2010). Assessment of depression and anxiety in adult cancer outpatients: A cross-sectional study. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-594"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/pon.3935","article-title":"Parenting concerns, quality of life, and psychological distress in patients with advanced cancer","volume":"25","author":"Park","year":"2016","journal-title":"Psychooncology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1093\/ejcts\/ezv336","article-title":"Risk factors for postoperative anxiety and depression after surgical treatment for lung cancer","volume":"49","author":"Park","year":"2016","journal-title":"Eur. J. Cardio-Thorac. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.biopsych.2020.12.031","article-title":"The Acute Stress Response in the Multiomic Era","volume":"89","author":"Waag","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.cobeha.2016.01.011","article-title":"Impact of stress on metabolism and energy balance","volume":"9","author":"Rabasa","year":"2016","journal-title":"Curr. Opin. Behav. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"103525","DOI":"10.1016\/j.mcn.2020.103525","article-title":"The impact of chronic stress on energy metabolism","volume":"107","year":"2020","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1093\/bja\/aeu187","article-title":"Metabolic response to the stress of critical illness","volume":"113","author":"Preiser","year":"2014","journal-title":"Br. J. Anaesth."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1017\/S1092852913000667","article-title":"Metabolic syndrome and major depression","volume":"19","author":"Marazziti","year":"2014","journal-title":"CNS Spectr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s10067-021-05968-1","article-title":"Biomarkers in axial spondyloarthritis and low back pain: A comprehensive review","volume":"41","author":"Reveille","year":"2022","journal-title":"Clin. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7657329","DOI":"10.1155\/2016\/7657329","article-title":"Investigating the Burden of Chronic Pain: An Inflammatory and Metabolic Composite","volume":"2016","author":"Sibille","year":"2016","journal-title":"Pain Res. Manag."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.metabol.2006.09.001","article-title":"Metabolic syndrome in women with chronic pain","volume":"56","author":"Loevinger","year":"2007","journal-title":"Metabolism"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14353","DOI":"10.1523\/JNEUROSCI.1910-15.2015","article-title":"Metabolic Connection of Inflammatory Pain: Pivotal Role of a Pyruvate Dehydrogenase Kinase-Pyruvate Dehydrogenase-Lactic Acid Axis","volume":"35","author":"Jha","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1177\/1099800420941105","article-title":"The Metabolomics of Chronic Pain Conditions: A Systematic Review","volume":"22","author":"Aroke","year":"2020","journal-title":"Biol. Res. Nurs."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Jha, S.C., Shutta, K.H., Huang, T., Balasubramanian, R., Clish, C.B., Hankinson, S.E., and Kubzansky, L.D. (2022). Psychological distress and metabolomic markers: A systematic review of posttraumatic stress disorder, anxiety, and subclinical distress. Neurosci. Biobehav. Rev., 143.","DOI":"10.1016\/j.neubiorev.2022.104954"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"20418","DOI":"10.1038\/s41598-020-76876-8","article-title":"Metabolomics and psychological features in fibromyalgia and electromagnetic sensitivity","volume":"10","author":"Piras","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/ggi.13585","article-title":"Association between plasma \u03b1-aminobutyric acid and depressive symptoms in older community-dwelling adults in Japan","volume":"19","author":"Adachi","year":"2019","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.psyneuen.2012.11.014","article-title":"Metabolomic profiles in individuals with negative affectivity and social inhibition: A population-based study of Type D personality","volume":"38","author":"Altmaier","year":"2013","journal-title":"Psychoneuroendocrinology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1038\/s41380-020-00870-9","article-title":"Associations of depression status with plasma levels of candidate lipid and amino acid metabolites: A meta-analysis of individual data from three independent samples of US postmenopausal women","volume":"26","author":"Huang","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e1899","DOI":"10.1212\/WNL.0000000000007313","article-title":"Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine","volume":"92","author":"Onderwater","year":"2019","journal-title":"Neurology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3604","DOI":"10.1002\/cam4.3914","article-title":"Patient-reported distress and age-related stress biomarkers among colorectal cancer patients","volume":"10","author":"Eddington","year":"2021","journal-title":"Cancer Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Boguszewicz, \u0141., Biele\u0144, A., Ciszek, M., Wendykier, J., Szczepanik, K., Skorupa, A., Mrochem-Kwarciak, J., Sk\u0142adowski, K., and Sok\u00f3\u0142, M. (2021). NMR-Based Metabolomics in Investigation of the Radiation Induced Changes in Blood Serum of Head and Neck Cancer Patients and Its Correlation with the Tissue Volumes Exposed to the Particulate Doses. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126310"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Boguszewicz, \u0141., Biele\u0144, A., Jarczewski, J.D., Ciszek, M., Skorupa, A., Sk\u0142adowski, K., and Sok\u00f3\u0142, M. (2021). Molecular response to induction chemotherapy and its correlation with treatment outcome in head and neck cancer patients by means of NMR-based metabolomics. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08137-4"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s11306-019-1576-4","article-title":"NMR-based metabolomics in real-time monitoring of treatment induced toxicity and cachexia in head and neck cancer: A method for early detection of high risk patients","volume":"15","author":"Boguszewicz","year":"2019","journal-title":"Metabolomics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s11306-016-1043-4","article-title":"1H NMR based metabolomic approach to monitoring of the head and neck cancer treatment toxicity","volume":"12","author":"Boguszewicz","year":"2016","journal-title":"Metabolomics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0304-3959(93)90148-I","article-title":"Increasing the reliability and validity of pain intensity measurement in chronic pain patients","volume":"55","author":"Jensen","year":"1993","journal-title":"Pain"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/acr.20543","article-title":"Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP)","volume":"63","author":"Hawker","year":"2011","journal-title":"Arthritis Care Res."},{"key":"ref_51","first-page":"1022","article-title":"Reliability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis","volume":"17","author":"Ferraz","year":"1990","journal-title":"J. Rheumatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"450","DOI":"10.6004\/jnccn.2023.0026","article-title":"NCCN Guidelines\u00ae Insights: Distress Management, Version 2.2023","volume":"21","author":"Riba","year":"2023","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S1548-5315(11)70702-1","article-title":"Emotional distress in patients with cancer: The sixth vital sign","volume":"5","author":"Bultz","year":"2006","journal-title":"Community Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1188\/17.ONF.329-336","article-title":"The Distress Thermometer: Cutoff Points and Clinical Use","volume":"44","author":"Cutillo","year":"2017","journal-title":"Oncol. Nurs. Forum"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/pon.3430","article-title":"Validation of the distress thermometer worldwide: State of the science","volume":"23","author":"Donovan","year":"2014","journal-title":"Psychooncology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.3390\/curroncol29060304","article-title":"Screening for Distress and Health Outcomes in Head and Neck Cancer","volume":"29","author":"Gascon","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.pneurobio.2017.05.004","article-title":"Uncertainty and stress: Why it causes diseases and how it is mastered by the brain","volume":"156","author":"Peters","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.adro.2018.11.001","article-title":"The long-lasting relationship of distress on radiation oncology-specific clinical outcomes","volume":"4","author":"Anderson","year":"2018","journal-title":"Adv. Radiat. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"577420","DOI":"10.3389\/fonc.2020.577420","article-title":"Alterations of Lipid Metabolism in Cancer: Implications in Prognosis and Treatment","volume":"10","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Arlauckas, S.P., Browning, E.A., Poptani, H., and Delikatny, E.J. (2019). Imaging of cancer lipid metabolism in response to therapy. NMR Biomed., 32.","DOI":"10.1002\/nbm.4070"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Lee, K., Kim, S., and Jo, J.K. (2022). The Relationships between Abnormal Serum Lipid Levels, Depression, and Suicidal Ideation According to Sex. J. Clin. Med., 11.","DOI":"10.3390\/jcm11082119"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e2021042","DOI":"10.4178\/epih.e2021042","article-title":"Stressful life events and serum triglyceride levels: The Cardiovascular and Metabolic Diseases Etiology Research Center cohort in Korea","volume":"43","author":"Anni","year":"2021","journal-title":"Epidemiol. Health."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Liu, C., Li, Y., Li, J., Jin, C., and Zhong, D. (2022). The Effect of Psychological Burden on Dyslipidemia Moderated by Greenness: A Nationwide Study from China. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph192114287"},{"key":"ref_64","first-page":"7991","article-title":"Impact of chronic psychological stress on nonalcoholic fatty liver disease","volume":"12","author":"Zhang","year":"2019","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1152\/physiolgenomics.90358.2008","article-title":"Isolation stress for 30 days alters hepatic gene expression profiles, especially with reference to lipid metabolism in mice","volume":"37","author":"Motoyama","year":"2009","journal-title":"Physiol. Genom."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nchembio.767","article-title":"Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin","volume":"8","author":"Patti","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1515\/sjpain-2020-0067","article-title":"Pain management in patients undergoing radiation therapy for head and neck cancer\u2014A descriptive study","volume":"21","author":"Schaller","year":"2020","journal-title":"Scand. J. Pain."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.clnu.2004.08.004","article-title":"Dyslipidemia and inflammation: An evolutionary conserved mechanism","volume":"24","author":"Esteve","year":"2005","journal-title":"Clin. Nutr."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/sc.2009.71","article-title":"Intensity of pain and biochemical changes in blood plasma in spinal cord trauma","volume":"48","author":"Rokyta","year":"2010","journal-title":"Spinal Cord"},{"key":"ref_70","first-page":"62","article-title":"Blood serum changes in patients with pain during bone fractures and acute pancreatitis","volume":"25","author":"Krikava","year":"2004","journal-title":"Neuroendocrinol. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.3389\/fphar.2019.01147","article-title":"Oxidized Lipids in Persistent Pain States","volume":"10","author":"Osthues","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Lin, P., Dai, L., Crooks, D.R., Neckers, L.M., Higashi, R.M., Fan, T.W.-M., and Lane, L.N. (2021). NMR Methods for Determining Lipid Turnover via Stable Isotope Resolved Metabolomics. Metabolites, 11.","DOI":"10.3390\/metabo11040202"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1038\/s12276-020-00504-8","article-title":"Glutamine reliance in cell metabolism","volume":"52","author":"Yoo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Cruzat, V., Macedo Rogero, M., Noel Keane, K., Curi, R., and Newsholme, P. (2018). Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients, 10.","DOI":"10.20944\/preprints201809.0459.v1"},{"key":"ref_75","first-page":"100261","article-title":"One-carbon and energy metabolism in major depression compared to chronic depression in adolescent outpatients: A metabolomic pilot study","volume":"6","author":"Kurkinen","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.cmet.2018.03.002","article-title":"Rewiring of Glutamine Metabolism Is a Bioenergetic Adaptation of Human Cells with Mitochondrial DNA Mutations","volume":"27","author":"Chen","year":"2018","journal-title":"Cell Metab."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/s41392-022-01151-3","article-title":"Lactate metabolism in human health and disease","volume":"7","author":"Li","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1159\/000339958","article-title":"Rise in plasma lactate concentrations with psychosocial stress: A possible sign of cerebral energy demand","volume":"5","author":"Kubera","year":"2012","journal-title":"Obes. Facts"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1006891","DOI":"10.3389\/fmed.2022.1006891","article-title":"One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: Relation to chromosomal dosage","volume":"9","author":"Vione","year":"2022","journal-title":"Front. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2016.08.009","article-title":"One-Carbon Metabolism in Health and Disease","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1079\/NRR2006119","article-title":"One-carbon metabolism in psychiatric illness","volume":"19","author":"Sugden","year":"2006","journal-title":"Nutr. Res. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.1007\/s12011-021-03068-4","article-title":"Betaine Ameliorates Depressive-Like Behaviors in Zinc Oxide Nanoparticles Exposed Mice","volume":"200","author":"Jeyhoonabadi","year":"2002","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/ene.15133","article-title":"Circulating choline pathway nutrients and depression after ischemic stroke","volume":"29","author":"Miao","year":"2022","journal-title":"Eur. J. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"0002","DOI":"10.3945\/ajcn.2009.27493","article-title":"Choline in anxiety and depression: The Hordaland Health Study","volume":"90","author":"Bjelland","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuroscience.2004.12.026","article-title":"Antinociceptive effects of choline against acute and inflammatory pain","volume":"132","author":"Wang","year":"2005","journal-title":"Neuroscience"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/ajmg.b.32680","article-title":"Biomarkers for major depressive and bipolar disorders using metabolomics: A systematic review","volume":"180","author":"MacDonald","year":"2019","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_87","first-page":"564","article-title":"\u201cFunctional\u201d or \u201cpsychosomatic\u201d symptoms, e.g. a flu-like malaise, aches and pain and fatigue, are major features of major and in particular of melancholic depression","volume":"30","author":"Maes","year":"2009","journal-title":"Neuroendocrinol. Lett."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0924-977X(95)00033-L","article-title":"Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression","volume":"5","author":"Altamura","year":"1995","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1549S","DOI":"10.1093\/jn\/137.6.1549S","article-title":"An overview of phenylalanine and tyrosine kinetics in humans","volume":"137","author":"Matthews","year":"2007","journal-title":"J. Nutr."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"9536","DOI":"10.1074\/jbc.RA118.004426","article-title":"Tyrosine aminotransferase is involved in the oxidative stress response by metabolizing meta-tyrosine in Caenorhabditis elegans","volume":"294","author":"Ipson","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Kim, E., Zhao, Z., Rzasa, J.R., Glassman, M., Bentley, W.E., Chen, S., Kelly, D.L., and Payne, G.F. (2021). Association of acute psychosocial stress with oxidative stress: Evidence from serum analysis. Redox Biol., 47.","DOI":"10.1016\/j.redox.2021.102138"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1016\/j.drudis.2020.05.001","article-title":"Role of oxidative stress in depression","volume":"25","author":"Bhatt","year":"2020","journal-title":"Drug Discov. Today"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"867","DOI":"10.2147\/NDT.S192307","article-title":"Objective diagnosis of post-stroke depression using NMR-based plasma metabonomics","volume":"15","author":"Hu","year":"2019","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_94","first-page":"742407","article-title":"Plasma amino acids changes in complex regional pain syndrome","volume":"2013","author":"Alexander","year":"2013","journal-title":"Pain Res. Treat."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1111\/j.1399-6576.2008.01638.x","article-title":"Increased plasma glutamate, glycine, and arginine levels in complex regional pain syndrome type 1","volume":"52","author":"Wesseldijk","year":"2008","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1642S","DOI":"10.1093\/jn\/137.6.1642S","article-title":"Lysine requirement through the human life cycle","volume":"137","author":"Bos","year":"2007","journal-title":"J. Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/pcn.12638","article-title":"Plasma metabolome analysis of patients with major depressive disorder","volume":"72","author":"Kawamura","year":"2018","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00702-006-0608-1","article-title":"Mental fatigue-induced decrease in levels of several plasma amino acids","volume":"114","author":"Mizuno","year":"2007","journal-title":"J. Neural Transm."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12986-018-0271-1","article-title":"Branched-chain amino acids in health and disease: Metabolism, alterations in blood plasma, and as supplements","volume":"15","year":"2018","journal-title":"Nutr. Metab."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"101198","DOI":"10.1016\/j.arr.2020.101198","article-title":"Branched chain amino acids, aging and age-related health","volume":"64","author":"Cogger","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jpsychires.2017.09.014","article-title":"Plasma amino acid profile in major depressive disorder: Analyses in two independent case-control sample sets","volume":"96","author":"Ogawa","year":"2018","journal-title":"J. Psychiatr. Res."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Baranyi, A., Amouzadeh-Ghadikolai, O., Von Lewinski, D., Rothenh\u00e4usler, H.B., Theokas, S., Robier, C., Mangge, H., Reicht, G., Hlade, P., and Meinitzer, A. (2016). Branched-Chain Amino Acids as New Biomarkers of Major Depression\u2014A Novel Neurobiology of Mood Disorder. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0160542"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1178646920936279","DOI":"10.1177\/1178646920936279","article-title":"Potential Role of Neuroactive Tryptophan Metabolites in Central Fatigue: Establishment of the Fatigue Circuit","volume":"13","author":"Yamashita","year":"2020","journal-title":"Int. J. 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