{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:14:43Z","timestamp":1791357283888,"version":"4.3.1"},"reference-count":50,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Vestre Viken Hospital Trust and Ringerike Psychiatric Center"},{"DOI":"10.13039\/501100005416","name":"Research Council of Norway","doi-asserted-by":"publisher","award":["223273"],"award-info":[{"award-number":["223273"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"name":"KG Jebsen Foundation (No. SKGJ-MED-008)"}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","europeanneuropsychopharmacology.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Neuropsychopharmacology"],"published-print":{"date-parts":[[2016,8]]},"DOI":"10.1016\/j.euroneuro.2016.05.005","type":"journal-article","created":{"date-parts":[[2016,5,27]],"date-time":"2016-05-27T21:42:46Z","timestamp":1464385366000},"page":"1286-1296","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"title":["Increased plasma levels of competing amino acids, rather than lowered plasma tryptophan levels, are associated with a non-response to treatment in major depression"],"prefix":"10.1016","volume":"26","author":[{"given":"Heidi","family":"Ormstad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Dahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3042-3293","authenticated-orcid":false,"given":"Robert","family":"Verkerk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole A.","family":"Andreassen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Maes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.euroneuro.2016.05.005_bib1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/mpr.138","article-title":"The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) surveys","volume":"12","author":"Andrade","year":"2003","journal-title":"Int. J. Methods Psychiatr. Res."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1097\/00000658-198007000-00014","article-title":"Muscle and plasma amino acids following injury. Influence of intercurrent infection","volume":"192","author":"Askanazi","year":"1980","journal-title":"Ann. Surg."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib3","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2015.11.015","article-title":"Tryptophan availability for kynurenine pathway metabolism across the life span: control mechanisms and focus on aging, exercise, diet and nutritional supplements","author":"Badawy","year":"2015","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib4","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/15622970701227829","article-title":"World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders in primary care","volume":"8","author":"Bauer","year":"2007","journal-title":"World J. Biol. Psychiatry: Off. J. World Fed. Soc. Biol. Psychiatry"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib5","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/978-1-4684-5952-4_39","article-title":"Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS","volume":"294","author":"Brown","year":"1991","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib6","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1210\/me.2014-1275","article-title":"Inflammation and ER stress regulate branched-chain amino acid uptake and metabolism in adipocytes","volume":"29","author":"Burrill","year":"2015","journal-title":"Mol. Endocrinol. (Baltimore, Md.)"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib7","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00726-004-0064-x","article-title":"The relationship between plasma cholesterol, amino acids and acute phase proteins in sepsis","volume":"27","author":"Chiarla","year":"2004","journal-title":"Amino Acids"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib8","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1192\/bjp.113.504.1237","article-title":"The biochemistry of affective disorders","volume":"113","author":"Coppen","year":"1967","journal-title":"British J. Psychiatry: J. Ment. Sci."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0165-0327(89)90051-7","article-title":"Decreased plasma tryptophan levels in major depression","volume":"16","author":"Cowen","year":"1989","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.psyneuen.2015.02.011","article-title":"Ongoing episode of major depressive disorder is not associated with elevated plasma levels of kynurenine pathway markers","volume":"56","author":"Dahl","year":"2015","journal-title":"Psychoneuroendocrinology"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.psyneuen.2014.03.019","article-title":"The plasma levels of various cytokines are increased during ongoing depression and are reduced to normal levels after recovery","volume":"45","author":"Dahl","year":"2014","journal-title":"Psychoneuroendocrinology"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib12","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.bbadis.2013.02.001","article-title":"Branched-chain amino acids influence the immune properties of microglial cells and their responsiveness to pro-inflammatory signals","volume":"1832","author":"De Simone","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib13","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1152\/physrev.1983.63.2.484","article-title":"Role of precursor availability in control of monoamine biosynthesis in brain","volume":"63","author":"Fernstrom","year":"1983","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib14","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/BF01256759","article-title":"Acute reduction of brain serotonin and 5-HIAA following food consumption: correlation with the ratio of serum tryptophan to the sum of competing amino acids","volume":"36","author":"Fernstrom","year":"1975","journal-title":"J. Neural Transm."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib15","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1097\/00000658-197911000-00003","article-title":"Plasma amino acids as predictors of the severity and outcome of sepsis","volume":"190","author":"Freund","year":"1979","journal-title":"Ann. Surg."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib16","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1002\/1521-4141(200108)31:8<2313::AID-IMMU2313>3.0.CO;2-S","article-title":"Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-gamma-independent mechanism","volume":"31","author":"Fujigaki","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib17","first-page":"449","article-title":"Normalization of dexamethasone suppression test: a laboratory index of recovery from endogenous depression","volume":"15","author":"Greden","year":"1980","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib18","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/da.20634","article-title":"Age differences in the prevalence and co-morbidity of DSM-IV major depressive episodes: results from the WHO World Mental Health Survey Initiative","volume":"27","author":"Kessler","year":"2010","journal-title":"Depression Anxiety"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib19","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev-publhealth-031912-114409","article-title":"The epidemiology of depression across cultures","volume":"34","author":"Kessler","year":"2013","journal-title":"Ann. Rev. Public Health"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib20","first-page":"93","article-title":"The World Mental Health (WMH) Survey Initiative Version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI)","volume":"13","author":"Kessler","year":"2004","journal-title":"Int. J. Methods\u00a0Psychiatr. Res."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib21","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.neubiorev.2011.12.005","article-title":"Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression","volume":"36","author":"Leonard","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib22","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1600-0447.1991.tb03163.x","article-title":"Depression-related disturbances in mitogen-induced lymphocyte responses and interleukin-1 beta and soluble interleukin-2 receptor production","volume":"84","author":"Maes","year":"1991","journal-title":"Acta Psychiatr. Scand."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib23","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s10787-011-0111-7","article-title":"New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates--Nrf2 activators and GSK-3 inhibitors","volume":"20","author":"Maes","year":"2012","journal-title":"Inflammopharmacology"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib24","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0165-1781(93)90102-M","article-title":"Relationships between lower plasma L-tryptophan levels and immune-inflammatory variables in depression","volume":"49","author":"Maes","year":"1993","journal-title":"Psychiatry Research"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib25","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/BF00808091","article-title":"The relationships between the availability ofL-tryptophan to the brain, the spontaneous HPA-axis activity, and the HPA-axis responses to dexamethasone in depressed patients","volume":"1","author":"Maes","year":"1991","journal-title":"Amino Acids"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib26","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0165-1781(94)90003-5","article-title":"Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: further evidence for an immune response","volume":"54","author":"Maes","year":"1994","journal-title":"Psychiatry Res."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib27","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1517\/14728222.2012.718331","article-title":"Targeting IL-1 in depression","volume":"16","author":"Maes","year":"2012","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib28","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0278-5846(93)90045-T","article-title":"Significantly increased expression of T-cell activation markers (interleukin-2 and HLA-DR) in depression: further evidence for an inflammatory process during that illness","volume":"17","author":"Maes","year":"1993","journal-title":"Prog. Neuro-psychopharmacol. Biol. Psychiatry"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib29","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/BF03033069","article-title":"Serotonin-immune interactions in major depression: lower serum tryptophan as a marker of an immune-inflammatory response","volume":"247","author":"Maes","year":"1997","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib30","doi-asserted-by":"crossref","first-page":"418681","DOI":"10.1155\/2015\/418681","article-title":"Elevated serum levels of cysteine and tyrosine: early biomarkers in asymptomatic adults at increased risk of developing metabolic syndrome","volume":"2015","author":"Mohorko","year":"2015","journal-title":"BioMed Res. Int."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib31","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1111\/j.1471-4159.1968.tb06827.x","article-title":"The effects of precursor loading in the cerebral metabolism of 5-hydroxyindoles","volume":"15","author":"Moir","year":"1968","journal-title":"J. Neurochem."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib32","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/0165-0327(90)90117-Q","article-title":"Plasma ratio tryptophan\/neutral amino acids in relation to clinical response to paroxetine and clomipramine in patients with major depression","volume":"18","author":"Moller","year":"1990","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib33","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jad.2006.07.013","article-title":"Kynurenine pathway in major depression: evidence of impaired neuroprotection","volume":"98","author":"Myint","year":"2007","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib34","series-title":"Depression in adults: recognition and management","author":"National Institute for Health and Clinical Excellence","year":"2009"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib35","doi-asserted-by":"crossref","first-page":"622","DOI":"10.2174\/138920008785821738","article-title":"Chronic immune stimulation correlates with reduced phenylalanine turnover","volume":"9","author":"Neurauter","year":"2008","journal-title":"Curr. Drug Metab."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib36","doi-asserted-by":"crossref","first-page":"e906","DOI":"10.4088\/JCP.13r08908","article-title":"Plasma L-tryptophan concentration in major depressive disorder: new data and meta-analysis","volume":"75","author":"Ogawa","year":"2014","journal-title":"J. Clin. Psychiatry"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib37","doi-asserted-by":"crossref","first-page":"e85945","DOI":"10.1371\/journal.pone.0085945","article-title":"Elevated levels of plasma phenylalanine in schizophrenia: a guanosine triphosphate cyclohydrolase-1 metabolic pathway abnormality?","volume":"9","author":"Okusaga","year":"2014","journal-title":"PloS One"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib38","doi-asserted-by":"crossref","DOI":"10.1007\/s12031-013-0097-2","article-title":"Inflammation-induced catabolism of tryptophan and tyrosine in acute ischemic stroke","author":"Ormstad","year":"2013","journal-title":"J. Mol.\u00a0Neurosci.: MN"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib39","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1600-0447.2011.01706.x","article-title":"Mood effects of the amino acids tryptophan and tyrosine: \u05f3Food for Thought\u05f3 III","volume":"124","author":"Parker","year":"2011","journal-title":"Acta Psychiatr. Scand."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib40","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1089\/jir.1997.17.589","article-title":"Quinolinic acid production by macrophages stimulated with IFN-gamma, TNF-alpha, and IFN-alpha","volume":"17","author":"Pemberton","year":"1997","journal-title":"J. Interferon Cytokine Res.: Off. J. Int. Soc. Interferon Cytokine Res."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib41","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jad.2012.02.008","article-title":"Low plasma levels of L-arginine, impaired intraplatelet nitric oxide and platelet hyperaggregability: implications for cardiovascular disease in depressive patients","volume":"140","author":"Pinto","year":"2012","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib42","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s00726-007-0625-x","article-title":"Serum phenylalanine in patients post trauma and with sepsis correlate to neopterin concentrations","volume":"35","author":"Ploder","year":"2008","journal-title":"Amino Acids"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib43","first-page":"91","article-title":"The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and select comorbid medical conditions","volume":"24","author":"Ramasubbu","year":"2012","journal-title":"Ann. Clin. Psychiatry: Off. J. Am. Acad. Clin. Psychiatr."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib44","doi-asserted-by":"crossref","DOI":"10.1002\/14651858.CD003198","article-title":"Tryptophan and 5-hydroxytryptophan for depression","author":"Shaw","year":"2002","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib45","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1097\/00003246-199106000-00004","article-title":"Amino acid alterations and encephalopathy in the sepsis syndrome","volume":"19","author":"Sprung","year":"1991","journal-title":"Crit. Care Med."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib46","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1097\/PSY.0b013e3181b0545c","article-title":"A psychological intervention reduces inflammatory markers by alleviating depressive symptoms: secondary analysis of a randomized controlled trial","volume":"71","author":"Thornton","year":"2009","journal-title":"Psychosom. Med."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib47","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0165-1781(03)00113-6","article-title":"Serum amino acids, biopterin and neopterin during long-term immunotherapy with interferon-alpha in high-risk melanoma patients","volume":"119","author":"Van Gool","year":"2003","journal-title":"Psychiatry Res."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib48","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/00000658-198901000-00009","article-title":"Plasma-amino acid profiles in sepsis and stress","volume":"209","author":"Vente","year":"1989","journal-title":"Ann. Surg."},{"key":"10.1016\/j.euroneuro.2016.05.005_bib49","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/0167-4889(89)90087-6","article-title":"Characteristics of interferon induced tryptophan metabolism in human cells in vitro","volume":"1012","author":"Werner-Felmayer","year":"1989","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.euroneuro.2016.05.005_bib50","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1073\/pnas.78.1.129","article-title":"Induction of pulmonary indoleamine 2,3-dioxygenase by interferon","volume":"78","author":"Yoshida","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA."}],"container-title":["European Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0924977X16300463?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0924977X16300463?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T20:30:00Z","timestamp":1567974600000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0924977X16300463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8]]},"references-count":50,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["S0924977X16300463"],"URL":"https:\/\/doi.org\/10.1016\/j.euroneuro.2016.05.005","relation":{},"ISSN":["0924-977X"],"issn-type":[{"value":"0924-977X","type":"print"}],"subject":[],"published":{"date-parts":[[2016,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Increased plasma levels of competing amino acids, rather than lowered plasma tryptophan levels, are associated with a non-response to treatment in major depression","name":"articletitle","label":"Article Title"},{"value":"European Neuropsychopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.euroneuro.2016.05.005","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Elsevier B.V. and ECNP. All rights reserved.","name":"copyright","label":"Copyright"}]}}