{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:21:34Z","timestamp":1740144094206,"version":"3.37.3"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,8,10]],"date-time":"2018-08-10T00:00:00Z","timestamp":1533859200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Telethon Perth Children's Hospital Research Fund"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s13063-018-2791-4","type":"journal-article","created":{"date-parts":[[2018,8,10]],"date-time":"2018-08-10T07:55:19Z","timestamp":1533887719000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Using acute tryptophan depletion to investigate predictors of treatment response in adolescents with major depressive disorder: study protocol for a randomised controlled trial"],"prefix":"10.1186","volume":"19","author":[{"given":"Richard M.","family":"Stewart","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean D.","family":"Hood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pradeep","family":"Rao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia K.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin C.","family":"Runions","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susannah E.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1994-3001","authenticated-orcid":false,"given":"Janice W. Y.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian D.","family":"Zepf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,8,10]]},"reference":[{"key":"2791_CR1","unstructured":"Lawrence D, Johnson S, Hafekost J, de Haan KB, Sawyer M, Ainley J, Zubrick SR: The Mental Health of Children and Adolescents: Report on the Second Australian Child and Adolescent Survey of Mental Health and Wellbeing. Department of Health Canberra. 2015."},{"key":"2791_CR2","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.4088\/JCP.v68n0805","volume":"68","author":"HH Stassen","year":"2007","unstructured":"Stassen HH, Angst J, Hell D, Scharfetter C, Szegedi A. Is there a common resilience mechanism underlying antidepressant drug response? Evidence from 2848 patients. J Clin Psychiatry. 2007;68:1195\u2013205.","journal-title":"J Clin Psychiatry"},{"key":"2791_CR3","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1021\/acschemneuro.6b00427","volume":"8","author":"M Manchia","year":"2017","unstructured":"Manchia M, Carpiniello B, Valtorta F, Comai S. Serotonin dysfunction, aggressive behavior, and mental illness: exploring the link using a dimensional approach. ACS Chem Neurosci. 2017;8:961\u201372.","journal-title":"ACS Chem Neurosci"},{"key":"2791_CR4","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/BF00431803","volume":"87","author":"SN Young","year":"1985","unstructured":"Young SN, Smith SE, Pihl RO, Ervin FR. Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology. 1985;87:173\u20137.","journal-title":"Psychopharmacology"},{"key":"2791_CR5","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1001\/archpsyc.1994.03950090019003","volume":"51","author":"C Benkelfat","year":"1994","unstructured":"Benkelfat C, Ellenbogen MA, Dean P, Palmour RM, Young SN. Mood-lowering effect of tryptophan depletion: enhanced susceptibility in young men at genetic risk for major affective disorders. Arch Gen Psychiatry. 1994;51:687\u201397.","journal-title":"Arch Gen Psychiatry"},{"key":"2791_CR6","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.1016\/S0140-6736(05)61726-6","volume":"349","author":"M Leyton","year":"1997","unstructured":"Leyton M, Young SN, Benkelfat C. Relapse of depression after rapid depletion of tryptophan. Lancet. 1997;349:1840\u20131.","journal-title":"Lancet"},{"key":"2791_CR7","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/S0893-133X(96)00262-X","volume":"16","author":"M Leyton","year":"1997","unstructured":"Leyton M, Young SN, Blier P, Ellenbogen MA, Palmour RM, Ghadirian A-M, Benkelfat C. The effect of tryptophan depletion on mood in medication-free, former patients with major affective disorder. Neuropsychopharmacology. 1997;16:294.","journal-title":"Neuropsychopharmacology"},{"key":"2791_CR8","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1007\/s00702-012-0793-z","volume":"119","author":"V Dingerkus","year":"2012","unstructured":"Dingerkus V, Gaber T, Helmbold K, Bubenzer S, Eisert A, S\u00e1nchez C, Zepf F. Acute tryptophan depletion in accordance with body weight: influx of amino acids across the blood\u2013brain barrier. J Neural Transm. 2012;119:1037\u201345.","journal-title":"J Neural Transm"},{"key":"2791_CR9","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/sj.mp.4001949","volume":"12","author":"HG Ruh\u00e9","year":"2007","unstructured":"Ruh\u00e9 HG, Mason NS, Schene AH. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry. 2007;12:331\u201359.","journal-title":"Mol Psychiatry"},{"key":"2791_CR10","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/S0006-3223(00)00893-3","volume":"48","author":"FA Moreno","year":"2000","unstructured":"Moreno FA, Heninger GR, McGahuey CA, Delgado PL. Tryptophan depletion and risk of depression relapse: a prospective study of tryptophan depletion as a potential predictor of depressive episodes. Biol Psychiatry. 2000;48:327\u20139.","journal-title":"Biol Psychiatry"},{"key":"2791_CR11","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1001\/archpsyc.1990.01810170011002","volume":"47","author":"PL Delgado","year":"1990","unstructured":"Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, Heninger GR. Serotonin function and the mechanism of antidepressant action: reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry. 1990;47:411\u20138.","journal-title":"Arch Gen Psychiatry"},{"key":"2791_CR12","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1055\/s-2007-1004593","volume":"41","author":"F Zepf","year":"2008","unstructured":"Zepf F, Holtmann M, Stadler C, Demisch L, Schmitt M, W\u00f6ckel L, Poustka F. Diminished serotonergic functioning in hostile children with ADHD: tryptophan depletion increases behavioural inhibition. Pharmacopsychiatry. 2008;41:60\u20135.","journal-title":"Pharmacopsychiatry"},{"key":"2791_CR13","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1002\/hup.896","volume":"23","author":"F Zepf","year":"2008","unstructured":"Zepf F, Stadler C, Demisch L, Schmitt M, Landgraf M, Poustka F. Serotonergic functioning and trait-impulsivity in attention-deficit\/hyperactivity-disordered boys (ADHD): influence of rapid tryptophan depletion. Hum Psychopharmacol Clin Exp. 2008;23:43\u201351.","journal-title":"Hum Psychopharmacol Clin Exp"},{"key":"2791_CR14","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/hup.934","volume":"23","author":"F Zepf","year":"2008","unstructured":"Zepf F, W\u00f6ckel L, Poustka F, Holtmann M. Diminished 5-HT functioning in CBCL pediatric bipolar disorder-profiled ADHD patients versus normal ADHD: susceptibility to rapid tryptophan depletion influences reaction time performance. Hum Psychopharmacol Clin Exp. 2008;23:291\u20139.","journal-title":"Hum Psychopharmacol Clin Exp"},{"key":"2791_CR15","doi-asserted-by":"publisher","first-page":"e35916","DOI":"10.1371\/journal.pone.0035916","volume":"7","author":"CS Biskup","year":"2012","unstructured":"Biskup CS, S\u00e1nchez CL, Arrant A, Van Swearingen AE, Kuhn C, Zepf FD. Effects of acute tryptophan depletion on brain serotonin function and concentrations of dopamine and norepinephrine in C57BL\/6J and BALB\/cJ mice. PLoS One. 2012;7:e35916.","journal-title":"PLoS One"},{"key":"2791_CR16","doi-asserted-by":"publisher","first-page":"26","DOI":"10.3389\/neuro.09.026.2009","volume":"3","author":"\u00c5 Hammar","year":"2009","unstructured":"Hammar \u00c5, \u00c5rdal G. Cognitive functioning in major depression-a summary. Front Hum Neurosci. 2009;3:26.","journal-title":"Front Hum Neurosci"},{"key":"2791_CR17","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1017\/S0033291702007018","volume":"33","author":"F Murphy","year":"2003","unstructured":"Murphy F, Michael A, Robbins T, Sahakian B. Neuropsychological impairment in patients with major depressive disorder: the effects of feedback on task performance. Psychol Med. 2003;33:455\u201367.","journal-title":"Psychol Med"},{"key":"2791_CR18","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/sj.npp.1301212","volume":"32","author":"FM van der Veen","year":"2007","unstructured":"van der Veen FM, Evers EA, Deutz NE, Schmitt JA. Effects of acute tryptophan depletion on mood and facial emotion perception related brain activation and performance in healthy women with and without a family history of depression. Neuropsychopharmacology. 2007;32:216\u201324.","journal-title":"Neuropsychopharmacology"},{"key":"2791_CR19","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1007\/s00213-002-1128-9","volume":"163","author":"F Murphy","year":"2002","unstructured":"Murphy F, Smith K, Cowen P, Robbins T, Sahakian B. The effects of tryptophan depletion on cognitive and affective processing in healthy volunteers. Psychopharmacology. 2002;163:42\u201353.","journal-title":"Psychopharmacology"},{"key":"2791_CR20","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1006\/nimg.2002.1142","volume":"16","author":"J Ahveninen","year":"2002","unstructured":"Ahveninen J, K\u00e4hk\u00f6nen S, Pennanen S, Liesivuori J, Ilmoniemi RJ, J\u00e4\u00e4skel\u00e4inen IP. Tryptophan depletion effects on EEG and MEG responses suggest serotonergic modulation of auditory involuntary attention in humans. Neuroimage. 2002;16:1052\u201361.","journal-title":"Neuroimage"},{"key":"2791_CR21","first-page":"191","volume-title":"Kiddie-SADS Present and Lifetime Version","author":"J Kaufman","year":"1996","unstructured":"Kaufman J, Birmaher B, Brent D, Rao U, Ryan N. Kiddie-SADS Present and Lifetime Version. Pittsburgh: University of Pittsburgh; 1996. p. 191."},{"key":"2791_CR22","volume-title":"Wechsler Abbreviated Scale Of Intelligence - Second Edition (WASI-II)","author":"D Wechsler","year":"2011","unstructured":"Wechsler D. Wechsler Abbreviated Scale Of Intelligence - Second Edition (WASI-II). USA: Pearson Clinical; 2011."},{"key":"2791_CR23","first-page":"I\/25","volume":"252","author":"L Demisch","year":"2002","unstructured":"Demisch L, Kewitz A, Schmeck K, Sadigorsky S, Barta S, Dierks T, Poustka F. Methodology of rapid tryptophan depletion (RTD): impact of gender and body weight. Eur Arch Psychiatry Clin Neurosci. 2002;252:I\/25.","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"2791_CR24","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1159\/000112951","volume":"56","author":"C Stadler","year":"2008","unstructured":"Stadler C, Zepf F, Demisch L, Schmitt M, Landgraf M, Poustka F. Influence of rapid tryptophan depletion on laboratory-provoked aggression in children with ADHD. Neuropsychobiology. 2008;56:104\u201310.","journal-title":"Neuropsychobiology"},{"key":"2791_CR25","doi-asserted-by":"crossref","unstructured":"Beck AT, Steer RA, Brown GK. Beck Depression Inventory-II. San Antonio, Tx: Psychological corporation; 1996.","DOI":"10.1037\/t00742-000"},{"key":"2791_CR26","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","volume":"23","author":"M Hamilton","year":"1960","unstructured":"Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56\u201362.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2791_CR27","first-page":"979","volume":"21","author":"E Poznanski","year":"1985","unstructured":"Poznanski E, Freeman L, Mokros H. Childrens depression rating-scale-revised (September 1984). Psychopharmacol Bull. 1985;21:979\u201389.","journal-title":"Psychopharmacol Bull"},{"key":"2791_CR28","volume-title":"Child Behavior Checklist\/4-18","author":"TM Achenbach","year":"1991","unstructured":"Achenbach TM. Child Behavior Checklist\/4-18. Burlington: University of Vermont, Department of Psychiatry; 1991."},{"key":"2791_CR29","unstructured":"McNair P, Lorr M, Droppleman L: POMS Manual Educational and Industrial Testing Service. San Diego: San Diego. 1981."},{"key":"2791_CR30","unstructured":"Zimmermann P, Fimm B: A test battery for attentional performance. Applied Neuropsychology of Attention: Theory, Diagnosis and Rehabilitation. London: Psychology press; 2002110\u2013151."},{"key":"2791_CR31","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1017\/S0033291715000240","volume":"45","author":"L Capit\u00e3o","year":"2015","unstructured":"Capit\u00e3o L, Murphy S, Browning M, Cowen P, Harmer C. Acute fluoxetine modulates emotional processing in young adult volunteers. Psychol Med. 2015;45:2295\u2013308.","journal-title":"Psychol Med"},{"key":"2791_CR32","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1016\/j.neuropsychologia.2006.03.030","volume":"44","author":"R Cools","year":"2006","unstructured":"Cools R, Altamirano L, D\u2019Esposito M. Reversal learning in Parkinson's disease depends on medication status and outcome valence. Neuropsychologia. 2006;44:1663\u201373.","journal-title":"Neuropsychologia"},{"key":"2791_CR33","first-page":"1","volume-title":"Depression in Children and Young People: Identification and Management, Clinical Guideline","author":"National Institute for Health and Care Excellence (NICE)","year":"2005","unstructured":"National Institute for Health and Care Excellence (NICE). Depression in Children and Young People: Identification and Management, Clinical Guideline. London: NICE; 2005. p. 1\u201359."},{"key":"2791_CR34","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/j.biopsych.2003.12.020","volume":"55","author":"JP O'Reardon","year":"2004","unstructured":"O'Reardon JP, Chopra MP, Bergan A, Gallop R, DeRubeis RJ, Crits-Christoph P. Response to tryptophan depletion in major depression treated with either cognitive therapy or selective serotonin reuptake inhibitor antidepressants. Biol Psychiatry. 2004;55:957\u20139.","journal-title":"Biol Psychiatry"},{"key":"2791_CR35","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/S0893-133X(00)00161-5","volume":"23","author":"P Moore","year":"2000","unstructured":"Moore P, Landolt H-P, Seifritz E, Clark C, Bhatti T, Kelsoe J, Rapaport M, Gillin JC. Clinical and physiological consequences of rapid tryptophan depletion. Neuropsychopharmacology. 2000;23:601\u201322.","journal-title":"Neuropsychopharmacology"},{"key":"2791_CR36","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.biopsych.2007.02.012","volume":"62","author":"E Walderhaug","year":"2007","unstructured":"Walderhaug E, Magnusson A, Neumeister A, Lappalainen J, Lunde H, Refsum H, Landr\u00f8 NI. Interactive effects of sex and 5-HTTLPR on mood and impulsivity during tryptophan depletion in healthy people. Biol Psychiatry. 2007;62:593\u20139.","journal-title":"Biol Psychiatry"},{"key":"2791_CR37","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3758\/BF03193146","volume":"39","author":"F Faul","year":"2007","unstructured":"Faul F, Erdfelder E, Lang A-G, Buchner A. G* power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175\u201391.","journal-title":"Behav Res Methods"},{"key":"2791_CR38","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1001\/archpsyc.64.10.1132","volume":"64","author":"JS March","year":"2007","unstructured":"March JS, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, Burns B, Domino M, McNulty S, Vitiello B. The treatment for adolescents with depression study (TADS): long-term effectiveness and safety outcomes. Arch Gen Psychiatry. 2007;64:1132\u201343.","journal-title":"Arch Gen Psychiatry"},{"key":"2791_CR39","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1002\/hup.1002","volume":"24","author":"FD Zepf","year":"2009","unstructured":"Zepf FD, Holtmann M, Stadler C, Magnus S, W\u00f6ckel L, Poustka F. Diminished central nervous 5-HT neurotransmission and mood self-ratings in children and adolescents with ADHD: no clear effect of rapid tryptophan depletion. Hum Psychopharmacol Clin Exp. 2009;24:87\u201394.","journal-title":"Hum Psychopharmacol Clin Exp"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-018-2791-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13063-018-2791-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-018-2791-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T19:11:36Z","timestamp":1565377896000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-018-2791-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,10]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["2791"],"URL":"https:\/\/doi.org\/10.1186\/s13063-018-2791-4","relation":{},"ISSN":["1745-6215"],"issn-type":[{"type":"electronic","value":"1745-6215"}],"subject":[],"published":{"date-parts":[[2018,8,10]]},"assertion":[{"value":"27 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study has received ethics approval from the Princess Margaret Hospital Human Research Ethics Committee (2015203EP), and reciprocal approval from The University of Western Australia Human Research Ethics Committee (RA\/4\/1\/8024). Participants will be recruited from Princess Margaret Hospital in Perth, as well as General Practice, and Headspace Clinics (early intervention services for youth mental health disorders) in the Perth metropolitan area. This trial is also registered with the Therapeutic Goods Administration, with a Clinical Trial Notification number of CT-2016-CTN-01070-1.Prior to study participation, informed consent will be obtained from subjects and their parents\/guardians by the study doctors. When obtaining informed consent from the patients and their parents\/guardians, focus will also be given to outline the need for blood sampling in this study, and the potential risks of lowered mood in the short term whilst under the influence of ATD (which is in line with the main hypothesis with regard to Phase A). Consent will be obtained at an initial screening session where participants will be assessed for eligibility to participate in the study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"FDZ was the recipient of an unrestricted award donated by the American Psychiatric Association (APA), the American Psychiatric Institute for Research and Education (APIRE) and AstraZeneca (Young Minds in Psychiatry Award). He has also received research support from the German Federal Ministry for Economics and Technology, the European Union (EU), the German Society for Social Paediatrics and Adolescent Medicine, the Paul and Ursula Klein Foundation, the Dr. August Scheidel Foundation, the IZKF fund of the University Hospital of RWTH Aachen University, the Telethon Kids Institute, the Telethon Perth Children\u2019s Hospital Research Fund, the Princess Margaret Hospital Foundation, and a travel stipend donated by the GlaxoSmithKline Foundation. He is the recipient of an unrestricted educational grant, travel support and speaker honoraria by Shire Pharmaceuticals, Germany. In addition, he has received support from the Raine Foundation for Medical Research (Raine Visiting Professorship), and editorial fees from Co-Action Publishing (Sweden). SEM has received consultancy payments from p1Vital and has participated in paid speaking engagements for Lilly UK. The other authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"434"}}