{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T11:28:10Z","timestamp":1779103690539,"version":"3.51.4"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2006,1,10]],"date-time":"2006-01-10T00:00:00Z","timestamp":1136851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2006,1,10]],"date-time":"2006-01-10T00:00:00Z","timestamp":1136851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2006,4,1]]},"DOI":"10.1038\/sj.mp.4001790","type":"journal-article","created":{"date-parts":[[2006,1,10]],"date-time":"2006-01-10T10:58:45Z","timestamp":1136890725000},"page":"352-360","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":120,"title":["The thermolabile variant of MTHFR is associated with depression in the British Women's Heart and Health Study and a meta-analysis"],"prefix":"10.1038","volume":"11","author":[{"given":"S J","family":"Lewis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D A","family":"Lawlor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Davey Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Araya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Timpson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I N M","family":"Day","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Ebrahim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2006,1,10]]},"reference":[{"key":"BF4001790_CR1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.2165\/00003495-199448020-00002","volume":"48","author":"T Bottiglieri","year":"1994","unstructured":"Bottiglieri T, Hyland K, Reynolds EH . The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994; 48: 137\u2013152.","journal-title":"Drugs"},{"key":"BF4001790_CR2","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S0166-2236(03)00032-8","volume":"23","author":"M Mattson","year":"2003","unstructured":"Mattson M, Shea T . Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 2003; 23: 137.","journal-title":"Trends Neurosci"},{"key":"BF4001790_CR3","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1002\/hup.614","volume":"19","author":"RTP Paul","year":"2004","unstructured":"Paul RTP, McDonnell AP, Kelly CB . Folic acid: neurochemistry, metabolism and relationship to depression. Hum Psychopharmacol Clin Exp 2004; 19: 477\u2013488.","journal-title":"Hum Psychopharmacol Clin Exp"},{"key":"BF4001790_CR4","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1159\/000068692","volume":"72","author":"MS Morris","year":"2003","unstructured":"Morris MS, Fava M, Jacques PF, Selhub J, Rosenberg IH . Depression and folate status in the US population. Psychother Psychosom 2003; 72: 80\u201387.","journal-title":"Psychother Psychosom"},{"key":"BF4001790_CR5","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3109\/10401239309148970","volume":"5","author":"GP Guaraldi","year":"1993","unstructured":"Guaraldi GP, Fava M, Mazzi F, la Greca P . An open trial of methyletrahydrofolate in elderly depressed patients. Ann Clin Psychiatry 1993; 5: 101\u2013105.","journal-title":"Ann Clin Psychiatry"},{"key":"BF4001790_CR6","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1177\/0269881104042630","volume":"18","author":"MJ Taylor","year":"2004","unstructured":"Taylor MJ, Carney SM, Goodwin GM, Geddes JR . Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. J Psychopharmacol 2004; 18: 251\u2013256.","journal-title":"J Psychopharmacol"},{"key":"BF4001790_CR7","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1176\/appi.ajp.158.10.1555","volume":"158","author":"C Nemeroff","year":"2001","unstructured":"Nemeroff C . Progress in the battle with the black dog: advances in the treatment of depression. Am J Psychiatry 2001; 158: 1555\u20131557.","journal-title":"Am J Psychiatry"},{"key":"BF4001790_CR8","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1016\/S0140-6736(02)11994-5","volume":"360","author":"JG Ray","year":"2002","unstructured":"Ray JG, Meier C, Vermeulen MJ, Boss S, Wyatt PR, Cole DE . Association of neural tube defects and folic acid food fortification in Canada. Lancet 2002; 360: 2047\u20132048.","journal-title":"Lancet"},{"key":"BF4001790_CR9","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.1001\/jama.285.23.2981","volume":"285","author":"MA Honein","year":"2001","unstructured":"Honein MA, Paulozzi LJ, Mathews TJ, Erickson JD, Wong LY . Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA 2001; 285: 2981\u20132986.","journal-title":"JAMA"},{"key":"BF4001790_CR10","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/ng0595-111","volume":"10","author":"P Frosst","year":"1995","unstructured":"Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111\u2013113.","journal-title":"Nat Genet"},{"key":"BF4001790_CR11","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1182\/blood.V101.7.2483","volume":"101","author":"L Kluijtmans","year":"2003","unstructured":"Kluijtmans L, Young IS, Boreham C, Murray L, McMaster D, McNulty H et al. Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults. Blood 2003; 101: 2483\u20132488.","journal-title":"Blood"},{"key":"BF4001790_CR12","doi-asserted-by":"publisher","first-page":"S141","DOI":"10.1046\/j.1523-1755.63.s84.52.x","volume":"84","author":"G Sunder-Plassmann","year":"2003","unstructured":"Sunder-Plassmann G, Fodinger M . Genetic determinants of the homocysteine level. Kidney Int Suppl 2003; 84: S141\u2013S144.","journal-title":"Kidney Int Suppl"},{"key":"BF4001790_CR13","first-page":"1427","volume":"41","author":"J Geisel","year":"2003","unstructured":"Geisel J, Hubner U, Bodis M . The role of genetic factors in the development of hyperhomocysteinemia. Clin Chem Lab Med 2003; 41: 1427\u20131434.","journal-title":"Clin Chem Lab Med"},{"key":"BF4001790_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ije\/dyg070","volume":"32","author":"G Davey Smith","year":"2003","unstructured":"Davey Smith G, Ebrahim S . \u2018Mendelian randomization\u2019: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol 2003; 32: 1\u201322.","journal-title":"Int J Epidemiol"},{"key":"BF4001790_CR15","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1093\/oxfordjournals.aje.a010290","volume":"151","author":"LD Botto","year":"2000","unstructured":"Botto LD, Yang Q . 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol 2000; 151: 862\u2013877.","journal-title":"Am J Epidemiol"},{"key":"BF4001790_CR16","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1016\/j.pnpbp.2005.06.027","volume":"29","author":"A Reif","year":"2005","unstructured":"Reif A, Pfuhlmann B, Lesch KP . Homocysteinemia as well as methylenetetrahydrofolate reductase polymorphism are associated with affective psychoses. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 1162\u20131168.","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"BF4001790_CR17","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.neurobiolaging.2004.03.007","volume":"26","author":"OP Almeida","year":"2005","unstructured":"Almeida OP, Flicker L, Lautenschlager NT, Leedman P, Vasikaran S, van Bockxmeer FM . Contribution of the MTHFR gene to the causal pathway for depression, anxiety and cognitive impairment in later life. Neurobiol Aging 2005; 26: 251\u2013257.","journal-title":"Neurobiol Aging"},{"key":"BF4001790_CR18","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1177\/026988110401800415","volume":"18","author":"CB Kelly","year":"2004","unstructured":"Kelly CB, McDonnell AP, Johnston TG, Mulholland C, Cooper SJ, McMaster D et al. The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland. J Psychopharmacol 2004; 18: 567\u2013571.","journal-title":"J Psychopharmacol"},{"key":"BF4001790_CR19","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1097\/00041444-200412000-00012","volume":"14","author":"EC Tan","year":"2004","unstructured":"Tan EC, Chong SA, Lim LC, Chan AO, Teo YY, Tan CH et al. Genetic analysis of the thermolabile methylenetetrahydrofolate reductase variant in schizophrenia and mood disorders. Psychiatr Genet 2004; 14: 227\u2013231.","journal-title":"Psychiatr Genet"},{"key":"BF4001790_CR20","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1001\/archpsyc.60.6.618","volume":"60","author":"I Bjelland","year":"2003","unstructured":"Bjelland I, Tell GS, Vollset SE, Refsum H, Ueland PM . Folate, vitamin B12, homocysteine, and the MTHFR 677C-T polymorphism in anxiety and depression. Arch Gen Psychiatry 2003; 60: 618\u2013626.","journal-title":"Arch Gen Psychiatry"},{"key":"BF4001790_CR21","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1017\/S0033291701004731","volume":"31","author":"I Hickie","year":"2001","unstructured":"Hickie I, Scott E, Naismith S, Ward PB, Turner K, Parker G et al. Late-onset depression: genetic, vascular and clinical contributions. Psychol Med 2001; 31: 1403\u20131412.","journal-title":"Psychol Med"},{"key":"BF4001790_CR22","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/sj.mp.4000390","volume":"3","author":"H Kunugi","year":"1998","unstructured":"Kunugi H, Fukuda R, Hattori M, Kato T, Tatsumi M, Sakai T et al. C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses. Mol Psychiatry 1998; 3: 435\u2013437.","journal-title":"Mol Psychiatry"},{"key":"BF4001790_CR23","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1002\/(SICI)1096-8628(19970919)74:5<526::AID-AJMG14>3.0.CO;2-E","volume":"74","author":"T Arinami","year":"1997","unstructured":"Arinami T, Yamada N, Yamakawa-Kobayashi K, Hamaguchi H, Toru M . Methylenetetrahydrofolate reductase variant and schizophrenia\/depression. Am J Med Genet 1997; 74: 526\u2013528.","journal-title":"Am J Med Genet"},{"key":"BF4001790_CR24","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1136\/jech.57.2.134","volume":"57","author":"DA Lawlor","year":"2003","unstructured":"Lawlor DA, Bedford C, Taylor M, Ebrahim S . Geographic variation in cardiovascular disease, risk factors and their control in older women: British Women's Heart and Health Study. J Epidemiol Community Health 2003; 57: 134\u2013140.","journal-title":"J Epidemiol Community Health"},{"key":"BF4001790_CR25","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","volume":"16","author":"SA Miller","year":"1988","unstructured":"Miller SA, Dykes DD, Polesky HF . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.","journal-title":"Nucleic Acids Res"},{"key":"BF4001790_CR26","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/9780470693926.ch18","volume-title":"Systematic Reviews in Health Care: Meta-Analysis in Context","author":"JAC Sterne","year":"2001","unstructured":"Sterne JAC, Bradburn MJ, Egger M . Meta-analysis in Stata. In: Egger M, Davey Smith G and Altman D (eds). Systematic Reviews in Health Care: Meta-Analysis in Context, 2nd edn. BMJ: London, 2001; 347\u2013369."},{"key":"BF4001790_CR27","volume-title":"Health Survey for England 1998: Cardiovascular Disease","author":"B Erens","year":"1999","unstructured":"Erens B, Primatesta P . Health Survey for England 1998: Cardiovascular Disease. The Stationary Office: London, 1999."},{"key":"BF4001790_CR28","first-page":"7136","volume":"61","author":"MJ Shrubsole","year":"2001","unstructured":"Shrubsole MJ, Jin F, Dai Q, Shu XO, Potter JD, Hebert JR et al. Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Res 2001; 61: 7136\u20137141.","journal-title":"Cancer Res"},{"key":"BF4001790_CR29","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1097\/00001648-200107000-00012","volume":"12","author":"TA Sellers","year":"2001","unstructured":"Sellers TA, Kushi LH, Cerhan JR, Vierkant RA, Gapstur SM, Vachon CM et al. Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology 2001; 12: 420\u2013428.","journal-title":"Epidemiology"},{"key":"BF4001790_CR30","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1161\/01.ATV.16.7.878","volume":"16","author":"DE Wilcken","year":"1996","unstructured":"Wilcken DE, Wang XL, Sim AS, McCredie RM . Distribution in healthy and coronary populations of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Arterioscler Thromb Vasc Biol 1996; 16: 878\u2013882.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"BF4001790_CR31","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1093\/clinchem\/45.10.1860","volume":"45","author":"JC Knight","year":"1999","unstructured":"Knight JC, McGuire W, Kortok MM, Kwiatkowski D . Accuracy of genotyping of single-nucleotide polymorphisms by PCR-ELISA allele-specific oligonucleotide hybridization typing and by amplification refractory mutation system. Clin Chem 1999; 45: 1860\u20131863.","journal-title":"Clin Chem"},{"key":"BF4001790_CR32","doi-asserted-by":"publisher","first-page":"2520","DOI":"10.1161\/01.CIR.98.23.2520","volume":"98","author":"L Brattstrom","year":"1998","unstructured":"Brattstrom L, Wilcken DE, Ohrvik J, Brudin L . Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis. Circulation 1998; 98: 2520\u20132526.","journal-title":"Circulation"},{"key":"BF4001790_CR33","doi-asserted-by":"crossref","unstructured":"Homocysteine Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomized trials. Br Med J 1998; 316: 894\u2013898.","DOI":"10.1136\/bmj.316.7135.894"},{"key":"BF4001790_CR34","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/S0140-6736(03)12715-8","volume":"361","author":"HM Colhoun","year":"2003","unstructured":"Colhoun HM, McKeigue PM, Davey Smith G . Problems of reporting genetic associations with complex outcomes. Lancet 2003; 361: 865\u2013872.","journal-title":"Lancet"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/4001790.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/4001790","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/4001790.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T03:06:58Z","timestamp":1648782418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/4001790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1,10]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2006,4,1]]}},"alternative-id":["BF4001790"],"URL":"https:\/\/doi.org\/10.1038\/sj.mp.4001790","relation":{},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1,10]]},"assertion":[{"value":"17 August 2005","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2005","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2005","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 January 2006","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}