{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:03:57Z","timestamp":1793160237230,"version":"4.5.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T00:00:00Z","timestamp":1567382400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T00:00:00Z","timestamp":1567382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Metab Brain Dis"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1007\/s11011-019-00486-1","type":"journal-article","created":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T08:05:25Z","timestamp":1567411525000},"page":"1781-1786","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Vitamin D supplementation ameliorates severity of generalized anxiety disorder (GAD)"],"prefix":"10.1007","volume":"34","author":[{"given":"Alaa","family":"Eid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawsan","family":"Khoja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shareefa","family":"AlGhamdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeil","family":"Alsufiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faten","family":"Alzeben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Alhejaili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haythum O.","family":"Tayeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6839-9378","authenticated-orcid":false,"given":"Frank I.","family":"Tarazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,2]]},"reference":[{"key":"486_CR1","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jsbmb.2016.12.017","volume":"175","author":"NM Al-Daghri","year":"2018","unstructured":"Al-Daghri NM (2018) Vitamin D in Saudi Arabia: prevalence, distribution and disease associations. J Steroid Biochem Mol Biol 175:102\u2013107","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"2","key":"486_CR2","doi-asserted-by":"publisher","first-page":"184","DOI":"10.12816\/0014485","volume":"26","author":"O Al-Modayfer","year":"2015","unstructured":"Al-Modayfer O, Alatiq Y (2015) A pilot study on the prevalence of psychiatric disorders among Saudi children and adolescents: a sample from a selected community in Riyadh city. Arab J Psychiatry 26(2):184\u2013192","journal-title":"Arab J Psychiatry"},{"key":"486_CR3","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1146\/annurev.med.60.042307.110802","volume":"60","author":"M Berger","year":"2009","unstructured":"Berger M, Gray JA, Roth BL (2009) The expanded biology of serotonin. Ann Rev Med 60:355\u2013366","journal-title":"Ann Rev Med"},{"issue":"suppl 2","key":"486_CR4","doi-asserted-by":"crossref","first-page":"S101","DOI":"10.33549\/physiolres.933082","volume":"64","author":"M Bicikova","year":"2015","unstructured":"Bicikova M, Duskova M, Vitku J, Kalvachova B, Ripova D, Mohr P (2015) Starka L (2015) vitamin D in anxiety and affective disorders. Physiol Res 64(suppl 2):S101\u2013S103","journal-title":"Physiol Res"},{"issue":"6","key":"486_CR5","doi-asserted-by":"publisher","first-page":"636","DOI":"10.2174\/1389450118666170425153356","volume":"19","author":"P Boldrini","year":"2018","unstructured":"Boldrini P, Fusco A, Nicoletti F, Badiani A, Saso L (2018) Potential use of modulators of oxidative stress as add-on therapy in patients with anxiety disorders. Curr Drug Targets 19(6):636\u2013650","journal-title":"Curr Drug Targets"},{"issue":"2","key":"486_CR6","doi-asserted-by":"publisher","first-page":"63","DOI":"10.4161\/oxim.2.2.7944","volume":"2","author":"J Bouayed","year":"2009","unstructured":"Bouayed J, Rammal H, Soulimani R (2009) Oxidative stress and anxiety: relationship and cellular pathways. Oxidative Med Cell Longev 2(2):63\u201367","journal-title":"Oxidative Med Cell Longev"},{"issue":"1","key":"486_CR7","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.foodchem.2011.02.052","volume":"128","author":"J Bouayed","year":"2011","unstructured":"Bouayed J, Hoffmann L, Bohn T (2011) Total phenolics, flavonoids, anthocyanins and antioxidant activity following simulated gastro-intestinal digestion and dialysis of apple varieties: bioaccessibility and potential uptake. Food Chem 128(1):14\u201321","journal-title":"Food Chem"},{"issue":"6","key":"486_CR8","doi-asserted-by":"publisher","first-page":"1689S","DOI":"10.1093\/ajcn\/80.6.1689S","volume":"80","author":"HF DeLuca","year":"2004","unstructured":"DeLuca HF (2004) Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 80(6):1689S\u20131696S","journal-title":"Am J Clin Nutr"},{"issue":"5","key":"486_CR9","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1111\/nan.12020","volume":"39","author":"GC DeLuca","year":"2013","unstructured":"DeLuca GC, Kimball SM, Kolasinski J, Ramagopalan SV, Ebers GC (2013) Review: the role of vitamin D in nervous system health and disease. Neuropathol Appl Neurobiol 39(5):458\u2013484","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"3 Suppl","key":"486_CR10","doi-asserted-by":"publisher","first-page":"26S","DOI":"10.1097\/00004714-199006001-00006","volume":"10","author":"MS Eison","year":"1990","unstructured":"Eison MS (1990) Serotonin: a common neurobiologic substrate in anxiety and depression. J Clin Psychopharmacol 10(3 Suppl):26S\u201330S","journal-title":"J Clin Psychopharmacol"},{"issue":"2","key":"486_CR11","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1515\/folmed-2017-0022","volume":"59","author":"J Fedotova","year":"2017","unstructured":"Fedotova J, Zarembo D, Dragasek J, Caprnda M, Kruzliak P, Dudnichenko T (2017) Modulating effects of cholecalciferol treatment on estrogen deficiency-induced anxiety-like behavior of adult female rats. Folia Med 59(2):139\u2013158","journal-title":"Folia Med"},{"issue":"3","key":"486_CR12","doi-asserted-by":"publisher","first-page":"244","DOI":"10.4103\/0019-5545.102424","volume":"54","author":"M Gautam","year":"2012","unstructured":"Gautam M, Agrawal M, Gautam M, Sharma P, Gautam AS, Gautam S (2012) Role of antioxidants in generalised anxiety disorder and depression. Indian J Psychiatry 54(3):244\u2013247","journal-title":"Indian J Psychiatry"},{"issue":"12","key":"486_CR13","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1017\/S0033291705006069","volume":"35","author":"BF Grant","year":"2005","unstructured":"Grant BF, Hasin DS, Stinson FS, Dawson DA, June Ruan W, Goldstein RB, Smith SM, Saha TD, Huang B (2005) Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA: results from the National Epidemiologic Survey on alcohol and related conditions. Psychol Med 35(12):1747\u20131759","journal-title":"Psychol Med"},{"issue":"3","key":"486_CR14","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/0163-7258(95)98597-J","volume":"65","author":"G Griebel","year":"1995","unstructured":"Griebel G (1995) 5-Hydroxytryptamine-interacting drugs in animal models of anxiety disorders: more than 30 years of research. Pharmacol Ther 65(3):319\u2013395","journal-title":"Pharmacol Ther"},{"key":"486_CR15","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1146\/annurev-nutr-071813-105557","volume":"34","author":"NJ Groves","year":"2014","unstructured":"Groves NJ, McGrath JJ, Burne TH (2014) Vitamin D as a neurosteroid affecting the developing and adult brain. Ann Rev Nutr 34:117\u2013141","journal-title":"Ann Rev Nutr"},{"issue":"12","key":"486_CR16","doi-asserted-by":"publisher","first-page":"5405","DOI":"10.3390\/nu6125405","volume":"6","author":"AL Hansen","year":"2014","unstructured":"Hansen AL, Olson G, Dahl L, Thornton D, Grung B, Graff IE, Froyland L, Thayer JF (2014) Reduced anxiety in forensic inpatients after a long-term intervention with Atlantic salmon. Nutrients 6(12):5405\u20135418","journal-title":"Nutrients"},{"key":"486_CR17","doi-asserted-by":"crossref","unstructured":"Hariri A (2016) Vitamin D deficiency\/insufficiency and anxiety among Saudis: degree and differences. Euro Scientific J 12(27)","DOI":"10.19044\/esj.2016.v12n27p93"},{"issue":"11","key":"486_CR18","doi-asserted-by":"publisher","first-page":"3238","DOI":"10.1007\/s10461-017-1788-4","volume":"21","author":"J Hellmuth","year":"2017","unstructured":"Hellmuth J, Colby D, Valcour V, Suttichom D, Spudich S, Ananworanich J, Prueksakaew P, Sailasuta N, Allen I, Jagodzinski LL, Slike B, Ochi D, Paul R (2017) Depression and anxiety are common in acute HIV infection and associate with plasma immune activation. AIDS Behav 21(11):3238\u20133246","journal-title":"AIDS Behav"},{"issue":"11","key":"486_CR19","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.4065\/mcp.2011.0208","volume":"86","author":"MT Hoang","year":"2011","unstructured":"Hoang MT, Defina LF, Willis BL, Leonard DS, Weiner MF, Brown ES (2011) Association between low serum 25-hydroxyvitamin D and depression in a large sample of healthy adults: the Cooper Center longitudinal study. Mayo Clin Proc 86(11):1050\u20131055","journal-title":"Mayo Clin Proc"},{"issue":"1","key":"486_CR20","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1002\/da.20257","volume":"25","author":"DL Hoffman","year":"2008","unstructured":"Hoffman DL, Dukes EM, Wittchen HU (2008) Human and economic burden of generalized anxiety disorder. Depress Anxiety 25(1):72\u201390","journal-title":"Depress Anxiety"},{"issue":"S2","key":"486_CR21","doi-asserted-by":"publisher","first-page":"V28","DOI":"10.1359\/jbmr.07s211","volume":"22","author":"MF Holick","year":"2007","unstructured":"Holick MF, Chen TC, Lu Z, Sauter E (2007) Vitamin D and skin physiology: a D-lightful story. J Bone Miner Res 22(S2):V28\u2013V33","journal-title":"J Bone Miner Res"},{"issue":"5","key":"486_CR22","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1001\/archpsyc.65.5.508","volume":"65","author":"WJ Hoogendijk","year":"2008","unstructured":"Hoogendijk WJ, Lips P, Dik MG, Deeg DJ, Beekman AT, Penninx BW (2008) Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Arch Gen Psychiatry 65(5):508\u2013512","journal-title":"Arch Gen Psychiatry"},{"issue":"4","key":"486_CR23","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1002\/da.22095","volume":"30","author":"DF Ionescu","year":"2013","unstructured":"Ionescu DF, Niciu MJ, Mathews DC, Richards EM, Zarate CA Jr (2013) Neurobiology of anxious depression: a review. Depressi Anxiety 30(4):374\u2013385","journal-title":"Depressi Anxiety"},{"issue":"6","key":"486_CR24","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1111\/j.1365-2796.2008.02008.x","volume":"264","author":"R Jorde","year":"2008","unstructured":"Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K (2008) Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med 264(6):599\u2013609","journal-title":"J Intern Med"},{"key":"486_CR25","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1146\/annurev.publhealth.29.020907.090847","volume":"29","author":"RC Kessler","year":"2008","unstructured":"Kessler RC, Wang PS (2008) The descriptive epidemiology of commonly occurring mental disorders in the United States. Ann Rev Public Health 29:115\u2013129","journal-title":"Ann Rev Public Health"},{"issue":"5","key":"486_CR26","doi-asserted-by":"publisher","first-page":"574","DOI":"10.2174\/1570159X15666170913110426","volume":"16","author":"Y-K Kim","year":"2018","unstructured":"Kim Y-K, Jeon SW (2018) Neuroinflammation and the immune-kynurenine pathway in anxiety disorders. Curr Neuropharmacol 16(5):574\u2013582","journal-title":"Curr Neuropharmacol"},{"key":"486_CR27","first-page":"22","volume":"62","author":"LJ Kirmayer","year":"2001","unstructured":"Kirmayer LJ (2001) Cultural variations in the clinical presentation of depression and anxiety: implications for diagnosis and treatment. J Clin Psychiatry 62:22\u201330","journal-title":"J Clin Psychiatry"},{"issue":"6","key":"486_CR28","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1016\/j.pnpbp.2005.03.012","volume":"29","author":"KP Lesch","year":"2005","unstructured":"Lesch KP, Gutknecht L (2005) Pharmacogenetics of the serotonin transporter. Prog Neuro-Psychopharmacol Biol Psychiatry 29(6):1062\u20131073","journal-title":"Prog Neuro-Psychopharmacol Biol Psychiatry"},{"issue":"4","key":"486_CR29","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.euroneuro.2005.04.010","volume":"15","author":"RE Lieb","year":"2005","unstructured":"Lieb RE, Becker E, Altamura C (2005) The epidemiology of generalized anxiety disorder in Europe. Eur Neuropsychopharmacol 15(4):445\u2013452","journal-title":"Eur Neuropsychopharmacol"},{"issue":"16","key":"486_CR30","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1016\/S0024-3205(02)01853-2","volume":"71","author":"M Maes","year":"2002","unstructured":"Maes M, Verkerk R, Bonaccorso S, Ombelet W, Bosmans E, Scharp\u00e9 S (2002) Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation. Life Sci 71(16):1837\u20131848","journal-title":"Life Sci"},{"issue":"4","key":"486_CR31","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/mp.2013.36","volume":"19","author":"Y Milaneschi","year":"2014","unstructured":"Milaneschi Y, Hoogendijk W, Lips P, Heijboer AC, Schoevers R, van Hemert AM, Beekman AT, Smit JH, Penninx BW (2014) The association between low vitamin D and depressive disorders. Mol Psychiatry 19(4):444\u2013451","journal-title":"Mol Psychiatry"},{"issue":"2","key":"486_CR32","doi-asserted-by":"publisher","first-page":"175","DOI":"10.2174\/1389200024605082","volume":"3","author":"C Murr","year":"2002","unstructured":"Murr C, Widner B, Wirleitner B, Fuchs D (2002) Neopterin as a marker for immune system activation. Curr Drug Metab 3(2):175\u2013187","journal-title":"Curr Drug Metab"},{"issue":"6","key":"486_CR33","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.1096\/fj.13-246546","volume":"28","author":"RP Patrick","year":"2014","unstructured":"Patrick RP, Ames BN (2014) Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB J 28(6):2398\u20132413","journal-title":"FASEB J"},{"issue":"3","key":"486_CR34","first-page":"533","volume":"51","author":"G Pi\u00f1eyro","year":"1999","unstructured":"Pi\u00f1eyro G, Blier P (1999) Autoregulation of serotonin neurons: role in antidepressant drug action. Pharmacol Rev 51(3):533\u2013591","journal-title":"Pharmacol Rev"},{"key":"486_CR35","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/B978-0-12-375000-6.00175-0","volume-title":"Encyclopedia of Human Behavior","author":"M.E. Portman","year":"2012","unstructured":"Portman ME, Riskind JH, Rector NA (2012) Generalized anxiety disorder. In: Encyclopedia of human behavior, Second edn. Academic Press, San Diego, pp 215\u2013220"},{"issue":"1","key":"486_CR36","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s10067-017-3874-4","volume":"37","author":"D Pu","year":"2018","unstructured":"Pu D, Luo J, Wang Y, Ju B, Lv X, Fan P, He L (2018) Prevalence of depression and anxiety in rheumatoid arthritis patients and their associations with serum vitamin D level. Clin Rheumatol 37(1):179\u2013184","journal-title":"Clin Rheumatol"},{"issue":"10","key":"486_CR37","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1001\/archinte.166.10.1092","volume":"166","author":"RL Spitzer","year":"2006","unstructured":"Spitzer RL, Kroenker K, Williams JB, Lowe B (2006) A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med 166(10):1092\u20131097","journal-title":"Arch Intern Med"},{"issue":"3","key":"486_CR38","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/S0165-0327(98)00221-3","volume":"51","author":"SM Stahl","year":"1998","unstructured":"Stahl SM (1998) Mechanism of action of serotonin selective reuptake inhibitors. Serotonin receptors and pathways mediate therapeutic effects and side effects. J Affect Disord 51(3):215\u2013235","journal-title":"J Affect Disord"},{"issue":"2","key":"486_CR39","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/S0301-0082(00)00032-0","volume":"64","author":"TW Stone","year":"2001","unstructured":"Stone TW (2001) Kynurenines in the CNS: from endogenous obscurity to therapeutic importance. Prog Neurobiol 64(2):185\u2013218","journal-title":"Prog Neurobiol"},{"key":"486_CR40","first-page":"15","volume":"62","author":"H-U Wittchen","year":"2001","unstructured":"Wittchen H-U, Hoyer J (2001) Generalized anxiety disorder: nature and course. J Clin Psychiatry 62:15\u201321","journal-title":"J Clin Psychiatry"}],"container-title":["Metabolic Brain Disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11011-019-00486-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11011-019-00486-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11011-019-00486-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T23:10:36Z","timestamp":1598915436000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11011-019-00486-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,2]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["486"],"URL":"https:\/\/doi.org\/10.1007\/s11011-019-00486-1","relation":{},"ISSN":["0885-7490","1573-7365"],"issn-type":[{"value":"0885-7490","type":"print"},{"value":"1573-7365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,2]]},"assertion":[{"value":"27 March 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that there are no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}