{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T15:40:32Z","timestamp":1758123632223,"version":"3.37.3"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alcohol use disorder (AUD) is one of the foremost public health problems. Alcohol is also frequently co-abused with cocaine. There is a huge unmet need for the treatment of AUD and\/or cocaine co-abuse. We recently demonstrated that skin grafts generated from mouse epidermal stem cells that had been engineered by CRISPR-mediated genome editing could be transplanted onto mice as a gene delivery platform. Here, we show that expression of the glucagon-like peptide-1 (GLP1) gene delivered by epidermal stem cells attenuated development and reinstatement of alcohol-induced drug-taking and seeking as well as voluntary oral alcohol consumption. GLP1 derived from the skin grafts decreased alcohol-induced increase in dopamine levels in the nucleus accumbens. In exploring the potential of this platform in reducing concurrent use of drugs, we developed a novel co-grafting procedure for both modified human butyrylcholinesterase (hBChE)- and GLP1-expressing cells. Epidermal stem cell-derived hBChE and GLP1 reduced acquisition of drug-taking and toxicity induced by alcohol and cocaine co-administration. These results imply that cutaneous gene delivery through skin transplants may add a new option to treat drug abuse and co-abuse.<\/jats:p>","DOI":"10.1038\/s41380-021-01043-y","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T18:02:47Z","timestamp":1614016967000},"page":"5266-5276","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Reducing alcohol and\/or cocaine-induced reward and toxicity via an epidermal stem cell-based gene delivery platform"],"prefix":"10.1038","volume":"26","author":[{"given":"Qingyao","family":"Kong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiping","family":"Yue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6378-3207","authenticated-orcid":false,"given":"Xiaoyang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9595-834X","authenticated-orcid":false,"given":"Ming","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"1043_CR1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition. 2013.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"1043_CR2","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1001\/jamapsychiatry.2015.0584","volume":"72","author":"BF Grant","year":"2015","unstructured":"Grant BF, Goldstein RB, Saha TD, Chou SP, Jung J, Zhang H, et al. Epidemiology of DSM-5 alcohol use disorder: results from the national epidemiologic survey on alcohol and related conditions III. JAMA Psychiatry. 2015;72:757\u2013766.","journal-title":"JAMA Psychiatry"},{"key":"1043_CR3","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/S0006-3223(97)00426-5","volume":"44","author":"EF McCance-Katz","year":"1998","unstructured":"McCance-Katz EF, Kosten TR, Jatlow P. Concurrent use of cocaine and alcohol is more potent and potentially more toxic than use of either alone\u2014a multiple-dose study. Biol Psychiatry. 1998;44:250\u2013259.","journal-title":"Biol Psychiatry"},{"key":"1043_CR4","doi-asserted-by":"publisher","first-page":"281","DOI":"10.4172\/2155-6105.1000281","volume":"7","author":"YS Althobaiti","year":"2016","unstructured":"Althobaiti YS, Sari Y. Alcohol interactions with psychostimulants: an overview of animal and human studies. J Addict Res Ther. 2016;7:281\u2013297.","journal-title":"J Addict Res Ther."},{"key":"1043_CR5","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1111\/j.1471-4159.1991.tb08205.x","volume":"56","author":"WL Hearn","year":"1991","unstructured":"Hearn WL, Flynn DD, Hime GW, Rose S, Cofino JC, Mantero-Atienza E, et al. Cocaethylene: a unique cocaine metabolite displays high affinity for the dopamine transporter. J Neurochem. 1991;56:698\u2013701.","journal-title":"J Neurochem"},{"key":"1043_CR6","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1046\/j.1360-0443.2002.00158.x","volume":"97","author":"EJM Pennings","year":"2002","unstructured":"Pennings EJM, Leccese AP, Wolff FA. Effects of concurrent use of alcohol and cocaine. Addiction. 2002;97:773\u2013783.","journal-title":"Addiction"},{"key":"1043_CR7","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1111\/j.1476-5381.1993.tb13569.x","volume":"109","author":"Z Qiu","year":"1993","unstructured":"Qiu Z, Morgan JP. Differential effects of cocaine and cocaethylene on intracellular Ca2+ and myocardial contraction in cardiac myocytes. Br J Pharm. 1993;109:293\u2013298.","journal-title":"Br J Pharm"},{"key":"1043_CR8","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1300\/J069v16n03_08","volume":"16","author":"P Andrews","year":"1997","unstructured":"Andrews P. Cocaethylene toxicity. J Addict Dis 1997;16:75\u201384.","journal-title":"J Addict Dis"},{"key":"1043_CR9","first-page":"40","volume":"23","author":"R Weathermon","year":"1999","unstructured":"Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health. 1999;23:40\u201354.","journal-title":"Alcohol Res Health"},{"key":"1043_CR10","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1152\/physrev.00034.2006","volume":"87","author":"JJ Holst","year":"2007","unstructured":"Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87:1409\u20131439.","journal-title":"Physiol Rev"},{"key":"1043_CR11","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/S0306-4522(03)00383-X","volume":"121","author":"C Gambarana","year":"2003","unstructured":"Gambarana C, Masi F, Leggio B, Grappi S, Nanni G, Scheggi S, et al. Acquisition of a palatable-food-sustained appetitive behavior in satiated rats is dependent on the dopaminergic response to this food in limbic areas. Neuroscience. 2003;121:179\u2013187.","journal-title":"Neuroscience"},{"key":"1043_CR12","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1523\/JNEUROSCI.17-02-00851.1997","volume":"17","author":"V Bassareo","year":"1997","unstructured":"Bassareo V, Di, Chiara G. Differential influence of associative and nonassociative learning mechanisms on the responsiveness of prefrontal and accumbal dopamine transmission to food stimuli in rats fed ad libitum. J Neurosci. 1997;17:851\u2013861.","journal-title":"J Neurosci"},{"key":"1043_CR13","doi-asserted-by":"publisher","first-page":"112771","DOI":"10.1016\/j.physbeh.2019.112771","volume":"215","author":"VR Konanur","year":"2020","unstructured":"Konanur VR, Hsu TM, Kanoski SE, Hayes MR, Roitman MF. Phasic dopamine responses to a food-predictive cue are suppressed by the glucagon-like peptide-1 receptor agonist Exendin-4. Physiol Behav. 2020;215:112771.","journal-title":"Physiol Behav"},{"key":"1043_CR14","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.celrep.2015.06.062","volume":"12","author":"X-F Wang","year":"2015","unstructured":"Wang X-F, Liu J-J, Xia J, Liu J, Mirabella V, Pang ZP. Endogenous glucagon-like peptide-1 suppresses high-fat food intake by reducing synaptic drive onto mesolimbic dopamine neurons. Cell Rep. 2015;12:726\u2013733.","journal-title":"Cell Rep"},{"key":"1043_CR15","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1038\/npp.2015.362","volume":"41","author":"HD Schmidt","year":"2016","unstructured":"Schmidt HD, Mietlicki-Baase EG, Ige KY, Maurer JJ, Reiner DJ, Zimmer DJ, et al. Glucagon-like peptide-1 receptor activation in the ventral tegmental area decreases the reinforcing efficacy of cocaine. Neuropsychopharmacology. 2016;41:1917\u20131928.","journal-title":"Neuropsychopharmacology"},{"key":"1043_CR16","doi-asserted-by":"publisher","first-page":"e77284","DOI":"10.1371\/journal.pone.0077284","volume":"8","author":"E Egecioglu","year":"2013","unstructured":"Egecioglu E, Engel JA, Jerlhag E. The glucagon-like peptide 1 analogue Exendin-4 attenuates the nicotine-induced locomotor stimulation, accumbal dopamine release, conditioned place preference as well as the expression of locomotor sensitization in mice. PloS ONE. 2013;8:e77284.","journal-title":"PloS ONE"},{"key":"1043_CR17","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1016\/j.psyneuen.2012.11.009","volume":"38","author":"E Egecioglu","year":"2013","unstructured":"Egecioglu E, Steensland P, Fredriksson I, Feltmann K, Engel JA, Jerlhag E. The glucagon-like peptide 1 analogue Exendin-4 attenuates alcohol mediated behaviors in rodents. Psychoneuroendocrinology. 2013;38:1259\u20131270.","journal-title":"Psychoneuroendocrinology"},{"key":"1043_CR18","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1111\/adb.12583","volume":"24","author":"NS Hernandez","year":"2019","unstructured":"Hernandez NS, O\u2019Donovan B, Ortinski PI, Schmidt HD. Activation of glucagon-like peptide-1 receptors in the nucleus accumbens attenuates cocaine seeking in rats. Addict Biol. 2019;24:170\u2013181.","journal-title":"Addict Biol"},{"key":"1043_CR19","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.neuropharm.2018.01.013","volume":"136","author":"E Jerlhag","year":"2018","unstructured":"Jerlhag E. GLP-1 signaling and alcohol-mediated behaviors; preclinical and clinical evidence. Neuropharmacology. 2018; 136:343\u2013349.","journal-title":"Neuropharmacology"},{"key":"1043_CR20","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.physbeh.2019.03.026","volume":"206","author":"NS Hernandez","year":"2019","unstructured":"Hernandez NS, Schmidt HD. Central GLP-1 receptors: novel molecular targets for cocaine use disorder. Physiol Behav. 2019;206:93\u2013105.","journal-title":"Physiol Behav"},{"key":"1043_CR21","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.pharmthera.2014.11.011","volume":"148","author":"O Lockridge","year":"2015","unstructured":"Lockridge O. Review of human butyrylcholinesterase structure, function, genetic variants, history of use in the clinic, and potential therapeutic uses. Pharm Ther. 2015;148:34\u201346.","journal-title":"Pharm Ther"},{"key":"1043_CR22","doi-asserted-by":"publisher","first-page":"16656","DOI":"10.1073\/pnas.0507332102","volume":"102","author":"Y Pan","year":"2005","unstructured":"Pan Y, Gao D, Yang W, Cho H, Yang G, Tai H-H, et al. Computational redesign of human butyrylcholinesterase for anticocaine medication. Proc Natl Acad Sci USA. 2005;102:16656\u201316661.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1043_CR23","doi-asserted-by":"publisher","first-page":"2715","DOI":"10.1038\/sj.npp.1301666","volume":"33","author":"S Brimijoin","year":"2008","unstructured":"Brimijoin S, Gao Y, Anker JJ, Gliddon LA, Lafleur D, Shah R, et al. A cocaine hydrolase engineered from human butyrylcholinesterase selectively blocks cocaine toxicity and reinstatement of drug seeking in rats. Neuropsychopharmacology. 2008;33:2715\u20132725.","journal-title":"Neuropsychopharmacology"},{"key":"1043_CR24","doi-asserted-by":"publisher","first-page":"163","DOI":"10.4155\/fmc.11.181","volume":"4","author":"CW Schindler","year":"2012","unstructured":"Schindler CW, Goldberg SR. Accelerating cocaine metabolism as an approach to the treatment of cocaine abuse and toxicity. Future Med Chem. 2012;4:163\u2013175.","journal-title":"Future Med Chem"},{"key":"1043_CR25","doi-asserted-by":"publisher","first-page":"601047","DOI":"10.1155\/2011\/601047","volume":"2011","author":"AM Rowzee","year":"2011","unstructured":"Rowzee AM, Cawley NX, Chiorini JA, Di Pasquale G. Glucagon-like peptide-1 gene therapy. Exp Diabetes Res. 2011;2011:601047.","journal-title":"Exp Diabetes Res"},{"key":"1043_CR26","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.stem.2017.06.016","volume":"21","author":"J Yue","year":"2017","unstructured":"Yue J, Gou X, Li Y, Wicksteed B, Wu X. Engineered epidermal progenitor cells can correct diet-induced obesity and diabetes. Cell Stem Cell. 2017;21:256\u2013263.e4.","journal-title":"Cell Stem Cell"},{"key":"1043_CR27","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/s41551-018-0293-z","volume":"3","author":"Y Li","year":"2019","unstructured":"Li Y, Kong Q, Yue J, Gou X, Xu M, Wu X. Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose. Nat Biomed Eng. 2019;3:105\u2013113.","journal-title":"Nat Biomed Eng"},{"key":"1043_CR28","first-page":"77","volume":"24","author":"B Tabakoff","year":"2000","unstructured":"Tabakoff B, Hoffman PL. Animal models in alcohol research. Alcohol Res Health. 2000;24:77\u201384.","journal-title":"Alcohol Res Health"},{"key":"1043_CR29","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/0091-3057(95)00098-H","volume":"52","author":"MD Schechter","year":"1995","unstructured":"Schechter MD, Meehan SM. The lethal effects of ethanol and cocaine and their combination in mice: implications for cocaethylene formation. Pharm Biochem Behav. 1995;52:245\u2013248.","journal-title":"Pharm Biochem Behav"},{"key":"1043_CR30","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.legalmed.2012.04.008","volume":"14","author":"K Usui","year":"2012","unstructured":"Usui K, Hayashizaki Y, Hashiyada M, Funayama M. Rapid drug extraction from human whole blood using a modified QuEChERS extraction method. Leg Med. 2012;14:286\u2013296.","journal-title":"Leg Med"},{"key":"1043_CR31","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1124\/jpet.102.041350","volume":"304","author":"A Kuzmin","year":"2003","unstructured":"Kuzmin A, Sandin J, Terenius L, Ogren SO. Acquisition. expression, and reinstatement of ethanol-induced conditioned place preference in mice: effects of opioid receptor-like 1 receptor agonists and naloxone. J Pharm Exp Ther. 2003;304:310\u2013318.","journal-title":"J Pharm Exp Ther"},{"key":"1043_CR32","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1002\/syn.10226","volume":"49","author":"I Boileau","year":"2003","unstructured":"Boileau I, Assaad J-M, Pihl RO, Benkelfat C, Leyton M, Diksic M, et al. Alcohol promotes dopamine release in the human nucleus accumbens. Synapse. 2003;49:226\u2013231.","journal-title":"Synapse"},{"key":"1043_CR33","doi-asserted-by":"publisher","first-page":"30771","DOI":"10.1074\/jbc.M115.671743","volume":"290","author":"H Liu","year":"2015","unstructured":"Liu H, Yue J, Huang H, Gou X, Chen S-Y, Zhao Y, et al. Regulation of focal adhesion dynamics and cell motility by the EB2 and Hax1 protein complex. J Biol Chem. 2015;290:30771\u201330782.","journal-title":"J Biol Chem"},{"key":"1043_CR34","doi-asserted-by":"publisher","first-page":"264ra163","DOI":"10.1126\/scitranslmed.3009540","volume":"6","author":"V Sebastiano","year":"2014","unstructured":"Sebastiano V, Zhen HH, Haddad B, Derafshi BH, Bashkirova E, Melo SP, et al. Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa. Sci Transl Med. 2014;6:264ra163.","journal-title":"Sci Transl Med"},{"key":"1043_CR35","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.psyneuen.2019.02.006","volume":"103","author":"D Vall\u00f6f","year":"2019","unstructured":"Vall\u00f6f D, Kalafateli AL, Jerlhag E. Brain region specific glucagon-like peptide-1 receptors regulate alcohol-induced behaviors in rodents. Psychoneuroendocrinology. 2019;103:284\u2013295.","journal-title":"Psychoneuroendocrinology"},{"key":"1043_CR36","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1385\/JMN:18:1-2:07","volume":"18","author":"AJ Kastin","year":"2002","unstructured":"Kastin AJ, Akerstrom V, Pan W. Interactions of glucagon-like peptide-1 (GLP-1) with the blood-brain barrier. J Mol Neurosci. 2002;18:7\u201314.","journal-title":"J Mol Neurosci"},{"key":"1043_CR37","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1517\/14740338.7.5.571","volume":"7","author":"B Sloan","year":"2008","unstructured":"Sloan B, Scheinfeld N. The use and safety of doxycycline hyclate and other second-generation tetracyclines. Expert Opin Drug Saf. 2008;7:571\u2013577.","journal-title":"Expert Opin Drug Saf"},{"key":"1043_CR38","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1523\/JNEUROSCI.4520-07.2008","volume":"28","author":"CM Gremel","year":"2008","unstructured":"Gremel CM, Cunningham CL. Roles of the nucleus accumbens and amygdala in the acquisition and expression of ethanol-conditioned behavior in mice. J Neurosci. 2008;28:1076\u20131084.","journal-title":"J Neurosci"},{"key":"1043_CR39","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s00213-018-5024-3","volume":"236","author":"TD Goode","year":"2019","unstructured":"Goode TD, Maren S. Common neurocircuitry mediating drug and fear relapse in preclinical models. Psychopharmacology. 2019;236:415\u2013437.","journal-title":"Psychopharmacology"},{"key":"1043_CR40","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/0305-4179(94)90017-5","volume":"20","author":"JM Still","year":"1994","unstructured":"Still JM, Orlet HK, Law EJ. Use of cultured epidermal autografts in the treatment of large burns. Burns. 1994;20:539\u2013541.","journal-title":"Burns"},{"key":"1043_CR41","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/nature24487","volume":"551","author":"T Hirsch","year":"2017","unstructured":"Hirsch T, Rothoeft T, Teig N, Bauer JW, Pellegrini G, De Rosa L, et al. Regeneration of the entire human epidermis using transgenic stem cells. Nature. 2017;551:327\u2013332.","journal-title":"Nature"},{"key":"1043_CR42","doi-asserted-by":"crossref","unstructured":"Douton JE, Augusto C, Stoltzfus B, Carkaci-Salli N, Vrana KE, Grigson PS. Glucagon-like peptide-1 receptor agonist, exendin-4, reduces reinstatement of heroin-seeking behavior in rats. Behav Pharmacol. 2020. Epub ahead of print.","DOI":"10.1101\/730408"},{"key":"1043_CR43","doi-asserted-by":"publisher","first-page":"2629","DOI":"10.1210\/en.2009-0915","volume":"151","author":"M Gil-Lozano","year":"2010","unstructured":"Gil-Lozano M, P\u00e9rez-Tilve D, Alvarez-Crespo M, Mart\u00eds A, Fernandez AM, Catalina PAF, et al. GLP-1(7-36)-amide and Exendin-4 stimulate the HPA axis in rodents and humans. Endocrinology. 2010;151:2629\u20132640.","journal-title":"Endocrinology"},{"key":"1043_CR44","doi-asserted-by":"publisher","first-page":"10701","DOI":"10.1523\/JNEUROSCI.3464-14.2015","volume":"35","author":"JW Maniscalco","year":"2015","unstructured":"Maniscalco JW, Zheng H, Gordon PJ, Rinaman L. Negative energy balance blocks neural and behavioral responses to acute stress by \u2018silencing\u2019 central glucagon-like peptide 1 signaling in rats. J Neurosci. 2015;35:10701\u201310714.","journal-title":"J Neurosci"},{"key":"1043_CR45","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.jchemneu.2008.07.009","volume":"36","author":"M Tauchi","year":"2008","unstructured":"Tauchi M, Zhang R, D\u2019Alessio DA, Stern JE, Herman JP. Distribution of glucagon-like peptide-1 immunoreactivity in the hypothalamic paraventricular and supraoptic nuclei. J Chem Neuroanat. 2008;36:144\u2013149.","journal-title":"J Chem Neuroanat"},{"key":"1043_CR46","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/nn.4540","volume":"20","author":"LM Tuesta","year":"2017","unstructured":"Tuesta LM, Chen Z, Duncan A, Fowler CD, Ishikawa M, Lee BR, et al. GLP-1 acts on habenular avoidance circuits to control nicotine intake. Nat Neurosci. 2017;20:708\u2013716.","journal-title":"Nat Neurosci"},{"issue":"Suppl 2","key":"1043_CR47","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1111\/jnc.14008","volume":"142","author":"I McLaughlin","year":"2017","unstructured":"McLaughlin I, Dani JA, De, Biasi M. The medial habenula and interpeduncular nucleus circuitry is critical in addiction, anxiety, and mood regulation. J Neurochem. 2017;142 (Suppl 2):130\u2013143.","journal-title":"J Neurochem"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01043-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01043-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01043-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,29]],"date-time":"2023-01-29T14:03:02Z","timestamp":1675000982000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01043-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,22]]},"references-count":47,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["1043"],"URL":"https:\/\/doi.org\/10.1038\/s41380-021-01043-y","relation":{},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"type":"print","value":"1359-4184"},{"type":"electronic","value":"1476-5578"}],"subject":[],"published":{"date-parts":[[2021,2,22]]},"assertion":[{"value":"19 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2021","order":4,"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 no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}