{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T22:36:48Z","timestamp":1794263808706,"version":"4.9.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T00:00:00Z","timestamp":1539907200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T00:00:00Z","timestamp":1539907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0501223"],"award-info":[{"award-number":["G0501223"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Exposure-based cognitive-behaviour therapy (CBT) for anxiety disorders is an effective intervention, but the brain mechanisms driving recovery are largely unknown. In this experimental medicine study, we investigated to what degree CBT affects neural markers of anxiety at an early stage of treatment, to identify dynamic mechanistic changes which might be crucial in the process of recovery as opposed to those seen following full treatment completion. In a randomised controlled trial, unmedicated patients with panic disorder either received four weekly sessions of exposure-based CBT (<jats:italic>N<\/jats:italic>\u2009=\u200914) or were allocated to a waiting group (<jats:italic>N<\/jats:italic>\u2009=\u200914). Symptom severity was measured before and after the intervention. During functional magnetic resonance imaging (fMRI), patients performed an emotion regulation task, either viewing negative images naturally, or intentionally down-regulating negative affect using previously taught strategies. Four-session CBT led to marked reductions in symptoms and 71% of patients reached recovery status (versus 7% in the control group). This intervention normalised brain hyperactivation previously seen in panic disorder, particularly in areas linked to threat monitoring, fear memory, and maladaptive emotion regulation, such as amygdala, dorsomedial and dorsolateral prefrontal cortex, and temporal gyrus. Our findings suggest that optimal treatment doses for panic disorder might be much lower than previously thought. Furthermore, this is the first study to show that neural markers of anxiety change very early during CBT, highlighting potential neural mechanisms that might drive clinical recovery. Such knowledge is important for the development of more compact combination treatments targeting these mechanisms more effectively. (Neural Effects of Cognitive-behaviour Therapy in Panic Disorder; clinicaltrials.gov; NCT03251235)<\/jats:p>","DOI":"10.1038\/s41398-018-0277-5","type":"journal-article","created":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T11:26:03Z","timestamp":1539948363000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Early effects of exposure-based cognitive behaviour therapy on the neural correlates of anxiety"],"prefix":"10.1038","volume":"8","author":[{"given":"Andrea","family":"Reinecke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai V.","family":"Thilo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Croft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine J.","family":"Harmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,19]]},"reference":[{"key":"277_CR1","doi-asserted-by":"publisher","first-page":"621","DOI":"10.4088\/JCP.v69n0415","volume":"69","author":"SG Hofmann","year":"2008","unstructured":"Hofmann, S. G. & Smits, J. A. Cognitive-behavioral therapy for adult anxiety disorders: a meta-analysis of randomized placebo-controlled trials. J. Clin. Psychiatry 69, 621\u2013632 (2008).","journal-title":"J. Clin. Psychiatry"},{"key":"277_CR2","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/46035","volume":"402","author":"M Botvinick","year":"1999","unstructured":"Botvinick, M., Nystrom, L. E., Fissell, K., Carter, C. S. & Cohen, J. D. Conflict monitoring versus selection-for-action in anterior cingulate cortex. Nature 402, 179\u2013181 (1999).","journal-title":"Nature"},{"key":"277_CR3","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.neuroimage.2011.11.096","volume":"60","author":"OJ Robinson","year":"2012","unstructured":"Robinson, O. J., Charney, D. R., Overstreet, C., Vytal, K. & Grillon, C. The adaptive threat bias in anxiety: amygdala-dorsomedial prefrontal cortex coupling and aversive amplification. Neuroimage 60, 523\u2013529 (2012).","journal-title":"Neuroimage"},{"key":"277_CR4","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1016\/S1053-8119(02)00051-4","volume":"18","author":"SF Taylor","year":"2003","unstructured":"Taylor, S. F., Phan, K. L., Decker, L. R. & Liberzon, I. Subjective rating of emotionally salient stimuli modulates neural activity. Neuroimage 18, 650\u2013659 (2003).","journal-title":"Neuroimage"},{"key":"277_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2015.160","volume":"5","author":"A Reinecke","year":"2015","unstructured":"Reinecke, A. et al. Effective emotion regulation strategies improve fMRI and ECG markers of psychopathology in panic disorder: implications for psychological treatment action. Transl. Psychiatry 5, e673 (2015).","journal-title":"Transl. Psychiatry"},{"key":"277_CR6","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1001\/archpsyc.59.5.425","volume":"59","author":"T Furmark","year":"2002","unstructured":"Furmark, T. et al. Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy. Arch. General. Psychiatry 59, 425\u2013433 (2002).","journal-title":"Arch. General. Psychiatry"},{"key":"277_CR7","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.biopsych.2007.04.024","volume":"62","author":"L Goossens","year":"2007","unstructured":"Goossens, L., Sunaert, S., Peeters, R., Griez, E. J. & Schruers, K. R. Amygdala hyperfunction in phobic fear normalizes after exposure. Biol. Psychiatry 62, 1119\u20131125 (2007).","journal-title":"Biol. Psychiatry"},{"key":"277_CR8","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1017\/S0033291713002237","volume":"44","author":"M Morgieve","year":"2014","unstructured":"Morgieve, M. et al. Dynamics of psychotherapy-related cerebral haemodynamic changes in obsessive compulsive disorder using a personalized exposure task in functional magnetic resonance imaging. Psychol. Med 44, 1461\u20131473 (2014).","journal-title":"Psychol. Med"},{"key":"277_CR9","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/S1053-8119(02)00030-7","volume":"18","author":"V Paquette","year":"2003","unstructured":"Paquette, V. et al. Change the mind and you change the brain: effects of cognitive-behavioral therapy on the neural correlates of spider phobia. Neuroimage 18, 401\u2013409 (2003).","journal-title":"Neuroimage"},{"key":"277_CR10","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1017\/S003329170700997X","volume":"37","author":"JF Peres","year":"2007","unstructured":"Peres, J. F. et al. Cerebral blood flow changes during retrieval of traumatic memories before and after psychotherapy: a SPECT study. Psychol. Med 37, 1481\u20131491 (2007).","journal-title":"Psychol. Med"},{"key":"277_CR11","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.biopsych.2012.07.026","volume":"73","author":"T Kircher","year":"2013","unstructured":"Kircher, T. et al. Effect of cognitive-behavioral therapy on neural correlates of fear conditioning in panic disorder. Biol. Psychiatry 73, 93\u2013101 (2013).","journal-title":"Biol. Psychiatry"},{"key":"277_CR12","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1016\/j.biopsych.2013.02.005","volume":"73","author":"A Reinecke","year":"2013","unstructured":"Reinecke, A., Waldenmaier, L., Cooper, M. J. & Harmer, C. J. Changes in automatic threat processing precede and predict clinical changes with exposure-based cognitive-behavior therapy for panic disorder. Biol. Psychiatry 73, 1064\u20131070 (2013).","journal-title":"Biol. Psychiatry"},{"key":"277_CR13","volume-title":"Structured clinical interview for DSM-IV axis I disorders, Clinician Version (SCID-CV)","author":"MB First","year":"1996","unstructured":"First, M. B., Spitzer, R. L., Gibbon, M. & Williams, J. B. W. Structured clinical interview for DSM-IV axis I disorders, Clinician Version (SCID-CV). (American Psychiatry Press, Inc., Washington, DC, 1996)."},{"key":"277_CR14","volume-title":"National adult reading test (NART): Tets manual","author":"HE Nelson","year":"1982","unstructured":"Nelson, H. E. National adult reading test (NART): Tets manual. (NFER-Nelson, Windsor, 1982)."},{"key":"277_CR15","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.brat.2014.07.017","volume":"62","author":"A Reinecke","year":"2014","unstructured":"Reinecke, A., Thilo, K., Filippini, N., Croft, A. & Harmer, C. J. Predicting rapid response to cognitive-behavioural treatment for panic disorder: The role of hippocampus, insula, and dorsolateral prefrontal cortex. Behav. Res. Ther. 62, 120\u2013128 (2014).","journal-title":"Behav. Res. Ther."},{"key":"277_CR16","volume-title":"ECDEU Assessment Manual for Psychopharmacology\u2014Revised (DHEW Publ No ADM 76-338)","author":"W Guy","year":"1976","unstructured":"Guy, W. ECDEU Assessment Manual for Psychopharmacology\u2014Revised (DHEW Publ No ADM 76-338). (U.S. Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs, Rockville, 1976)."},{"key":"277_CR17","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1111\/j.1600-0447.1983.tb09716.x","volume":"67","author":"AS Zigmond","year":"1983","unstructured":"Zigmond, A. S. & Snaith, R. P. The hospital anxiety and depression scale. Acta Psychiatr. Scand. 67, 361\u2013370 (1983).","journal-title":"Acta Psychiatr. Scand."},{"key":"277_CR18","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1037\/0022-006X.52.6.1090","volume":"52","author":"DL Chambless","year":"1984","unstructured":"Chambless, D. L., Caputo, G. C., Bright, P. & Gallagher, R. Assessment of fear of fear in agoraphobics-the body sensations questionnaire and the agoraphobic cognitions questionnaire. J. Consult. Clin. Psychol. 52, 1090\u20131097 (1984).","journal-title":"J. Consult. Clin. Psychol."},{"key":"277_CR19","volume-title":"International affective picture system (IAPS): Technical manual and affective ratings","author":"PJ Lang","year":"1997","unstructured":"Lang, P. J., Bradley, M. M. & Cuthbert, B. N. International affective picture system (IAPS): Technical manual and affective ratings. (National Institute of Mental Health Centre for the Study of Emotion and Attention, Gainesville, 1997)."},{"key":"277_CR20","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1006\/nimg.2002.1132","volume":"17","author":"M Jenkinson","year":"2002","unstructured":"Jenkinson, M., Bannister, P., Brady, M. & Smith, S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 17, 825\u2013841 (2002).","journal-title":"Neuroimage"},{"key":"277_CR21","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1002\/hbm.10062","volume":"17","author":"SM Smith","year":"2002","unstructured":"Smith, S. M. Fast robust automated brain extraction. Human Brain Mapp. 17, 143\u2013155 (2002).","journal-title":"Human Brain Mapp."},{"key":"277_CR22","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1006\/nimg.2001.0931","volume":"14","author":"MW Woolrich","year":"2001","unstructured":"Woolrich, M. W., Ripley, B. D., Brady, M. & Smith, S. M. Temporal autocorrelation in univariate linear modeling of FMRI data. Neuroimage 14, 1370\u20131386 (2001).","journal-title":"Neuroimage"},{"key":"277_CR23","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1016\/S1053-8119(03)00435-X","volume":"20","author":"CF Beckmann","year":"2003","unstructured":"Beckmann, C. F., Jenkinson, M. & Smith, S. M. General multilevel linear modeling for group analysis in FMRI. Neuroimage 20, 1052\u20131063 (2003).","journal-title":"Neuroimage"},{"key":"277_CR24","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.biopsych.2004.10.030","volume":"57","author":"KL Phan","year":"2005","unstructured":"Phan, K. L. et al. Neural substrates for voluntary suppression of negative affect: a functional magnetic resonance imaging study. Biol. Psychiatry 57, 210\u2013219 (2005).","journal-title":"Biol. Psychiatry"},{"key":"277_CR25","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1017\/S135246581200077X","volume":"41","author":"A Croft","year":"2013","unstructured":"Croft, A. & Hackmann, A. Agoraphobia: an outreach treatment programme. Behav. Cogn. Psychother. 41, 359\u2013364 (2013).","journal-title":"Behav. Cogn. Psychother."},{"key":"277_CR26","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1037\/0022-006X.65.2.203","volume":"65","author":"DM Clark","year":"1997","unstructured":"Clark, D. M. et al. Misinterpretation of body sensations in panic disorder. J. Consult. Clin. Psychol. 65, 203\u2013213 (1997).","journal-title":"J. Consult. Clin. Psychol."},{"key":"277_CR27","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1176\/appi.ajp.2013.12070974","volume":"170","author":"SG Hofmann","year":"2013","unstructured":"Hofmann, S. G. et al. D-Cycloserine as an augmentation strategy with cognitive-behavioral therapy for social anxiety disorder. Am. J. Psychiatry 170, 751\u2013758 (2013).","journal-title":"Am. J. Psychiatry"},{"key":"277_CR28","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1017\/S1352465808004694","volume":"36","author":"N Grey","year":"2008","unstructured":"Grey, N., Salkovskis, P., Quigley, A., Clark, D. M. & Ehlers, A. Dissemination of cognitive therapy for panic disorder in primary care. Behav. Cogn. Psychother. 36, 509\u2013520 (2008).","journal-title":"Behav. Cogn. Psychother."},{"key":"277_CR29","volume-title":"Parental bonding, pathological development, and fear of losing control among agoraphobics and normals","author":"JL Bibb","year":"1988","unstructured":"Bibb, J. L. Parental bonding, pathological development, and fear of losing control among agoraphobics and normals. (The American University, Washington, DC, 1988)."},{"key":"277_CR30","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1162\/089892902760807212","volume":"14","author":"KN Ochsner","year":"2002","unstructured":"Ochsner, K. N., Bunge, S. A., Gross, J. J. & Gabrieli, J. D. Rethinking feelings: an FMRI study of the cognitive regulation of emotion. J. Cogn. Neurosci. 14, 1215\u20131229 (2002).","journal-title":"J. Cogn. Neurosci."},{"key":"277_CR31","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.cpr.2015.08.004","volume":"42","author":"AG Loerinc","year":"2015","unstructured":"Loerinc, A. G. et al. Response rates for CBT for anxiety disorders: need for standardized criteria. Clin. Psychol. Rev. 42, 72\u201382 (2015).","journal-title":"Clin. Psychol. Rev."},{"key":"277_CR32","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.cpr.2007.04.009","volume":"28","author":"SG Hofmann","year":"2008","unstructured":"Hofmann, S. G. Cognitive processes during fear acquisition and extinction in animals and humans: Implications for exposure therapy of anxiety disorders. Clin. Psychol. Rev. 28, 199\u2013210 (2008).","journal-title":"Clin. Psychol. Rev."},{"key":"277_CR33","first-page":"77","volume":"3","author":"A Reinecke","year":"2015","unstructured":"Reinecke, A. & Harmer, C. A cognitive-neuropsychological account of treatment action in anxiety: can we augment clinical efficacy? Psychopathol. Rev. 3, 77\u2013109 (2015).","journal-title":"Psychopathol. Rev."},{"key":"277_CR34","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/npp.2009.83","volume":"35","author":"LM Shin","year":"2010","unstructured":"Shin, L. M. & Liberzon, I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology 35, 169\u2013191 (2010).","journal-title":"Neuropsychopharmacology"},{"key":"277_CR35","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.tics.2007.05.008","volume":"11","author":"SJ Bishop","year":"2007","unstructured":"Bishop, S. J. Neurocognitive mechanisms of anxiety: an integrative account. Trends Cogn. Sci. 11, 307\u2013316 (2007).","journal-title":"Trends Cogn. Sci."},{"key":"277_CR36","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1001\/archgenpsychiatry.2008.525","volume":"66","author":"PR Goldin","year":"2009","unstructured":"Goldin, P. R., Manber, T., Hakimi, S., Canli, T. & Gross, J. J. Neural bases of social anxiety disorder emotional reactivity and cognitive regulation during social and physical threat. Arch. General Psychiatry 66, 170\u2013180 (2009).","journal-title":"Arch. General Psychiatry"},{"key":"277_CR37","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.biopsycho.2011.10.010","volume":"89","author":"H Klumpp","year":"2012","unstructured":"Klumpp, H., Angstadt, M. & Phan, K. L. Insula reactivity and connectivity to anterior cingulate cortex when processing threat in generalized social anxiety disorder. Biol. Psychol. 89, 273\u2013276 (2012).","journal-title":"Biol. Psychol."},{"key":"277_CR38","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1001\/archpsyc.62.8.922","volume":"62","author":"OA van den Heuvel","year":"2005","unstructured":"van den Heuvel, O. A. et al. Disorder-specific neuroanatomical correlates of attentional bias in obsessive-compulsive disorder, panic disorder, and hypochondriasis. Arch. General Psychiatry 62, 922\u2013933 (2005).","journal-title":"Arch. General Psychiatry"},{"key":"277_CR39","first-page":"340","volume":"25","author":"J Prasko","year":"2004","unstructured":"Prasko, J. et al. The change of regional brain metabolism ((18)FDG PET) in panic disorder during the treatment with cognitive behavioral therapy or antidepressants. Neuroendocrinol. Lett. 25, 340\u2013348 (2004).","journal-title":"Neuroendocrinol. Lett."},{"key":"277_CR40","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1006\/nimg.2000.0538","volume":"11","author":"RS Dolan","year":"2000","unstructured":"Dolan, R. S., Lane, R., Chua, P. & Fletcher, P. Dissociable temporal lobe activations during emotional episodic memory retrieval. Neuroimage 11, 203\u2013209 (2000).","journal-title":"Neuroimage"},{"key":"277_CR41","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/0006-3223(95)94504-P","volume":"37","author":"TA Kimbrell","year":"1995","unstructured":"Kimbrell, T. A. et al. Regional brain activity during self-induced anger and anxiety. Biol. Psychiatry 37, 617\u2013618 (1995).","journal-title":"Biol. Psychiatry"},{"key":"277_CR42","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1176\/ajp.156.4.575","volume":"156","author":"LM Shin","year":"1999","unstructured":"Shin, L. M. et al. Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: a PET investigation. Am. J. Psychiatry 156, 575\u2013584 (1999).","journal-title":"Am. J. Psychiatry"},{"key":"277_CR43","doi-asserted-by":"crossref","unstructured":"Buckner, R. L., Andrews-Hanna, J. R., Schacter, D. L. The brain\u2019s default network-Anatomy, function, and relevance to disease. (eds. Kingstone A., Miller M. B.) Year in Cognitive Neuroscience. 1124, 1\u201338, (2008). https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18400922","DOI":"10.1196\/annals.1440.011"},{"key":"277_CR44","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1093\/brain\/awt162","volume":"137","author":"R Leech","year":"2014","unstructured":"Leech, R. & Sharp, D. J. The role of the posterior cingulate cortex in cognition and disease. Brain 137, 12\u201332 (2014).","journal-title":"Brain"},{"key":"277_CR45","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1002\/hbm.10075","volume":"18","author":"RJ Maddock","year":"2003","unstructured":"Maddock, R. J., Garrett, A. S. & Buonocore, M. H. Posterior cingulate cortex activation by emotional words: fMRI evidence from a valence decision task. Human. Brain Mapp. 18, 30\u201341 (2003).","journal-title":"Human. Brain Mapp."},{"key":"277_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1098\/rstb.2014.0213","volume":"370","author":"MB Warren","year":"2015","unstructured":"Warren, M. B., Pringle, A. & Harmer, C. J. A neurocognitive model for understanding treatment action in depression. Phil. Trans. R. Soc. B-Biol. Sci 370, 1\u201312 (2015).","journal-title":"Phil. Trans. R. Soc. B-Biol. Sci"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-018-0277-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-018-0277-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-018-0277-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T11:33:00Z","timestamp":1671535980000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-018-0277-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,19]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["277"],"URL":"https:\/\/doi.org\/10.1038\/s41398-018-0277-5","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,19]]},"assertion":[{"value":"23 February 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 August 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 October 2018","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"C.H. has valueless shares in p1vital and serves on their advisory panel. She has received consultancy payments from p1vital, Servier, Eli-Lilly, Astra Zeneca, Lundbeck and is a director of Oxford Psychologists Ltd. The remaining authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"225"}}