{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:45:24Z","timestamp":1788871524461,"version":"build-2803163510"},"reference-count":71,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,6,5]],"date-time":"2014-06-05T00:00:00Z","timestamp":1401926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"6th European Framework project EUCLOCK","award":["018741"],"award-info":[{"award-number":["018741"]}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Velux Foundation"},{"name":"University of Zurich Clinical Research Priority Program \u2018Sleep and Health\u2019"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Various lines of evidence suggest a mechanistic role for altered cAMP\u2010CREB (cAMP response element \u2010 binding protein) signaling in depressive and affective disorders. However, the establishment and validation of human inter\u2010individual differences in this and other major signaling pathways has proven difficult. Here, we describe a novel lentiviral methodology to investigate signaling variation over long periods of time directly in human primary fibroblasts. On a cellular level, this method showed surprisingly large inter\u2010individual differences in three major signaling pathways in human subjects that nevertheless correlated with cellular measures of genome\u2010wide transcription and drug toxicity. We next validated this method by establishing a likely role for\n                    <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\n                    \u2010mediated signaling in a human neuroendocrine response to light \u2013 the light\u2010dependent suppression of the circadian hormone melatonin \u2013 that shows wide inter\u2010individual differences of unknown origin\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Finally, we show an overall greater magnitude of cellular\n                    <jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content>\n                    signaling in individuals with bipolar disorder, suggesting a possible role for this signaling pathway in susceptibility to mental disease. Overall, our results suggest that genetic differences in major signaling pathways can be reliably detected with sensitive viral\u2010based reporter profiling, and that these differences can be conserved across tissues and be predictive of physiology and disease susceptibility.\n                  <\/jats:p>","DOI":"10.1111\/ejn.12602","type":"journal-article","created":{"date-parts":[[2014,6,5]],"date-time":"2014-06-05T00:30:41Z","timestamp":1401928241000},"page":"2206-2215","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Human cellular differences in\n                    <scp>cAMP<\/scp>\n                    \u2010\n                    <scp>CREB<\/scp>\n                    signaling correlate with light\u2010dependent melatonin suppression and bipolar disorder"],"prefix":"10.1111","volume":"40","author":[{"given":"Ludmila","family":"Gaspar","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Zurich 190 Winterthurerstrasse Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maan","family":"van de Werken","sequence":"additional","affiliation":[{"name":"Department of Chronobiology Center for Life Sciences University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Sophie","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ermanno","family":"Moriggi","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Zurich 190 Winterthurerstrasse Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Owe\u2010Larsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janwillem W. 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