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Conversely, alternations of circadian rhythms are a risk factor for the development of psychiatric disorders. This assumption is supported by animals with clock gene mutations which often display behaviors that resemble human psychiatric disorders. In this study, we performed an in\u2010depth behavioral analysis with male mice lacking the central clock genes <jats:italic>Cryptochrome 1<\/jats:italic> and <jats:italic>2<\/jats:italic> (<jats:italic>Cry1\/2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>), which are thus unable to express endogenous circadian rhythms. With wild\u2010type and <jats:italic>Cry1\/2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice, we performed an extensive behavioral analysis to study their cognitive abilities, social behavior, and their expression of depression\u2010like and anxiety\u2010like behavior. While <jats:italic>Cry1\/2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice showed only mild abnormalities at cognitive and social behavioral levels, they were consistently more anxious than wildtype mice. Anxiety\u2010like behavior was particularly evident in reduced mobility in new environments, altered ability to habituate, compensatory behavior, and consistent restless behavior across many behavioral tests. In line with their anxiety\u2010like behavioral phenotype, <jats:italic>Cry1\/2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice have higher <jats:italic>c\u2010Fos<\/jats:italic> activity in the amygdala after exposure to an anxiogenic stressor than wild\u2010type mice. In our study, we identified <jats:italic>Cry1\/2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice as animals that qualify as a translational mouse model for anxiety disorder in humans because of its consistent behavior of restlessness, increased immobility, and dysfunctional habituation in new environments.<\/jats:p>","DOI":"10.1111\/gbb.12661","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T18:33:19Z","timestamp":1588185199000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["An in\u2010depth neurobehavioral characterization shows anxiety\u2010like traits, impaired habituation behavior, and restlessness in male <i>Cryptochrome<\/i>\u2010deficient mice"],"prefix":"10.1111","volume":"19","author":[{"given":"Anisja","family":"H\u00fchne","sequence":"first","affiliation":[{"name":"Circadian Biology Group, Department of Molecular Neurobiology, Clinic of Psychiatry and Psychotherapy Ludwig Maximilian University  Munich Germany"},{"name":"Munich Medical Research School Ludwig Maximilian University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Volkmann","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurobiology, Clinic of Psychiatry and Psychotherapy Ludwig Maximilian University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Stephan","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurobiology, Clinic of Psychiatry and Psychotherapy Ludwig Maximilian University  Munich Germany"},{"name":"International Max Planck Research School for Translational Psychiatry (IMPRS\u2010TP)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Rossner","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurobiology, Clinic of Psychiatry and Psychotherapy Ludwig Maximilian University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1328-1871","authenticated-orcid":false,"given":"Dominic","family":"Landgraf","sequence":"additional","affiliation":[{"name":"Circadian Biology Group, Department of Molecular Neurobiology, Clinic of Psychiatry and Psychotherapy Ludwig Maximilian University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61611-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.62.6.617"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2010.05.017"},{"issue":"3","key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.31887\/DCNS.2003.5.3\/lstaner","article-title":"Sleep and anxiety 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