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Disentangling the effect of adversity and the underlying mechanistic pathway is therefore difficult. The association between adversity (i.e., maltreatment) accumulated over the life course and cognitive flexibility, as well as two potential mediators (i.e., intra-individual variability in reaction time and depression) of this association, were investigated. Data stem from the baseline population of the UK Biobank study (<jats:italic>N<\/jats:italic>\u2009=\u200973,489,<jats:italic>Mdn<\/jats:italic><jats:sub><jats:italic>age<\/jats:italic><\/jats:sub>\u2009=\u200956,<jats:italic>SD<\/jats:italic><jats:sub><jats:italic>age<\/jats:italic><\/jats:sub>\u2009=\u20097.628, 55.740% of women). Cumulative life course adversity (specifically maltreatment) was measured with items based on the Childhood Trauma Questionnaire (CTS-5) and items adapted from the British Crime Survey. Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9). Intra-individual variability in reaction time was measured with a reaction time test \u201csnap game\u201d and the Trail Making Test A and B were used as a measure of cognitive flexibility. A path analysis was performed on these data. Higher cumulative adverse experiences were associated with lower performance in cognitive flexibility (\u03b2\u2009=\u2009.016,<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001, 95% CI [0.009, 0.024]), and this effect was partly mediated by the level of depression (22.727% of the total effect of cumulative life course adversity on cognitive flexibility was mediated by depression (\u03b2\u2009=\u2009.005,<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001, 95% CI [0.004, 0.007])). No association between cumulative life course adverse experiences and intra-individual variability in reaction time was found, nor was any indirect association between cumulative life course adversity and performance in cognitive flexibility via intra-individual variability in reaction time. The association between cumulative life course adversity, depression, and performance in cognitive flexibility has been highlighted. In contrast, no indirect effect between cumulative life course adversity and performance in cognitive flexibility via intra-individual variability in reaction time was found, suggesting that it is not a potential mechanism underlying the association between cumulative life course adversity and executive function.<\/jats:p>","DOI":"10.1038\/s41598-022-18928-9","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T20:04:09Z","timestamp":1661803449000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cumulative life course adversity, mental health, and cognition in the UK biobank"],"prefix":"10.1038","volume":"12","author":[{"given":"M.","family":"K\u00fcnzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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