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This is the first study to compare HPA axis changes in individuals with CWP and those at high risk of symptom development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We sought to determine differences in morning and evening salivary cortisol levels in FM (<jats:italic>n<\/jats:italic>\u00a0=\u00a019), those at\u2010risk (<jats:italic>n<\/jats:italic>\u00a0=\u00a020) and pain\u2010free controls (<jats:italic>n<\/jats:italic>\u00a0=\u00a017). Risk factors included non\u2010CWP pain, somatic symptoms, illness behaviour and sleep disturbance. We conducted the study in the absence of centrally acting medication, to address limitations of previous research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Repeated measures ANOVA revealed significant main effects of group (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.003), and time of day (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.002), with no significant interaction. Cortisol levels were higher in FM (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.027) and at\u2010risk (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.003) groups, compared to controls, but there was no significant difference between FM and at\u2010risk groups. The main effect of group remained significant with sleep problems (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.021) and life events (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.007), but was not significant with anxiety (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.076) or depression (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.098) scores as covariates. With sleep problems as a covariate, cortisol levels remained significantly higher only in the at\u2010risk group (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.017).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study indicates elevated salivary cortisol in FM and those at high risk, and identifies anxiety, depression and sleep problems as potential contributing factors. The results shed light on the dynamic relationship between stress, mood and sleep disorders and the brain's resilience to pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study examines neurobiological changes in chronic widespread pain and high risk individuals. One strength of the study is the absence of centrally acting medication. We found high salivary cortisol common to Fibromyalgia and those at risk and identified contributing factors. Our results offer insight into the early mechanistic changes underlying Fibromyalgia development and open up possibilities for early diagnosis and prevention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1854","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T18:50:50Z","timestamp":1630003850000},"page":"197-206","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Morning and evening salivary cortisol levels in patients with chronic widespread pain and those at high risk"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6803-6956","authenticated-orcid":false,"given":"Nayab","family":"Begum","sequence":"first","affiliation":[{"name":"Division of Neuroscience and Experimental Psychology Human Pain Research Group University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7871-448X","authenticated-orcid":false,"given":"Jason R","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Neuroscience and Experimental Psychology Human Pain Research Group University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Neuroscience and Experimental Psychology Human Pain Research Group University of Manchester Manchester UK"},{"name":"Department of Psychological Sciences University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8323-8687","authenticated-orcid":false,"given":"Jonathan","family":"Rajan","sequence":"additional","affiliation":[{"name":"Division of Neuroscience and Experimental Psychology Human Pain Research Group University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0684-9318","authenticated-orcid":false,"given":"Brian","family":"Keevil","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry University Hospital South Manchester NHS Foundation Trust Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Pye","sequence":"additional","affiliation":[{"name":"Division of Neuroscience and Experimental Psychology Human Pain Research Group University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Rainey","sequence":"additional","affiliation":[{"name":"Division of Neuroscience and Experimental Psychology Human Pain Research Group University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6944-9365","authenticated-orcid":false,"given":"Anthony","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Neuroscience and Experimental Psychology Human Pain Research Group University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2016.02.021"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891\u2010018\u20102310\u20105"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2340\/16501977\u20102162"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.1090"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2011.01.011"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1017\/S003329170002105X"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529\u20100131(200002)13:1<51:AID\u2010ART8>3.0.CO;2\u2010Q"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.20047"},{"issue":"1","key":"e_1_2_8_10_1","first-page":"128","article-title":"Effect of acupressure on postpartum low back pain, salivary cortisol, physical limitations, and depression: A randomized controlled pilot study","volume":"40","author":"Cheng H. 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