title: Chronic multisite pain in major depression and bipolar disorder: cross-sectional study of 149,611 participants in UK Biobank.
abstract: BACKGROUND
  Chronic pain has a strong association with major depressive disorder (MDD), but there is a relative paucity of studies on the association between chronic multisite pain and bipolar disorder (BD). Such studies are required to help elucidate the complex biological and psychological overlap between pain and mood disorders. The aim of this study is to investigate the relationship between chronic multisite pain and mood disorder across the unipolar-bipolar spectrum.
  
  
  METHODS
  We conducted a cross-sectional study of 149,611 UK Biobank participants. Self-reported depressive and bipolar features were used to categorise participants into MDD and BD groups and a non-mood disordered comparison group. Multinomial logistic regression was used to establish whether there was an association between extent of chronic pain (independent variable) and mood disorder category (dependent variable), using no pain as the referent category, and adjusting for a wide range of potential sociodemographic, lifestyle and comorbidity confounders.
  
  
  RESULTS
  Multisite pain was significantly more prevalent in participants with BD and MDD, for example, 4-7 pain sites: BD 5.8%, MDD 4.5%, and comparison group 1.8% (p < 0.001). A relationship was observed between extent of chronic pain and risk of BD and persisted after adjusting for confounders (relative to individuals with no chronic pain): 2-3 sites RRR of BD 1.84 (95% CI 1.61, 2.11); 4-7 sites RRR of BD 2.39 (95% CI 1.88, 3.03) and widespread pain RRR of BD 2.37 (95% CI 1.73, 3.23). A similar relationship was observed between chronic pain and MDD: 2-3 sites RRR of MDD 1.59 (95% CI 1.54, 1.65); 4-7 sites RRR of MDD 2.13 (95% CI 1.98, 2.30); widespread pain RRR of MDD 1.86 (95% CI 1.66, 2.08).
  
  
  CONCLUSIONS
  Individuals who report chronic pain and multiple sites of pain are more likely to have MDD and are at higher risk of BD. These findings highlight an important aspect of comorbidity in MDD and BD and may have implications for understanding the shared neurobiology of chronic pain and mood disorders.
authors.affiliation: Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland, UK. Barbara.Nicholl@glasgow.ac.uk.
authors.forename: Barbara I
authors.initials: BI
authors.lastname: Nicholl
authors.affiliation: Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland, UK. Daniel.Mackay@glasgow.ac.uk.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mackay
authors.affiliation: Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland, UK. Breda.Cullen@glasgow.ac.uk.
authors.forename: Breda
authors.initials: B
authors.lastname: Cullen
authors.affiliation: Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland, UK. Daniel.Martin@glasgow.ac.uk.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Martin
authors.affiliation: Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland, UK. z.ul-haq.2@research.gla.ac.uk.
authors.forename: Zia
authors.initials: Z
authors.lastname: Ul-Haq
authors.affiliation: Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland, UK. Frances.Mair@glasgow.ac.uk.
authors.forename: Frances S
authors.initials: FS
authors.lastname: Mair
authors.affiliation: Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland, UK. Jonathan.Evans@glasgow.ac.uk.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Evans
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK. andrew.mcintosh@ed.ac.uk.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
authors.affiliation: Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland, UK. Gallacher@cf.ac.uk.
authors.forename: John
authors.initials: J
authors.lastname: Gallagher
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK. beverly.roberts@ed.ac.uk.
authors.forename: Beverly
authors.initials: B
authors.lastname: Roberts
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK. iand@staffmail.ed.ac.uk.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.affiliation: Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland, UK. Jill.Pell@glasgow.ac.uk.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Pell
authors.affiliation: Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland, UK. Daniel.Smith@glasgow.ac.uk.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D018070:Biological Specimen Banks / Q000639:trends; D001714:Bipolar Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000523:psychology; D059350:Chronic Pain / Q000175:diagnosis / Q000453:epidemiology* / Q000523:psychology; D015331:Cohort Studies; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D006113:United Kingdom / Q000453:epidemiology