Depression and the risk of autoimmune disease: a nationally representative, prospective longitudinal study

Andersson, Niklas Worm; Gustafsson, Lennart; Okkels, Niels; Taha, Farah; Cole, Steve W.; Munk‐Jørgensen, Povl; Goodwin, Renée D.

doi:10.1017/s0033291715001488

Cited by 85 publications

(74 citation statements)

References 71 publications

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“…We also demonstrated an effect of autoimmune disorder onset increasing hazard of subsequent depression onset; this effect was broadly independent of the effect of genetic risk factors influencing hazard of depression. These results highlight the utility of a longitudinal approach to problems of medical comorbidities in epidemiology; our epidemiological results replicate those of Andersson et al [6],and build on them by including individuals who had not sought specialist mental health care, but who had explicitly answered questionnaires on history and current status of depression, within a population-based sample. There are a number of alternative explanatory models for the observed findings…”

Section: Discussionsupporting

confidence: 82%

“…These relatively small clinical studies have been supplemented by two recent large-scale population-based studies. The first, on a Danish population, reported that depression is associated with a significantly increased risk of subsequent autoimmune disease (IRR = 1.25, 95% CI 1.19–1.31) [6]. The second, on a Taiwanese population, found a similar effect of depression on increased risk of subsequent rheumatoid arthritis (HR = 1.65, 95% CI = 1.41–1.77) [7].…”

Section: Introductionmentioning

confidence: 99%

“…Using confirmed hospital diagnoses to identify cases, Andersson et al showed that depression elevated the hazard of autoimmune disorder onset in a Danish population cohort [6]. The use of hospital-confirmed diagnoses has the advantage of minimising ascertainment bias and any confounding effects of attrition.…”

Section: Introductionmentioning

confidence: 99%

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A bidirectional relationship between depression and the autoimmune disorders – New perspectives from the National Child Development Study

et al. 2017

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BackgroundDepression and the autoimmune disorders are comorbid—the two classes of disorders overlap in the same individuals at a higher frequency than chance. The immune system may influence the pathological processes underlying depression; understanding the origins of this comorbidity may contribute to dissecting the mechanisms underlying these disorders.MethodWe used population cohort data from the 1958 British birth cohort study (the National Child Development Study) to investigate the ages at onset of depression and 23 autoimmune disorders. We used self-report data to ascertain life-time history of depression, autoimmune disorders and their ages at onset. We modelled the effect of depression onset on subsequent autoimmune disorder onset, and vice versa, and incorporated polygenic risk scores for depression and autoimmune disorder risk.ResultsIn our analytic sample of 8174 individuals, 315 reported ever being diagnosed with an autoimmune disorder (3.9%), 1499 reported ever experiencing depression (18.3%). There was significant comorbidity between depression and the autoimmune disorders (OR = 1.66, 95% CI = 1.27–2.15). Autoimmune disorder onset associated with increased subsequent hazard of depression onset (HR = 1.39, 95% CI = 1.11–1.74, P = 0.0037), independently of depression genetic risk. Finally, depression increased subsequent hazard of autoimmune disorder onset (HR = 1.40, 95% CI = 1.09–1.80, P = 0.0095), independently of autoimmune disorder genetic risk.DiscussionOur results point to a bidirectional relationship between depression and the autoimmune disorders. This suggests that shared risk factors may contribute to this relationship, including both common environmental exposures that increase baseline inflammation levels, and shared genetic factors.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

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A bidirectional relationship between depression and the autoimmune disorders – New perspectives from the National Child Development Study

et al. 2017

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“…A bidirectional association between depression and the immune system has been also reported [33, 34]. Depression has been linked with increased inflammatory markers and depression risk alleles have been found to be associated with regulating genes of the immune response [35]. However, the current work did not show apparent relationship between LHPP, thyroid disorders, and MDD.…”

Section: Discussionmentioning

confidence: 60%

Relationship between the LHPP Gene Polymorphism and Resting-State Brain Activity in Major Depressive Disorder

et al. 2016

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A single-nucleotide polymorphism at the LHPP gene (rs35936514) has been reported in genome-wide association studies to be associated with major depressive disorder (MDD). However, the neural system effects of rs35936514 that mediate the association are unknown. The present work explores whether the LHPP rs35936514 polymorphism moderates brain regional activity in MDD. A total of 160 subjects were studied: a CC group homozygous for the C allele (23 individuals with MDD and 57 controls) and a T-carrier group carrying the high risk T allele (CT/TT genotypes; 22 MDD and 58 controls). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Brain activity was assessed using the amplitudes of low-frequency fluctuations (ALFF). MDD patients showed a significant increased ALFF in the left middle temporal gyrus and occipital cortex. The T-carrier group showed increased ALFF in the left superior temporal gyrus. Significant diagnosis × genotype interaction was noted in the bilateral lingual gyri, bilateral dorsal lateral prefrontal cortex (dlPFC), and left medial prefrontal cortex (mPFC) (P < 0.05, corrected). Results demonstrated that MDD patients with LHPP rs35936514 CT/TT genotype may influence the regional brain activity. These findings implicate the effects of the rs35936514 variation on the neural system in MDD.

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“…(Bale and Epperson, 2015) In addition, estrogen is known to trigger B-cell mediated diseases and may play a role in EBV reactivation as the virus infects and remains latent in B-lymphocytes unless reactivation occurs with physical or psychosocial stress. (Christian et al, 2009; Ford and Stowe, 2013; Glaser et al, 1991; Stowe et al, 2010) Because depression(Andersson et al, 2015; Euesden et al, 2017) and EBV(Niller et al, 2008) are both linked to certain autoimmune disorders (e.g. systemic lupus erythematosus) known to occur more frequently in females,(Brandt et al, 2015; Dunn et al, 2015; Ngo et al, 2014) further research testing causal pathways and the role of sex hormones in EBV reactivation and immune irregularities among adolescents is warranted.…”

Section: 0 Discussionmentioning

confidence: 99%

Depressive symptoms are associated with salivary shedding of Epstein-Barr virus in female adolescents: The role of sex differences

Ford

Stowe

2017

Psychoneuroendocrinology

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Background Adolescent females have a higher prevalence of depression in comparison to their male peers - a disparity that has been increasing over the past decade. Depression is of concern as it is associated with chronic disease and to immune dysregulation, which may be one mechanism linking depression to future pathology. This study examined the extent to which sex moderated the association between depressive symptoms and immune dysregulation during adolescence using Epstein-Barr virus (EBV) reactivation, a biomarker of cellular immune response, as a model. Methods A representative community sample of 259 female and 279 male adolescents aged 11 to 17 years who were EBV IgG positive were examined. Trained interviewers collected the data during two home visits, one week apart. Depressive symptoms were measured at the first visit using the 9 item short-form of the Center for Epidemiologic Studies-Depression scale. EBV biomarkers were collected via saliva at the second visit and included a qualitative measure of EBV viral capsid antigen immunoglobulin G to assess prior EBV infection and a quantitative measure of EBV DNA to assess the number of viral copies shed in the saliva. Results In multivariable logistic regression analyses, increasing depressive symptoms were significantly associated with salivary shedding of EBV DNA for adolescent females only (logit=0.66, se=0.30, p<0.05), and the interaction between sex and depressive symptoms on salivary shedding of EBV DNA was statistically significant (logit= −1.19, se=0.42, p<0.01). Sensitivity analyses were conducted in which sex was examined as a moderator in the relationship between depressive symptoms and salivary EBV DNA quantitative copies via Tobit regression; results were consistent with the presented findings. Conclusions Depressive symptoms are associated with EBV reactivation among EBV positive female adolescents, but not males. Future research is needed to examine EBV reactivation in female adolescents as a mechanism linking depression to future chronic disease and the role of sex hormones in explaining sex differences in the relationship between depressive symptoms and EBV reactivation.

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Depression and the risk of autoimmune disease: a nationally representative, prospective longitudinal study

Cited by 85 publications

References 71 publications

A bidirectional relationship between depression and the autoimmune disorders – New perspectives from the National Child Development Study

A bidirectional relationship between depression and the autoimmune disorders – New perspectives from the National Child Development Study

Relationship between the LHPP Gene Polymorphism and Resting-State Brain Activity in Major Depressive Disorder

Depressive symptoms are associated with salivary shedding of Epstein-Barr virus in female adolescents: The role of sex differences

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