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

Abstract

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.

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

“…(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.…”

Cytokine secretion and the risk of depression development in patients with connective tissue diseases

“…Consistent observations have shown an increased prevalence of MDD diagnosis amongst patients afflicted with a range of chronic inflammatory conditions. Inflammatory conditions, including rheumatic disease, have been implicated to have a significant influence on the risk of depression development . Particularly, higher levels of inflammation due to chronic medical illnesses are associated with increased severity of depression .…”

Tumor necrosis factor receptor 2: A potential target for antidepressant drug development

“…During infection, TNF levels increase, and sustained TNF elevation and dysregulation have been implicated in the development of autoimmune diseases, including rheumatoid arthritis and Crohn's disease . Interestingly, autoimmune diseases share significant comorbidity with mood disorders, to an extent that cannot be explained by chance . Furthermore, both severe infection and autoimmune disease have been cited as risk factors for the development of depressive symptoms; in particular, repeated infections have been shown to be associated with an increase in the likelihood of the onset of depressive symptoms …”

“…31 Interestingly, autoimmune diseases share significant comorbidity with mood disorders, to an extent that cannot be explained by chance. [32][33][34] Furthermore, both severe infection and autoimmune disease have been cited as risk factors for the development of depressive symptoms; 34,35 in particular, repeated infections have been shown to be associated with an increase in the likelihood of the onset of depressive symptoms. 35 Currently, studies in the periphery provide the strongest link implicating TNF in the pathophysiologies of mood disorders, with these data arguing a relationship between immune-related dysfunction and mood disorder pathology.…”