Systemic autoimmune diseases are associated with an increased risk of bipolar disorder: A nationwide population-based cohort study

Wang, Lingyi; Chiang, Jen‐Huai; Chen, Shih-Fen; Shen, Yu-Chih

doi:10.1016/j.jad.2017.10.027

Cited by 43 publications

(30 citation statements)

References 43 publications

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“…In the prespecified plan of analyses, we planned to address bias or confounding by indication of use of the agent of interest in two different ways: Firstly, in the design of the study, we chose to estimate the rate of mania/bipolar disorder during successive prescription periods of the drug compared with the rate during prescription periods 1‐2. We systematically confirmed in all analyses that the prescription periods 1‐2 was associated with increased HR of mania/bipolar disorder compared with the period with the non‐use period (see Figures and , [although not statistically significantly for allopurinol] illustrating confounding by indication since the drugs were prescribed for physical disorders associated with increased rate of developing mania/bipolar disorder including pain (NSAID), osteoarthritis (NSAID), prevention and treatment of cardiovascular and thromboembolic events (low‐dose aspirin), arthritis urica (allopurinol) and other kinds of arthritis (NSAID), hypercholesterolemia (statins) and hypertension (angiotensin inhibitors), and congestive heart failure (angiotensin inhibitors). However, it is possible that low‐dose aspirin, statins, allopurinol, and angiotensin agents are more likely to be used for prophylaxis in relatively asymptomatic people, whereas as noted in the methods, NSAID and high‐dose aspirin are more likely to be used for acute and chronic pain, which are drivers of mood symptoms.…”

Section: Discussionmentioning

confidence: 52%

New drug candidates for bipolar disorder—A nation‐wide population‐based study

et al. 2019

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Objective Drug repurposing is an increasingly promising idea in many fields of medicine. We systematically used Danish nation‐wide population‐based registers to investigate whether continued use of non‐aspirin non‐steroidal anti‐inflammatory drugs (NSAIDs), low‐dose aspirin, high‐dose aspirin, statins, allopurinol, and angiotensin agents decrease the rate of incident mania/bipolar disorder. Methods A nation‐wide population‐based longitudinal study using Poisson regression analyses including all persons in Denmark who purchased the exposure medication of interest and a random sample of 30% of the Danish population. The follow‐up period comprised a 10 years period from 2005 to 2015. Two different outcome measures were included, (1) a diagnosis of mania/bipolar disorder at a psychiatric hospital contact as inpatient or outpatient and (2) a combined measure of a diagnosis of mania/bipolar disorder or initiation of lithium use. Results A total of 1,605,365 subjects were exposed to one of the six drugs of interest during the exposure period from 2005 to 2015, median age 57 years [quartiles: 43;69], and female proportion of 53.1%. Continued use of low‐dose aspirin, statins, and angiotensin agents were associated with decreased rates of incident mania/bipolar disorder on both outcome measures. Continued uses of non‐aspirin NSAIDs as well as high‐dose aspirin were associated with an increased rate of incident bipolar disorder. There were no statistically significant associations for allopurinol. Conclusions The study supports the potential of agents acting on inflammation and the stress response system in bipolar disorder and illustrates that population‐based registers can be used to systematically identify drugs with repurposing potentials.

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Section: Discussionmentioning

confidence: 52%

New drug candidates for bipolar disorder—A nation‐wide population‐based study

et al. 2019

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“…Conversely, patients with BD have increased serum anti‐gliadin IgG antibodies 22 . There is also an increased frequency of BD in each of the following autoimmune diseases: pemphigus, 23 systemic lupus erythematosus, 24,25 rheumatoid arthritis, 25 autoimmune vasculitis, 25 Sjögren's syndrome 25 and Crohn's disease 25 . Moreover, the female children of parents with BD have an increased prevalence of autoimmune thyroiditis 26 .…”

Section: Evidence That Bd Is An Autoimmune Diseasementioning

confidence: 99%

Hypothesis: bipolar disorder is an Epstein–Barr virus‐driven chronic autoimmune disease – implications for immunotherapy

Pender

2020

Clin & Trans Imm

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Bipolar disorder (BD) is a chronic disease characterised by episodes of major depression and episodes of mania or hypomania, with a worldwide prevalence of 2.4%. The cause of BD is unknown. Here, I propose the hypothesis that BD is a chronic autoimmune disease caused by Epstein-Barr virus (EBV) infection of autoreactive B cells. It is postulated that EBV-infected autoreactive B cells accumulate in the brain where they provide costimulatory survival signals to autoreactive T cells and differentiate into plasma cells producing pathogenic autoantibodies targeting brain components such as the N-methyl-D-aspartate receptor. It is also proposed that the accumulation of EBV-infected autoreactive B cells in the brain is a consequence of a genetically determined defect in the ability of CD8 + T cells to control EBV infection. The theory is supported by studies indicating that autoimmunity, EBV infection and CD8 + Tcell deficiency all have roles in the pathogenesis of BD. According to the hypothesis, BD should be able to be treated by EBV-specific T-cell therapy and to be prevented by vaccination against EBV in early childhood. Exposure to sunlight or appropriate artificial light should also be beneficial in BD by augmenting CD8 + T-cell control of EBV infection.

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“…Possible associations between autoimmune mechanisms and the underlying neurobiology of BD are suggested by three types of studies: Epidemiologic studies reporting that autoimmune diseases are more prevalent in BD (4,61,67); studies reporting that patients with autoimmune diseases are more prone to develop BD (4,68); and several case-control studies reporting higher prevalence of several antibodies in BD (69-71). More recently, increased NMDA-R antibodies have been shown in BD (35,36,40) suggesting that the well-documented disturbances in NMDA functioning in BD may be caused by increased levels of circulating NMDA-R antibodies.…”

Section: Nmda-r Antibodiesmentioning

confidence: 99%

“…Bipolar Disorder (BD) is a chronic, severe mental illness, which has been repeatedly associated with high comorbidity with various types of autoimmune diseases (1)(2)(3)(4)(5)(6). Certain types of autoimmune diseases, such as thyroiditis (7), systemic lupus erythematosus (8)(9)(10) and multiple sclerosis (11,12), share some similar symptoms (i.e.…”

Section: Introductionmentioning

confidence: 99%

Increased serum levels of NMDA receptor antibodies in female patients with bipolar disorder

Ceylan¹,

Akan²,

Doyuran³

et al. 2018

J Clin Psy

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Objective: Glutamatergic/GABAergic imbalance due to autoimmune antibodies targeting N-methyl-D-aspartate receptors (NMDA-R) is considered to be one of the shared pathways between bipolar disorder (BD) and autoimmune diseases. Evidence shows female vulnerability to autoimmune disorders, and suggests a sex-specific approach in autoimmunity research in BD. We aimed to assess serum concentrations of NMDA-R antibodies and density of NMDA and GABA receptors on platelets in euthymic patients with BD in comparison to healthy individuals; and to determine the impact of sex on serum concentrations of NMDA-R antibodies and the density of NMDA and GABA receptors on platelets. Method: NMDA antibody IgG were detected in serum samples of 27 DSM IV euthymic patients with bipolar disorder (16 females, 11 males) and 33 healthy individuals (17 females, 16 males), using ELISA method. The densities of NMDA and GABA receptors on platelets were investigated using immunocytochemical methods. Results: Patients with BD presented higher serum levels of NMDA-R antibodies in comparison to healthy individuals (p<0.001). The densities of NMDA and GABA receptor on platelets were similar in both groups. The NMDA-R antibody levels were influenced by both diagnosis and sex (F=5.813, df=1, p =0.020). Tserum lithium levels showed a significant linear association with the serum NMDA-R antibody levels even adjusting for age, sex, body mass index (F=-56.26, t=-2.52, p = 0.015, CI: -101.12/-11.40). Discussion: Our findings support a potential role of NMDA-R antibodies in the underlying pathophysiology of BD, particularly for females.

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Systemic autoimmune diseases are associated with an increased risk of bipolar disorder: A nationwide population-based cohort study

Cited by 43 publications

References 43 publications

New drug candidates for bipolar disorder—A nation‐wide population‐based study

New drug candidates for bipolar disorder—A nation‐wide population‐based study

Hypothesis: bipolar disorder is an Epstein–Barr virus‐driven chronic autoimmune disease – implications for immunotherapy

Increased serum levels of NMDA receptor antibodies in female patients with bipolar disorder

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