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Autoimmune diseases, especially in women, are associated with nearly a two-fold increased risk for affective disorders, new research showed.

An analysis of 1.5 million adults showed that the lifetime prevalence of self-reported diagnoses of depression, bipolar disorder, and anxiety was 28.8% among individuals with an autoimmune condition vs 17.9% among those without an autoimmune condition (q < .001).

“Our results suggest that people with autoimmune conditions may have nearly double the risk of experiencing mental health issues compared to the general population. So regular mental health screenings in this patient group may be useful for prevention and early detection of mental health conditions,” study investigator Arish Mudra Rakshasa-Loots, MD, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, Scotland, told Medscape Medical News.

However, he added, the study is observational in nature and direct inference of causal mechanisms cannot be made, so further research is necessary to translate these findings to the clinic, he added.

The study was published online on June 24 in BMJ Mental Health.

Leveraging a Large Research Cohort 

Chronic inflammation has been linked to several psychiatric disorders, raising the possibility that individuals with persistent inflammatory conditions may be at increased risk for mental health issues. To explore this hypothesis, researchers set out to investigate whether individual living with chronic inflammatory diseases experience higher rates of psychiatric symptoms compared to the general population.

For the study, investigators analyzed data from 1,563,155 million adults across the UK in the recently established, prospective Our Future Health cohort.

This study is the first to use data from the Our Future Health cohort, “which is already the world’s largest consented cohort study, so we were able to analyze the relationship between inflammatory conditions and mental health issues with unprecedented precision,” Mudra Rakshasa-Loots said.

At baseline, participants provided demographic, health, and lifestyle information through an online questionnaire that included the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7 (GAD-7)-item Scale. Physical measurements and blood samples were also collected during a clinic visit. Their mean age was 53.2 years, 56.9% were women, and 90.2% self-identified as White individuals.

In the absence of direct measurements of inflammatory biomarkers, an autoimmune condition was considered an indirect indicator of chronic inflammation. Six autoimmune conditions were included in the analysis: rheumatoid arthritis, Graves’ syndrome, inflammatory bowel disease, lupus, multiple sclerosis, and psoriasis. Affective disorders were defined as depression, anxiety, and bipolar disorder.

In all, 37,808 individuals reported autoimmune conditions and 1,525,347 did not. Participants with an autoimmune condition were significantly more likely to be women (74.4% vs 56.5%), identify as White individuals (92.5% vs 90.1%), and to report lifetime diagnoses of affective disorders for their biological mothers (15.5% vs 10.6%) and fathers (7.6% vs 5.4%).

Individuals with any autoimmune disorder had a higher lifetime prevalence than the general population of depression (25.5% vs 15.2%), anxiety (21.2% vs 12.5%), and bipolar disorder (0.9% vs 0.5%; q < .001 for all).

In linear regression models, the risk for affective disorders was significantly higher among people with autoimmune conditions (odds ratio [OR], 1.86; 95% CI, 1.82-1.90) and remained high after controlling for age, sex, and ethnicity (OR, 1.75; 95% CI, 1.71-1.79) and further controlling for household income, parental history of psychiatric illness, chronic pain experience, and degree of social isolation (OR, 1.48; 95% CI, 1.44-1.52).

After adjusting for sociodemographic factors, the risk for depression, anxiety, and bipolar disorder in those with autoimmune conditions was identical (OR, 1.49 for each).

Novel Results, Next Steps

The lifetime prevalence of affective disorders was significantly higher in each of the six autoimmune condition groups than in the general population.

Those with autoimmune conditions were also more likely to have current depression (18.6% vs 10.5%) and current anxiety (19.9% vs 12.9%), based on a PHQ-9 score ≥ 10 and a GAD-7 score ≥ 8, respectively.

The prevalence of affective disorders was significantly and consistently higher among women than among men with the same physical health conditions: 31.6% vs 20.7% with an autoimmune disorder and 21.9% vs 12.7% in the general population (q < .001 for both).

The authors noted the mechanisms underlying the higher prevalence are unclear, but theories suggest sex hormones, chromosomal factors, and differences in circulating antibodies may partly explain the differences.

There also may be sex differences in inflammatory biomarkers, with a recent meta-analysis reporting that the levels of C-reactive protein and interleukin-6 are elevated only among women with depression compared to healthy controls.

“It is therefore possible that women may experience the compounding challenges of increased occurrence of autoimmunity and stronger effects of immune responses on mental health, resulting in the substantially higher prevalence of affective disorders in this study,” they wrote.

Limitations include self-reported diagnoses of physical and mental health conditions, a lack of information on the time or duration of illness, and no direct measurements of inflammation.

“A critical next step will be to use blood-based biomarkers of inflammation as objective measures to test for associations between chronic inflammation and mental health risk in people with autoimmune conditions,” Mudra Rakshasa-Loots said. “We also hope to see longitudinal research that can provide insights into whether chronic inflammation precedes mental health conditions in this group, or vice versa.”

Large Dataset a Major Strength

Commenting on the study, Charles B. Nemeroff, MD, PhD, professor and chair, Department of Psychiatry and Behavioral sciences, Dell Medical School, The University of Texas at Austin, said there is increasing evidence of a role for inflammation in the pathophysiology of depression and related mood disorders.

“Previous studies have sought to determine whether patients with autoimmune disorders, by definition associated with an increase in inflammation, have higher rates of depression but these studies were largely underpowered,” he told Medscape Medical News. “This large study confirms and extends those findings.”

Nemeroff agreed it would have been helpful to have some idea of treatment response and measurement of inflammatory markers in the cohort. Moreover, autoimmune conditions such as Hashimoto thyroiditis, Crohn’s disease, and many others were not included.

He added that many unanswered questions remain. “How such patients respond to treatment is the question of paramount importance,” he said. “Do they require anti-inflammatory treatment? Do they respond as well to conventional evidence-based pharmacotherapy or psychotherapy?”

Mudra Rakshasa-Loots and coauthor Daniel J. Smith were supported by funding from the UK Medical Research Council. The authors and Nemeroff reported no competing interests.