Mega-cohort data show the striking burden of depression and anxiety among people with autoimmune conditions, especially women.
People living with autoimmune conditions face almost twice the risk of developing affective disorders compared with the general population, researchers say.
An analysis of more than 1.5 million participants in the Our Future Health research program – the largest consented health research cohort in the world – found that lifetime prevalence of depression, anxiety or bipolar disorder was 28.8% among people with autoimmune conditions, compared with 17.9% in the wider population (OR=1.86, 95% CI 1.82–1.90).
Even after adjusting for age, sex, ethnicity, socioeconomic status, family history, chronic pain and social isolation, the odds of affective disorders remained elevated by nearly 50% (aOR=1.48, 95% CI 1.44–1.52).
Sex-based differences were pronounced, with women with autoimmune conditions reporting affective disorders at much higher rates than men with the same diagnoses (31.6% vs 20.7%).
The gap persisted across depression, anxiety and bipolar disorder. Rates of current clinically relevant depressive symptoms (PHQ-9 ≥10) were 18.6% in the autoimmune group versus 10.5% in the general population, while current anxiety symptoms (GAD-7 ≥ 8) were reported by 19.9% of those with autoimmune diagnoses compared with 12.9% of the reference group.
The findings, published in BMJ Mental Health, add weight to the hypothesis that chronic systemic inflammation contributes to psychiatric morbidity. While causal direction cannot yet be confirmed, the results align with smaller studies suggesting immune dysregulation plays a role in mood and anxiety disorders.
The researchers said their findings aligned with recent research which has reported bidirectional associations between autoimmune diseases and mental health conditions.
“The prevalence of affective disorders is consistently higher among people with autoimmune conditions such as rheumatoid arthritis, psoriasis and inflammatory bowel disease.
“Conversely, people with mental health conditions are also found to have higher risk for developing autoimmune conditions.”
They said effect size estimates of the association between affective disorders and autoimmune conditions observed in their study were comparable to those in previous studies.
“For instance, a recent meta-analysis, focusing on people with systemic lupus erythematosus, reported a high prevalence of depressive (22.4%), anxiety (12.5%) and bipolar (1.6%) disorders, largely consistent with those observed in the current study (26.1%, 20.3% and 0.9%, respectively),” the researchers wrote.
“Similarly, the odds for depression (OR=1.66) and bipolar disorder (OR=1.54) among people with autoimmune conditions reported in previous studies are comparable to those in our study.
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“A particular strength of our study in the context of previous research is the very large sample size of the OFH cohort, which enabled us to quantify these associations with unprecedented precision.”
The authors noted some limitations in their study, including the fact that the observational and cross-sectional design limited any inferences of causal mechanisms.
“No data on the time or duration of illness were available in OFH; thus, we cannot determine whether diagnoses of autoimmune conditions preceded, co-occurred with, or followed diagnoses of affective disorders,” they wrote.
“No direct measurements of inflammation are currently available in OFH, and as a result, it was not possible to establish the presence, nature, chronicity or severity of inflammation among people who reported receiving diagnoses of autoimmune conditions.
“Although some of the autoimmune conditions included in this group are characterised by severe and chronic inflammation resulting in clinical presentation, it is possible that participants with other conditions (e.g., psoriasis) might have experienced milder or more short-lived inflammation.”
Additionally, findings for autoimmune conditions considered together may be influenced by clinical and immunological heterogeneity across autoimmune disorders, although the authors said they observed consistent trends across individual disorders as well.
The authors noted that integrating routine mental health screening into care pathways for people with autoimmune diseases could allow earlier detection and intervention – particularly for women, who bear a greater burden.
“Future studies should seek to determine whether putative biological, psychological and social factors – for example, chronic pain, fatigue, sleep or circadian disruptions and social isolation – may represent potentially modifiable mechanisms linking autoimmune conditions and affective disorders,” the authors concluded.
“Longitudinal studies may also help to establish whether exposure to chronic inflammation precedes the development of affective disorders, or vice versa.
“Additionally, quantifying peripheral inflammatory biomarkers in this cohort may help to extend the findings from the current study by (1) confirming that people with autoimmune conditions indeed exhibit increased concentrations of peripheral inflammatory biomarkers, and (2) determining whether the degree of inflammation in people with autoimmune conditions may be proportional to their risk of developing affective disorders.”
