More than half of patients with primary Sjögren’s syndrome (pSS) experience depression and anxiety, shedding light on the role of inflammation in neuropsychiatric symptoms associated with chronic autoimmune diseases. Evidence from both animal and clinical studies indicates that elevated levels of the cytokine interleukin 6 (IL 6), whether in the peripheral circulation or central nervous system, play a significant role in stress responses and depressive disorders, particularly in patients with physical illnesses accompanied by depression. Increased IL 6 release has also been linked to the prognosis and therapeutic response of major depressive disorder, affecting a broad range of depressive symptoms.
Excessive IL 6 activity may contribute to depression by activating the hypothalamic pituitary adrenal axis or altering neurotransmitter metabolism. The recognition of neuroinflammation as a key mechanism in the development of depressive disorders has prompted researchers to consider combining blood IL 6 levels with other cytokine profiles to define biological subtypes of depression, potentially enabling more targeted and effective treatments.
A cross-sectional study published in Biochemia Medica investigated the association between IL 6 and mood disorders in female patients with pSS. The study enrolled 60 patients diagnosed at Sestre Milosrdnice University Hospital Center between 2019 and 2021. Psychological symptoms were assessed using the Hospital Anxiety and Depression Scale, while inflammatory biomarkers, including erythrocyte sedimentation rate, rheumatoid factor, ferritin, fibrinogen, CRP, C3, C4, and IL 6, were measured alongside disease activity indices ESSDAI and ESSPRI.
The results revealed that 39 of the 60 patients exhibited depression, while 34 reported anxiety symptoms. Patients with either depression or anxiety had significantly higher IL 6 concentrations compared to those without these psychological manifestations. Logistic regression analysis identified IL 6 as an independent predictor of depression, with an odds ratio of 3.23, while fatigue measured by ESSPRI emerged as a significant predictor of anxiety, with an odds ratio of 2.01.
The study suggests that IL 6 could serve as a biomarker for depression as an extraglandular manifestation of pSS, while ESSPRI fatigue assessments may help identify patients at risk for anxiety. These findings underscore the complex interplay between inflammatory pathways and neuropsychiatric symptoms in chronic autoimmune conditions. Researchers emphasize the importance of integrating mental health screening into routine pSS management, noting that inflammation targeted strategies could improve both psychological well being and overall patient care.
References
- Mrsić F, Vukasović I, Tešija Kuna A, Ladika Davidović B, Markeljević J. Association of inflammatory markers with depression and anxiety in female patients with primary Sjögren’s syndrome. Biochem Med (Zagreb). 2025 Oct 15;35(3):030701.
- Ting EY, Yang AC, Tsai SJ. Role of Interleukin-6 in Depressive Disorder. Int J Mol Sci. 2020 Mar 22;21(6):2194.