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Updated: Feb 2, 2026

Author Spotlight: Unveiling the Connection Between Sleep Disorders and Cognitive Symptoms in Depression
Published on: April 26, 2024
Elevation of tumor necrosis factor alpha levels is associated with restless legs symptoms in clinically depressed
Piritta Auvinen1, Pekka Mäntyselkä2, Hannu Koponen3
1Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
Background:
Restless legs syndrome is a sensorimotor disorder associated with several mental illnesses particularly depression.
Methods:
A cross-sectional study of primary care patients. The prevalence of restless legs symptoms was studied in 706 patients with depressive symptoms and 426 controls without a psychiatric diagnosis by using a structured questionnaire. The depressive symptoms were evaluated with the BDI and the psychiatric diagnosis was confirmed by means of a diagnostic interview (M.I.N.I.). The subjects with elevated depressive symptoms were divided into two groups subjects with depressive symptoms with and without clinical depression.
Results:
The prevalence of restless legs symptoms was 24.8% in the controls, 50.0% in the patients with clinical depression and 42.4% in the patients with depressive symptoms. CRP value was significantly higher (p = .003) in the clinically depressed patients than in the other groups. There was a higher concentration of TNF-α in the subjects with restless legs symptoms (7.4 ng/l ± 3.2) compared with the subjects without symptoms (6.7 ng/l ± 2.3)(p < .001). There was a significant difference in the TNF-α levels between the subjects with and without restless legs symptoms in the depression group (p < .001) and among the patients with depressive symptoms but no a depression diagnosis (p = .022). In these groups, restless legs symptoms were associated with elevated levels of TNF-α.
Conclusions:
TNF-α level was associated with restless legs symptoms only among subjects with depressive symptoms whether they had clinical depression or not. We suggest that TNF-α could be an underlying factor between restless legs symptoms and comorbidities.
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