Depressive symptoms are associated with tumor necrosis factor alpha in systemic lupus erythematosus

Abstract

BackgroundTumor necrosis factor alpha (TNF-α) is deeply related to pathogenesis of neurodevelopmental disorders, especially depression. The aim of this study was to explore potential relationships between sera TNF-α levels and mood and anxiety disorders in systemic lupus erythematosus (SLE) patients.MethodsWe included 153 consecutive SLE patients (women 148; median age 30; range 10–62) and 40 (women 37; mean age 28.5; range 12–59) age- and sex-matched healthy controls. Mood and anxiety disorders were determined through Beck Depression and Beck Anxiety Inventory. SLE patients were further assessed for clinical and laboratory SLE manifestations. TNF-α levels were measured by enzyme-linked immunosorbent assay using commercial kits.ResultsDepressive symptoms were identified in 70 (45.7 %) SLE patients and in 10 (25 %) healthy controls (p < 0.001). Anxiety symptoms were identified in 93 (60.7 %) SLE patients and in 16 controls (40 %) (p < 0.001). Sera TNF-α levels were increased in SLE patients with depressive symptoms (p < 0.001) and with anxiety symptoms (p = 0.014). A direct correlation between the severity of depressive symptoms and sera TNF-α levels (r = 0.22; p = 0.003) was observed. TNF-α levels were significantly increased in patients with active disease (p = 0.012). In addition, we observed a correlation between sera TNF-α levels and disease activity (r = 0.28; p = 0.008). In the multivariate analysis, sera TNF-α levels were independently associated with depressive symptoms (t = 3.28; 95 % CI 1.08–2.2; p = 0.002).ConclusionsSera TNF-α levels are increased in SLE patients with mood and anxiety disorders. In SLE, sera TNF-α levels are independently associated with mood disorders. The etiology of mood disorders is still debated in SLE, but our findings suggest the presence of immunological basis for depression in SLE.

Definition of NPSLE: Does the ACR Nomenclature Still Hold?

“…Depending on the type of manifestations included and the method used for evaluation, the frequency of neuropsychiatric (NP) manifestations varies widely across studies (3, 4). NP involvement may be considered primary if result directly from immune-mediated injury or secondary when related to treatment, infections, metabolic abnormalities, or other systemic manifestations, not related to SLE (3, 5). In major cohorts, approximately 60% of NP manifestations are due to secondary causes (4–8).…”

“…A high index of clinical suspicion is necessary, in addition to laboratory and neuroimaging findings, to support diagnosis, and exclude confounding diagnosis (1–5). …”

“…The pathogenesis of primary NPSLE is yet not completely elucidated, and considering the diversity of manifestations, probably one or more mechanism of pathogenicity is implicated (3, 5). Several studies have described autoantibodies and cytokines as possible mediators, affecting cerebral vasculature, and/or interfering with neuronal connectivity (3, 5, 6).…”

“…Several studies have described autoantibodies and cytokines as possible mediators, affecting cerebral vasculature, and/or interfering with neuronal connectivity (3, 5, 6). …”

Neuropsychiatric Lupus in clinical practice

“…Mood disorders were associated with disease activity, high prednisone doses (≥ 20 mg), cutaneous disease, and longitudinal extensive transverse myelitis 31 . Adverse drug events may also contribute to the occurrence or exacerbation of depressive symptoms in some patients 32 .…”