In Patients With Stable Heart Failure, Soluble TNF-Receptor 2 Is Associated With Increased Risk for Depressive Symptoms

Abstract

Objectives Researchers have proposed biological (inflammation) and psychological (depression) factors as potential mechanisms for poorer outcomes and readmissions in heart failure (HF) patients. However, studies investigating the link between inflammation and depressive symptoms in these patients are few. We examined the relationships between levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and soluble tumor necrosis factor receptor 2 (sTNR2) and depressive symptoms in HF outpatients. Method 55 patients (74.5% men; 60% Whites; mean age 71.6 ± 11.3 years) with New York Heart Association Class II, III, or IV HF (49%, 47%, and 4%, respectively) and mean ejection fraction (EF) 29.9 ± 7.1% completed the Patient Health Questionnaire (PHQ)-9 as a measure of depressive symptoms. We also obtained height, weight, and CRP, IL-6, and sTNFR2 levels. We used multivariate regressions to assess the predictive value of PHQ-9 scores on each inflammatory marker. Results 22 (40%) participants reported depressive symptoms (PHQ-9 score ≥ 5). After controlling for age, gender, body mass index, HF etiology, EF, and statin use, we found significant relationships between levels of both sTNFR2 (β = .35, p = .01) and IL-6 (β = .30, p = .04), but not CRP (β = −.96, p = .52), and depression scores. Conclusion Our findings add to a growing body of evidence supporting the proposition that heightened inflammation explains the effect depression has on HF. Health care providers should screen for depression in HF patients, as they may be at higher risk of augmented inflammation and poor outcomes.

Lipid Peroxidation and Immune Biomarkers Are Associated with Major Depression and Its Phenotypes, Including Treatment-Resistant Depression and Melancholia

“…Previously, it was shown that depression is accompanied by increased sTNF-R2 levels (Grassi-Oliveira et al 2009 ), while sTNF-R2 levels are also elevated in late life depression (Diniz et al 2010 ). In patients with stable heart failure, increased sTNF-R2 levels are associated with an increased risk of depression (Moughrabi et al 2014 ). In the Rizavi et al ( 2016 ) study, depression was not only accompanied by increased lymphocytic sTNF-R1, but also sTNF-R2 mRNA levels.…”

“…These meta-analyses showed additionally that Th2 and Tregulatory (Treg) cytokines (including IL-10, IL4, and IL-5) were not significantly altered in major depression indicating that major depression is characterized by M1 and Th1 activation. There are also some reports that plasma levels of soluble TNF receptor 60 kDa (sTNF-R1) and 80 kDa (sTNF-R2) are elevated in depression (Grassi-Oliveira et al 2009 ; Moughrabi et al 2014 ; Rizavi et al 2016 ). These TNFα receptor subtypes act as decoy receptors by binding sTNFα thereby attenuating TNFα signaling and thus inhibiting TNFα activities (Selinsky et al 1998 ; Su et al 1998 ).…”

Increased TG/HDL‐C in female G allele carriers of rs1061622 at gene of tumour necrosis factor receptor 2 with suicidal ideation

“…On the other hand, a reduction of TNF‐RII gene ( TNF‐RII ) mRNA level was found in Brodmann's area 46 in subjects with mood disorders, including major depressive disorders 12 . There was a significant relationship between sTNF‐RII and depression scores in heart failure patients even after adjustments for age, gender, BMI and heart failure aetiology 13 . Meanwhile, a higher sTNF‐RII level was shown to be associated with antidepressant use in women 14 .…”

“…12 There was a significant relationship between sTNF-RII and depression scores in heart failure patients even after adjustments for age, gender, BMI and heart failure aetiology. 13 Meanwhile, a higher sTNF-RII level was shown to be associated with antidepressant use in women. 14 Therefore, TNF-RII may play an important role in depressive disorder or antidepressant treatment.…”

Reduced Recovery of Depression in Female T Allele Carriers of TNF-RII rs1061622 at Earlier Stage after Wenchuan Earthquake

“…In fact, it has been documented that TNF-RII is related with depression [ 15 ]. Increased mRNA levels of TNF-α and TNF-RII in lymphocytes were found for depression patients [ 16 ], and increased levels of serum TNF-RII in heart failure and depression patients [ 17 ]. However, no significant correlation was found in the levels of TNF-α among depressed female patients [ 18 ].…”