There is evidence that patients with depression have high levels of inflammatory markers, high body mass index, and/or markers of metabolic dysregulation, which may predispose them to medical comorbidity and treatment resistance.1,2
A seminal study found that inhibition of tumor necrosis factor (TNF) signaling, a key regulator of inflammation, with infliximab reduced depressive symptoms in patients with treatment resistant depression (TRD) high baseline plasma C-reactive protein (CRP; > 5 mg/L), and also lowered concentrations of CRP and other inflammatory cytokines in these patients.3 Gene expression analysis showed that antidepressant response to infliximab were predicted by baseline transcripts related to inflammation and TNF-signaling, as well as glucose and lipid metabolism, suggesting a role for metabolic dysregulation in these patients.4
There is evidence that in patients with rheumatoid arthritis, treatment with infliximab is associated with improvements in indices of glucose and lipid metabolism.5 However, whether these relationships exist in patients with infliximab-treated patients with TRD remains unknown. Bekhbat and colleagues6 measured a panel of plasma biomarkers of glucose and lipid metabolism in patients with TRD to determine their association with (1) antidepressant response to infliximab, (2) gene transcripts predictive of infliximab response, and (3) baseline CRP levels.
Blood plasma and RNA samples were collected during a 12-week randomized, double-blind trial of infliximab versus placebo in patients with TRD.3 Depression severity was measured by the HAM-D-17. Treatment response was defined as a 50% reduction in the HAM-D-17 at any point during the 12-week study. Subjects received infliximab 5 mg/kg or placebo at baseline, week 2, and week 6. Blood was collected after 30 minutes of rest at baseline and again prior to the second infusion at week 2 for a panel of metabolic biomarkers (leptin, resistin, adiponectin, glucose, lipids, and CRP), as well as gene expression analysis.
Multivariate linear regression models were used to identify baseline plasma markers that differed between patients with and without antidepressant response to either infliximab or placebo. Multivariate repeated measures general linear models were used to assess the effects of a single infusion of infliximab at 2 weeks compared with placebo on metabolic biomarkers, and whether potential treatment effects over time were different in patients with plasma CRP >5 mg/L.
1. Shelton RC, Falola M, Li L, et al. The proinflammatory profile of depressed patients is (partly) related to obesity. J Psychiatr Res. 2015;70:91–97.
2. Haroon E, Daguanno AW, Woolwine BJ, et al. Antidepressant treatment resistance is associated with increased inflammatory markers in patients with major depressive disorder. Psychoneuroendocrinology. 2018;95:43–49.
3. Raison CL, Rutherford RE, Woolwine BJ, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013;70:31–41.
4. Mehta D, Raison CL, Woolwine BJ, et al. Transcriptional signatures related to glucose and lipid metabolism predict treatment response to the tumor necrosis factor antagonist infliximab in patients with treatment-resistant depression. Brain Behav Immun. 2013;31:205–215.
5. Tam LS, Tomlinson B, Chu T, et al. Impact of TNF inhibition on insulin resistance and lipids levels in patients with rheumatoid arthritis. Clin Rheumatol. 2007;26:1495–1498.
6. Bekhbat M, Chu K, Le N-A. Glucose and lipid-related biomarkers and the antidepressant response to infliximab in patients with treatment-resistant depression. Psychoneuroendocrinology 2018, https://doi.org/10.1016/j.psyneuen.2018.09.004