Leptin mediates improvements in cognitive function following treatment with infliximab in adults with bipolar depression.

Mansur RB, Subramaniapillai M, Lee Y, Pan Z, Carmona NE, Shekotikhina M, Iacobucci M, Rodrigues N, Nasri F, Rashidian H, Rosenblat JD, Brietzke E, Cosgrove VE, Kramer NE, Suppes T, McIntyre RS. Leptin mediates improvements in cognitive function following treatment with infliximab in adults with bipolar depression. Psychoneuroendocrinology. 2020 Oct 1; 120:104779.

Dimensions for VA is a web-based tool available to VA staff that enables detailed searches of published research and research projects.

If you have VA-Intranet access, click here for more information vaww.hsrd.research.va.gov/dimensions/

VA staff not currently on the VA network can access Dimensions by registering for an account using their VA email address.    Search Dimensions for VA for this citation
* Don't have VA-internal network access or a VA email address? Try searching the free-to-the-public version of Dimensions

Search for Abstract from PubMed

---

Abstract:

A potential role for leptin in the pathophysiology of bipolar disorder (BD) has been proposed. We recently investigated the effects of the tumor necrosis factor-alpha (TNF-a) antagonist infliximab in individuals with bipolar depression. Leptin is known to interact with the TNF-a system. Herein, we aimed to explore infliximab''s effects on leptin and its relationship with brain structure and function. Sixty adults with bipolar depression were enrolled in this randomized, double-blind, 12-week clinical trial of adjunctive infliximab (n = 29) and saline control (n = 31), which were administered intravenously at weeks 0, 2, and 6. Plasma concentrations of leptin, TNF-a and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. We observed a significant decrease in leptin levels in infliximab-treated patients, relative to placebo. Infliximab treatment also significantly reduced TNF-a and sTNFR2, but not sTNFR1 levels. Changes in sTNR2 levels at week 6 significantly determined changes in leptin at week 12 in infliximab-, but not placebo-treated participants. Improvements in verbal memory and increases in global cortical volume were associated with reduction in leptin levels in the treatment group. Mediation analysis indicated that cognitive improvement in infliximab-treated patients was mediated by reductions in leptin levels, which in its turn were determined by decreases in sTNR2 levels. In conclusion, infliximab treatment reduced plasma leptin levels in individuals with BD, through modulation of sTNFR2. Decreases in leptin signaling were associated with an increase in global cortical volume and better performance in a verbal memory task.