Patients on etanercept had greater improvements on measures of depression (as measured by Beck Depression Inventory) than those on placebo. Notably, these improvements were not associated with reduction in psoriatic plaques or joint pain, which indicates a primary effect of TNF antagonism on depression, not simply a cosmetic or click here analgesic effect.108 These effects were confirmed in subsequent longer term studies in psoriasis patients109,110 and in patients with Inhibitors,research,lifescience,medical rheumatoid arthritis.111 A similar effect has been shown with the TNF-α
monoclonal antibody infliximab.112,113 Adiposity as a possible causal pathway to depression In considering possible sources of inflammation leading to depression, there has been increasing interest in the role of obesity. Rates of overweight and obesity have increased tremendously in recent years in both adults and children.114-119 Along with this has been an epidemic of related metabolic conditions Inhibitors,research,lifescience,medical like type 2 diabetes, dyslipidemias, cardiovascular and fatty liver disease, and certain forms of cancer.120-122 The bulk of evidence links obesity and its attendant complications to inflammation.123-125 Inhibitors,research,lifescience,medical The possible relationship between depression and obesity appears to be bidirectional, as evidence indicates that being depressed also increases the risk for the subsequent development of obesity, probably mediated, in part, by inactivity.126 Obesity
as an Inhibitors,research,lifescience,medical inflammatory state Adipose tissue is now understood as being a very complex organ system.127 White adipose tissue (WAT) is the main location for long-term fat storage in the body. WAT, particularly in the abdomen, is the main contributor to metabolic diseases.122,128,129 Adipocytes in WAT secrete a variety of hormones, inflammatory factors including cytokines (referred to Inhibitors,research,lifescience,medical as adipocytokines or adipokines).130,131 These factors include hormones traditionally associated with adipose tissue such as leptin, adiponectin, resistin, and visfatin; however, adipocytes can also secrete
IL-6 and TNF-α.130,130 Nevertheless, one of the primary mechanisms for the induction of inflammation in adipose tissue is the secretion of chemokines, particularly MCP-1. MCP-1 attracts leukocytes such as macrophages, T lymphocytes, and dendritic cells to adipose tissue, which in turn secrete cytokines including IL1, IL6, and TNF-α.132,133 Thus, chemokines and cytokines produced by WAT may contribute to widespread mafosfamide immune activation, potentially causing or exacerbating diseases associated with inflammation such as type 2 diabetes, cardiovascular disease, cancer, and depression.130 Leptin is another important peptide produced by adipocytes that regulates dietary intake. It regulates appetite by acting on leptin receptors in brain, particularly the hypothalamus.134 In the case of obesity, a state of leptin resistance develops in which circulating levels are actually increased but responsiveness is reduced.