Depression and anxiety in patients with multiple sclerosis treated with interferon-beta or fingolimod: Role of indoleamine 2,3-dioxygenase and pro-inflammatory cytokines

Abstract

Depression/anxiety (D/A) occurs in up to 50% of multiple sclerosis (MS) patients. Proinflammatory cytokines induce classical symptoms of depression. Activation of the inflammatory response also triggers production of indoleamine 2,3-dioxygenase (IDO), which catabolizes tryptophan, the amino acid precursor of serotonin and melatonin. It has been suggested that IDO is the link between the immune and serotonergic systems. This study aimed to quantify the levels of IDO and pro-inflammatory and anti-inflammatory cytokines in patients with MS and depression, according to treatment with interferon-beta (IFN-β) or fingolimod. The study inclusion criteria were age 18–60 years and a clinical and radiological diagnosis of MS. One hundred and thirty-two patients diagnosed by McDonald’s criteria and followed up at Brasília District Hospital, Brazil, with relapsing-remitting MS were identified as potential study participants. Thirty-five of these patients were identified to be receiving treatment with fingolimod or IFN-β and to have a diagnosis of D/A. IDO and pro-inflammatory and anti-inflammatory cytokine levels were compared between these 35 patients and 18 healthy controls. The level of IL-10 (an anti-inflammatory cytokine) was lower in both the fingolimod-treated ( P ​< ​0.001) and IFN-β-treated ( P ​< ​0.01) patient groups than in the control group. IFN-β-treated patients showed increased IDO expression and decreased inflammatory cytokine levels. In contrast, fingolimod-treated patients showed significantly decreased expression of IDO and significantly increased levels of proinflammatory cytokines produced by innate immune cells, including tumor necrosis factor-alpha and interleukin-6. The agents used to treat MS maintain symptoms of D/A in patients with MS via different mechanisms.

Impact of Multiple Sclerosis and Its Association with Depression: An Analytical Case-Control Investigation

“…Taking into account our findings and the bibliographic review, it is necessary for patients with MS to be aware of the importance of depression on their quality of life and to offer them a multidisciplinary team to establish good management of this pathology. In addition, biomarkers have been studied in some research with MS subjects, but all of them refer to the need for a larger sample for better consistency to thus complete the aspects of depressive studies and their possible causes in MS [ 11 , 40 ].…”

“…Recent studies have identified that the inflammatory process is closely related to the neurodegenerative pathways associated with depression, with proinflammatory cytokines being important in its pathophysiology [ 10 ]. In autonomic diseases such as MS, proinflammatory cytokine production triggers episodes of depression [ 11 ]. Another way to measure depression-related biomarkers is through saliva where the anti-inflammatory cytokine IL-10 is significantly associated with depression severity in MS patients [ 12 ].…”

A Review of the Role of Interleukin-2 in the Pathophysiology of Major Depressive Disorder in Hospitalized Patients

“…Major depression is not just a temporary feeling of sadness, grief, or nostalgia. 15 Depression is a condition beyond being sad or very sad about the loss of a loved one. Sadness and grief are natural and temporary reactions to the stresses of life.…”

The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases

“…Increased flux down the kynurenine pathway with an accompanying deficiency of the substrate, tryptophan, may contribute to various pathological conditions, such as depression and anxiety [ 9 , 10 , 11 ]. In addition, some metabolites, such as quinolinic acid in the kynurenine pathway, have neurotoxic properties.…”