Inflammatory Biomarkers and Depression

Abstract

Antidepressants, predominantly serotonin- and/or noradrenaline reuptake inhibiting drugs have several shortcomings. The exact pathophysiological mechanisms leading to serotonergic-, noradrenergic- or dopaminergic dysfunction are still unclear. An inflammatory mechanism has been postulated and will be discussed here including possible therapeutic advantages of cyclooxygenase-2 (COX-2) inhibitors. Differences in the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and in the tryptophan-kynurenine metabolism resulting in an increased tryptophan and serotonin degradation and probably in an increased production of quinolinic acid might play a key role in major depression (MD). These differences are associated with an imbalance in the glutamatergic neurotransmission, which may contribute to an overweight of N-methyl-D: -aspartate agonism in MD. The immunological imbalance results in an increased prostaglandin E₂ production and probably also in an increased COX-2 expression. Although there is strong evidence for the view that the interactions of the immune system, IDO, the serotonergic system and the glutamatergic neurotransmission play a key role in MD, several gaps, e.g. the roles of genetics, disease course, sex, different psychopathological states, etc., have to be bridged by intense further research. There were already hints that anti-inflammatory therapy might have beneficial effects in MD. COX-2 inhibitors, however, have been tested in animal models and in preliminary clinical studies showing favourable effects compared to placebo in MD. The effects of COX-2 inhibition in the CNS as well as the different components of the inflammatory system, the kynurenine-metabolism and the glutamatergic neurotransmission, however, still need careful further scientific evaluation including clinical studies in bigger samples of patients.

Immunology of Major Depression

“…In accordance with the findings of increased monocytes and macrophages, an increased level of neopterin has also been described [45,46,47,48]. The role of cellular immunity, cytokines, the innate and the adaptive immune system in depression has been recently reviewed [49,50]. …”

Biomarkers: Symptoms, Survivorship, and Quality of Life

“…10,43-45 In addition, a recent meta-analysis of associations between depression, C-reactive protein (CRP), IL1, and IL6 46 found that each biomarker was positively associated with depressive symptoms. In a recent study of patients with advanced metastatic cancer, 47 higher levels of IL6 were associated with higher levels of depressive symptoms.…”

“…Second, symptom management and QOL researchers, for the most part, worked in a relative vacuum and lacked expertise in the development and testing of biomarkers based on molecular mechanisms. However, as the underlying mechanisms for the most common symptoms experienced by cancer patients and survivors (i.e., pain, 4 fatigue, 5,6 sleep disturbance, 7-9 depression 10-12 ) are being elucidated through studies in both animals and humans, the need to identify clinically relevant biomarkers for individual symptoms and symptom clusters, 13-15 as well as QOL outcomes has become a scientific imperative.…”

Toward a Neuroimaging Treatment Selection Biomarker for Major Depressive Disorder

“…For example, in cancer 13 and heart disease, 14 biomarkers are currently used to optimize initial treatment selection as well as guide treatment modifications with disease progression. Over the past several decades, a number of potential markers to guide antidepressant treatment have been investigated including clinical, 15 immune, 16 inflammatory, 17 endocrine, 18 genetic, 19–21 and imaging/electroencephalography 22–27 measures. Despite this extensive research, to our knowledge, no clinically useful marker to guide treatment selection has emerged.…”