Basal and LPS-stimulated inflammatory markers and the course of individual symptoms of depression

Abstract

Multiple studies show an association between inflammatory markers and major depressive disorder (MDD). People with chronic low-grade inflammation may be at an increased risk of MDD, often in the form of sickness behaviors. We hypothesized that inflammation is predictive of the severity and the course of a subset of MDD symptoms, especially symptoms that overlap with sickness behavior, such as anhedonia, anorexia, low concentration, low energy, loss of libido, psychomotor slowness, irritability, and malaise. We tested the association between basal and lipopolysaccharide (LPS)-induced inflammatory markers with individual MDD symptoms (measured using the Inventory of Depressive Symptomatology Self-Report) over a period of up to 9 years using multivariate-adjusted mixed models in 1147-2872 Netherlands Study of Depression and Anxiety (NESDA) participants. At baseline, participants were on average 42.2 years old, 66.5% were women and 53.9% had a current mood or anxiety disorder. We found that basal and LPSstimulated inflammatory markers were more strongly associated with sickness behavior symptoms at up to 9-year follow-up compared with non-sickness behavior symptoms of depression. However, we also found significant associations with some symptoms that are not typical of sickness behavior (e.g., sympathetic arousal among others). Inflammation was not related to depression as a unified syndrome but rather to the presence and the course of specific MDD symptoms, of which the majority were related to sickness behavior. Anti-inflammatory strategies should be tested in the subgroup of MDD patients who report depressive symptoms related to sickness behavior.

Molecular and functional properties of PFC astrocytes during neuroinflammation-induced anhedonia

“…This supports genetic, neuropathological, and cellular studies that link immune cell dysfunction to several neurological and psychiatric disorders (Prinz and Priller, 2014;Barnes et al, 2017;Ferrer, 2017;Lai et al, 2017;Hickman et al, 2018;Perez-Nievas and Serrano-Pozo, 2018;Pimenova et al, 2018;Pouget, 2018;Syed et al, 2018;Hammond et al, 2019;Matthews, 2019). Furthermore, there are known associations between inflammation and inflammatory markers with MDD-related phenotypes (Syed et al, 2018;van Eeden et al, 2020). Based on such discoveries, there is a need to understand how neuroinflammation affects relevant cell types in brain nuclei known to contribute to brain disorders and therefore begin to explore the significance of neuroinflammation to disease related phenotypes including, but not limited to, MDD.…”

Inflammation and depression in young people: a systematic review and proposed inflammatory pathways

“…Nonetheless, higher levels of pro-inflammatory cytokines have also been associated with opposing neurovegetative symptoms including fragmented sleep, decreased appetite, and weight loss [147,148]. Additionally, higher cytokine levels have been linked to other symptoms of depression, including reward abnormalities and social withdrawal [110,113].…”

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

“…Moreover, the prevalence of depression is higher among patients suffering from immune-mediated inflammatory disorders ( 10 ), and immunomodulation improves their depressive symptomatology irrespective of their effects on physical illness ( 11 ). Increased inflammatory markers have also been associated with specific subgroups of depressed patients, particularly those responding poorly to conventional antidepressants ( 12 , 13 ), and those with high levels of anxiety ( 14 ), sleep disturbance ( 15 ), anhedonia ( 16 ), and psychomotor retardation ( 17 , 18 ) — a cluster of symptoms that have been referred to as “depressive-inflammatory.” Therefore, targeting inflammation in depression may be a viable treatment strategy, and recent meta-analyses have described encouraging effects of anti-inflammatory agents as adjunctive treatments in depressed patients ( 19 ).…”