Neuroimmunomodulation in unipolar depression: a focus on chronobiology and chronotherapeutics

Abstract

The rising burden of unipolar depression along with its often related sleep disturbances, as well as increasing rates of sleep restriction in modern society, make the search for an extended understanding of the aetiology and pathophysiology of depression necessary. Accumulating evidence suggests an important role for the immune system in mediating disrupted neurobiological and chronobiological processes in depression. This review aims to provide an overview of the neuroimmunomodulatory processes involved with depression and antidepressant treatments with a special focus on chronobiology, chronotherapeutics and the emerging field of immune-circadian bi-directional crosstalk. Increasing evidence suggests that chronobiological disruption can mediate immune changes in depression, and likewise, immune processes can mediate chronobiological disruption. This may suggest a bi-directional relationship in immune-circadian crosstalk. Furthermore, given the immunomodulatory effects of antidepressants and chronotherapeutics, as well as their associated beneficial effects on circadian disturbance, we--and others--suggest that these therapeutic agents may exert their chronobiotic effects partially via the neuroimmune system. Further research is required to better elucidate the mechanisms of immune involvement in the chronobiology of depression.

Electro-Acupuncture Alleviates Chronic Unpredictable Stress-Induced Depressive- and Anxiety-Like Behavior and Hippocampal Neuroinflammation in Rat Model of Depression

“…As is common knowledge, microglia is the main source of pro-inflammatory cytokines in the brain (Harry and Kraft, 2012 ). The pro-inflammatory cytokines are suggested to be involved in the pathophysiology of MDD (Yirmiya et al, 2000 ; Dantzer et al, 2008 ; Song and Wang, 2011 ; Eyre and Baune, 2012 ). The activation of microglia may have detrimental effects on neurons by expressing and synthesizing pro-inflammatory cytokines such as IL-1β, which induces neuro-inflammation and eventually induces the death of neurons under these conditions (Brown and Vilalta, 2015 ; Dao-Ung et al, 2015 ).…”

“…Depression is the most common psychiatric disorder with a high mortality and morbidity rate 2 . In the past decades, preclinical studies have demonstrated that neuroinflammation, described by the increase of inflammatory cytokines in the brain, contributed to the development of depressive behavior (Yirmiya et al, 2000 ; Dantzer et al, 2008 ; Eyre and Baune, 2012 ). Patients with major depressive disorder (MDD) have greater pro-inflammatory cytokines in peripheral circulation and some in brain regions, such as: interleukin-6 (IL-6), IL-1β and C-reactive protein (CRP; Howren et al, 2009 ; Jacoby et al, 2016 ).…”

The Circadian System in Alzheimer’s Disease: Disturbances, Mechanisms, and Opportunities

“…One aspect that might be of importance is the role of neuroinflammation in AD on SCN and circadian function. Alzheimer's disease, like many other neurodegenerative diseases, is associated with neuroinflammation (91) which can impact on SCN and circadian function (9,92,93). Another area worthy of further investigation is the role that cholinergic cell loss has in circadian rhythm disturbance in AD and whether anti-cholinesterase drugs might impact on such rhythms in AD.…”

Treating Depression and Depression-Like Behavior with Physical Activity: An Immune Perspective

“…Humoral factors include PICs, AICs, C-reactive protein (CRP) as well as other immunomodulatory factors like CX3CL1, CD200, and IGF-1 (Eyre and Baune, 2012b). Cellular factors include resident glia (e.g., astrocytes, microglia) and centrally migrating immune cells involved in protective immunosurveillance (e.g., CD4+ T cells and macrophages; Eyre and Baune, 2012b). …”