Abstract
Major depressive disorder (MDD) is a mood disorder of multifactorial origin affecting millions of people worldwide. The alarming estimated rates of prevalence and relapse make it a global public health concern. Moreover, the current setback of available antidepressants in the clinical setting is discouraging. Therefore, efforts to eradicate depression should be directed towards understanding the pathomechanisms involved in the hope of finding cost-effective treatment alternatives. The pathophysiology of MDD comprises the breakdown of different pathways, including the hypothalamus-pituitary-adrenal (HPA) axis, the glutamatergic system, and monoaminergic neurotransmission, affecting cognition and emotional behavior. Inflammatory cytokines have been postulated to be the possible link and culprit in the disruption of these systems. In addition, evidence from different studies suggests that impairment of glial functions appears to be a major contributor as well. Thus, the intricate role between glia, namely microglia and astrocytes, and the central nervous system’s (CNSs) immune response is briefly discussed, highlighting the kynurenine pathway as a pivotal player. Moreover, evaluations of different treatment strategies targeting the inflammatory response are considered. The immuno-modulatory properties of vitamin D receptor (VDR) suggest that vitamin D is an attractive and plausible candidate in spite of controversial findings. Further research investigating the role of VDR in mood disorders is warranted.
Highlights
Depression is a common neuropsychiatric disorder constituting one of the leading causes of disability worldwide, estimated to affect 350 million people, and projected to be the leading cause of disease burden by 2030 (World-Health-Organization, 2008; World-Federation-for-Mental-Health, 2012)
Elevated microglial quinolinic acid (QUIN) expression was reported in the cingulate cortex, whereas a decrease or no change in microglial QUIN immunoreactivity was observed in the hippocampus of acutely depressed patients (Steiner et al, 2011; Busse et al, 2014)
Cytokine-induced sickness behavior is proposed to culminate in major depressive disorder (MDD) by promoting the activation of the KYN pathway and glucocorticoid receptor (GR) resistance, compromising the monoaminergic and glutamatergic neurotransmission along with the HPA axis hyperactivation
Summary
Depression is a common neuropsychiatric disorder constituting one of the leading causes of disability worldwide, estimated to affect 350 million people, and projected to be the leading cause of disease burden by 2030 (World-Health-Organization, 2008; World-Federation-for-Mental-Health, 2012). The comorbid state of depression together with a number of other physical and psychiatric disorders results in increased disability and mortality rates. Inflammation and glial pathology in depression mental disorders between 2004 and 2010 in the European Union, rates in this period remained more or less stable with the increase in better detection and health care systems. In a previous study the prevalence of persons affected each year was estimated to be 38.2%, depression being the second most prevalent form of mental disorders (6.9%; Wittchen et al, 2011). The aim of this review is to connect the different pathophysiological pathways of depression in an effort to find suitable treatments
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