Inflammation and neuronal plasticity: a link between childhood trauma and depression pathogenesis

Abstract

During the past two decades, there has been increasing interest in understanding and characterizing the role of inflammation in major depressive disorder (MDD). Indeed, several are the evidences linking alterations in the inflammatory system to Major Depression, including the presence of elevated levels of pro-inflammatory cytokines, together with other mediators of inflammation. However, it is still not clear whether inflammation represents a cause or whether other factors related to depression result in these immunological effects. Regardless, exposure to early life stressful events, which represent a vulnerability factor for the development of psychiatric disorders, act through the modulation of inflammatory responses, but also of neuroplastic mechanisms over the entire life span. Indeed, early life stressful events can cause, possibly through epigenetic changes that persist over time, up to adulthood. Such alterations may concur to increase the vulnerability to develop psychopathologies. In this review we will discuss the role of inflammation and neuronal plasticity as relevant processes underlying depression development. Moreover, we will discuss the role of epigenetics in inducing alterations in inflammation-immune systems as well as dysfunction in neuronal plasticity, thus contributing to the long-lasting negative effects of stressful life events early in life and the consequent enhanced risk for depression. Finally we will provide an overview on the potential role of inflammatory system to aid diagnosis, predict treatment response, enhance treatment matching, and prevent the onset or relapse of Major Depression.

Depression in cancer: The many biobehavioral pathways driving tumor progression

“…The most studied epigenetic modifications include changes in the methylation of cytosineguanine dinucleotides (CpGs), but include as well histone modifications, silencing of the extra copy of the X-chromosome in females, genomic imprinting and alterations in non-coding RNA 120 . Life adversities may influence molecular pathways relevant to the HPA-axis signaling and immune activation, leading to long-lasting immunological and endocrine dysfunction, which confers increased vulnerability to the subsequent development of depression and inflammatory diseases 121 .…”

The Impact of Stress on Immunity, Mechanism and Pathways Involved

“…[62] Stress in the early life has also a very vital impact on the improvement of neurological systems concerned in mood and stress responses, thus increasing the susceptibility to stress and so the risk of developing depression later in life, specifically in response to secondary stress. [63][64][65][66][67][68] Preclinical studies shows that gut permeability can be increased by the psychological stress, therefore enabling gut flora to reach the systemic system. [69] Another study reported that in www.wjpr.net lipopolysaccharide (LPS) could activate the systemic low grade inflammatory response in the stressed patients, but that mechanism is not fully cleared.…”

Depression: An Immuno-Inflammatory Cascade

“…Indeed, systemic infections and stressful life events triggers activation of the peripheral immune system (required response of the body to cope with the adverse condition) however, when the activation of the immune system is prolonged because of a persistence and continuation of the adverse event cytokines and other immune modulators access the brain and affect different brain systems that play a role in enhancing vulnerability to depressive disorders 25,26 . Thus immune system oriented cytokine production seems to play an intriguing role in the beginning cascade of depression.…”

“…There are plethora of routes by which cytokines can access the brain, influence central neuronal chemistry and functions and cause behavioral changes, a coordinated set of psychological and physiological modifications that develop during the course of an infection 44 and that resemble depressive symptoms. One pathway may involve macrophagelike cells located in the circumventricular organs and the choroid plexus, which detect and respond to circulating pathogen associated molecular patterns by producing pro inflammatory cytokines; these cytokines can then cross the Blood Brain Barrier (BBB) and affect neuronal function and microglia activation 26 .…”