Putative Inflammatory Sensitive Mechanisms Underlying Risk or Resilience to Social Stress

Abstract

It has been well recognized that exposure to stress can lead to the onset of psychosocial disorders such as depression. While there are a number of antidepressant therapies currently available and despite producing immediate neurochemical alterations, they require weeks of continuous use in order to exhibit antidepressant efficacy. Moreover, up to 30% of patients do not respond to typical antidepressants, suggesting that our understanding of the pathophysiology underlying stress-induced depression is still limited. In recent years inflammation has become a major focus in the study of depression as several clinical and preclinical studies have demonstrated that peripheral and central inflammatory mediators, including interleukin (IL)-1β, are elevated in depressed patients. Moreover, it has been suggested that inflammation and particularly neuroinflammation may be a direct and immediate link in the emergence of stress-induced depression due to the broad neural and glial effects that are elicited by proinflammatory cytokines. Importantly, individual differences in inflammatory reactivity may further explain why certain individuals exhibit differing susceptibility to the consequences of stress. In this review article, we discuss sources of individual differences such as age, sex and coping mechanisms that are likely sources of distinct changes in stress-induced neuroimmune factors and highlight putative sources of exaggerated neuroinflammation in susceptible individuals. Furthermore, we review the current literature of specific neural and glial mechanisms that are regulated by stress and inflammation including mitochondrial function, oxidative stress and mechanisms of glutamate excitotoxicity. Taken together, the impetus for this review is to move towards a better understanding of mechanisms regulated by inflammatory cytokines and chemokines that are capable of contributing to the emergence of depressive-like behaviors in susceptible individuals.

Narcissistic and Borderline Personality Disorders: Relationship With Oxidative Stress

“…Although sources of oxidative stress outside the brain cannot be ruled out, brain metabolism accounts for 20% of the body's oxygen (O 2 ) budget, out of proportion to its mass. This is because the principal sources of oxidative species are neural activity itself (Halliwell, 1992), intracellular energy cycling (Cobley, Fiorello, & Bailey, 2018), nitrosamine signaling between neurons (Finnell & Wood, 2018), and catabolism of monoamine neuromodulators such as serotonin and norepinephrine by the mitochondrial enzyme monoamine oxidase A (MAO-A; Kolla et al, 2016). Increased neural signaling during periods of psychological stress would thus be expected to increase the oxidation burden.…”

To stress or not to stress: Brain-behavior-immune interaction may weaken or promote the immune response to SARS-CoV-2

“…Oxidative stress results both from the environment (e.g. UV light, heavy metals, cigarette smoke) and from endogenous processes, such as the enzymatic production of reactive oxygen species (ROS) by mitochondria or by neutrophils activated by danger-associated molecular patterns during inflammation ( Finnell and Wood, 2018 ; Marx et al, 2017 ; Schiavone et al, 2013 ). A direct link between glucocorticoids and oxidative stress has been demonstrated in mice exposed to psychosocial stress ( Lee et al, 2009 ).…”

“…At the same time, suggestive evidence exists that relaxation techniques, behavioral therapy, psychodynamic procedures and other psychotherapeutic approaches may all be effectively reducing the health deteriorating effects generated for example by life adversities or smoldering conflicts such as posttraumatic stress, anxiety or depression. Effective coping capacities and high resilience can be achieved by respective interventions and counteract chronic psychosocial stress ( Finnell and Wood, 2018 ; Zozulya et al, 2008 ). A selection of these measures are discussed in detail below.…”

Modelling resilience in adolescence and adversity: a novel framework to inform research and practice

“…It is increasingly recognised that stress/adversity stimulates the release of proinflammatory cytokines from microglia and increases neuroinflammation in stress-sensitive brain regions, altering their structure and function 112,113 . However, suppression of pro-inflammatory cytokines may be markers of resilience 112,114,115 , and heightened peripheral inflammation may be a predictor or consequence of resilience to stress, perhaps because inflammatory markers influence behavioural outcomes via HPA axis regulation and hippocampal neurogenesis 116 . Although attenuation of inflammation seems to be linked to resilience from adversity 117,118 , this line of investigation is still in its infancy.…”