Pathophysiology Of Depression

Another interesting part of this book, talks about the decreased immune response during times of stress. Hans Selye, one of the godfathers of stress physiology, discovered the first evidence of stress-induced immunosuppression back in the 1930s. Selye learned that the same glucocorticoids that are responsible for sympathetic response, was also a large contributor in immune system suppression. Glucocorticoids stop the formation of lymphocytes as well as inhibit the release of interleukins and interferons which make already circulating lymphocytes less responsive to infections. Sapolsky hypothesized why evolution would create this process from happening. He wanted to know why

Stress has a huge impact on the immune system. The immune system is interconnected. For example the immune, nervous, and endocrine system is linked through specialized communication pathways involving hormones, neurotransmitters, neuropeptides, and immune cell productions. Stress reactions can directly affect the various response systems and how they handle the neuroendocrine-products. This stress reaction directly affects the hypothalamus and pituitary peptides through the sympathetic branch of the autonomic nervous system. Some of these stressors might be life events, anxiety, and excitements.

Most studies of the relationship between stress and the immune system have focussed on acute(i.e. short lived) stressors and have found a decrease in immune cell function.

These adaptive mechanisms can become maladaptive if unresolved after precipitating events have passed, leading to interferences in emotional regulation (Liston, McEwen, & Casey, 2009; Juster et al., 2011). Imaging studies show alterations in the brain structures that assist in regulation of the stress response—the amygdala, hippocampus, and prefrontal cortex—due to prolonged exposure to stress (Carrion et al. 2010; Rao et al. 2010). The over activation of this fear circuitry in the brain can lead to distorted processing, contributing to depression (Thienkrua et al., 2006; Neria, Besser, Kiper, & Westphal, 2010; Rao et al., 2010), anxiety (Derryberry and Reed, 2002; Goldin et al., 2009; Graham and Milad, 2014), and mood impairments (Kobasa, 1979; Linehan, 1993; Haller and Miles, 2004). These cognitive changes can also contribute to insomnia, chronic pain, addictive disorders, impairment of immunity, and development of coping mechanisms such as smoking, use of alcohol or drugs, overeating, and other survival mechanisms (Raja, 2012). The allostatic load of a chronically over-activated hypothalamus-pituitary-adrenal system can lead to development of comorbid health conditions such as cardiovascular disease,

stress hormones, it inhibits the growth of nerve cells in this part of the brain. In these depressed

Microglia, in the same way as vascular cells, can bind to Aβ resulting in an amplified production of cytokines, glutamate and nitric oxide (6, 7). Some studies suggest that chemokines can recruit monocytes from the peripheral blood into plaque bearing brain.(8) Related to this neuroinflammation are the alterations of type I and type II Interferon (IFN) levels in AD mice model, PDGFB-APPSwInd (J20), where an enhanced type I IFN signaling at the brain barriers and hippocampus, and decreased type II IFN response, only at the barriers were observed.(9) Of interest the blockage of IFN type I response at the central nervous system is able to partial revert the cognitive decline in aged mice.(10) However the role of this blockage on an AD mice model is still

The experiments conducted used mice in two groups, an experimental group that underwent chronic early life stress and a control. Hormone production analysis for each subject occurred as the experiment proceeded. The mice underwent object recognition tasks, followed by sucrose and forced swim tests to quantify the effects of depression and anhedonia. Reduction of CRH production then occurred via short-hairpin RNA intervention in target mice. The mice were then retested, and given a social play test. The experiment then analyzed the synapse function of the control and CES mice. Cell imaging determined neuron expression, with further testing being conducted that focused on the analysis of microglial cells in a developing fetus.

What is more, several metabolomic studies to investigate drug response on patients with a chronic mild stress (CMS) model of depression were performed. One of these, conducted by Zhao and colleges, identified biochemical changes induced by two widely used anti-depressants: fluoxetine and imipramine [83]. Metabolic profiling of hippocampus of C57BL/6J mouse by gas chromatography-mass spectrometry

A journal article that was co-authored by Nancy Rothwell discussed the role of interleukin (IL-1) in inflammation of the brain leading to injury of the central nervous system (CNS) and disease. IL-1 is a cytokine

The effects of stress are thought to be mediated by the activation of the hypothalamic–pituitary–adrenal (HPA) axis, culminating in increased levels of glucocorticoids [5]. Which are the end products of HPA axis activity, glucocorticoids (GCs),regulate many physiological functions and play an important role in affective regulation and dysregulation[1].

Stress is one of the most major factors responsible for depressive disorders [1,2]. The chronic mild stress (CMS) model, a widely used rodent model of depression, consists of repeated exposure to various of unpredictable and mild stressors and it. And it has been shown a decrease in reward sensitivity in various behavioural paradigms [3] induces changes in hypothalamic-pituitary-adrenal (HPA) axis [4,5] but also of other biological and behavioural markers of human depression, including architectural sleep abnormalities[6,7] disturbances in circadian rhythms related to locomotor activity[8]using of variety of drug treatments during the application of stress can be reversed these disturbances

Initially developed as a model to screen antidepressant drugs, chronic unpredictable mild stress (CUMS) is increasingly used as a means to investigate behavioural, neurochemical and structural changes underlying anxiety and depression [5, 6]. CUMS acts as a suitable model with strong predictive validity as evidenced by decreased intake of sucrose, increase in anxiety- and depression-like behaviour, and reversal of these abnormalities by antidepressant drugs [7, 8].

Inflammation, if prolonged, is known to cause adverse effects on the CNS and consequent cognitive dysfunction, via pro-inflammatory cytokines produced during the process. The cytokine TNF-α is one of major mediators of the innate immune response, and is implicated in neurodegenerative diseases. Therefore, it is of interest to study the effects of TNF-α on the central nervous system and cognition. This review examines, in detail, Jing et al.’s investigation on the effects of intra-amygdala injection of TNF-α on fear conditioning in rats, provides insight on the study, and proposes future directions for further research.

Stress is one of the most important factors responsible for depressive disorders [11]. The chronic mild stress (CMS) model, a widely used rodent model of depression, consists of repeated exposure to an array of varying and unpredictable, mild stressors and it induces changes in hypothalamic-pituitary-adrenal (HPA) axis Katz et al. 1981Vollmayr B, Henn FA (2003)

Extended activation of the stress response can jeopardize our body’s homeostasis, resulting in dysregulation as well as a change in cortisol levels. Cortisol’s has a direct influence on our immune system leading to chronic