Depression May Be Caused by Inflammation

[minkeygirl]

http://www.pbs.org/wgbh/nova/next/body/depression-may-caused-inflammation/

 

[anciendaze]

"Inflammation" is another extremely broad term which can result from a wide range of etiologies. I'm interested in going beyond this.

A recent post elsewhere concerned a Facebook post by Maryann Spurgin. I've seen a copy, even though I don't use Facebook. It concentrates on yet another weird systemic problem prevalent in ME/CFS, circulatory disorders falling short of normal standards for clinical disease. I could add the comment that every cardiologist is aware that depression goes along with heart disease, just as every psychiatrist is aware that depression regularly follows "flu-like" infections. Neither specialty has felt motivated to go much farther than these observations.

At one time I went looking through medical literature for possible etiologies for both diastolic dysfunction and less localized circulatory impairment. This led me to consider research on endothelial dysfunction, particularly those papers with clues to possible etiology. What I found were reports from pathologists describing invasion of endothelial tissues by CD8+ T-cells. This was interesting to me, because I had also seen reports of neurological impairment, particularly in the more accessible parts of the nervous system affecting autonomic function, which indicated ganglia were being invaded by CD8+ T-cells. A final aspect of this coincidence is that research on endocrine disturbances leading to GWI found a surprising number of cases of pituitary hypophysitis. (I hope I don't need to tell anyone here that symptoms of GWI are strikingly similar to ME/CFS.) Looking up causes there also led to reports of CD8+ T-cells invading the pituitary. Three very mysterious manifestations of ME/CFS all could be results of immune response about which the IOM report is largely silent.

This could mean there is an undetected viral infection behind these problems, or it could mean we have an autoimmune response in the cellular immune system. These two categories are not exclusive, because it is definitely possible for immune cells to be infected. Reports of illness resolving after cancer treatment which depleted a specific class of immune cells support either hypothesis. For the subset of patients who repeatedly present with active EBV infections there is even a report of successful treatment using adoptive immunotherapy which stimulates and cultures cytotoxic T-cells outside the body to destroy a very specific subset of immune cells which might either be infected or involved in a malfunctioning immune response.

Savoldo, B., Huls, M. H., Liu, Z., Okamura, T., Volk, H. D., Reinke, P., ... & Rooney, C. M. (2002). Autologous Epstein-Barr virus (EBV)___specific cytotoxic T cells for the treatment of persistent active EBV infection. Blood, 100(12), 4059-4066.

 

[Hip]

"Inflammation" is another extremely broad term which can result from a wide range of etiologies. I'm interested in going beyond this.

Psychiatry has yet to fully appreciate the studies indicating immune activation (Iinflammation) can lead to mental conditions such as depression, anxiety or schizophrenia.

You can certainly go beyond, and look for the cause of the inflammation that induces these mental symptoms. And the cause may well be linked to infectious pathogens in many cases.

I am just happy to see that the link between the immune system and mental or cognitive symptoms is gaining traction.

 

[MeSci]

Just come across a couple of scientific papers on this subject:

Neuropsychopharmacology. 2015 Jan 19

Sex Differences in Depressive and Socioemotional Responses to an Inflammatory Challenge: Implications for Sex Differences in Depression

Sex Differences in Depressive and Socioemotional Responses to an Inflammatory Challenge: Implications for Sex Differences in Depression.

Moieni M1, Irwin MR2, Jevtic I1, Olmstead R2, Breen EC2, Eisenberger NI1.

Abstract

Substantial evidence demonstrates that inflammatory processes may underlie depression for a subset of patients, including work showing that healthy subjects exposed to an inflammatory challenge show increases in depressed mood and feelings of social disconnection. However, despite the fact that depression is two times as likely to occur in females than males, the vast majority of this work has been carried out in males. Thus, the objective of this study was to determine whether females (vs males) would show greater increases in proinflammatory cytokines, depressed mood, and social disconnection in response to an inflammatory challenge. One hundred and fifteen healthy participants (69 female) completed this double-blind, placebo-controlled, randomized clinical trial in which participants were randomly assigned to receive either a single infusion of low-dose endotoxin (derived from Escherichia coli; 0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), depressed mood, and feelings of social disconnection were assessed hourly. Results showed that endotoxin (vs placebo) led to increases in proinflammatory cytokines (TNF-α, IL-6), depressed mood, and feelings of social disconnection. Females exposed to endotoxin showed greater increases in depressed mood and feelings of social disconnection. Furthermore, increases in TNF-α and IL-6 were correlated with increases in social disconnection for females but not for males. These sex differences in the relationships between inflammatory and socioemotional responses to an inflammatory challenge may be particularly important for understanding why females are two times as likely as males to develop depressive disorders.

Brain Behav Immun. 2015 Mar 10

Inflammation impairs social cognitive processing: A randomized controlled trial of endotoxin

Moieni M1, Irwin MR2, Jevtic I1, Breen EC2, Eisenberger NI3.

Inflammation impairs social cognitive processing: A randomized controlled trial of endotoxin.

Abstract

Neuropsychiatric disorders (e.g., autism, schizophrenia) are partially characterized by social cognitive deficits, including impairments in the ability to perceive others' emotional states, which is an aspect of social cognition known as theory of mind (ToM). There is also evidence that inflammation may be implicated in the etiology of these disorders, but experimental data linking inflammation to deficits in social cognition is sparse. Thus, we examined whether exposure to an experimental inflammatory challenge led to changes in ToM. One hundred and fifteen (n=115) healthy participants were randomly assigned to receive either endotoxin, which is an inflammatory challenge, or placebo. Participants completed a social cognition task, the Reading the Mind in the Eyes (RME) test, at baseline and at the peak of the inflammatory response for the endotoxin group. The RME test, a validated measure of ToM, evaluates how accurately participants can identify the emotional state of another person by looking only at their eyes. We found that endotoxin (vs. placebo) led to decreases in performance on the RME test from baseline to the peak of inflammatory response, indicating that acute inflammation can lead to decreases in the ability to accurately and reliably comprehend emotional information from others. Given that deficits in ToM are implicated in neuropsychiatric disorders, including those which may have an inflammatory basis, these results may have implications for understanding the links between inflammation, social cognition, and neuropsychiatric disorders.

 

[MeSci]

This could mean there is an undetected viral infection behind these problems, or it could mean we have an autoimmune response in the cellular immune system. These two categories are not exclusive, because it is definitely possible for immune cells to be infected. Reports of illness resolving after cancer treatment which depleted a specific class of immune cells support either hypothesis. For the subset of patients who repeatedly present with active EBV infections there is even a report of successful treatment using adoptive immunotherapy which stimulates and cultures cytotoxic T-cells outside the body to destroy a very specific subset of immune cells which might either be infected or involved in a malfunctioning immune response.

Savoldo, B., Huls, M. H., Liu, Z., Okamura, T., Volk, H. D., Reinke, P., ... & Rooney, C. M. (2002). Autologous Epstein-Barr virus (EBV)___specific cytotoxic T cells for the treatment of persistent active EBV infection. Blood, 100(12), 4059-4066.

HIV is of course an example of a virus that infects - and destroys - immune cells.

 

[anciendaze]

HIV is of course an example of a virus that infects - and destroys - immune cells.

So does HTLV-1, it is just much slower and less lethal.