The Influence of Antidepressants on the Immune System

[pattismith]

Looking for more information about low T lymphocytes CD8 / low NK activity, I found it's a finding in Bipolar Disorder and Major Depression Disorder that is not uncommon!

Neuroinflammation is also a common finding in these two disorders.

The Influence of Antidepressants on the Immune System
Łukasz P. Szałach,1 Katarzyna A. Lisowska,

1 and Wiesław J. Cubała2
Author information Article notes Copyright and License information Disclaimer
2019

Abstract
Depression is one of the most frequently diagnosed condition in psychiatry.

Despite the availability of many preparations, over 30% of treated patients do not achieve remission.

Recently the emphasis is put on the contribution of the body’s inflammatory response as one of the causes of depression.

The interactions between nervous and immune systems are the main issue addressed by psychoneuroimmunology.

In patients suffering from depression changes in the plasma concentrations of cytokines and in the number and level of activation of immune cells has been found.

Attention is paid to the high levels of pro-inflammatory cytokines, the prevalence of Th1 responses to Th2, weakening of NK cell cytotoxicity and changes in lymphocyte proliferation and apoptosis.

A number of studies focus on influence of antidepressants and non-standard methods of depression treatment, such as ketamine infusion, on patients’ immunology.

Many of them seem to regulate the immune responses.

The study results encourage to look for new ways to treat depression with immunomodulatory drugs.

In this article authors present the current knowledge about immune system changes accompanying depression as well as the study results showing the influence of drugs on the immune system, especially in the context of reducing the symptoms of depression.

 

[andyguitar]

Recently the emphasis is put on the contribution of the body’s inflammatory response as one of the causes of depression.

This has been in the news a bit recently. Unfortunatly the significance of it has been lost amongst the covid news. I suspect that we will be hearing a lot more about it when life gets back to normal. One possibility is that anti-inflammatory drugs like ibuprofen will be used instead of anti-depressants.

 

[pattismith]

This has been in the news a bit recently. Unfortunatly the significance of it has been lost amongst the covid news. I suspect that we will be hearing a lot more about it when life gets back to normal. One possibility is that anti-inflammatory drugs like ibuprofen will be used instead of anti-depressants.

I think research will do one more step by targeting neuroinflammation and lymphocyte functions.

this is an older study (2015)

Natural killer cell activity in patients with major depressive disorder treated with escitalopram☆☆☆
Author links open overlay panelE-JinParkaJe-HoonLeebDea-ChulJeongcSang-IckHanaYang-WhanJeona
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https://doi.org/10.1016/j.intimp.2015.06.031Get rights and content

Highlights

•
The changes in number and activity natural killer cells have repeatedly been reported.
•
Antidepressant pharmacotherapy has been associated with natural killer cell number or activity.
•
Natural killer cells play an important in improving the depressive symptoms responding to SSRIs.

Abstract

Background

An association between depression and altered immunity has been suggested by many studies, although the findings are not fully consistent. The present investigation examined the effects of escitalopram on cellular immunity in patients with major depressive disorder (MDD).

Methods

Fifty-one patients with MDD were evaluated with the Hamilton Rating Scale for Depression and Montgomery–Åsberg Depression Rating Scale. The patients were grouped into responders (n = 32) and non-responders (n = 19). Adrenocorticotropic hormone, cortisol, CD4, CD8, CD19, and natural killer cells were measured at baseline and after a 4 week treatment with escitalopram. Plasma hormones and immune parameters were compared between groups.

Results

Responders showed increased activity, but not number, of natural killer cells after a 4 week treatment with escitalopram. There were no differences in plasma hormones and other immune parameters between groups, even though cortisol was decreased and CD19 was increased across both groups compared to baseline.

Conclusions

The results suggest that natural killer cells play an important role in improving the symptoms of depressive patients responding to selective serotonin inhibitors. To deepen our understanding of the pathogenesis of depression, interactions between serotonin and the immune system should be further explored.

 

[pattismith]

this 2018 study found that serotonine uptake inhibitors were effective to increase NK activity in Depression.

They also found "Severe depression was associated with lower CD8-positive cells in a large-scale meta-analysis among medically healthy persons, and as severity of depression may decrease after medication, CD4/CD8 ratio is correlated with the severity of depression [9, 28]. "

"From the results, we carefully suggest that NKCActivity could be the possibility of being a diagnostic biomarker of anxiety-dominant depression subtype.
CD+8 may also be an objective indicator of the severity and change of depression. "

"Subjects were treated with escitalopram (N = 27; mean daily dose, 12.8 mg; range, 5–20 mg/day),
paroxetine (N = 12; mean daily dose, 50 mg; range, 25–50 mg/day),
and sertraline (N = 10; mean daily dose, 75 mg; range, 50–100 mg/day). "

 

[Wishful]

Depression is one of the most frequently diagnosed condition in psychiatry.

Translation: "This is the most profitable diagnosis, and no one can disprove the diagnosis."

 

[YippeeKi YOW !!]

Translation: "This is the most profitable diagnosis, and no one can disprove the diagnosis."

 

[pattismith]

Circulating T lymphocyte subsets, cytokines, and immune checkpoint inhibitors in patients with bipolar II or major depression: a preliminary study 2017

WeiWu1, Ya-li Zheng2,3, Li-pingTian2,4, Jian-bo Lai5,6, Chan-chan Hu5,6, Peng Zhang2,3, Jing-kaiChen5,6, Jian-bo Hu5,6, Man-li Huang5,6, NingWei5,6, Wei-juanXu5,6, Wei-huaZhou5,6, Shao-jia Lu5,6, Jing Lu5,6, Hong-liQi5,6, Dan-danWang5,6, Xiao-yiZhou5,6, Jin-feng Duan5,6, YiXu5,6,* & Shao-hua Hu5,6,*

This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD).

A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited.

The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated.

The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected.

In results, blood proportion of cytotoxic T cells significantly decreased in BD patients than in either MD patients or HCs.

The plasma level of IL-6 increased in patients with BD and MD.

The expression of TIM-3 on cytotoxic T cells significantly increased, whereas the expression of PD-L2 on monocytes significantly decreased in patients with BD than in HCs.

These findings extended our knowledge of the immune dysfunction in patients with affective disorders.

 

[pattismith]

After a short trial with low dose Escitalopram and a short one with methylphenidate, I had improvement in my CD8 count, but never improved my CD4/CD8 ratio which is always changing for the higher. It is currently 5.28...

Each time I manage to increase my CD8 count, my CD4 count gets much higher and my ratio stays stuck at the top, like if it was genetically programmed....

 

[lenora]

Hi @pattismith ....I find that the older I get, the more the body changes. Some things go and others replace them, or just stay the same. Our bodies are so individuals to each of us.

One of the reasons why finding a "cure" for this isn't simple and will require more than the discovery of one thing. It's complicated b/c the body itself is complicated. I wish you well in the years ahead. Yours, Lenora.

 

[pattismith]

It's important to read this article and to understand that too much serotonin in the brain can produce neuroinflammation. This might be the cause for SSRI induced apathy!

Frontiers | The Effects of Serotonin in Immune Cells (frontiersin.org) 2017

In contrast, involving other receptors, we found in 2005 that serotonin modulated the release of the following cytokines in LPS-stimulated human blood monocytes: IL-1β, IL-6, IL-8/CXCL8, IL-12p40, and TNF-α (23). Serotonin had no effect on the production of IL-18 and IFN-γ in our studies.
The upregulation of IL-1β, IL-6, and IL-8/CXCL8 secretion was 5-HT3 receptor mediated.
Activation of the 5-HT4 and 5-HT7 receptors increased the LPS-induced release of IL-1β, IL-6, IL-8/CXCL8, and IL-12p40, while, on the contrary, it inhibited LPS-induced TNF-α release.

Microglia

Krabbe et al. found mRNA expression of 5-HT2A, 5-HT2B, 5-HT3B 5-HT5A, and 5-HT7 in brain microglia (58).
They described that serotonin promoted the microglial injury-induced motility by serotonin receptor activation. I
n 2015, Maroteaux et al. found that the 5-HT2B receptor subtype is expressed on brain resident macrophages (microglia) and is involved in brain maturation (59).
In amyotrophic lateral sclerosis, a disease associated with neuroinflammation, the upregulation of the 5-HT2B receptor was associated with slowed disease progression by less and slower degeneration of mononuclear phagocytes (60).

Dendritic Cells

Dendritic cells express several functional 5-HT receptor subtypes that are expressed in different amounts in the different stages of maturation (61).

Idzko and colleagues found in 2004 that stimulation of 5-HT3, 5-HT4, and 5-HT7 receptor subtypes mediated the release of IL-1β and IL-8 (61).

Dendritic cells are able to take up serotonin released from activated T-cells (which synthesize serotonin) and the microenvironment via the SERT and store it in LAMP-1+ vesicles and subsequently release it via Ca2+ sensitive exocytosis to promote T-cell proliferation and differentiation of naive T-cells (62). In 2009, Müller et al. described that serotonin induces oriented migration of immature dendritic cells via the activation of the 5-HT1 and 5-HT2 receptor subtypes.

They also found that via the binding to 5-HT3, 5-HT4, and 5-HT7 receptors serotonin upregulates the production of IL-6 (31).

 

[Wishful]

That serotonin might increase neuroinflammation is an interesting theory, and I could conclude that is why TRP worsened my ME symptoms, except that 5-HTP, which skips a step in the production of serotonin, did not affect my symptoms, so that's actually counterevidence to the theory.

Simple test: does supplemental 5-HTP affect the severity of anyone else's ME symptoms?

 

[L'engle]

Simple test: does supplemental 5-HTP affect the severity of anyone else's ME symptoms?

I used it for a while during a period of disrupted sleep. Just made me tired mostly so I don't tkae it under normal circumstances. It did seem to help the temporary insomnia though not the basic cause of it (which was something else).

 

[pattismith]

That serotonin might increase neuroinflammation is an interesting theory,

Serotonin has both inflammatory and antiinflammatory effects if you read the articles I quoted.

For example serotonin has anti TNF alpha effect!

Otherwise stimulation of 5HT3 5HT4 and 5HT7 may increase neuroinflammation.

Here an interesting atypical antidepressant with both proserotonin and antiserotonin effects, Vortioxetine:

A Focus on Vortioxetine - Mechanism of Action and Efficacy (psychscenehub.com)

 

[Wishful]

Serotonin has both inflammatory and antiinflammatory effects if you read the articles I quoted.

Theories about "could maybe possibly have an effect" are common. My point was that my observations of the effects of 5-HTP (which would increase serotonin) didn't support the theory. I don't recall any other threads about observations of serotonin levels having a reliable effect on ME, which indicates a lack of support for the theory.

For any easy-to-test (serotonin is easy to modulate) theory, a quick "does it match reality" check should be done before getting to excited about it.

 

[cheeseater]

A good rundown on serotonin overdose... Serotonin syndrome. You can actually achieve it without taking SSRI's, but SSRI's make it infinitely easier to get there. Good for a scare or three: https://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/symptoms-causes/syc-20354758

 

[percyval577]

That serotonin might increase neuroinflammation is an interesting theory, and I could conclude that is why TRP worsened my ME symptoms, except that 5-HTP, which skips a step in the production of serotonin, did not affect my symptoms, so that's actually counterevidence to the theory.

Simple test: does supplemental 5-HTP affect the severity of anyone else's ME symptoms?

If I remember rightly, SER does not cross the brain bloood barrier.

This is the reason, why medicin prescribes SER reuptake inhibitors.

 

[Wishful]

If I remember rightly, SER does not cross the brain bloood barrier.

5-HTP does cross the BBB, so it should increase SER in the brain. If the 5-HTP->SER mechanism isn't working even with excess 5-HTP, I think there would be fairly severe problems (more than ME symptoms).