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“Dysregulated Relationship of Inflammation and Oxidative Stress in Major Depression”

Dolphin

Senior Member
Messages
17,567
Although I don't necessarily like ME/CFS to be associated with Major Depression, I thought I'd highlight this as Twisk/Maes has highlighted some similar types of findings in Major Depression and ME/CFS before.


“Dysregulated Relationship of Inflammation and Oxidative Stress in Major Depression”

Brain, Behavior, and Immunity

Available online 29 November 2012

B. Rawdina,
S.H. Mellonb,
F.S. Dhabharc, d,
E.S. Epela,
E. Putermana,
Y. Sue,
H.M. Burkea,
V.I. Reusa,
R. Rossera,
S.P. Hamiltona,
J.C. Nelsona,
O.M. Wolkowitza, ,

a Department of Psychiatry, University of California, San Francisco, San Francisco, CA
b Department of Obstetrics & Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA
c Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA
d Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA
e SilverCreek Technologies, Gilbert, AZ

Corresponding author. 401 Parnassus Ave., San Francisco, CA, 94143-0984, USA, Tel.: +1 451 476 7433; fax: +1 415 502 2661.Available online 29 November 2012

http://dx.doi.org/10.1016/j.bbi.2012.11.011, How to Cite or Link Using DOI


________________________________

Abstract*

Chronic inflammation and oxidative stress have been implicated in the pathophysiology of Major Depressive Disorder (MDD), as well as in a number of chronic medical conditions.

The aim of this study was to examine the relationship between peripheral inflammatory and oxidative stress markers in un-medicated subjects with MDD compared to non-depressed healthy controls and compared to subjects with MDD after antidepressant treatment.

We examined the relationships between IL-6, IL-10, and the IL-6/ IL-10 inflammatory ratio vs. F2-isoprostanes (F2-IsoP), a marker of oxidative stress, in un-medicated MDD patients (n=20) before and after eights weeks of open-label sertraline treatment (n=17), compared to healthy non-depressed controls (n=20).

Among the un-medicated MDD subjects, F2-IsoP concentrations were positively correlated with IL-6 concentrations (p< 0.05) and were negatively correlated with IL-10 concentrations (p< 0.01).
Accordingly, F2-IsoP concentrations were positively correlated with the ratio of IL-6/ IL-10 (p< 0.01). In contrast, in the control group, there were no significant correlations between F2-IsoPs and either cytokine or their ratio.

After MDD subjects were treated with sertraline for 8 weeks, F2-IsoPs were no longer significantly correlated with IL-6, IL-10 or the IL-6/ IL-10 ratio.

These data suggest oxidative stress and inflammatory processes are positively associated in untreated MDD.

Our findings are consistent with the hypothesis that the homeostatic buffering mechanisms regulating oxidation and inflammation in healthy individuals become dysregulated in untreated MDD, and may be improved with antidepressant treatment.

These findings may help explain the increased risk of comorbid medical illnesses in MDD.

Keywords

Inflammation;
Oxidation;
Oxidative stress;
IL-6;
IL-10;
F2-isoprostane;
Depression;
Sertraline


*I gave each sentence its own paragraph
 

WillowJ

คภภเє ɠรค๓թєl
Messages
4,940
Location
WA, USA
oxidative stress and inflammation is overlap with lots and lots of diseases, not just ME/CFS and MDD.

However, this can explain why there is some amount of symptom overlap and an MDD patient can fulfill Fukuda criteria if the MDD dx is missed.

Also like Twisk and Maes said, gives a physiological explanation for why people with chronic illness may be depressed.

Another paper like this is:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487348/
Grenon et al. Association Between Depression and Peripheral Artery Disease: Insights From the Heart and Soul Study. J Am Heart Assoc. 2012 August; 1(4): e002667.
Prevalent PAD was reported by 12% (24/199) of patients with depressive symptoms and 7% (60/825) of participants without depressive symptoms (base model adjusted for age and sex: odds ratio 1.79, 95% confidence interval [CI] 1.06–3.04, P=0.03).

This association remained strong after adjustment for individual clusters, including comorbid conditions, PAD risk factors, inflammation, and health behaviors. However, it was no longer significant after adjustment for all mediators together (Table 3; full model: odds ratio 1.59, 95% CI 0.90–2.83, P=0.11; refer to Table 4 for full model details).

A paper which discusses an overall model of inflammation and depression (in chronic illness and, iirc, primary depression) is:
From inflammation to sickness and depression: when the immune system subjugates the brain
Nat Rev Neurosci. Author manuscript; available in PMC 2010 August 10.
Published in final edited form as:
Nat Rev Neurosci. 2008 January; 9(1): 46–56.
doi: 10.1038/nrn2297
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Oxidative stress occurs due to many issues. One of those is a failure of antioxidant mechanisms. Those failures involving methylation related pathways may lead to a decline in tetrahydrobiopterin, which in turn will induce a decline in neurotransmitter syntheses. It may turn out that 99% of mental disorders are basically non-mental biochemisty. Biopsychiatry might be heading in the right direction. There is increasing evidence that psychopsychiatry is headed in the wrong direction.
 
Messages
445
Location
Georgia
alex3619
Very astute observation. Psychiatric medicine is moving radically away from the serotonin principle to other explanations for mental illnesses (or conditions) such as major depression. And inflammation, or oxidative stress, I've heard is very high on the list of areas of current interest. Some doctors are successfully treating depression with Tramadol.

I have noticed that a considerable number of ME/CFS patients have parents or siblings with major depression, bipolar and so on. My father and sister both had serious depression. I think this tight relationship has lead rather obtuse doctors and researchers (ahem, Wessley) to think we are just depressed. Because we have a family connection. Might there be a genetic susceptibility that can be treated? I'm optimistic.
 

AFCFS

Senior Member
Messages
312
Location
NC
Have had depression throughout parts of my life. Pdoc was first to suggest CFS to me, but then still wanted to treat it with an SSRI.
 
Messages
445
Location
Georgia
Have had depression throughout parts of my life. Pdoc was first to suggest CFS to me, but then still wanted to treat it with an SSRI.

My father swears Prozac worked for him. I don't tell him any different. Don't quarrel with success.

Did it help you?
 

jimells

Senior Member
Messages
2,009
Location
northern Maine
I wish I could understand the abstract. Of the people who received treatment, did their MDD improve? What happened to the levels of cytokines and F2-IsoPs? Are they suggesting that the sertraline directly affected cytokines and/or F2-IsoPs, or that sertraline 'fixed' the MDD, and the improved brain function somehow changed the levels of cytokines and F2-IsoPs?

I suspect they simple assume that sertraline is effective, which is apparently a leap of faith.

Perhaps I could answer my questions by actually studying the detail, but I don't have the strength to do that today.
 

AFCFS

Senior Member
Messages
312
Location
NC
My father swears Prozac worked for him. I don't tell him any different. Don't quarrel with success.

Did it help you?
Yep, it worked pretty good for years (at least that I could tell, coming off of it always shows a bit of a contrast to not being on it that often allows a better take on how it was acting) - but the really only effective anti-depressant I had tried. In time had started to notice some cognitive clouding, memory issues, some restless leg syndrome, some anxiety, perhaps some other issues on it. Other SSRIs have not worked at all, and have had terrible side effects from the getco. One thing I liked about Prozac was that when stopping it, the half-life generally seemed sufficient to ween off of it. I understand some people have hellish experiences coming off SSRIs. If it works, it works.
 
Messages
445
Location
Georgia
Yep, it worked pretty good for years (at least that I could tell, coming off of it always shows a bit of a contrast to not being on it that often allows a better take on how it was acting) .

I've listened to psychiatric conferences on Doctor Radio, on Sirius XM, and very esteemed physicians do say a percentage of patients do have serotonin problems, and have positive results with Prozac. You were obviously one of them.
 

AFCFS

Senior Member
Messages
312
Location
NC
I wish I could understand the abstract. Of the people who received treatment, did their MDD improve? What happened to the levels of cytokines and F2-IsoPs? Are they suggesting that the sertraline directly affected cytokines and/or F2-IsoPs, or that sertraline 'fixed' the MDD, and the improved brain function somehow changed the levels of cytokines and F2-IsoPs?

I suspect they simple assume that sertraline is effective, which is apparently a leap of faith.

Perhaps I could answer my questions by actually studying the detail, but I don't have the strength to do that today.
Well, it is a bit ambiguous, especially form just having the abstract. But they are not making any direct claims that sertraline is effective for MDD, just that it may break the correlation between a marker of oxidative stress and inflammatory test results. That they then broaden there conclusion:
Our findings are consistent with the hypothesis that the homeostatic buffering mechanisms regulating oxidation and inflammation in healthy individuals become dysregulated in untreated MDD, and may be improved with antidepressant treatment.
seems a bit loose, as "antidepressant treatment" includes many meds and med types besides sertraline.
 

AFCFS

Senior Member
Messages
312
Location
NC
I've listened to psychiatric conferences on Doctor Radio, on Sirius XM, and very esteemed physicians do say a percentage of patients do have serotonin problems, and have positive results with Prozac. You were obviously one of them.

Also in line with the OP, is this:

Fluoxetine affords robust neuroprotection in the postischemic brain via its anti-inflammatory effect.
Lim CM, Kim SW, Park JY, Kim C, Yoon SH, Lee JK.
Source

Department of Anatomy, Inha University School of Medicine, Inchon, Korea.
Abstract

Fluoxetine is a selective serotonin reuptake inhibitor that is widely used in the treatment of major depression including after stroke. In this study, we tested whether fluoxetine protects neuronal death in a rat cerebral ischemia model of middle cerebral artery occlusion (MCAO). The administration of fluoxetine intravenously (10 mg/kg) at 30 min, 3 hr, or 6 hr after MCAO reduced infarct volumes to 21.2+/-6.7%, 14.5+/-3.0%, and 22.8+/-2.9%, respectively, of that of the untreated control. Moreover, the neuroprotective effect of fluoxetine was evident when it was administered as late as 9 hr after MCAO/reperfusion. These neuroprotective effects were accompanied by improvement of motor impairment and neurological deficits. The fluoxetine-treated brain was found to show marked repressions of microglia activation, neutrophil infiltration, and proinflammatory marker expressions. Moreover, fluoxetine suppressed NF-kappaB activity dose-dependently in the postischemic brain and also in lipopolysaccharide-treated primary microglia and neutrophil cultures, suggesting that NF-kappaB activity inhibition explains in part its anti-inflammatory effect. These results demonstrate that curative treatment of fluoxetine affords strong protection against delayed cerebral ischemic injury, and that these neuroprotective effects might be associated with its anti-inflammatory effects.
On the other hand, there is also ample research and backlash against Prozac and SSRIs in general.