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Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroend

Kati

Patient in training
Messages
5,497
Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model.
Milrad SF1, Hall DL2, Jutagir DR1, Lattie EG3, Czaja SJ4, Perdomo DM4, Fletcher MA5, Klimas N5, Antoni MH6.
Author information
1Department of Psychology, University of Miami, United States.
2Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, United States.
3Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, United States.
4Department of Psychiatry and Behavioral Sciences, University of Miami, United States.
5Institute for Neuro Immune Medicine, Nova Southeastern University, United States.
6Department of Psychology, University of Miami, United States. Electronic address: mantoni@miami.edu.

Abstract

INTRODUCTION:
Chronic Fatigue Syndrome (CFS) is a poorly understood illness that is characterized by diverse somatic symptoms, hypothalamic pituitary adrenal (HPA) axis dysfunction and heightened inflammatory indicators. These symptoms are often exacerbated and accompanied by psychological distress states and depression. Since depression is known to be associated with HPA axis dysfunction and greater inflammation, a psychoneuroendocrinological (PNE) model of inflammation was examined in persons diagnosed with CFS in order to uncover underlying biopsychosocial mechanisms in this poorly understood chronic illness.

METHODS:
Baseline data were drawn from two randomized controlled trials testing the efficacy of different forms of psychosocial intervention, and included psychological questionnaires, di-urnal salivary cortisol, and blood samples. Data were analyzed with structural equation modeling (SEM).

RESULTS:
The sample (N=242) was mostly middle-aged (Mage=49.36±10.9, range=20-73years), Caucasian (70.1%), female (84.6%), highly educated (88.6% completed some college, college, or graduate program), and depressed (CES-D M=23.87±12.02, range 2-57). The SEM supporting a psychoneuroendocrinological model of immune dysregulation in CFS fit the data χ2 (12)=17.725, p=0.1243, RMSEA=0.043, CFI=0.935, SRMR=0.036. Depression was directly related to evening salivary cortisol and inflammation, such that higher evening cortisol predicted greater depressive symptoms (β=0.215, p<0.01) and higher pro-inflammatory cytokines (interleukin-2 [IL-2], IL-6, and tumor necrosis factor-alpha [TNF-α] levels (β=0.185, p<0.05), when controlling for covariates.

DISCUSSION:
Results highlight the role of depression, cortisol and inflammation in possible biological mechanisms involved in the pathophysiology of CFS. Time-lagged, longitudinal analyses are needed to fully explore these relationships.

https://www.ncbi.nlm.nih.gov/pubmed/28918107
 

ivorin

Senior Member
Messages
152
Hmm, let's take this person, turn her over and wonder why their head looks more like a vagina than a head. Talk about a non-biased sample...
 

Paralee

Senior Member
Messages
571
Location
USA
Hmm, let's take this person, turn her over and wonder why their head looks more like a vagina than a head. Talk about a non-biased sample...

Seriously, do we need to compare everything to women's private parts? Unless somehow that was part of the study....in that case I apologize.
 

ukxmrv

Senior Member
Messages
4,413
Location
London
So they took a bunch of depressed people and highlighted the role that depression played. :whistle:

But ones with higher cortisol at night which is against the normal expectations of what happens in depression

I'll have to read the whole paper though to see if I am on the right track
 

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
Salivary cortisol is influenced by a variety of factors including diurnal rhythm and activity levels that are often different between patients and controls. It looks like this study didn't find anything particularly noteworthy.

I've said it before, and I'll say it again, this is why measuring just salivary cortisol and nothing else (or just cortisol and a bunch of cytokines that probably aren't related to this disease) and a bunch of questionnaires isn't terribly useful.
 
Messages
3,263
This is a bit confused. If you want to study things like ‘depression’ you first of all have to know what the construct means, and then understand how your chosen scale actually goes about measuring that construct. They are SO not the same thing.

Then you need to consider whether the scale you’re using is appropriate for the population you’re studying. Many depression scales can produce misleading results if you give them to people suffering from a chronic illness.

Just look at some of the questions in the 20-question CESD-R (I assume the CESD is similar in content)

Two questions asking about fatigue (yes!)
“I was tired all the time”
“I could not get going”

Two questions about concentration (no kidding!):
"I could not focus on important things"
"I had trouble keeping my mind on what I was doing"

Two questions about appetite:
"My appetite was poor"
"I lost a lot of weight without trying to"

Two questions about sleep:
"My sleep was restless"
"I had a lot of trouble getting to sleep"

Other items that might give erroneous results in ME patients:
"I felt fidgety"
"I lost interest in my usual activities"
"I felt like I was moving too slowly"

That accounts for more than 50% of the items.

So you can see that its quite likely that all those various cortisol and cytokine measures will be associated with higher scores on this scale. Its going to correlate with CFS severity massively, for purely artifactual reasons.

We're got ourselves in such an incredible mess with the concept of depression, so that we are measuring all sorts of things we never intended to be part of the original construct. So now we're in this mess where suddenly depression seems to look the same as inflammation.
 

Hip

Senior Member
Messages
17,820
The CES-D questionnaire used in the study is found here. Out of its 20 questions, I can only see 3 that enter the territory of ME/CFS symptoms, which are:

5. I had trouble keeping my mind on what I was doing.

7. I felt that everything I did was an effort.

20. I could not get “going.”

Question 20 I don't think is about fatigue; I think it's more about motivation, which can be poor in depression, but I guess this question could me misconstrued as "I don't have the energy to do anything".



Question 11 about sleep I don't necessarily think applies to ME/CFS:

11. My sleep was restless.

The main sleep issues in ME/CFS are unrefreshing sleep, circadian rhythm disruptions, and sometimes insomnia. Those are different to restless sleep.
 

Hip

Senior Member
Messages
17,820
I cannot get hold of the full paper, but it would be interesting to see what percentage of ME/CFS patients this study found were depressed, and how that correlates to a poll on this forum which found around 37% of ME/CFS patients suffer from depression.
 
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3,263
The CES-D questionnaire used in the study is found here. Out of its 20 questions, I can only see 3 that enter the territory of ME/CFS symptoms, which are:
Well found. Yes, I see there are slightly fewer of the worrying items on the CES-D than on the CESD-R. In fact, the whole scale is much better, with much more of an emphasis on mood, and less on behaviour. And its true they did use the CES-D not the CESD-R.

There are still quite a few though. So there's the ones you mention:
- I had trouble keeping my mind on what I was doing.
- I felt that everything I did was an effort.
- I could not get “going.”

But also:
- I did not feel like eating; my appetite was poor (common in the severely ill)
- I talked less than usual (could have been a bad ME period).

I would also argue that many of us would respond yes to this, depressed tor no:
- My sleep was restless.

The paper doesn't give the rates of people that meet the test cutoff for depression, but by the looks of the mean and the standard deviation, I'd estimate its well over 50%.

These scales are okay as a sort of screening, but if you want to ask meaningful questions about whether cytokines/cortisol levels affects mood and affect, then you need an measure that is a pure measure of mood and affect, and isn't contaminated by all the other things that get mixed up in measures of depression.
 
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Hip

Senior Member
Messages
17,820
But also:
- I did not feel like eating; my appetite was poor (common in the severely ill)
- I talked less than usual (could have been a bad ME period).

I did see those, and wondered about them, and consulted the CCC. The CC talks of "anorexia or abnormal appetite" in ME/CFS; but on these forums, it's rare to hear discussions about poor appetite, which suggests that this is not common in ME/CFS.

And yes, sometimes (especially during PEM), ME/CFS patients find it hard to talk, they find it hard to muster up sentences (this is a symptom I experience now and then), but I am not sure how common it is.



In some ways it is unfortunate that psychology has to rely on questionnaires. It would be better if people had the ability to accurately sense and articulate their own mental states.

But I think the trouble is that lots of people are a bit low on empathy, and empathy is linked to self-awareness (empathy allows you to more deeply "enter into" other's minds, but also allows you to enter into your own mind). Self-awareness is sometimes described as the "inner eye" we have in our own mind; but if self-awareness is a bit weak, you are not going to able to report very well on your own mind.
 

greeneagledown

Senior Member
Messages
213
I don't think it's possible right now to study depression and CFS simultaneously in the same subjects, since we don't have any objective diagnostic tests for CFS. If someone has significant depression, how do we know they even have CFS, since major depression can cause severe fatigue? This is why the best studies on CFS specifically exclude depressed patients at the outset. I guess maybe you could get around this by only selecting patients whose CFS started well before their depression, but that is still tricky and I doubt they did that in this study.
 

Hip

Senior Member
Messages
17,820
If someone has significant depression, how do we know they even have CFS, since major depression can cause severe fatigue?

ME/CFS is a lot more than just fatigue, and I don't think any purely depressed patient would satisfy the CCC.

In fact the CCC contains a paragraph which indicates how to distinguish ME/CFS from depression:
Depression: Reactions to exercise (see chart on page 4) are helpful in distinguishing ME/CFS from depression.

ME/CFS patients have symptoms such as joint and muscle pain, severe headaches, recurrent sore throats and upper respiratory infections, tender lymph nodes, cardiopulmonary symptoms, COI, tachycardia, and a cluster of cognitive impairments, which are not commonly seen in depression.

Some ME/CFS patients may suffer from reactive depression due to their pathophysiological impairments and reduced quality of life, but many objective indices can differentiate ME/CFS from primary depression.



I have had experience of both pure major depression on its own (this occurred decades ago, due to unfortunate life events), and the neurologically-caused depression that can appear in ME/CFS (which for me is not present all the time, but comes and goes, and this coming and going helps me distinguish it from my ever-constant ME/CFS).

The interesting thing was that during this period of pure major depression decades ago, I found that exercise was pretty helpful in mitigating the low mood, and in fact I started running every day during that period, because of the antidepressant mood-boosting effects of exercise. Exercise is known to help depression.

However, in ME/CFS, exercise will often make you feel worse, due to the PEM effects. And even if you are someone like me that does not suffer much from physical PEM (I can run a mile without too much difficultly), since getting ME/CFS, I noticed that the normal antidepressant mood-boosting effects of exercise are almost completely absent.

Indeed, I have read that ME/CFS is characterized by the loss of the antidepressant effects of exercise (this might be to do with the endorphin abnormalities in ME/CFS, since "runner's high" is thought might be due to endorphin release). So I can no longer use exercise to treat my ME/CFS-associated depression.
 
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ukxmrv

Senior Member
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4,413
Location
London
I don't think it's possible right now to study depression and CFS simultaneously in the same subjects, since we don't have any objective diagnostic tests for CFS. If someone has significant depression, how do we know they even have CFS, since major depression can cause severe fatigue? This is why the best studies on CFS specifically exclude depressed patients at the outset. I guess maybe you could get around this by only selecting patients whose CFS started well before their depression, but that is still tricky and I doubt they did that in this study.

This goes both ways as we have no test for depression either.

I'm not read the paper so no idea how they were sure their subjects had depression
 
Messages
3,263
but if self-awareness is a bit weak, you are not going to able to report very well on your own mind.
Perhaps. But depression, at its core, is about feelings (and to a lesser extent, thoughts). If you don't have the feelings that define depression, then you don't have depression. You have something else.

It has been argued that there are people out there who don't recognise when they're experiencing a negative feeling, or can't correctly label it. So in these cases, it may be possible to indirectly identify their feelings though their behaviour. The first claim may or may not be true. But the second claim is very problematic, especially for those of us who show the so-called 'depression' behaviours for other good reasons.

I think, if you diagnose a psychological disorder that is characterised by low mood/numbness/loss of pleasure in usual things then you need to be able to show that the person has those characteristics. You can't show that through sleep practices and concentration levels.
 
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