Poll on depression and interferon-gamma

[sianrecovery]

I did a year on interferon alpha/ribavirin for Hep C. It's a regime that packs a hefty pyschological punch as well as physiological. Hence sucide being listed as one of its 'severe' side-effects. They used to prescribe anti-depressants with it. I didn't take them. Without doubt, interferon alpha can induce depression - my experience of it was that the dark thoughts and low mood magically wore off as each dose did. This was in 1998, prior to the once a week shots.

 

[Richie]

I did a year on interferon alpha/ribavirin for Hep C. It's a regime that packs a hefty pyschological punch as well as physiological. Hence sucide being listed as one of its 'severe' side-effects. They used to prescribe anti-depressants with it. I didn't take them. Without doubt, interferon alpha can induce depression - my experience of it was that the dark thoughts and low mood magically wore off as each dose did. This was in 1998, prior to the once a week shots.

Exactly why I say some mechanisms e.g. interferon gamma elevation may be connected to both ME and depressive symptoms in a given individual, WITHOUT equating ME and depression.
Fork in the road stuff.
Infection produces elevated IF gamma, produces depression down one fork, ME down another. Some go one way, others go the other , some do a bit of both.
On this basis it is possible to conceive of ME and depression having no symptomatic overlap, no common biolgy and still concede that in agiven individual there may be a common root cause of both, which for that individual could be clinically very useful.

 

[Valentijn]

On this basis it is possible to conceive of ME and depression having no symptomatic overlap, no common biolgy and still concede that in agiven individual there may be a common root cause of both, which for that individual could be clinically very useful.

But the same could be said of literally any other disease. It seems like a rather pointless exercise to speculate on how two diseases with little symptom overlap or treatment overlap might somehow be similar.

It's like saying that two diseases have a shared origin because both occur in the human body. It's so broad and vague that it's completely useless.

 

[Richie]

Valentij

But the same could be said of literally any other disease. It seems like a rather pointless exercise to speculate on how two diseases with little symptom overlap or treatment overlap might somehow be similar.

It's like saying that two diseases have a shared origin because both occur in the human body. It's so broad and vague that it's completely useless.

If there is a common root but divergent pathways, seek out and get rid of the common root. Surely that makes sense. Presented with a Lyme patient the doc who knows Lyme could be behind FM or CFS/ME type symptoms and depression, is better equipped not to come out with the "you're just a somatising depressive" line.

It is imo empowering to ME patients, especially on first encounter with a medic, to know depression may arise from e.g. immune activation, so that they do not get pushed down the "you're just depressed" track. I know this from bitter experience, even though most of my depression was for years circumstantial.

Since there is an open debate as to whether we/how many of us have an onging infection and ongoing infection can cause both mental and physical symptoms, I see sense in considering this issue. If you don't then fair enough, though I find your position hardline and unusual given my Lyme example.

In practice there is an overlap. or else we would not be complaining that Oxford catches a lot of primary depressives. if there were no overlap there would be no basis for confusion and hence no need for more specific criteria, such as CC/ICC. The source of this overlap is also of legitimate interest e.g. why are some depressives tired, but with due diligence to ensure correct grouping. This is how 2 day delayed PEM was identified in the first place by checking ME/CFS against e.g. sarcoidosis.That does broaden out into questions of the usefulness of studying fatigue across a number of illnesses in further research, and I accept that many in the ME community are against this, and I have some sympathy with that position. But it does also help in elucidating what may be special about ME.

I checked out one of the 2 day PEM. trial and as far as I understood, 50% of the CFS/ME cohort did not display the 2 day PEM.

Anyway, you know depression is not ME, as I do. We both have long term experience of symptoms which do not fit depression but do fit ME, we both want proper physical investigation and treatment, so let's hope that things will go better for all of us.

This is difficult stuff for many of us, I understand and I certainly do not want to encourage any ME/CFS= depression equation.

 

[sianrecovery]

If many of us live with elevated cytokines or other abnormal immune responses, it's not meaninglessly broad to speculate how the biochemistry of ME itself may produce depressive symptoms surely? Why should a phenomenon be excluded from discussion because it has a psychological aspect to its presentation?
My point about the interferon alpha/ribavirin regime was that the suicidal ideation etc was so clearly a product of the medication. I have not experienced depression in another context. But the morning after the shot, I'd wake up, and there the destructive thoughts would be. I knew they would, the prescriber had warned me, so I would ignore them, get up, have a cup of tea. I normalised them because I knew they would be transient, and they had a context. Knowledge really is power.

 

[sianrecovery]

The other thought that occurs to me here is of my friends with ME who have killed themselves. Obviously the grinding awfulness of a disease that your health care professional thinks is a neurotic symptom takes it toll, but what if an underlying symptomology was elucidated and they'd been told, like I was on interferon - be watchful, this may happen, and if it does, you may need assistance to cope with it...would it have helped?

 

[Mary]

@MeSci - My sister-in-law took interferon for a year for Hep C from a blood transfusion. (She really hit the jackpot - first leukemia and blood transfusions, and she did go into remission from the leukemia, then some ten years later hepatitis C from the transfusions.)

Anyways, she took interferon for a year, it made her very depressed as she was told it probably would, they put her on ADs and she's been told she has to take them for the rest of her life because the interferon destroyed something in her system - I was going to say serotonin receptors, or maybe her body no longer makes serotonin, something like that. So yes - there's a definite connection between interferon and depression as sianrecovery said.

 

[MeSci]

@MeSci - My sister-in-law took interferon for a year for Hep C from a blood transfusion. (She really hit the jackpot - first leukemia and blood transfusions, and she did go into remission from the leukemia, then some ten years later hepatitis C from the transfusions.)

Anyways, she took interferon for a year, it made her very depressed as she was told it probably would, they put her on ADs and she's been told she has to take them for the rest of her life because the interferon destroyed something in her system - I was going to say serotonin receptors, or maybe her body no longer makes serotonin, something like that. So yes - there's a definite connection between interferon and depression as sianrecovery said.

I've never heard of interferons stopping serotonin production permanently. I wonder if your sister-in-law should get a second opinion?

You may find this thread about interferon-induced depression interesting.

 

[Mary]

@MeSci - I think we've gone full circle! I think you and I had a discussion about BCAAs relieving fatigue, and somehow this related to 5-HT (not 5-htp) and tryptophan.

In the thread you linked above, you state:

This abstract :

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816380/?report=classic

....
That also says :

“In animal experiments, treatment with Peony root (Paeonia lactiflora Pall.) inhibits 5-HT synthesis and tryptophan hydroxylase expression, which may reduce fatigue, both during exercise and the resting state (24).”

This seems inconsistent with associations between depression and fatigue. Why would reducing 5-HT synthesis reduce fatigue? Maybe an example of the unreliability of animal ‘models’.

This article which I've linked on my other post about BCAAs talks about inhibiting 5-HT and trypophan, which can reduce fatigue: http://jn.nutrition.org/content/136/2/544S.full

I don't think it has to do with the unreliability of animal models.

And here's a quote from another article: http://www.sportsci.org/jour/9901/rbk.html

Collectively, the decline in plasma BCAAs and increase in free tryptophan during prolonged endurance exercise alters the ratio of free tryptophan to BCAAs and increases the entry of tryptophan into the brain (Newsholme et al., 1991). An increased concentration of tryptophan in the brain promotes the formation of the neurotransmitter 5-hydroxytryptamine (5-HT). 5-HThas been shown to induce sleep, depress motor neuron excitability, influence autonomic and endocrine function, and suppress appetite in animal and human studies. An exercise-induced imbalance in the ratio of free tryptophan to BCAAs has been implicated as a possible cause of acute physiological and psychological fatigue (central fatigue).It has also been hypothesized that chronic elevations in 5-HTconcentration, which may occur in athletes maintaining high-volume training, explains some of the reported signs and symptoms of the overtraining syndrome: postural hypotension, anemia, amenorrhea, immunosuppression, appetite suppression, weight loss, depression, and decreased performance (Newsholme et al.,1991; Gastmann and Lehmann, 1998;Kreider, 1998).

I don't know how this does or does not link to interferon, and I don't want to spend the energy to understand it. But just wanted to point out that I'd come across the same concept of inhibiting 5-HT and trypophan to reduce central fatigue, which I think is PEM, and which BCAAs are helping me with a great deal.

 

[energyoverload]

If peripheral production of IFN-y were affecting tryptophan degradation, for example principally in dendritic cells, then although kynurenine is produced and trp is lowered in some PBMC's, this may increase kynurenine:tryptophan ratio in plasma, but this may not necessarily be enough to deplete e.g. hippocampal tryptophan and thus serotonin. Further localised glial activation may be required in specific brain regions to cause symptoms of any particular neurological disease, through furthering conversion of kynurenine to quinolinic acid, which effectively increases synaptic glutamate - highly linked to depression. Next generation antidepressants modulate NMDA-R.

 

[MeSci]

@MeSci - I think we've gone full circle! I think you and I had a discussion about BCAAs relieving fatigue, and somehow this related to 5-HT (not 5-htp) and tryptophan.

In the thread you linked above, you state:

This article which I've linked on my other post about BCAAs talks about inhibiting 5-HT and trypophan, which can reduce fatigue: http://jn.nutrition.org/content/136/2/544S.full

I don't think it has to do with the unreliability of animal models.

And here's a quote from another article: http://www.sportsci.org/jour/9901/rbk.html

I don't know how this does or does not link to interferon, and I don't want to spend the energy to understand it. But just wanted to point out that I'd come across the same concept of inhibiting 5-HT and trypophan to reduce central fatigue, which I think is PEM, and which BCAAs are helping me with a great deal.

I can't quite get my brain around all this (it is currently fuzzy, likely due to gut dysfunction), but I see that 5-HT is another name for serotonin. I'm trying to figure out whether 'central fatigue' is related to PEM, so have done some searching. I found this paper, for example (can't read it at present but it does suggest that they are related). I see that this paper has been discussed in this thread, so will try to read that.

For easy reference, the other thread where we 'met' is here.

It might also be interesting to relate this to Jonathan Edwards's thread about fatigue.