ME Epidemiology - prevalence and peak ages of onset

[Simon M]

Moderator note: This post and the next two have been copied, and subsequent posts moved from this thread:
JAMA -"Advances in understanding the Pathophysiology of Chronic Fatigue Syndrome" by Anthony Komaroff

Posts about sex ratio have been moved to a new thread:
ME/CFS Epidemiology - sex ratios, female predominance

Those for me would be things like:

1. Epidemiological studies have shown that there is a consistent cohort of people, independent of geography, who suffer from a well defined clinical syndrome that deserves to be distinguished by the name ME/CFS.
2. Re-analysis of trials of therapist-delivered treatments has established that a psychological model of disease perpetuation is not supported and made very implausible.
3. A population based ME Biobank has been set up and is distributing samples worldwide.
4. Well executed trials have shown that B cell depletion is not a useful treatment.
5. Immunological and microbiological studies have indicated that it is very unlikely that ME causation relates to an NK defect allowing reactivation of, or repeated infection with, viruses.
6. A number of studies indicate that mitochondrial metabolic pathways may be diverted, perhaps involving amino acids, although the exact nature of any shift has not yet been identified.
7. Preliminary genetic screening and epidemiological studies have suggested that there may be a significant heritable aspect to ME. Plans are being developed to set up more powerful genetic screening studies.
8. A number of studies are focusing on the key feature of post exertion malaise and beginning to clarify the physiological changes that can be documented.

That is just off the top of my head

That’s a good list and I’m sure that’s the right way to go to really interest people in the field. I think two other findings are worth adding to the list:

The fact that, consistently, around 80% of patients are women. This is pretty unusual, I think. And while more females receive a mental health diagnosis, I thought that typically this was around 2/3, rather than the 80% same for any CFS.

Also, the remarkable “two peaks“ age profile of the honours, with the first peak in adolescence/early adult hood (with the gender difference emerging during puberty) in the second pic starting in people‘s thirties. It’s hard to explain this finding, but it surely a sign that something unusual is going on here.

 

[Jonathan Edwards]

I think two other findings are worth adding to the list:

Yes, I agree. I guess the female predominance has been known for a while so is not so much 'progress'. The double peak would follow point 1. I am not sure that it has been replicated across geography but the emergence of gender predominance in adolescents certainly has.

 

[ME/CFS Skeptic]

Epidemiological studies have shown that there is a consistent cohort of people, independent of geography, who suffer from a well defined clinical syndrome that deserves to be distinguished by the name ME/CFS.

I think there have only been decent epidemiological studies in the US and the UK. A study on the European mainland, by Euromene for example, would be useful.

more females receive a mental health diagnosis, I thought that typically this was around 2/3, rather than the 80% same for any CFS.

I think there's only one study that reported 80% of ME/CFS patients being female; the Wichita, Kansas study (Reyes et al. 2003) which reported 83,2%. Jason et al. said it was more around 70% (23/32) and the study by Nacul in the UK found a much lower figure of around 50%. So I don't know if there's clear differences between the % being female in mental health diagnoses.

the remarkable “two peaks“ age profile of the honours, with the first peak in adolescence/early adult hood (with the gender difference emerging during puberty) in the second pic starting in people‘s thirties. It’s hard to explain this finding, but it surely a sign that something unusual is going on here.

I thought that was just one study (Bakken et al. 2014). Does it show in other publications as well?

I would add another finding that has been confirmed by multiple research teams: the prevalence of ME/CFS is increased following infections such as EBV-infection. I think Wessely and others initially thought this was a spurious finding and that ME/CFS patients just wanted to make sense of their symptoms by making that connection with infections. But Peter Whites study showed that the prevalence of ME/CFS increased following EBV-infection while this was not the case for mood disorders such as depression. That seems like an important finding to me.

 

[Amw66]

That’s a good list and I’m sure that’s the right way to go to really interest people in the field. I think two other findings are worth adding to the list:

The fact that, consistently, around 80% of patients are women. This is pretty unusual, I think. And while more females receive a mental health diagnosis, I thought that typically this was around 2/3, rather than the 80% same for any CFS.

Also, the remarkable “two peaks“ age profile of the honours, with the first peak in adolescence/early adult hood (with the gender difference emerging during puberty) in the second pic starting in people‘s thirties. It’s hard to explain this finding, but it surely a sign that something unusual is going on here.

I know I do not have a science back ground but
HORMONES!!!
Puberty and pregnancy have huge hormonal shifts which also require co factors, pathways etc. Perimenopause can also start in 30s with shifts in estrogen production.
Iodine deficiency is seemingly common, B12 and magnesium are required for hormone synthesis ( MTHFR/ COMT and issues with P450 processes have impact here), low cholesterol could be an issue..... If there is another input ( say in puberty growth spurts/ immune differences in pregnancy) which places another stress on the body' s systems ( particularly if producing inflammation/ oxidative stress) then it may be this that acts as a facilitator for something like a viral infection to tip the scales.
I don't think the age peaks are difficult to understand at all.

 

[adambeyoncelowe]

HORMONES!!!

This is my assumption, too.

 

[Jonathan Edwards]

I don't think the age peaks are difficult to understand at all.

So why do men have the same second age peak at around 30?

 

[Jonathan Edwards]

I think there have only been decent epidemiological studies in the US and the UK.

I think the Norwegian study may be the most interesting.

 

[Amw66]

So why do men have the same second age peak at around 30?

Testosterone starts dropping in 30s.
Same biochemical impacts hold re synthesis pathways, cofactors and deficiencies.
Perhaps the low cholesterol diet is responsible for other impacts other than the rise of T2 diabetes.

 

[Jonathan Edwards]

Testosterone starts dropping in 30s.

So if it starts dropping and goes on dropping, which it does, why doesn't the incidence go on going up? In other words why is there a PEAK? And why is it the same in both sexes - pretty precisely?

 

[Hoopoe]

Is it because the biochemistry in every decade of life is distinct, and the biochemistry of people in their 30's increases vulnerability against ME?

 

[Jonathan Edwards]

Is it because the biochemistry in every decade of life is distinct, and the biochemistry of people in their 30's increases vulnerability against ME?

Yes it must be but if you have ever owned a Boehringer Mannheim Biochemical Pathway Wallchart you will know that there are rather a lot of bio-chemicals!

 

[Amw66]

So if it starts dropping and goes on dropping, which it does, why doesn't the incidence go on going up? In other words why is there a PEAK? And why is it the same in both sexes - pretty precisely?

I wish I had a clue. Flinging a few things in

perhaps testosterone drops off a cliff for some rather than starts gradually.

That the lack of cholesterol in diets precludes productions of sufficient pregnenolone

Impact of pesticides on hormonal synthesis - most pesticide safety use relates to single ones and not the effect of a cocktail combination . This relates to food not just the process of growing it.

Stress - this is usually the age when people work all hours to establish themselves in their career choice.

That lots of these issues impact liver and @ Mario vitali may be onto something

I don't think it is any one thing ( or else it should have been found) it is an enigma code of combinations

 

[Hoopoe]

I looked at how sex hormones change with age and it didn't fit the peak in the 30's well. If I remember right the hormonal changes are more gradual and occurred later.

Of course you could come up with all sorts of ways to make is still fit, like thresholds. But it didn't seem to fit in any obvious way.

The peak in teenage years does seem to fit much better with hormones.

 

[Amw66]

I looked at how sex hormones change with age and it didn't fit the peak in the 30's well. If I remember right the hormonal changes are more gradual and occurred later.

Perhaps ME peeps are outliers

 

[Hoopoe]

If the peak in teenage is due to hormones, and the peak in the 30's is due to something else, that might explain why there are two peaks.

 

[rvallee]

So why do men have the same second age peak at around 30?

The data is so bad I doubt this should be trusted. It's probably an artifact. It's very hard to have proper data on onset anyway since time from onset to diagnosis ranges from months to decades, made even worse by a subset that experiences slow decline with an undefined beginning and we can't tell how significant that subset is to the whole.

 

[Wilhelmina Jenkins]

I’m wondering - taking into account that all of the statistics for this disease are fairly unreliable since studies are small, definitions differ, etc., which statistics do you all consider the most reliable? I am always uncomfortable quoting almost all of them.

I do believe, for example, that there are more women with this disease than men since every study indicates that and it’s consistent with other immune-related diseases, but I’m uncomfortable with the percentages.

How close are we to accurate on any of the stats?

 

[Marco]

I looked at how sex hormones change with age and it didn't fit the peak in the 30's well. If I remember right the hormonal changes are more gradual and occurred later.

Anecdotally (and acknowledging that sex hormones may be acomplete red herring or hormone levels may be affected by ME/CFS rather than the other way round) my testosterone levels dropped at age 34 to below normal range co-incidentally with a severe and permanent downturn in my health. Given that total testosterone levels are based on an all adult age range, I suddenly had T levels below that of a 75 year old (male).

 

[ProudActivist]

Anecdotally (and acknowledging that sex hormones may be acomplete red herring or hormone levels may be affected by ME/CFS rather than the other way round) my testosterone levels dropped at age 34 to below normal range co-incidentally with a severe and permanent downturn in my health. Given that total testosterone levels are based on an all adult age range, I suddenly had T levels below that of a 75 year old (male).

There is definitely some relationship with hormones, whether chicken or egg... I am female and my testosterone is basically undetectable in tests I have had. Doctors don’t seem to think this is an issue. My hormonal cycle affects my symptoms vastly. My first symptom of illness (neuropathic pain/itch after contact with water) came age 13 despite “proper” post viral onset being age 22.

 

[Simon M]

I think there's only one study that reported 80% of ME/CFS patients being female; the Wichita, Kansas study (Reyes et al. 2003) which reported 83,2%. Jason et al. said it was more around 70% (23/32) and the study by Nacul in the UK found a much lower figure of around 50%. So I don't know if there's clear differences between the % being female in mental health diagnoses.

The Nacul 2011 Prevalence study found around 80% female cases for ME/CFS (Table 4 https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91). The huge Norwegian study gives an incidence ratio of 3.2 female cases for every male case (76% female). And just about every mecfs study ever done, covering many thousands of cases, have 75%-80% female cases (I always check). So there does seem to be solid evidence that the female ratio is higher than for psych cases.

I thought that was just one study (Bakken et al. 2014). Does it show in other publications as well?

As @Jonathan Edwards said, there is at least one UK study replicating the adolescent age peak. As you say, there is just the Norwegian study for the adult peak but that Norwegian study is based on the highly-rated Norwegian health database which covers the National population and is regarded as one is the best sources of health data in the world. It included nearly 6000 cases of ME/CFS. And it confirms what is widely reported by clinicians, an adults peak in the 30s (the data show this is more pronounced for women than for men).

So I think the age peak is pretty robust as well, with strong enough evidence to cite to outside researchers as a reason to take interest in the field.

I would add another finding that has been confirmed by multiple research teams: the prevalence of ME/CFS is increased following infections such as EBV-infection. I think Wessely and others initially thought this was a spurious finding and that ME/CFS patients just wanted to make sense of their symptoms by making that connection with infections. But Peter Whites study showed that the prevalence of ME/CFS increased following EBV-infection while this was not the case for mood disorders such as depression. That seems like an important finding to me.

Agreed, this is also replicated and worth reporting.
Good point. There's also the famous Dubbo study which also shows significant rates of CFS following Ross River virus and Q-fever. Simon Wessley ran a study that find no increase in rates of CFS following common infections, but it was seriously flawed, not least in being hopelessly underpowered to detect credible rates of CFS. So we still don't know about a link between common infections and ME/CFS.