Thesis Hypothalamic Dysfunction and Neurotransmitter Abnormalities in the Postviral Fatigue Syndrome, 1992, Bakheit

Are these two studies fukuda?
For Bakheit 1992, it was a custom postviral fatigue syndrome criteria based on Holmes 1988 (CDC) and Sharpe 1991 (Oxford). From the Bakheit thesis:
Our diagnostic criteria incorporate those of Holmes et al (1988) and also the diagnostic guidelines of the Medical Research Council (Sharpe et al, 1991). In addition, these criteria emphasise the important role of a viral infection in initiating PVFS and they also attempt to exclude patients with possible or known psychiatric illness. We have previously published these criteria (Behan, 1991, Behan & Bakheit, 1991) which we summarise below.

1) a history of a definite or probable viral infection preceding the onset of symptoms. This history must be corroborated by the appropriate laboratory tests;

2) the presence of severe fatigue for six months or more which reduced the patient's premorbid level of activity by 50% or more. The fatigue is precipitated or made worse by physical or mental effort and is not improved with bed rest;

3) at least three of the following symptoms must be present: myalgia, dizziness, sleep disturbances, poor memory and concentration, anxiety, hypochondriasis, the typical depression as described earlier (see section on psychiatric symptoms, pages 27-31), early satiety, diarrhoea alternating with constipation, abdominal bloating, poor appetite, fluctuations in body weight and menstrual irregularities;

4) chronic infections, malignancy, autoimmune disorders and other medical conditions which may cause fatigue must be excluded with the appropriate investigations;

5) patients with a past medical or family history of depression or any other major psychiatric illness are excluded;

6.) all patients must have a well-adjusted premorbid personality (defined as ability to cope with every day life stress) and all must have a good work record.

We make the diagnosis of PVFS if the patient fulfils all of these criteria.

For Majeed 1996, it was essentially Fukuda, but where depression was excluded:
Patients included in the studies of this thesis fulfilled the following criteria:

1. Acute onset of fatigue, which was severe enough to prevent them continuing in their occupation, prevented women from carrying out their household duties and dramatically altered their social and personal lives. It fluctuated with time and was made worse by exercise.

2. At least two of the following four were present:

a. Sleep disturbance (hypersomnia or insomnia).​
b. Myalgia/arthralgia.​
c. Neurobehavioural complaints (inability toconcentrate,difficulty thinking, forgetfulness, anomia, atypical depression, generalised headaches).​
d. Symptoms of irritable bowel syndrome- bloated stomach, colicky abdominal pain, alternating diarrhoea or constipation.​

3. Patients with complaints of excessive sweating, chest pains, palpitations, dysequilibrium and recurrent infections were also included but this was not mandatory for inclusion into the studies.

4. Patients who were excluded from the studies included:

a. Patients with established medical conditions known to cause chronic fatigue.​
b. Patients with a current diagnosis of schizophrenia, manic depressive psychosis or substance abuse.​
In addition, all the patients incuded were seen at the Institute of Neurological Sciences and were hospitalized as inpatients. Detailed present and previous medical histories, a family, drug and occupational history were taken; physical and neurological examination and psychiatric evaluation were carried out. Laboratory tests included ESR, complete blood count and differential white blood count, protein electrophesis, serum electrolytes, glucose, creatine, blood urea, serum calcium and phosphate, liver function tests, muscle enzymes (CPK and aldolase), urinalysis, chest x-rays, thyroid function tests, serum cortisol and anti-nuclear antibodies screen were also carried out in order to exclude any other medical cause for their fatigue.

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All patients were selected according to the criteria outlined in the introduction of this thesis and they also fulfilled the CDC criteria laid down by Fakuda et al in 1994. Those with co-existing depression were excluded. [emphasis added] Essentially, patients meeting the CDC criteria had to have persisting or relapsing, debilitating fatigue for at least six months in the absence of any medical diagnosis which would explain the syndrome. Laboratory tests which include ESR, complete blood count and differential, protein electrophoresis, serum electrolytes, glucose, creatinine, blood urea, serum calcium and phosphate, liver function tests, muscle enzymes, urinalysis, chest x-rays, thyroid function tests, antinuclear antibodies screen were carried out to exclude any other medical cause for their fatigue.
 
Good idea. Here's a box plot:

View attachment 33916
It does seem like the control group has a glob of points at the very bottom that the CFS group does not have.

I made a violin plot as well with default seaborn settings, though I don't consider these very easy to interpret. For example, this gives the impression of a cluster of points in the CFS group that are lower than anyone in the control group, but that's not what the plot of individual points looks like to me.
View attachment 33910

One more, with values rounded to the nearest 100:
View attachment 33911

Just noting again that these values were from the paper's plot, and some might not closely match participant values. But they're probably pretty close, since the t-test p-value was the same.
I like the box plot the most. I think it makes the differences very clear.
 
It occurred to me that the Majeed plot includes both males and females (15 of each for ME/CFS and same for controls).

If combining males and females together in the Bakheit plot, it might look fairly similar. The abnormal response in males with PVFS is about the same magnitude as healthy response in females.

So good idea to analyze males and females separately to most clearly see the differences. The Majeed finding might have looked a lot more impressive if they had plotted the sexes separately.
Just as a little experiment, I checked what the plot for Majeed's thesis would look like if I assumed that the lowest 15 prolactin response values in each group are male and the highest 15 values are female. (There are 30 total participants in each group, where half were female.)

Smallest 15 values in each group (assumed to be mostly males)
1788012899209.webp

Largest 15 values in each group (assumed to be mostly females)
1788012946577.webp

So there is still overlap, but the separation between groups looks a little clearer. But still not as clear as the separation in Bakheit's study.

Edit: Fixed plots to start at 0.
 
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