they presumably must be referring to long-term effects of high IFNγ in the short-duration patients. (Otherwise, they seemingly have forgotten their own findings of lower IFNγ in long-duration patients, or are giving no significance to it relative to the controls.)
Methods In this randomised, double-blind study, we recruited 44 patients to the depressed CFS group, and 52 to the non-depressed CFS group. In each group participants were randomly assigned to receive either fluoxetine (20 mg once daily) or placebo for 8 weeks. The effect of fluoxetine was assessed by questionnaires, selfobservation lists, standard neuropsychological tests, and a motion-sensing device (Actometer), which were applied on the day treatment started and on the last day.
Findings The two groups were well matched in terms of age, sex distribution, employment and marital status, and duration of CFS. There were no significant differences between the placebo and fluoxetine-treated groups in the change during the 8-week treatment period for any dimension of CFS. There was no change in subjective assessments of fatigue, severity of depression, functional impairment, sleep disturbances, neuropsychological function, cognitions, or physical activity in the depressed or the non-depressed subgroup.
Though depressive symptoms are common in chronic fatigue syndrome, patients with major depression have unchanged or lowered prolactin responses to D-fenfluramine,2 making it unlikely that chronic fatigue syndrome and depression share a common pathophysiology. [...] Raised brain serotonin activity might explain the excessive fatigue experienced by patients with the chronic fatigue syndrome.3 Increased prolactin release mediated by serotonin in the chronic fatigue syndrome might, however, be a secondary consequence of behavioural changes such as prolonged inactivity or disturbance of the sleep-wake cycle.
There was no significant difference in baseline prolactin concentrations between patients with postviral fatigue syndrome and healthy subjects or those with primary depression. However, the percentage difference between peak and baseline values was significantly higher in patients with postviral fatigue syndrome than the control groups (one way analysis of variance: women, p = 0.003; men, p = 0.004). CONCLUSIONS--The results suggest upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome but not in those with primary depression. The buspirone challenge test may therefore be useful in distinguishing these two conditions. Larger studies are required to explore the potential value of drugs acting on central 5-hydroxytryptamine receptors in the treatment of patients with the postviral fatigue syndrome.
Baseline-circulating cortisol levels were highest in the depressed, lowest in the CFS and intermediate between the two in the control group (P = 0.01). Prolactin responses to the selective 5-HT-releasing agent d-fenfluramine were lowest in the depressed, highest in the CFS and intermediate between both in the healthy group (P = 0.01). Matched pair analysis confirmed higher prolactin responses in CFS patients than controls (P = 0.05) and lower responses in depressed patients than controls (P = 0.003). There were strong inverse correlations between prolactin and cortisol responses and baseline cortisol values. These data confirm that depression is associated with hypercotisolaemia and reduced central 5-HT neurotransmission and suggest that CFS may be associated with hypocortisolaemia and increased 5-HT function. The opposing responses in CFS and depression may be related to reversed patterns of behavioural dysfunction seen in these conditions. These findings attest to biological distinctions between these disorders.
The opposing responses in CFS and depression may be related to reversed patterns of behavioural dysfunction seen in these conditions.
I am very hapy with this news. I don’t wanne be negative but i don’t think there will be a significant change in the medical community at this point. Also i don’t expect more budget for research. So what did we ‘win’ with this medical campagne? Nothing yet. Paradigma change will only occure with substantial evidence and repliction. This is not the case yet. Cytokines will not lead to objective test because they are not consistent.
For example: il17a is not consistent  and Lipkin et al., think it is a very important finding. So his ‘house’ is not build on solid ground.
1. Journal of Translational Medicine 2009, 7:96 Plasma cytokines in women with Chronic Fatigue Syndrome Mary Ann Fletcher* 1,2, Xiao Rong Zeng1,2, Zachary Barnes1, Silvina Levis1,2 and Nancy G Klimas* 1,2 1Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL USA 2Miami Veterans Health Care Centre, 1201 NW 16th St, Miami, FL USA
Maybe professor Edwards can explain these fluctuations of cytokine?
I have a question for professor Edward: can cytokines flair up or go down by both mental- or physical stress (running)?
This article seems to me to be all about trying to downplay the results, and suggest issues with the design of the study.... I gave it an 'unhelpful' rating on the website.
The consistent modest shift in levels between populations looks to me much more like some general shift in regulation of metabolism rather than specific signalling.
It doesn't matter that they used Fukuda if they found unique problems. I would much rather be recognised and treated for a unique problem, than wait for the proof that you can line up a particular biomarker with a particular symptom (PEM). That proof may never come, so why wait for it when we already have unique proof of illness?That Schutzer study used the infamous Fukuda criteria for diagnosing "CFS," meaning that PEM was not a strict requirement, but rather an optional requirement. So it may be hard to say how useful the specific results from it are.
The methodology might otherwise be good though when PEM is required.
If this is merely some sort of energy conservation strategy, shouldn't all cytokines be lower and not just the ones that previously were high? Or can the body enact energy conservation strategies on an individual cytokine basis?
Yes, Alex, I was also wondering if there might be some relation to corticosteroid receptor dysregulation or blockade. The cytokine results might be a knock on effect from an HPA axis log jam. As you say, there are so many possibilities but this may be a start.
Thank you for you reply professor Edwards.
Alex do you refer to this article?
Post-exertion malaise in chronic fatigue syndrome: symptoms and gene expression.
Fatigue: Biomedicine, Health & Behavior. 2013 Oct 2. doi: 10.1080/21641846.2013.838444.
Meyer JD, Light AR, Shukla SK, Clevidence D, Yaled S, Stegner AJ, Cook DB
The latter scenario could potentially explain why there is no significant change in symptoms at 3 years despite a change in cytokine levels: if cytokine receptors are blocked/inhibited then the specific level of circulating cytokines may make little difference in terms of their effect.I just had an idea that maybe these results could be telling us the opposite of what they first look like. What if in early disease there is a block to some generic mechanism that inhibits cytokine production or even clears cytokines by receptor uptake. Maybe in early ME/CFS cytokine receptor expression is downregulated so the cytokines float about for longer and do not do much. The levels look higher but nothing is happening.