Chronic Fatigue Syndrome and various factors

The paper by Kate Lievesley and colleagues [1] documenting various "predisposing, precipitating and perpetuating factors in Chronic Fatigue Syndrome in children and adolescents" caught my eye recently. Based on a review of the research literature around the topic of Chronic Fatigue Syndrome (CFS) [in childhood], the authors set about detailing some of the important factors linked to the condition and in doing so, highlighted how physiology and psychology might combine when it comes to aetiology and pathology.

View from... @ Wikipedia 

I'll immediately lay my opinion out on CFS. Like its counterpart, myalgic encephalomyelitis (ME), I am a great believer in physiology being a driving force behind the presentation of these 'overlapping fatigue conditions' [2]. I've read too much about issues with the immune system (see here), mitochondrial dysfunction (see here) and the -omic of the hour, the gut microbiome (see here) (with more to come apparently) to be involved so as to reach any other satisfying opinion. Neuroinflammation is the latest thing to be added to the list of correlates. The fact also that an anti-viral therapy also seems to impact on some cases of CFS, a 'subset' of cases of CFS (see here), further enhances that previous sentence, bearing in mind no medical or clinical advice is given or intended.

By saying all that though, I don't doubt however that the presentation of CFS also contains a psychological element to it. This could be due to the impact that the various symptoms have on a person day-in-day-out and the effect on their quality of life (impacted by something like resilience for example), or it could be part of that physiology-behaviour axis [3] that seems to be sprouting up everywhere these days. Debates continue in this area.

The Lievesley paper makes a number of important points in their review. So:

• "Studies suggested that many children and adolescents with CFS reported that their illness began with an infection and there was some objective and prospective evidence to support this". Aetiology is an important research area for CFS. The authors note that EBV (Epstein-Barr virus) is linked to the onset of CFS in quite a few reports and certainly there are some well-documented cases in the research literature as per the case report by Geller & Giclas [4]. Indeed, the Montoya results [5] looking at the use of the anti-viral valganciclovir relied on "elevated IgG antibody titers against HHV-6 and EBV" for participant entrance to their trial. That being said, other infectious agents have also been mentioned in the peer-reviewed literature also.
• "The strongest and most consistent finding was that rates of psychiatric co-morbidity, predominantly anxiety and depressive disorders, were higher in young people with CFS compared to healthy controls or illness control groups". This is where controversy can creep into the topic of CFS. Those who know a little bit about the history of CFS will already have come across some of the 'discussions' about the PACE trial [6] and the subsequent results that have followed [7]. The idea behind PACE was to test various combinations of adaptive pacing therapy (APT), graded exercise therapy (GET) and/or cognitive behaviour therapy (CBT) on the presentation of CFS. The results suggested some significant effects to be had, but the trial has been the topic of various discussions too. With my cold, objective scientific hat on, there is some evidence that CBT can impact on the presentation of issues like anxiety and depression. Even in a condition like autism where anxiety can in some instances be utterly disabling, there is emerging evidence on the value of the talking therapies compared with treatment-as-usual [8]. That being said, I'd also like to think that issues like anxiety and depression might also benefit from more biological-based intervention, such as the use of probiotic therapy reported by Rao and colleagues [9]. Physiology and psychology united together.
• "Preliminary evidence suggested a link between CFS and a family history of CFS...". I've on purpose snipped this sentence down from it's original manifestation focusing on personality traits et al in relation to cognitive styles and CFS. Again, drawing on the experiences of autism research down the years and how the word 'refrigerator' set autism research back decades, I don't want to discuss such concepts here. What I will focus on is the potentially important issue of genes and CFS and where that might take us. Genes have certainly turned up when it comes to the presentation of CFS [10]. It is not at the point where science has been able to say conclusively that CFS is a genetic condition, but certainly there may be candidates for further inspection when it comes to risk. The science of epigenetics, as per a comment in the article by Landmark-Høyvik and colleagues [11] is "nonexistent" (and that paper was written in 2010). But there may be clues that epigenetics is involved in at least some cases of ME/CFS as per the very preliminary work on HERVs (human endogenous retroviruses) (see here) and not forgetting the growing interest in transgenerational epigenetic inheritance although with caveats. I don't doubt we are, once again, looking at some variable interaction between genetics and environment across CFS as per lots of other conditions.

There is little more for me to add to this quite rambling post. I would echo the authors' call for further 'prospective' research into CFS, although ensuring that physiology and psychology take the research journey hand in hand. Certainly with the estimates of 1 in 100 school-aged children potentially presenting with CFS at least here in the UK, one would expect quite a bit more research commitment to be put into finding out what causes CFS and what one can do to ameliorate the condition and the obvious distress that it causes bearing in mind the idea of a 'spectrum' of fatigue conditions as kinda hinted at by Porter and colleagues [12].

Now, how about a spot of NOFX and Happy Guy (who is 'just a man' and not a scientist we are told).

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[1] Lievesley K. et al. A review of the predisposing, precipitating and perpetuating factors in Chronic Fatigue Syndrome in children and adolescents. Clin Psych Rev. 2014. March 1.

[2] Whiteley P. et al. Correlates of Overlapping Fatigue Syndromes. J Nutr Enviro Med. 2004; 14: 247-259.

[3] McCusker RH. & Kelley KW. Immune–neural connections: how the immune system’s response to infectious agents influences behavior. J Exp Biol 2013; 216: 84-98.

[4] Geller RD. & Giclas PC. Chronic fatigue syndrome and complement activation. BMJ Case Rep. 2009; 2009: bcr08.2008.0819.

[5] Montoya JG. et al. Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome. J Med Virol. 2013 Dec;85(12):2101-9.

[6] White PD. et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. Mar 5, 2011; 377(9768): 823–836.

[7] White PD. et al. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychological Med. 2013.

[8] Storch EA. et al. The effect of cognitive-behavioral therapy versus treatment as usual for anxiety in children with autism spectrum disorders: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry. 2013 Feb;52(2):132-142.e2.

[9] Rao AV. et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009; 1: 6.

[10] Kaushik N. et al. Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome. J Clin Pathol. Aug 2005; 58(8): 826–832.

[11] Landmark-Høyvik H. et al. The genetics and epigenetics of fatigue. PM R. 2010 May;2(5):456-65.

[12] Porter N. et al. A Comparison of Immune Functionality in Viral versus Non-Viral CFS Subtypes. J Behav Neurosci Res. 2010 Jun 1;8(2):1-8.

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Lievesley, K., Rimes, K., & Chalder, T. (2014). A review of the predisposing, precipitating and perpetuating factors in Chronic Fatigue Syndrome in children and adolescents Clinical Psychology Review DOI: 10.1016/j.cpr.2014.02.002