Psychological Stresses in Children Trigger Cytokine- and Kynurenine Metabolite-Mediated Abdominal Pain and Proinflammatory Changes, 2021, Myint et al

Andy

Retired committee member
Recurrent abdominal pain (RAP) is a common medically unexplained symptom among children worldwide. However, the biological mechanisms behind the development of functional and behavioral symptoms and changes in blood markers have not been well explored.

This study aimed to assess changes in the concentrations of inflammatory markers, including cytokines and tryptophan catabolites, in the serum of children with RAP compared to those with subclinical infections. Children with RAP but without organic diseases were included, and those with asymptomatic intestinal parasitic infections were used as a subclinical infection cohort. Blood samples were collected and used to measure the cytokine profile using Multiplex Immunoassay and tryptophan catabolites using high performance liquid chromatography.

Children with RAP showed significantly higher concentrations of serum tumor necrotic factor-α, p<0.05, but lower concentrations of IL-10, p<0.001, IL-6, p<0.001 and brain-derived neurotrophic factors (BDNF) p<0.01. In addition, a significant increase in the metabolite of the kynurenine pathway, 3-hydroxyanthranilic acid (3-HAA) p<0.01, a significant decrease in the concentrations of anthranilic acid (AA) p<0.001, together with an increased ratio of serum 3-HAA to AA (3-HAA/AA) p<0.001, was found in this cohort.

These findings indicate the significant activation of the immune system and presence of inflammation in children with RAP than those with subclinical parasitic infections. Moreover, children with RAP tested with the Strengths and Difficulties Questionnaire (SDQ), displayed high psychological problems though these SDQ scores were not statistically associated with measured cytokines and kynurenine metabolites.

We however could hypothesize that the pro-inflammatory state together with concomitant low concentrations of BDNF in those children with RAP could play a role in psychological stress and experiencing medically unexplained symptoms.

Open access, https://www.frontiersin.org/articles/10.3389/fimmu.2021.702301/full
 
So they put their hypothesis, not the original hypothesis but a subsequent hypothesis, into the title based entirely on speculative musings? What kind of joke of an editing process allows that? Especially as they recognize there isn't even any correlation, not that this should mean anything anyway. Asking about stomach aches is even a question on the damn questionnaire. What is this clown show?

They are aware that children put all sorts of dirty things in their mouths, right? I've had so many episodes of mild food poisoning in my childhood I couldn't even venture a guess as to how many. This isn't rocket science or anything.

Honestly this is too much like trying to force a religious system into science, going out of their way to put it there, just because. And it seems all to avoid having to admit to the elephant in the room, like putting some magical force that keeps demons at bay. It's like there is a true pervasive refusal to accept the germ theory of disease, like it's too good of an explanation that it feels wrong. So damn bizarre.
 
As @rvallee notes, the Strengths and weaknesses questionnaire that supposedly tells us if a child has ' psychological problems' asks if the child 'complains of stomach-aches'. The resulting score is provided as evidence that children complaining of stomach aches have psychological problems.

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This is such a bad paper. It's only in a table that you find out the numbers of children involved: the study involved 10 children with recurrent abdominal pain and 17 children with asymptomatic gut parasite infections.

The paper seems to suggest, with absolutely no evidence, that the children with RAP have had tough childhoods and this has cause pro-inflammatory cytokines.
Growing up in a socially tough environment (13), childhood abuse (14) and maltreatment (15), and also acute stressful life events (16) are all associated with an increased production of pro-inflammatory cytokines.

The children with RAP were recruited from an outpatient clinic in Kuala Lumpur, the capital city of Malaysia. The children with the asymptomatic gut parasite infections are identified as Orang Asli, a group name for various tribes of people indigenous to the Malayan peninsula. Speaking generally, Orang Asli have a much much harder time in Malaysia than the people who have access to outpatient clinics in Kuala Lumpur. They face enormous discrimination and hardship. Wikipedia says of the Orang Asli tribes:
they are all mostly on the sidelines of the social, economic, and cultural life of the country's development.

I'd suggest that if tough childhoods caused pro-inflammatory cytokines, then the Orang Asli children would have been much more likely to have higher levels. It seems to me quite likely that gut parasite infections reduce inflammatory responses - this is the basis of studies into deliberate infection of people with inflammatory conditions with intestinal worms. Therefore, it is likely that the presence of the gut parasite infections are, at the very least, a major confounding factor in the supposed difference in cytokine levels between the two small samples.

Evaluations of mental health were only done for the children with RAP, and only the results of the Strengths and Weaknesses Questionnaire are reported. Possibly other assessments were not reported. There is no reporting of what children from a similar socio-economic background score on the Strengths and Weaknesses Questionnaire - the ten children with RAP may in fact not have higher scores than their peers, or at least may not have higher scores than children experiencing chronic pain due to clear physical causes.


And then the conclusion notes:
Our results strongly suggest that the decrease in BDNF concentrations and concomitantly, the production of the neuroactive KP metabolites, 3-HAA, and, to a lesser extent, 3-HK, may lead to the alteration of physiological processes and possibly explain the emergence of psychological symptoms in these children.
So they are suggesting that the levels of BDNF and metabolites might be causing psychological symptoms in the children with RAP. But, as @rvallee notes, the title of the paper suggests that psychological stresses (of which this paper gives absolutely no evidence aside from the fact that the children are experiencing chronic pain) trigger pro-inflammatory changes.

It's a complete mess of experimental design and analysis.
 
Authors' affiliations include:

  • Neuroinflammation Group, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
  • Psychoneuroimmunology Research Group, European Collaborative Project, Munich, Germany
 
My son had recurrent migraines as a child with bad stomach problems. He now has coeliac disease but that may be a coincidence.

I was told that children have such small tummies that when the lymph glands in the stomach swell up they cause more problems than they do in adults. More stomach problems then equal more immune activation with no need for psychology to be involved.
 
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