The interplay of chronic stress and genetic traits discriminates between patients suffering from multisomatoform disorder..., 2022, Buhck et al

[Andy]

Full title: The interplay of chronic stress and genetic traits discriminates between patients suffering from multisomatoform disorder with pain as the leading symptom and matched controls

Highlights

• In patients with multisomatoform disorder significant gene environmental interactions exist.
• A relevant determinant of MSD diagnosis is chronic stress as measured by TICS.
• Genetic determinants are SNPs of the COMT and dopamine receptor 4 genes.
• CART analysis revealed stress and SNPs of COMT and serotonine receptor interaction.

Abstract

Objective
Somatoform disorders and functional somatic syndromes (FSS) with symptoms that are not sufficiently explained by physical or technical examination are among the most challenging underlying causes. Many different somatoform disorders and FSS have overlapping symptoms, often with pain as the most prevalent one, leading to a high burden of disease. The concept of multisomatoform disorder (MSD) has been developed to acknowledge that fact. We analyzed a group of 151 patients and 149 matched controls to identify interactions of genetic and environmental factors with a possible influence on the development of MSD.

Design
In a retrospective case-control study, we performed a statistical analysis on 151 patients and 149 matched controls using logistic regression and a Classification and Regression Tree (CART) analysis.

Results
The logistic regression analysis of genes and environmental factors demonstrated significant differences in the results of the Trier Inventory of Chronic Stress (TICS) questionnaire, the single nucleotide polymorphism rs1800955 of the dopamine receptor D4 and the single nucleotide polymorphism rs4818 of the enzyme catechol-O-methyltransferase between patients with MSD and healthy controls. The resulting decision tree of the CART analysis determined that the TICS questionnaire was able to differentiate patients and controls most accurately, followed by certain genotypes of the 5-hydroxytryptamine receptor 2A and a single nucleotide polymorphism of the enzyme catechol-O-methyltransferase.

Conclusions
The results of the statistical analysis identified a gene-environmental interaction possibly leading to MSD. The resulting identifiers could be used as a reference to inform diagnostic algorithms to easier identify patients suffering from MSD.

Paywall, https://www.sciencedirect.com/science/article/abs/pii/S0165032722004256

 

[Trish]

Can anyone explain the function of the specific genes identified?

I would assume the stress is a result of suffering form multiple symptoms including pain, the detrimental effect on daily life, and probably not being believed by doctors.

 

[rvallee]

Probably not as helpful as someone who actually understands it, but since SNPs are well-documented.

rs1800955: "It is located in the promoter region of the DRD4 gene. This gene codes for the dopamine receptor D4."

But, frankly, I'm not really convinced that much of this is credible, given, uh, this: "The SNP has been investigated with respect to novelty seeking, — a personality trait that may be measured with the Temperament and Character Inventory.[2][3] A 2008 meta-analysis indicates a possible association between novelty seeking and C-521T though rather small.[4]"

rs4818 yields even less useful results. Appears to mostly be studied in psychiatry in relation to schizophrenia, but nothing useful has been found. Seems to be involved in Catechol-O-Methyltransferase.

I don't think anyone actually understands any of this beyond speculation.

 

[Mithriel]

I tried to find the Trier scale but only managed to see a short sample of the questions but a lot of them were of the sort we are used to where physical symptoms confound the answers.

Things like

54 I feel overwhelmed by my tasks
55 In spite of the effort I make, I am unable to manage my tasks properly

describe the physical aspects of ME
while

57 Sometimes I feel overburdened by my responsibilities toward others
40 There are situations in which I find it difficult to be obliging

are caused by ME not ME caused by them.

That is 4 from a sample of 9 questions.

 

[Hoopoe]

Can anyone explain the function of the specific genes identified?

It helps degrade catecholamines, including dopamine, adrenaline and noradrenaline.

The variant rs4818 of the COMT gene is very common in the general population so one would not expect it to have a large effect.