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

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.