Neurohumoral Profiles and Childhood Adversity of Patients with Multisomatoform Disorder and Pain as the Leading Bodily Symptom.

OBJECTIVE: Patients suffering from chronic pain often present with multifactorial underlying conditions, sometimes without concrete pathological physical findings. Functional somatic syndromes (FSS) and somatoform disorders show a high prevalence of 8-20% and are often associated with adverse childhood experiences (ACE) and chronic stress. As many different FSS have overlapping symptoms, the concept of multisomatoform disorder (MSD) has been introduced as an encompassing concept. We hypothesize that a common neurohumoral profile is present in patients with MSD that is distinct from gender- and age-matched controls and thus provides insight into possible common underlying mechanisms. DESIGN: In 151 patients with MSD (138 females) and 149 matched controls (131 females), we determined ACE by the Childhood Trauma Questionnaire (CTQ) and chronic stress by the Trier Inventory for Chronic Stress (TICS). Furthermore, the serum levels of leptin, FSH, LH, cortisol, DHEA-S, and IGF-1 have been assessed. RESULTS: There were significant differences in the levels of leptin, FSH, IGF-1, and cortisol between patients and controls, mainly driven by female participants. Levels of leptin were significantly correlated with BMI in patients, in controls, and in the female subgroup. This correlation was exaggerated in female patients when compared to female controls. Both CTQ and TICS predicted MSD directly and indirectly through the levels of leptin. CONCLUSION: There is evidence of a distinct neurohumoral profile in female patients with MSD when compared to matched healthy controls, similar to what has been demonstrated in other chronic pain states. The observed profile can be taken as possible evidence for a dysregulated response to chronic stress and metabolic balance as well as a state of hypocortisolism and HPA-axis dysfunction. ACE and chronic stress play a major role in the development of MSD and altered neurohumoral profile.

Association of TNF-α polymorphism rs1800629 with multisomatoform disorder in a group of German patients and healthy controls: an explorative study.

INTRODUCTION: The etiology of multisomatoform disorder (MSD) is still largely unknown, but genetic factors seem to have an influence on pathogenesis. Pain is a major symptom of MSD and polymorphisms of different proinflammatory cytokines have been found associated with pain in former studies. Therefore, we presumed that cytokine polymorphisms could also be associated with MSD. PATIENTS AND METHODS: Groups of 148 MSD patients with pain as the leading clinical symptom and 149 age and gender matched healthy controls participated in this study. Nine cytokine polymorphisms were genotyped and statistically analyzed for associations with MSD. RESULTS: Allelic and genotypic associations were found for rs16944 (interleukin 1ß), rs1800629 (tumor necrosis factor) and rs909253 (lymphotoxin α). After correcting for multiple testing, the association of rs1800629 with MSD remained significant. The rare A-allele was correlated with MSD (p=0.007). DISCUSSION: Since the common G-allele of rs1800629 (TNFα) occurs much more often in the control group than in the MSD group it is assumed to be protective. Being carrier of the A-allele seems to be a risk factor for MSD.

Interaction of the dopaminergic and serotonergic systems significantly influences the risk for multisomatoform disorder: a controlled pilot study.

The etiology of multisomatoform disorder (MSD) is largely unknown, but an influence of genetic factors is likely. Since pain is a major component of MSD and dopamine as well as serotonin are involved in pain pathways, genes of the dopaminergic and serotonergic system are promising candidate genes and we assumed that polymorphisms could be associated with MSD. One hundred forty-nine patients with MSD and 149 age- and gender-matched healthy controls participated in this study. DNA from all participants was genotyped for 22 single nucleotide polymorphisms (SNPs) within genes of the dopaminergic and serotonergic system by polymerase chain reaction, a restriction enzyme analysis, and pyrosequencing. The distribution of SNP alleles, genotypes, and haplotypes was compared between patients and controls. Neither an allelic nor a genotypic association was found for any individual SNP, but testing for a haplotypic association revealed that a haplotype of the serotonergic genes HT(1B) and HT(1D) indicated a lower risk. However, this statistically insignificant protective effect became highly significant on the background of two DAT1 haplotypes. Interestingly, if these two DAT1 haplotypes are analyzed without considering the serotonergic genes as confounders, they are significantly associated with an enhanced risk. Taking into account observations from recent publications, this apparent contradiction might be explained with the complex interaction of the dopaminergic and serotonergic systems. To conclude, our results reveal an involvement of polymorphisms in dopaminergic and serotonergic genes in the etiology of MSD in patients of German descent, but their exact role in MSD requires further investigation.

Catechol-O-methyltransferase gene polymorphisms are not associated with multisomatoform disorder in a group of German multisomatoform disorder patients and healthy controls.

The etiology of multisomatoform disorder (MSD) is largely unknown, but genetic disposition may be one of several risk factors. As pain is a major component of MSD, and polymorphisms in the catechol-O-methyltransferase (COMT) gene are associated with COMT enzymatic activity and pain sensitivity, we assumed that COMT polymorphisms could be associated with MSD. One hundred and forty-nine patients with MSD and 149 age- and sex-matched healthy controls participated in this study. The inclusion criteria for MSD were in accordance with the structured clinical interview of the diagnostic and statistical manual of mental disorders IV. DNA from MSD patients and controls was genotyped for six single-nucleotide polymorphisms (SNPs) within the COMT locus by polymerase chain reaction and restriction enzyme analysis. The distribution of COMT SNP alleles, genotypes, and haplotypes was compared between patients and controls. None of the investigated SNPs, including the functionally relevant common SNP in codon 158 (Val158Met), showed a statistically significant allelic, genotypic, or haplotypic association with MSD. We conclude that COMT polymorphisms on their own do not seem to play a relevant role as major genetic risk factors for MSD.