Genetics and Gene Expression Involving Stress and Distress Pathways in Fibromyalgia with and without Comorbid Chronic Fatigue Syndrome

Abstract

In complex multisymptom disorders like fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) that are defined primarily by subjective symptoms, genetic and gene expression profiles can provide very useful objective information. This paper summarizes research on genes that may be linked to increased susceptibility in developing and maintaining these disorders, and research on resting and stressor-evoked changes in leukocyte gene expression, highlighting physiological pathways linked to stress and distress. These include the adrenergic nervous system, the hypothalamic-pituitary-adrenal axis and serotonergic pathways, and exercise responsive metabolite-detecting ion channels. The findings to date provide some support for both inherited susceptibility and/or physiological dysregulation in all three systems, particularly for catechol-O-methyl transferase (COMT) genes, the glucocorticoid and the related mineralocorticoid receptors (NR3C1, NR3C2), and the purinergic 2X4 (P2X4) ion channel involved as a sensory receptor for muscle pain and fatigue and also in upregulation of spinal microglia in chronic pain models. Methodological concerns for future research, including potential influences of comorbid clinical depression and antidepressants and other medications, on gene expression are also addressed.

Associations Between Neurotransmitter Genes and Fatigue and Energy Levels in Women After Breast Cancer Surgery

“…62 Alterations in the COMT gene were associated with fatigue and pain in breast cancer patients through interactions with two stress pathways (i.e., hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS)). 62–64 In our study, patients who were heterozygous or homozygous for the rare C allele for COMT rs9332377 had a 52% lower odds of belonging to the Higher Fatigue class. This intronic SNP is located near the 3′ UTR of the COMT gene.…”

Overlap between functional GI disorders and other functional syndromes: what are the underlying mechanisms?

“…There are various genes of interest in FM and CFS, such as those linked to COMT and glucocorticoid and mineralocorticoid receptors. 205 Also, glutamate recep-tor genes involved in the circadian rhythm have been studied in CFS. 206 In a recent meta-analysis, 11 genes were identified, which may be associated with CFS symptoms.…”

Similarities and differences between health-related quality of life in patients with exhaustion syndrome and chronic fatigue syndrome

“…Long-lasting stress can, in principle, reduce immune system activity and make a host less resistant to infectious pathogens [34]. At the same time, interactions between the immune and stress-regulating systems [35] might lead to the development of additional co-morbidities such as infections, pain, and sleep disorders, creating a vicious circle without less chance of recovery. From the rehabilitation perspective, it is important to accurately diagnose the condition (ES vs. CFS) in order to tailor rehabilitation interventions and to create realistic expectations and tasks for the patient.…”