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.