Epigenetic Modulation of Gene Expression

[webslave]

Editorial - Developmental Influences on Medically Unexplained Symptoms

Written by Philip M. Hanno, MD
Friday, 17 April 2009
BERKELEY, CA (UroToday.com) -

Epigenetic Modulation of Gene Expression May Play Role in Medically Unexplained Conditions

Medically unexplained (functional) symptoms (MUS) are described as ‘physical symptoms that prompt the sufferer to seek healthcare but remain unexplained after an appropriate evaluation. They may affect as many as one third of people seeking medical care. In a provocative article, Tony Buffington of Columbus, Ohio suggests that BPS/IC and feline interstitial cystitis may be manifestations of MUS, and categorizing these conditions in that way may explain many findings that have been difficult to account for. In essence, he advances the migration from an organ specific disease to a pain syndrome one step further.

Commonalities across the different MUS include over-representation of females, history of adverse early experiences, sudden onset often occurring after a distinct precipitating event, and the presence of multiple comorbid MUS in the same individual. Buffington develops the hypothesis that developmental factors may play a role in some cases of MUS. Maternal perception of a threatening environment may be transmitted to the fetus when hormones cross the placenta and affect fetal physiology, effectively programming the fetal stress response system toward enhanced vigilance that can be unmasked later in life. One specific mechanism discussed is epigenetic modulation of gene expression. It has been shown to occur in the offspring of pregnant females exposed to stressors and result in long-term neuroendocrine abnormalities. Patients with BPS/IC can also have other medical problems including irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, panic disorder, social anxiety, and mitral valve prolapsed.

Buffington notes that drugs to reverse the processes of epigenetic modulation of gene expression are under active investigation as cancer chemotherapeutic agents. This theory may explain some of the efficacy noted from central approaches to therapy of MUS including tricyclic antidepressants, psychological interventions, and education. Elgavish from Birmingham, Alabama has proposed a similar hypothesis (J. Urol., 181:980-984, 2009), and this intriguing perspective could, as Buffington suggests, result in new avenues of research and treatment.

Buffington CA

Psychother Psychosom. 2009 Mar 9;78(3):139-144
10.1159/000206866

PubMed Abstract
PMID: 19270468