Thesis A Psychobiological Approach to Gulf War Illness: Acute Exercise & DNA Methylation, 2025, Boruch

[forestglip]

A Psychobiological Approach to Gulf War Illness: Acute Exercise & DNA Methylation

Alexander E. Boruch

Thesis advisor: Dane B. Cook

[Line breaks added]

Background
Gulf War Illness (GWI) is a form of chronic multi-symptom illness characterized by medically unexplained and heterogenous symptoms (e.g., fatigue, pain, cognitive decline) that affect ~30% of personnel deployed during the 1990-1991 Persian Gulf War.

Controlled high- intensity or maximal aerobic exercise (i.e., an exercise challenge) have been used to modulate physiological stress responses in GWI. Investigations of DNA methylation in GWI are seldom, and exercise-induced changes in DNA methylation may provide insight into the molecular interactions underlying GWI pathophysiology.

Purpose
The primary purpose of the present dissertation is to compare differences in DNA methylation following an acute aerobic exercise challenge in Gulf War Veterans with and without GWI.

Methods
Differences in DNA methylation measured via microarray were tested in Gulf War Veterans with GWI (N = 27) compared to control Gulf War Veterans (N = 25) pre-, 30-minutes post-, and 24 hours post-exercise. Associations between DNA methylation, ventilatory equivalents during exercise, and pre-post symptom responses were also tested in Gulf War Veterans with and without GWI.

Results
Gulf War Veterans with GWI had differentially methylated positions (DMPs) in genes with established metabolic and immune functions, and DMP-associated genes with select inflammatory functions (e.g., response to IFN-β) were observed only after exercise.

Select DMPs were significantly associated with fatigue and mood disturbance 30-minutes post-exercise, and pre-exercise a DMP within the oxoglutarate dehydrogenase [OGDH] demonstrated modest classification accuracy (Area Under the Curve [AUC] = 0.796) between GWI cases compared to controls.

Conclusions
DMP-associated genes that participate in inflammation and metabolism are consistent with previous GWI investigations, including those that have studied DNA methylation. DNA methylation changes following an exercise challenge support involvement from the immune and metabolic systems in GWI pathophysiology and signify potential heightened risk of chronic comorbidities (e.g., cardiovascular or metabolic disease)

Web | PDF | Thesis: University of Wisconsin-Madison | Open Access

 

[rvallee]

I have no idea why they use the "psychobiological" term. There's discussion of PEM and ME/CFS, which isn't too far off course.

While the pathophysiological advances in GWI are promising, many questions about the underlying mechanisms remain, warranting integrative study approaches that assess a psychobiological model of disease.

They clearly mean typical biopsychosocial, but seem less militant about it. Maybe biopsychosocial is starting to lose its shine? I don't know.

 

[bobbler]

A Psychobiological Approach to Gulf War Illness: Acute Exercise & DNA Methylation

Alexander E. Boruch

Thesis advisor: Dane B. Cook

[Line breaks added]

Background
Gulf War Illness (GWI) is a form of chronic multi-symptom illness characterized by medically unexplained and heterogenous symptoms (e.g., fatigue, pain, cognitive decline) that affect ~30% of personnel deployed during the 1990-1991 Persian Gulf War.

Controlled high- intensity or maximal aerobic exercise (i.e., an exercise challenge) have been used to modulate physiological stress responses in GWI. Investigations of DNA methylation in GWI are seldom, and exercise-induced changes in DNA methylation may provide insight into the molecular interactions underlying GWI pathophysiology.

Purpose
The primary purpose of the present dissertation is to compare differences in DNA methylation following an acute aerobic exercise challenge in Gulf War Veterans with and without GWI.

Methods
Differences in DNA methylation measured via microarray were tested in Gulf War Veterans with GWI (N = 27) compared to control Gulf War Veterans (N = 25) pre-, 30-minutes post-, and 24 hours post-exercise. Associations between DNA methylation, ventilatory equivalents during exercise, and pre-post symptom responses were also tested in Gulf War Veterans with and without GWI.

Results
Gulf War Veterans with GWI had differentially methylated positions (DMPs) in genes with established metabolic and immune functions, and DMP-associated genes with select inflammatory functions (e.g., response to IFN-β) were observed only after exercise.

Select DMPs were significantly associated with fatigue and mood disturbance 30-minutes post-exercise, and pre-exercise a DMP within the oxoglutarate dehydrogenase [OGDH] demonstrated modest classification accuracy (Area Under the Curve [AUC] = 0.796) between GWI cases compared to controls.

Conclusions
DMP-associated genes that participate in inflammation and metabolism are consistent with previous GWI investigations, including those that have studied DNA methylation. DNA methylation changes following an exercise challenge support involvement from the immune and metabolic systems in GWI pathophysiology and signify potential heightened risk of chronic comorbidities (e.g., cardiovascular or metabolic disease)

Web | PDF | Thesis: University of Wisconsin-Madison | Open Access

Where’s the psycho bit at all with any of this abstract findings or tests other than it being shoved before the word biology or pathology in eg the title in a way it wouldn’t be for any illness like eg cancer psychopathology for finding that exercise caused worsening in certain chemical findings and inflammatory indicators - it would just be cancer pathology or findings without the bs

Have they not been through enough - are people really going to now shove veterans under MUS too just to ensure no vulnerable or ostracised or population with less power so can be coerced is untouched.

I find it so interesting when you think of the bps/psychosomaticists/pseudosciencepropagandists being the subject of study that they’ve picked illnesses affecting women , probably children within that get the even more horrific situation of coercion and misbehavior and then it’s soldiers . Who must be the toughest by virtue of their training and job and demographics plus, the filters thing must go through to be selected to be still on the front line. And yet in a position power wise that is different to people in other types of roles that are not in the military, so I can only assume that the control exerted there is a factor/issue.

 

[forestglip]

I started reading section "2.2.1. Post-Exertional Malaise in GWI". This is the first sentence about prevalence of PEM in GWI:

Prevalence estimates suggest that up to 96% (n=23/24) of GWVs with GWI report experiencing PEM.[6]

The study cited is this:

Peripheral cholinergic function in humans with chronic fatigue syndrome, Gulf War syndrome and with illness following organophosphate exposure (2004, Khan et al, Clin Sci)

The GWS group consisted of 24 patients, and these were veterans of the Gulf War who had developed chronic-fatigue-like symptoms. All patients had reported taking the cholinesterase inhibitor pyridostigmine bromide as nerve agent protection and reported possible exposure to one of a number of organophosphate insecticides used routinely at the time of the conflict in early 1991. They were recruited from a register of patients held by the Gulf War Veterans and Families Association, and all had symptoms classified as moderate to severe.

All 94 remaining patients fulfilled the Fukuda
1994 Centres for Disease Control classification for CFS.

Every one of the 24 GWI participants fulfilled the Fukuda CFS criteria (as did all the CFS and organophosphate exposed cases). 23/24 cases with GWI reported PEM.

This makes me think the study was specifically recruiting people with CFS, as another much larger study (Steele 2000) found that about 34% of gulf war veterans reported gulf war illness, but only around 7% reported CFS.

So I think the claim in the thesis - that 96% of veterans with GWI report PEM - may be based on a misunderstanding.