The CDC and Chronic Fatigue Syndrome: Altered Selves?

[Guest guest]

The CDC and Chronic Fatigue Syndrome: Altered Selves?

A Big Fish In A Small Pond: The Centers for Disease Control’s (CDC) chronic

fatigue syndrome (ME/CFS) research program is not a large one by medical

standards; it’s funding peaked at about 8 million dollars a year a couple of

years ago and is now down to about $4,000,000 a year. But since the disbanding

of the CFS ative Research Centers in 2002 by the NIH it’s the only

‘large

’ chronic fatigue syndrome (ME/CFS) research program in the United States.

Indeed it and the Japanese program are the only ‘large’ ME/CFS research

programs in the world.

Beside research the CDC has played the dominant role in defining chronic

fatigue syndrome (ME/CFS) and an important role in elucidating the prevalence,

economic costs and disability associated with the disease. It is the only

federal institution that has a training program for physicians, it has the

largest federal website on ME/CFS and it recently used ME/CFS to kick off it’s

first ever media campaign on a disease.

All this activity means the CDC’s chronic fatigue syndrome (ME/CFS) team,

lead by a Dr. Reeves, a vigorous if controversial figure, is a big fish in the

small pond that is ME/CFS. What the CDC says has the potential, at least, to

make a large difference in how ME/CFS is viewed. While the CDC has obviously

never been in lock step with the ME/CFS research community some recent

evidence suggests they are moving a new direction.

History: 2000-2007 - Since 2000 the CDC research team has been a pioneer in

gene expression research and in using innovative, multi-disciplinary means to

study ME/CFS. The Pharmacogenomic’s papers which combined data mining and

information systems experts, geneticists and biologists set a benchmark for

innovation. For the last five or six years the CDC CFS research team,

originally

composed mostly of virologists, has eschewed its immunological base to take

a primarily neuroendocrine approach to the disease. As the CDC drifted away

from immune research, however, the creation of the -Whittemore

Neuro-immune Institute and Dr. Chia's and Dr. Montoya's findings suggest a new

front

on immune issues has opened.

The advent of a controversial new definition for ME/CFS (Empirical

Definition) in 2005 indicated a substantial split between the With the advent

of this

theory paper the CDC’s research team appears ready to take its first more or

less complete stab at explaining ME/CFS. CDC’s view of CFS and a significant

group of other researchers has occurred. In an attempt to move from a fatigue

to an ‘unwellness’ based definition the CDC discounted fatigue and added an

emotional aspect to the definition for the first time. At the same time a

coterie of other researchers mostly associated with International Association

of Chronic Fatigue Syndrome/ME (IACFS/ME) were focusing more closely than ever

on a special kind of fatigue called ‘post-exertional malaise’. As

post-exertional malaise essentially disappeared from the CDC’s Empirical

Definition of

ME/CFS this group created pediatric and adult definitions which placed it

front and center.

With the advent of Dr. theory paper – the first by a CDC CFS

researcher that I know of – the CDC’s research team appears ready to take

its first

more or less complete stab at explaining ME/CFS. This paper suggests that Dr.

, if not the CDC team itself, feels the pieces are beginning to come

together. Dr. Reeves recent talk at the Nov. 07 CFSAC meeting suggests he is in

agreement with at least the broad outlines of the paper. Given the CDC’s

clout this paper is an important event in the field of ME/CFS research.

In this issue of Phoenix Rising we’ll first take a look at the theory paper

and then provide Dr. Reeve’s overview of the CDC’s research program at the

Nov CFSAC to get an overall direction of where this program is headed.

An Altered Self in CFS?

, J. 2007. An extended concept of altered self: chronic fatigue and

post-infection syndromes. Psychoneuroendocrinology. Feb;33(2):119-29. This is

the

first CDC ‘theory’ paper I can remember reading. More designed to provoke

discussion and thought than to explain CFS it focuses on a new interpretation

of chronic fatigue syndrome (ME/CFS).

Dr. first identifies what he believes chronic fatigue syndrome

(ME/CFS) is and is not: is it a disease or an illness? A ‘disease’ (e.g.

infectious

mononucleosis) is a state of ill health characterized by ‘overtly abnormal

findings’. An ‘illness’ is a state of poor health in which ‘overtly

abnormal

findings’ are not found; chronic fatigue syndrome, he believes, is an ‘

illness’.

An ‘illness’ is a state of poor health in which ‘overtly abnormal

findings’

are not found; chronic fatigue syndrome, he believes, is an ‘illness’.

To back up this characterization he notes the many ‘inconclusive’ attempts

to tie CFS to a specific pathogen and the over 100 immune studies that,

despite the immune alterations found, have often had inconsistent results. He

also

notes the HPA axis abnormalities and increasing evidence of sympathetic

nervous system problems and the potential for these problems to cause immune

disruption and autonomic and behavioral problems. Despite these abnormalities

he

believes chronic fatigue syndrome (ME/CFS) is an illness.

Dr. doesn’t suggest that there are no abnormal findings in chronic

fatigue syndrome (ME/CFS); he simply appears to believe they not ‘overtly

abnormal’ enough or significant enough to cause an ‘illness’ of this

severity.

Laymen’s Speculation - We can now point to many abnormalities in ME/CFS; NK

cell dysfunction, low blood volume, low HPA axis dysfunction, brain atrophy,

etc., very few of which appeared to have really ‘wowed’ the medical

research

community. Some appear to be only mildly abnormal (HPA axis functioning)

while others may be too new (RNase L fragmentation, pathogen studies) for the

research community to know what to do with. Some are just plain inconsistent

(cytokine studies, etc.).

When taken in total he believes these abnormalities are important but they’

re not so much important in and of themselves as what they signify. They

indicate to him a failure of the brain to adapt that’s probably centered in

the

stress response system. This is where the HPA axis and autonomic nervous system

and immune abnormalities come from; ME/CFS patient’s brains are not

responding well to the everyday demands put on them – they’re basically

stuck in a

kind of maladaptive state.

An Altered ‘Immune Self’. In order to frame his ‘altered self’ theory

Dr

introduces examples of the type of ‘self’ he is referring to. Several

types of altered immune ‘selves’ have been found. One occurs in autoimmune

disease in which the body mistakes itself for a pathogen and attacks itself.

During an infection the immune system in conjunction with the brain produces a

different kind altered ‘personal’ self which shows up in what researchers

call ‘sickness behavior’.

The infectious illness process affects our physiology (fever, swollen

glands), mental processes (slowed thinking), sensory system (fatigue) and

emotions

(irritability, a desire to be alone). Researchers speculate that these

changes are the brains way of getting us to devote energy to getting well and

isolate us in order to thwart the spread of infectious diseases. They have

documented changes in the central nervous system (prefrontal cortex and

anterior

cingulate) that occur during ‘sickness behavior’. This is powerful evidence

that far below our level of consciousness the brain can instill physical,

mental

and emotional states that it has decided will help us survive. Intriguingly

brain imaging studies have documented abnormalities in these same regions in

chronic fatigue syndrome (ME/CFS).

An Altered Central Nervous System Self – Given the similarity between ‘

sickness behavior’ and ME/CFS its not surprising that the altered self that

occurs during infection plays a key role in Dr. theory. Symptomatically

ME/CFS patients do look a lot like people with a chronic infection; they’re

very

fatigued, they’re sleepy, their muscles hurt, they’re a bit irritable, they

have trouble thinking, and they often become quite isolated.

But while many cases of chronic fatigue syndrome (ME/CFS) start with an

infection Dr. believes a different kind of ‘altered self’ - an

‘extended

altered self’ – is present. Why? Because studies have not consistently

found

the kinds of wildly altered immune processes known to create sickness

behavior in infection. ME/CFS studies, for instance, that measure cytokines

which

are believed to be the chief agents of sickness behavior, have had inconsistent

results. Dr. believes something else is at play. That something else

relies heavily on a relatively new theory about how the brain works called ‘

interoception’

Focus On Interoception

Recent theories posit that a portion of the brain unique to humans (called

the anterior insula) builds representations or pictures of the body. These

ideas appear to have been prompted by the discovery of a set of very small

nerves paralleling the sympathetic nervous system which deliver enormous

amounts

of information on the temperature, blood pressure, pH, lactic acid, histamine,

serotonin, etc. levels in the body to the lower part of the brain. In humans

the information appears to be sent to areas on both sides of the brain where

researchers believe a picture is formed of the body’s functioning. They

believe the brain uses this ‘picture’ to generate both conscious

(emotional/cognitive) and unconscious responses (blood pressure, heart rate,

etc.) to

maintain the body’s well-being or homeostasis.

Researchers have just begun teasing out which parts of the brain are

responsible for maintaining the different kinds of homeostasis found in the

body.

They are mostly found in the prefrontal cortex and anterior cingulate regions

mentioned above and connect with areas in the midbrain and brainstem.

The Altered Self in Chronic Fatigue Syndrome. This interoceptive self is a

third kind of self; one built by the brain to monitor and respond to the

signals of the body. This is the ‘self’ that Dr. believes is

dysfunctional

in chronic fatigue syndrome (ME/CFS). Dr. theory suggests that at very

deep level the brain has become confused or stuck in a maladaptive state. If I

’m reading this right Dr believes the brain

“this essay (is)…based on the premise that the illnesses in question stem

from responses to previous infections and not to ongoing viral or immunologic

factors†still thinks the body has an infection and its sending out message

consonant with this idea; it’s telling the body it’s fatigued, that it

should

slow down, that’s it dangerous to move, etc. It does this by prompting

certain thoughts and by altering the physiology of the body. Dr. believes

the ‘sickness behavior’ found in chronic fatigue syndrome (ME/CFS) was once

driven by an infection but is now being driven by the brain; it has become stuck

in sickness mode. This brain driven process is causing many of the endocrine

and immune abnormalities seen in ME/CFS.

Something must be causing this aberrant brain behavior and high up on the

list of Dr. suspects are immune processes in the brain. He proposes that

future research projects examine ‘immune/inflammatory system products’, and

both brain (and body) microglial cells and astrocytes as well as indications

that the autonomic nervous system is altered. Microglial cells man the first

line of immune defense in the central nervous system. Astrocytes are nerve

cells.

Researchers are beginning to figure out why some individuals may be more

disposed to enter in ‘sickness behavior’ mode than others. They’ve found,

for

instance, that a hyperactive stress response and increased levels of several

cytokines (IL-6, TNF) appear to predispose cancer patients given the immune

factor, Interferon alpha (IFN-a).

Since ‘sickness behavior’ is a ‘danger-driven’ process that activates

the

stress response many of the problems in ME/CFS could be due to a chronically

activated stress response. These presumably include the HPA axis dysfunction,

high rates of oxidative stress/inflammation, metabolic syndrome, NK cell

dysfunction, autonomic nervous system abnormalities, etc. found in ME/CFS.

Given his belief that ME/CFS constitutes a failure by the brain to adapt it’

s not surprising to see Dr. propose that studies which challenge the

different systems of the body are best suited to ME/CFS. He proposes that

challenge experiments using brain imaging technology should, in particular,

examine the areas of the brain involved in interpreting signals from the body

and

producing a response.

This is an intriguing idea because stress tests (fMRI’s, HPA axis stress

tests. etc) have, in fact, generally been more successful at uncovering

abnormalities than studies of the body when its at rest.

Treatment Dr. targets two parts of the brain; the higher brain areas

(prefrontal cortex) where the behavioral responses to the interoceptive

picture of the body are generated, and the lower parts of the brain where the

unconscious aspects of the interoceptive response (heart rate, breathing, blood

chemistry, etc.) are regulated. He proposes that the

“the term ‘altered self’..constitutes in the case of a prolonged illness,

a

failure to adapt to a different stateâ€. therapy of choice should depend on

which parts of the brain that brain imaging experiments indicate are impaired.

Abnormalities found in higher brain functioning would be meet with behavior

therapies designed to challenge the maladaptive thoughts generated by the ‘

wrong’ picture of the body. Abnormalities found in lower brain functioning

that

regulate breathing, heart rate, blood chemistry, etc. would be met with

drugs, biofeedback or meditation. The ultimate goal would be to ‘break the

‘

circle’ of chronic sickness behavior’ with all the connotations that the

medical

interpretation of behavior implies. The ultimate goal is to ‘return (the

ME/CFS patient) to a functional self state’.

Editorial. Some chronic fatigue syndrome (ME/CFS) patients have questioned

how Dr. , a virologist by training, could be speaking on a field like

interoception. The CDC’s original focus on chronic fatigue syndrome (ME/CFS)

was

on identifying the pathogen causing it and its program was placed in the

viral division under the direction of several virologists (Dr. Reeves, Vernon,

). These researchers presumably would have loved to find a virus at the

heart of this disorder. Rightly or wrongly at least Dr. Reeves and Dr.

no longer appear to believe this is true and they are looking elsewhere.

The senior members of CDC’s CFS research team are ending up spending a good

deal of their careers on this disease. Like researchers everywhere their

reputations will rise and fall on the strength of their ideas. While their

conception may be disturbing to some patients they should be examined in the

context of a group of researchers who’ve taken a long look at this disease.

They

may be right or they may wrong but their ideas should never be discarded out of

hand.

Dr. Reeves Report to the Chronic Fatigue Syndrome Advisory Panel on the CDC’

s CFS Research Program. Nov, 2007

Dr. Reeves report suggests that the CDC’s understanding of chronic fatigue

syndrome (ME/CFS) is in congruence with many of Dr. ideas. He reports

that ME/CFS, for instance, is highly associated with increased stress. The

markers of ‘allostatic load’ which measures the body’s ability to adapt

to

stress, are six times higher in ME/CFS patients than in the general population.

How ME/CFS occurs is unclear but Dr. Reeves believes it is an ‘adaptation

disorder’ that is associated with ‘early adverse experiences’ which can

range

from childhood abuse, infections, malnutrition and surgery. Whatever the

initiating problem the focus is on ‘early’; this is presumably a necessary

corollary of the allostatic load concept which requires that an accumulation of

insults occur over time. This is possibly why the rates of CFS - as do many

chronic systemic diseases – rise over time; incidence is lowest in childhood,

higher in adolescents and appears to peak in middle age. " People with CFS are

six times more likely...to have suffered severe childhood trauma...People

with CFS also have about a six-fold excess of allostatic load - a physiologic

marker of accumulated stress "

The allostatic stress paradigm also suggests why Dr. Reeves believes that

chronic fatigue syndrome (ME/CFS) is the type of illness that leads to disease.

These diseases (metabolic syndrome ???) presumably occur when after years of

a dysfunctional stress response different facets of the body finally break

down. The CDC’s detailed documentation of their study populations has

revealed

ME/CFS patients have a high incidence of other (usually untreated) physical

problems.

The pattern of cognitive problems in ME/CFS suggests damage has occurred to

the parts of the brain Dr. referred to; the circuits that link the

frontal cortex and the basal ganglia. Abnormalities in brain wave patterns

during

sleep suggest problems with ‘sleep homeostasis’ or attaining normal sleep

are present. The faster heart rates, lower heart rate variability,

Research Hot