Swedish research exchange

10 March 2009
University research helping to remove the barriers people face when returning to
work has been shared with policy makers at a leading conference in Stockholm.
Professor Mansel Aylward CB, Director of the Centre for Psychosocial and
Disability Research in the School of Psychology, headed a British team of
academics to the first conference of the new Social Council of Sweden at the
Ministry of Health and Social Affairs in Stockholm.
Professor Aylward, Dr Debbie Cohen and Professor Gordon Waddell outlined key
pieces of University research helping to explain and address the obstacles people
face in the UK when returning to work.

(From left to right) Dr Bob

Grove, Professor Dame Carol
Black, Professor Mansel
In his keynote address, Professor Aylward chronicled the development of
Pathways to Work in the UK and drew upon research undertaken by his team at Aylward, Dr Debbie Cohen,
Professor Gordon Waddell and
Cardiff which further explored obstacles to return to work and interventions to
Professor Peter White
address them..
Professor Aylward said: The first conference of the new Social Council of Sweden, at the invitation of the Swedish
Government, was an opportunity to share our research knowledge with academics, researchers, healthcare
professionals and senior government advisors, officials and politicians - including Swedens Secretary for Health
and Social Affairs, Bettina Kashefi , on what works.
We hope our presentations will provide the scientific and research knowledge to inform the Swedish
Governments plans for Welfare reform.
The Conference was also addressed by other key UK academics. Dr Bob Grove of The Sainsbury Centre, Kings
College London gave an update on the evaluation of the Pathways to Work project; Professor Peter White of
Barts and the London School of Medicine discussed Symptoms Defined Illness and their handling in occupational
rehabilitation and Professor Dame Carol Black, UK National Director for Health, Work and Well-being, outlined the
findings of a review of the health of Britain's working age population: Working for a healthier tomorrow.
Professor Aylward and his team from Cardiff also spent a day at the Karolinska Institute. Meeting with Professor
Alexanderson, who chairs the Swedish Social, it was an opportunity to explore joint research opportunities.
Professor Aylward added: The visit to the Karolinska Institute allowed us to discuss and set out the basis for
collaboration between the Karolinska Institute and Cardiff University. We hope this will lead to joint research in the
area of health and work.

Related links
Centre for Psychosocial and Disability Research
Department for Work and Pensions

What helps occupational

rehabilitation when the doctor
cannot explain the symptoms?

Peter White

Agenda
Symptom defined illnesses (SDIs)
The example of chronic fatigue
syndrome
Biopsychosocial management is best
Prevention is even better

10
8

Symptoms
Organic Cause

3-Year 6
Incidence
4
(%)
2

ss
ain tigue iness ache dema Pain hagia mnia in
e
p
n
t
b
k sp nso l Pa
E
es Fa Dizz Head
c
m
a
h
u
I
y
B
C
N
D
ina
m
o
Abd
Kroenke, et. al., AJM, 1989

Prevalence of unexplained
symptoms in hospital clinics
Clinic

Prevalence %

Chest
Cardiology
Gastroenterology
Rheumatology
Neurology
Dental
Gynaecology

59
56
60
58
55
49
57

Total

56

Symptom defined illnesses

Tension headaches,
Atypical facial and chest pains
Fibromyalgia (chronic widespread pain)
Other chronic pain disorders
Irritable bowel syndrome
Multiple chemical sensitivity
Chronic (postviral) fatigue syndrome (ME)

How common is CFS?

0.2 - 2.6 % population or primary care

Risk (OR) of depressive illness with

chronic physical disorders
CFS

7.2

Fibromyalgia

3.4

Peptic ulcers
COPD
Migraine
Back pain
Cancer
MS

2.8
2.7
2.6
2.3
2.3
2.3

UK costs of CFS
118,000 on incapacity benefit
19,000 on disability living allowance
+ Cost of medical and social care
+ Loss of employment

Outcome is poor without treatment

Systematic review of longitudinal studies
5 % (range 0 - 31) recovered by follow up
39 % (range 8 - 63) some improvement
Cairns R, Hotopf M, Occup Med 2005

Use the biopsychosocial model

The biopsychosocial model takes into
account the patient, the social content in
which he lives and ... the physician role and
the health care system.
George Engel, 1977

Management is biopsychosocial
Biological
e.g. medication, physical rehabilitation
Psychological
e.g. CBT

Social
Remove the barriers to recovery Relationships .. at work or home
Iatrogenic .. bad healthcare advice
Benefit gap .. financial incentives

The lost art of rehabilitation

We have forgotten not only how to
rehabilitate patients, but that we need to do
so for the patient to make a full recovery.

Graded exercise therapy for CFS

Exercise = an activity requiring physical
effort

Percentage improved with GET

70
60
50
GET
Control

40
30
20
10
0
UK

UK

UK

NZ

Austral

Percentage improved with CBT

80
70
60
50
CBT
Control
Control

40
30
20
10
0
UK

UK

NL

NL

UK

But do these treatments help patients

return to work?
Only cognitive behavior therapy,
rehabilitation, and exercise therapy
interventions were associated with restoring
the ability to work.
- Even without occupation as the aim.
Systematic review: SD Ross et al, Arch Intern
Med 2004

Predictions of non-response to
GET
High psychological distress
Membership of a self-help group
Sickness benefit
R Bentall et al, 2002

Social risks
If you have to prove you are ill, you cant get
well. (N Hadler, 1996)
ME is an incurable disease.
(UK doctor, 2008)

Does the BPS approach work?

CFS
Low back pain
IBS
Depressive illness
(Cardiac disease)
(DM)

Preventing SDIs
Patients with infectious mononucleosis
Brief rehabilitation, with graded return to
activities
Compared to leaflet

By 6 months, 26% had abnormal fatigue after

rehab, compared to 50% of controls.
B Candy et al, 2004

What is chronic fatigue syndrome;

and what is ME?

Peter White
Barts and the London

Agenda
What is CFS?
ICD-10
Research criteria
Clinical criteria
One functional somatic syndrome versus heterogeneity

What is ME?
Original epidemic ME
Diagnostic labels affect prognosis

Is it physical or mental? Its both

Does the ICD-10 help us?

No At least five ways to classify CFS

Myalgic Encephalomyelitis
G93.3 in Neurology chapter of ICD-10
Postviral fatigue syndrome,
Includes:
benign myalgic encephalomyelitis
Chronic fatigue syndrome, postviral

Neurasthenia
F48 in ICD-10 mental disorders chapter
Neurasthenia
Excludes postviral fatigue syndrome
Includes fatigue syndrome

Other ways to classify CFS

F45.1 Undifferentiated somatoform disorder
F45.3 Somatoform autonomic dysfunction
Includes:
Da Costa syndrome,
Neurocirculatory asthenia

F45.9 Somatoform disorder, unspecified

Other ways to classify CFS

R53.82 Chronic fatigue, unspecified
Includes:
Chronic fatigue syndrome NOS

R54 Senile asthenia!

7 research criteria

CDC 1988
Australian 1990
Oxford 1991
London ME 1993
CDC revised 1994
CDC revised 2003
Brighton (post-vaccine) Collaboration, 2007

CDC (international) definition of

CFS
6/12 of persistent/relapsing unexplained
fatigue
of new onset
not the result of on-going exertion
not substantially relieved by rest

CDC CFS
4 associated symptoms:
sore throat
tender lymph glands
myalgia
arthralgia
new headaches
unrefreshing sleep
post-exertion malaise
poor memory or concentration

CDC definition of CFS

Substantial disability
Medical and psychiatric exclusions

No empirical support
Population study of Swedish twins (31,000):
CFS-like illness; no CDC specificity
Sullivan et al, 2005, Kato et al

Population study of 1,468 pairs of 8-17 year olds

CDC not delineated
Fowler et al, 2005

CDC population studies in Wichita & Georgia:

For every patient with CDC CFS, 2-8 times more with
disabling fatigue.

3 clinical criteria
Canadian 2003
RCPCH 2004
NICE 2007

Canadian criteria for ME

Fatigue
Post-exertional fatigue/malaise
Sleep dysfunction
Pain

Any 2 of:
confusion, impairment of concentration and short-term
memory consolidation, disorientation, difficulty with
information processing, categorizing and word retrieval,
and perceptual and sensory disturbances e.g. spatial
instability and disorientation and inability to focus
vision. Ataxia, muscle weakness and fasciculations are
common. There may be overload phenomena: cognitive,
sensory e.g. photophobia and hypersensitivity to noise
- and/or emotional overload, which may lead to crash
periods and/or anxiety.

At Least One Symptom from Two of the Following:

__ a. Autonomic Manifestations: orthostatic intolerance - neurally
mediated hypotension (NMH), postural orthostatic tachycardia
syndrome (POTS), delayed postural hypotension; light-headedness;
extreme pallor; nausea and irritable bowel syndrome; urinary
frequency and bladder dysfunction; palpitations with or without
cardiac arrhythmias; exertional dyspnea.
__ b. Neuroendocrine Manifestations: loss of thermostatic stability
subnormal body temperature and marked diurnal fluctuation,
sweating episodes, recurrent feelings of feverishness and cold
extremities; intolerance of extremes of heat and cold; marked weight
change - anorexia or abnormal appetite; loss of adaptability and
worsening of symptoms with stress.
__ c. Immune Manifestations: tender lymph nodes, recurrent sore
throat, recurrent flulike symptoms, general malaise, new sensitivities
to food, medications and/or chemicals.

NICE
4 months of fatigue with:
new or specific onset (not life long)
persistent and/or recurrent
unexplained
substantial reduction in activity
- characterised by post-exertional
malaise/fatigue

NICE 2
One of:
- The 8 CDC symptoms plus:
- general malaise or flu-like symptoms
- dizziness and/or nausea
- palpitations in the absence of identified
cardiac pathology
- Normal exclusions

RCPCH
..generalised fatigue causing significant
impairment for 6/12 months for which no
alternative explanation has been found...
..the fatigue is likely to be associated with
other classical symptoms (..) such as
difficulty in concentrating and disturbed sleep
patterns and is classically exacerbated by effort
(both mental and physical).

One functional somatic syndrome

CFS patients have close comorbidity with:
Irritable bowel syndrome
Fibromyalgia
Regional pain disorders
Are they all part of the same disorder,
presenting to different specialists?
YES - Wessely and Sharpe, Lancet 1999
NO White, 2004

CFS studies with symptoms and

demographics
744 clinic patients: 68% neurasthenia, 32%
somatoform disorder
Hickie et al, 1995 & 2001

All studies since have found heterogeneity

Is the CFS endophenotype

heterogeneous?

Analysis
Latent Class Analysis (LCA)
121 chronically fatigued women
38 healthy matched controls

Five ill sub-groups

1.
2.
3.
4.
5.

Obese & hypnoeic

Obese, hypnoeic & stressed
Insomnia & pain (myalgia)
Polysymptomatic, depressed
Polysymptomatic, depressed, stressed,
insomniac and menopausal
Vollmer-Conna et al, 2006

External validation of groups

5 groups: demographic and clinical

2 groups; gene expression
3 groups: gene polymorphisms
Replication in Georgian sample

Should we give up the diagnosis of

CFS/ME?
A working hypothesis:

CFS/ME may be the final common pathway

from several different diseases with the same
clinical presentation
It has utility, particularly for treatment

To lump or split?
Population study of Swedish twins (31,000):
Two latent comorbid traits
1 dominated by mood disorders
2 all other disorders (FM, CFS, IBS, headaches)
neither lumpers nor splitters are correct
Kato et al (in press)

GPRD study
4,388 patients with CFS/ME/PVFS
IBS and healthy matched controls
Both ill groups - more premorbid mood and
other functional disorders
But triggering infections differentiated
them.
Gallagher et al, submitted

What is ME?
Myalgic encephalomyelitis
First described in a 1956 Lancet editorial
describing epidemics of fatigue with
neurological symptoms and signs the
author later regretted doing this.

Royal Free epidemic of 1955

(Ramsay)
74% showed objective evidence of
involvement of the central nervous system
- heavy involvement of the cranial nerves
- Objective evidence of brain stem and
spinal cord involvement..
- Paralysis of the face occurred in just under
20%..

ME
April 1978 conference - at the RSM!
Organic incurable neurological disease
What message does this give our patients?

The effect of a doctors ME

label on prognosis
ME lasted longer than CFS.
ME patients had more consultations both
in general and specifically for fatigue.
No differences before diagnosis

Conclusions
CFS/ME exists, but is hard to define
Broad based definitions are best
Both heterogeneity and comorbidity should
be addressed
Beware what you mean when you give a
diagnosis

Robert Kendell: The distinction

between mental and physical illness
Not only is the distinction between mental
and physical illness ill-founded and
incompatible with contemporary
understanding of disease, it is also
damaging to the long-term interests of
patients themselves.
BJ Psych 2001

Kendell again
..if we do continue to refer to mental and
physical illnesses we should preface both
with so-called, to remind ourselves and
our audience that these are archaic and
deeply misleading terms.
BJ Psych 2001

What is CFS, and what is ME?

Peter White
Bergen, October 20th 2009

Agenda

What is CFS?
What is ME?
Define your phenotype

XMRV and CFS

How you define CFS will

determine what you find

Does the ICD-10 help?

No At least six ways to classify CFS

Myalgic Encephalomyelitis
G93.3 in Neurology chapter of ICD-10
Postviral fatigue syndrome,
Includes:
benign myalgic encephalomyelitis
Chronic fatigue syndrome, postviral

Neurasthenia
F48 in ICD-10 mental disorders chapter
Neurasthenia
Excludes postviral fatigue syndrome
Includes fatigue syndrome

Other ways to classify CFS

F45.1 Undifferentiated somatoform disorder
F45.3 Somatoform autonomic dysfunction
Includes:
Da Costa syndrome,
Neurocirculatory asthenia

F45.9 Somatoform disorder, unspecified

Other ways to classify CFS

R53.82 Chronic fatigue, unspecified
Includes:
Chronic fatigue syndrome NOS

R54 Senile asthenia!

Can we use research criteria?

7 to choose from

7 research criteria

CDC 1988
Australian 1990
Oxford 1991
London ME 1993
CDC revised 1994
CDC revised 2003
Brighton (post-vaccine) Collaboration, 2007

CDC (international) definition of

CFS
6/12 of persistent/relapsing unexplained
fatigue
of new onset
not the result of on-going exertion
not substantially relieved by rest

CDC CFS
4 associated symptoms:
sore throat
tender lymph glands
myalgia
arthralgia
new headaches
unrefreshing sleep
post-exertion malaise
poor memory or concentration

CDC definition of CFS

Substantial disability
Medical and psychiatric exclusions

Recent audit of my clinic

250 new patients seen
54 (22%) - alternative psychiatric diagnosis
47 (19%) - alternative medical diagnosis

Risk of major depressive illness with

chronic physical disorders
CFS
Fibromyalgia
Peptic ulcers
COPD
Migraine
Back pain
Cancer
MS

7.2
3.4
2.8
2.7
2.6
2.3
2.3
2.3

SB Patten et al, 2005 (n = 115,071)

No empirical support for CDC

criteria
Swedish twin population study
(n = 31,000):
CFS-like illness; no CDC specificity
Sullivan et al, 2005, Kato et al, 2008
CDC population studies in USA:
For every patient with CDC CFS, 2-8
times more with disabling fatigue.

3 clinical criteria
Canadian 2003
RCPCH 2004
NICE 2007

Canadian criteria for ME

Fatigue
Post-exertional fatigue/malaise
Sleep dysfunction
Pain

Any 2 of:
confusion, impairment of concentration and short-term
memory consolidation, disorientation, difficulty with
information processing, categorizing and word retrieval,
and perceptual and sensory disturbances e.g. spatial
instability and disorientation and inability to focus
vision. Ataxia, muscle weakness and fasciculations are
common. There may be overload phenomena: cognitive,
sensory e.g. photophobia and hypersensitivity to noise
- and/or emotional overload, which may lead to crash
periods and/or anxiety.

At Least One Symptom from Two of the Following:

__ a. Autonomic Manifestations: orthostatic intolerance - neurally
mediated hypotension (NMH), postural orthostatic tachycardia
syndrome (POTS), delayed postural hypotension; light-headedness;
extreme pallor; nausea and irritable bowel syndrome; urinary
frequency and bladder dysfunction; palpitations with or without
cardiac arrhythmias; exertional dyspnoea.
__ b. Neuroendocrine Manifestations: loss of thermostatic stability
subnormal body temperature and marked diurnal fluctuation,
sweating episodes, recurrent feelings of feverishness and cold
extremities; intolerance of extremes of heat and cold; marked weight
change - anorexia or abnormal appetite; loss of adaptability and
worsening of symptoms with stress.
__ c. Immune Manifestations: tender lymph nodes, recurrent sore
throat, recurrent flulike symptoms, general malaise, new sensitivities
to food, medications and/or chemicals.

NICE
4 months of fatigue with:
new or specific onset (not life long)
persistent and/or recurrent
unexplained
substantial reduction in activity
- characterised by post-exertional
malaise/fatigue

NICE 2
One of:
- The 8 CDC symptoms plus:
- general malaise or flu-like symptoms
- dizziness and/or nausea
- palpitations in the absence of identified
cardiac pathology
- Normal exclusions

CDC criteria give you reliability,

but not validity.
Always measure comorbid
conditions.

Is the CFS heterogeneous?

The measures, US style!

Medical and drug history
Hormones ++
Immune tests +
Polysomnography
Gene polymorphisms
Gene expression

Symptoms
Disability
IQ
Psychiatric exam

Analysis

Principal components analysis (PCA)

Latent Class Analysis (LCA)
121 chronically fatigued women
38 healthy matched controls
Vollmer-Conna U et al, 2006

Five endophenotypes
1.
2.
3.
4.
5.

Obese & hypnoeic

Obese, hypnoeic & stressed
Insomnia & pain (myalgia)
Symptomatic, depressed
Symptomatic, depressed, insomnia,
stressed and menopausal

External validation of
endophenotypes

5 groups: demographic and clinical

3 groups; gene expression
3 groups: SNPs
Replication in Georgian sample
Aslakson E et al, 2009

One functional somatic syndrome

CFS patients have close comorbidity with:
Irritable bowel syndrome
Fibromyalgia
Regional pain disorders
Are they all part of the same disorder,
presenting to different specialists?
YES - Wessely and Sharpe, Lancet 1999
NO Wessely and White, 2004

UK GPRD study
4,388 patients with CFS/ME/PVFS
IBS and healthy matched controls
Both ill groups - more premorbid mood and
other functional disorders
But triggering infections differentiated
them.
Gallagher A et al, 2009

Common factors predispose to all

functional somatic syndromes

Uncommon triggers differentiate

functional somatic syndromes

What is ME?
Myalgic encephalomyelitis
First described in a 1956 Lancet editorial
describing epidemics of fatigue with
neurological symptoms and signs.

Royal Free hospital epidemic of

1955
(M Ramsay)
74% showed objective evidence of
involvement of the central nervous system
- heavy involvement of the cranial nerves
- Objective evidence of brain stem and
spinal cord involvement..
- Paralysis of the face occurred in just under
20%..

When did ME become endemic?

1978 conference - at the UK RSM
Epidemic ME became endemic
Organic incurable neurological disease
What message does this give our patients?

The effect of a doctors ME

label on prognosis
ME lasted longer than CFS.
ME patients had more consultations both
in general and specifically for fatigue.
No differences before diagnosis
Hamilton WT et al, 2005

Conclusions

CFS exists, but is hard to define

Make sure its not something else
Watch out for comorbid disorders
Beware what you mean when you give a
diagnosis

What causes CFS/ME, and does this

determine treatment?

Peter White
Bergen, October 20th 2009

Agenda
What causes it?
Predisposing
Triggers

What maintains it?

Perpetuating

Do these determine treatments?

Predisposing risk markers

Female
Age puberty to retirement (39)
Previous functional somatic
syndromes
(Previous mood disorders)
(Childhood traumas)

Stress as antecedents
3 8 times risk of childhood trauma
C Heim et al, 2006 & 2008 (retrospective)
1.6 risk of feeling stressed, measured 25 years
previously (case control)
6 x risk of feeling stressed compared to co-twin
K Kato et al, 2006 (prospective)

Genes
Gene expression highly variable and not
replicated.
Glucocorticoid receptor SNP x 3 risk
Rajeevan M et al, 2007
Sub-groups associated with MA and GR
SNPs
Smith A et al, 2006

Predisposing activity
Childhood inactivity?
Childhood and adult overactivity?
Retrospective perception of
overactivity/super fit and
healthy?

Activity and birth cohorts

Underactive childhood (1970 BC)
Overactive childhood (1946 BC)
Overactive adulthood (1946 BC)
None of the above (1958 BC)

Triggering risk markers

Certain infections:
e.g. EBV, Coxiella Burnetii,
Hepatitis A,
Parvo? Giardiasis?

Stressful events or difficulties?

Not: immunisations

Maintaining risk markers

Older age, mood disorders, illness
beliefs, inactivity, sleep problems,
search for legitimacy, benefits,
diagnostic label
Not: immune or viral measures

The biopsychosocial and

biomedical models
Biomedical model is the reduction of illness
to measurable biological parameters
Edward Shorter, 2003

Biopsychosocial model takes into account

the patient, the social content in which he
lives and ... the physician role and the
health care system.
George Engel, 1977

Does knowledge of causes

determine treatment?

Yes and no

Treatment of CFS
Cognitive behaviour therapy
Graded exercise therapy

D Chambers et al, 2006

J Malouf et al, 2008

Initial
infection
Beliefs
Rest or
boom & bust

Fatigue
Bodily
adaptation
Sleep
problems

What changes with GET?

Physical fitness and strength
Exercise capacity
Perception of effort

Physiological changes with GET

13 % increase in peak VO2
27 % increase in strength
Not associated with feeling better
Reduced sub-max heart rate response to exercise
Associated with 18 % increase in treadmill time

Sense of effort normalises with GET

Graded Exercise Therapy

Graded Exposure Therapy
(Physical reconditioning)

It changes the brain more than the body

Beliefs and behaviour change with

GET
15 % believed physical deconditioning was the
cause of CFS before, compared to 81 % after
treatment.
= BCT

Conclusion
CFS is multifactorial
Biological, psychological and social
Heterogeneous and homogeneous
Rehabilitation works, but not as we know it.

The distinction between mental and

physical illness
The distinction between mental and physical
illness is ill-founded and incompatible with
contemporary understanding of disease

Robert Kendell, BJ Psych 2001

Robert Kendell again

..if we do continue to refer to mental and
physical illnesses we should preface both
with so-called, to remind ourselves and
our audience that these are archaic and
deeply misleading terms.

Treatments for chronic fatigue

syndrome

Peter White
Bergen, 2009

Agenda

Trials of graded exercise therapy

Trials of cognitive behaviour therapy
How do they work?
What we dont know PACE trial

How do you treat it?

By helping the patient remove the barriers
to their recovery.

5 systematic reviews all conclude

that behavioural treatments work
with little or no harm

Graded exercise therapy

Percentage improved with GET

70
60
50
GET
Control

40
30
20
10
0
UK

UK

UK

NZ

Austral

Wearden A et al, 1998

33% dropped out (<12% in other trials)

Only 5 sessions in 3/12
Higher initial intensity of exercise
Physiological improvement before
increasing exercise

Graded Exercise Therapy

Exercise = an activity requiring physical
effort

Graded Exercise Therapy

Explanation/education
Assess physical capacity
Establish baseline activity
Individualised home exercise
Duration then intensity
Target heart rates
Feedback and explanation

Cognitive behaviour therapy

Trials of CBT

10 randomised trials
Excluding 2 not aimed to help recovery
Excluding 2 not using CB therapists
Excluding Lenny Jasons trial

Percentage improved with CBT

80
70
60
50
CBT
Control
Control

40
30
20
10
0
UK

UK

NL

NL

UK

CBT for CFS

(a) Assessment of illness beliefs and coping
strategies
(b) Structuring of daily rest, sleep and
activity, with a gradual return to normal
activity
(c) Challenging unhelpful beliefs about
symptoms and activity

Do effects last?
Yes
2 years after GET
5 years after CBT
Those who stop self-management relapse?

Are they cures?

In some - Yes
23% recovered immediately after CBT
25 % recovered 5 years after CBT
(compared to 5 % without treatment)

Fears of behavioural approaches

50% report being worse after graded
exercise therapy in a patient charity survey
CBT means its all in my mind

Whats the problem?

..when it comes to ICD10 G93.3 Myalgic
Encephalomyelitis, the somatoform
psychiatrists are fundamentally wrong.
Meanwhile the "fatigue" clinics will ..
be fiddling with ME patients - testing them
with nothing other than psychological
interventions that do not address the
underlying biomedical abnormalities in
people with Myalgic Encephalomyelitis.

Banishing fears of behavioural

approaches
Those reporting harm with GET had not
received appropriately supervised graded
exercise therapy, and diagnosis uncertain.
CBT is associated with 5 mls increase in
grey matter in the brain and normalisation
of HPA axis.

What we dont know

Why do some not improve?

Is pacing as effective?
How about therapy AND good medical care?
Mediators
Moderators

Pacing, graded Activity and

Cognitive behaviour therapy: a
randomised Evaluation
White PD, Sharpe MC, Chalder T, (PIs)

Aims

Efficacy and adverse effects

Health economics and societal costs
Moderators
Mediators

Problems and solutions

How to define the illness
Oxford criteria widest generalisation
Stratify by CDC and ME most different

Moderators
Stratify by comorbid major depression

What are the outcomes?

Both symptoms and disability

Inclusion criteria
Chalder Fatigue Questionnaire score is 6
or more
SF-36 physical function sub-scale score
is 65 or less
> 17 years old

Exclusion criteria
Medical exclusions
Risk of self harm and other exclusionary
psychiatric diagnoses, assessed by SCID
Those unable to do therapies e.g. language
problems

Treatments
Manualised
Each based on different model
1st session 90 minutes and subsequent sessions up to 50
mins
14 + 1 booster follow up session at 36 weeks
Some by telephone if necessary

Integrity of therapy

Group and individual supervision

Manuals patients and therapists
Pilot patients
Measuring competency
Listening and rating tapes throughout trial
What happens when some-one leaves
Measures of treatment adherence

Primary Outcomes
Summary stats on fatigue and disability
Clinically significant?
Fatigue (50% reduction in fatigue or a score of 3
or less)
SF-36 (a score of 75 or 50% increase from
baseline)

Secondary outcomes

Other CFS criteria & symptoms (ME)

Clinical Global Impression change score
Adverse effects
Activity and fitness
Mood
Sleep
Economic

Adverse Events

Serious adverse events (SAEs)

Serious adverse reactions (SARs)
Non serious adverse events
Follow up after adverse events
Policy for deteriorating participants

What PM thought about PACE

As will all serious illnesses, it is important
that patients, their families and the
healthcare professionals looking after them
have the best scientific information
available and the PACE trial has been
designed to help them decide for themselves
what treatment is likely to be best from
them.
www.number-10.gov.uk/output/Page14656.asp

Recruitment problems

New centre
Extending trial
Publicity
Prime Ministers support!

Other trial difficulties

Departures from protocol
Additional therapy during & after the trial
Absence of a therapist (holidays, sick leave,
maternity cover)
Recruitment and training of new therapists

Treatment issues

Ownership
Non-specific therapist effects
Ensuring equipoise
Doctors!

641 patients
3% drop out from follow up
6% drop out from treatment
Follow up ends in December
Results autumn 2010?

Conclusions
Individually delivered CBT and GET are
the best evidence based treatments
We should offer them to all our patients
Which treatment for which patient?
Can we do them more quickly?
Can we do better?

PeterWhite,CFS:neurological,psychologicalorboth?

THEBRITISHNEUROPSYCHIATRYASSOCIATION
www.bnpa.org.uk
NeurologyandPsychiatrySpRsTeachingWeekend
12to14December2008
StAnnesCollegeOxford
WoodstockRoad,OX26HS

THEESSENTIALSOFNEUROPSYCHIATRY
TheBritishNeuropsychiatryAssociation
NeurologyandPsychiatrySpRsTeachingWeekend
12to14December2008
StAnnesCollege,Oxford
NeurologyandPsychiatrySpRsTeachingWeekend.Handbook.
www.bnpa.org.uk

Welcome

Introduction

Neurologistsandpsychiatristsbothcareforpatientswithdisordersofthebrain
and its functions, yet there is remarkably little common training in the two
disciplines.Thereisoftenbothaculturalandphysicaldividebetweenthecare
ofthebrainandthecareofthemind.Theaimofthisweekend,thefirstofits
kind, is to bring together roughly equal numbers of neurology and psychiatry
trainees, for a course that will cover the more basic aspects of assessment
history taking and examination in the two specialties, review the use of the
commonapproachestoinvestigation,andthencoveraseriesofmajortopicsin
neuropsychiatry, particularly in areas that tend to be neglected, such as
functionalorsomatoformdisordersanddisordersofsleep.Weaimtoinspireas
well as instruct, so we have leavened the mix with some talks that will give
glimpses of exciting current research on mind and brain. We hope that the
meetingasawholewillbeinformalandhighlyinteractive.

This a new venture for the British Neuropsychiatry Association which exists to
foster education in the middle ground between these disciplines. Our main
activity is to hold an annual twoday meeting, in February, which, uniquely,
attractspsychiatrists,psychologistsandneurologists.Ifyouenjoythisweekend,
why not join the BNPA, and come to our 2009 meeting (56th February at the
InstituteofChildhealth)?

We are very grateful to UCB and Biogen for substantial support from
unrestrictededucationalgrantswhichhavekeptdownthecostofthemeeting.

AdamZeman
BNPAChairman

TheBritishNeuropsychiatryAssociation
NeurologyandPsychiatrySpRsTeachingWeekend
12to14December2008
StAnnesCollege,Oxford
NeurologyandPsychiatrySpRsTeachingWeekend.Handbook.
www.bnpa.org.uk

Chronicfatiguesyndrome:neurological,psychologicalorboth?

PeterWhite,ProfessorofPsychologicalMedicine,
BartsandtheLondonMedicalSchool
p.d.white@qmul.ac.uk

EpidemiologyoffatigueandCFS

Fatigueisacommonsymptominboththecommunityandprimarycare.When
asked,between10and20percentofpeopleinthecommunitywillreportfeeling
abnormally tired at any one time. At the same time, fatigue is continuously
distributedwithinthecommunity,withnopointofrarity.Thereforeanycutoff
is arbitrary and the prevalence will vary by how the question is asked, the
symptom volunteered, and its context. Between 1.5 % and 6.5 % of European
patients will consult their general practitioner with a primary complaint of
fatigueeveryyear,theincidencevaryingbyageandpopulation.Fatigueismore
commonly reported and presented to general practitioners by women and the
middleaged, and is most closely associated with mood disorders and reported
stress.ItdoesnotseemtovarybyethnicityintheUK,butthereisanintriguing
paradoxinthatitisreportedmorecommonlybythoseinhighincomecountries,
yetispresentedtomedicalcaremoreofteninlowincomecountries.

Prolonged or chronic fatigue is significantly less common than the symptom of

fatigueanditisonlyinthelast10yearsthatconsensushasemergedaboutthe
existence of a chronic fatigue syndrome (CFS), also called myalgic
encephalomyelitis (ME). CFS is now accepted as a valid diagnosis by medical
authoritiesintheUK,intheUnitedStatesofAmerica,aswellasinternationally.
Aboutonethirdofpatientspresentingtotheirdoctorwithsixmonthsoffatigue
will meet criteria for a chronic fatigue syndrome. The other two thirds have
fatiguesecondarytoanothercondition,mostcommonlymoodandprimarysleep
disorders. Its primary symptom is fatigue, both physical and mental, which
particularly follows exertion. Other symptoms agreed in consensual guidelines
include poor concentration and memory, sleep disturbance, headache, sore
throat, tender lymph glands, muscle and joint pain. There are several criterion
baseddefinitionsofCFS.Thesedefinitionswerederivedbyconsensusandhave
notbeensupportedbyempiricalstudies,andcontinuetoberefined.Theirutility
stems from providing reliable criteria for research studies, rather than clinical
use. The prevalence of CFS is between 2.5 % and 0.4 % depending on the
definition used and whether comorbid mood disorders are excluded (that is

mood disorders that are not thought to be the primary diagnoses). It is most
commoninwomen,themiddleaged,andethnicminorities(unlikefatigue)at
leastinEnglishspeakingcountries.

ThediagnosisandclassificationofCFS

The clinical taxonomy for CFS is a mess. The ICD10 classification defines CFS
within both the neurology chapter and mental health chapters. Myalgic
encephalomyelitis, the alternative name for CFS, is classified as a neurological
disease (G93.3)(a.k.a. postviral CFS), whereas neurasthenia (a.k.a. CFS not
otherwise specified) is classified within mental health (F48). (Incidentally, this
mess is not specific to CFS, since there are several conditions within the
neurology chapter of ICD10 that are also classified in the mental and
behavioural disorders chapter. For instance, Alzheimers disease is classified
within neurology, whereas dementia due to Alzheimers disease is classified
under mental health. My personal view is that it is high time that all mental
health disorders and neurological diseases affecting the brain were classified
within the same chapter, simply called diseases/disorders of the brain and
nervous system.) There is also a current debate between lumpers and
splitters about the nosology of functional somatic syndromes (symptom
defined conditions), such as CFS, IBS and fibromyalgia. Some argue that the
closeassociationsbetweenthesyndromes(thosewithCFSarealsomorelikely
to have fibromyalgia and/or IBS) argues in favour of their being different
manifestations of one overarching functional somatic syndrome (the
lumpers).Othersarguethatthesesyndromesarebestunderstoodbyexploring
their heterogeneity (the splitters). There is evidence to support both
arguments,buttwolargeandrecentepidemiologicalstudiessuggestthatchronic
unexplained fatigue, for one, is both associated with and separate from other
functional somatic syndromes. In particular, predisposing risk factors are
sharedwhereastriggeringfactorsaredifferent.

CFSisnotaneasydiagnosistomake,sincemisdiagnosisiscommoninpatients
diagnosedashavingCFS.ArecentauditofmyCFSclinicrevealedthat4outof10
newpatients(n=250)assesseddidnothaveCFS,andthatwasafterathirdof
referrals had already been rejected as not being CFS. The most common
misdiagnoses were mood disorders, especially depressive disorders, and
primarysleepdisorders,particularlysleepapnoea.Othermisdiagnosesincluded
coeliac disease and autoimmune conditions. Alternative neurological diagnoses
weremadein2%.

Aetiologyandpathophysiology

The aetiology of CFS is unknown, but there is evidence that different risk
markers are associated with predisposition, triggering, and maintenance of the
illness. Predisposing risk markers include female sex, middle age, mood
disorders(especiallydepressivedisorders),othersymptomdefinedsyndromes,
such as irritable bowel syndrome, and possibly either sedentary behaviour or
excessive activity. As might be expected CFS patients are more likely to have
attended their GP, than healthy matched controls, even up to 15 years before

onset, but recent work shows that those with IBS (and no CFS) have the same
tendency.

Triggeringriskmarkersarelesswellestablished,butthereissufficientevidence
tosupportcertaininfectionsasaetiologicalfactorsnotonlyforfatiguebutalso
CFS, with the best replicated evidence supporting a role for EpsteinBarr virus
infection, which triggers CFS in 10% of those infected. Maintaining or
perpetuating risk markers are most important in determining treatment
programmes, since reversing maintaining factors should lead to improvement.
Reasonablywellestablishedfactorsincludemooddisorders,suchasdysthymia,
illness beliefs such as believing the whole condition is physical, pervasive
inactivity,avoidantcoping,membershipofapatientsupportgroup,andbeingin
receiptofordisputeaboutfinancialbenefits.

Few pathophysiological findings in CFS have been replicated in independent

studies. Those that have been include downregulated hypothalamicpituitary
adrenal axis, physical deconditioning, and discrepant reports between
perception of symptoms and disability and their objective tests. The latter
findingisnowsupportedbyfunctionalbrainscanningstudiessuggestingaltered
brainactivitywithspecifictasks.Thediscrepancybetweensubjectivestatesand
objectivetestshasbeenfoundbeforeinothersymptomdefinedsyndromes,such
asfibromyalgia,andmayberelatedtoenhancedinteroception(theperception
of visceral phenomena), a concept first described by Charles Sherrington in
1904.Onehypothesiscurrentlybeingtestedisthatthecommonpredisposition
tofunctionalsomaticsyndromesiscausedbyenhancedinteroception.Recent
worksuggeststhatthesefactorsmaybereversedbyrehabilitation.

Prognosis

Without treatment the prognosis of CFS is poor with a systematic review of

outcomesfindingthemedianfullrecoveryratewas5%(range031%)andthe
median proportion of patients who improved of 39.5% (range 863%). Being
younger,havinglessfatiguebaseline,asenseofcontroloversymptomsandnot
attributingillnesstoaphysicalcausewereallassociatedwithabetteroutcome.
Theprognosisisconsiderablybetteraftertreatment.

Treatment

The NICE guidelines, published in 2007, were based on an updated systematic

review.Theessenceofspecialistcareisrehabilitation,providedonanindividual
basiswithanappropriatelyqualifiedandtrainedtherapist.Thetwoapproaches
withthegreatestevidenceofefficacyarecognitivebehaviourtherapy(CBT)and
gradedexercisetherapy(GET).Approximately60%ofpatientsreportsignificant
improvementwiththeseapproachesandabout25%reportfullrecovery,which
lasts. No pharmacological treatments are recommended (antidepressants are
ineffective), but symptomatic pharmacotherapy for specific symptoms (such as
pain) or comorbid conditions (such as depressive illness) can be helpful
complementarytreatments.

These rehabilitation approaches have not received universal approval from

patient charities, with concerns that patients may be harmed by exercise
therapiesorthatCBTimplyingthattheconditionispsychological.

IsCFSneurologicalorpsychological?

This is a nonsensical question when one considers the neuroscience of

consciousness and recent advances in functional brain physiology. The
philosopher, John Searle, stated the answer to this Cartesian dualism that still
bedevils western medicine. Conscious states are caused by neurophysiological
mechanisms,andarerealisedinneurophysiologicalsystems.Thereforeitisnot
possible to have a psychological process or event without a neurological
mediatingprocess.Itisneitherofthemindorbody;itisboth.

Fatiguesecondarytoneurologicaldiseases

Fatigueiscommonlyassociatedwithchronicmedicaldisorders,butitshouldbe
differentiatedfromfatiguability.Fatiguabilityistheonsetofaphysicalsensation
of fatigue and weakness after exertion and is commonly reported with
neurologicaldiseasessuchasmultiplesclerosisandmyopathies.

Apartfrommeasuresofdiseaseactivity,otherassociationsofsecondaryfatigue
in general that have been repeatedly found include sleep disturbance, mood
disorders, inactivity and physical deconditioning. Studies of fatigue associated
with multiple sclerosis are instructive and exemplary. As in all studies of
secondary fatigue, measures of the severity or pathophysiology of the disease
itselfareassociatedwithfatigue.Somecytokinesareassociated,butothersare
not. Associations vary depending on the fatigue measure, confirming the
multidimensional nature of fatigue, but all measures are associated with
depression. Objectively confirmed sleep disturbance is also associated with
fatigue. Fatigue associated with MS therefore requires biopsychosocial
management.

There have been a number of studies of various treatments aimed at reversing

the associations of secondary fatigue in general, in the hope they would help
fatiguedirectly,withvariableresults.AswithCFS,themostconsistentevidence
ofefficacyhasbeenwithgradedexerciseprogrammesandCBT.

Bibliography

AttarianHP,BrownKM,DuntleySP,etal.Therelationshipofsleepdisturbances
andfatigueinmultiplesclerosis.Arch.Neurol.61(2004),5258.

Baker R, Shaw EJ. Diagnosis and management of chronic fatigue syndrome or

myalgicencephalomyelitis(orencephalopathy):summaryofNICEguidance.BMJ
2007doi:10.1136/bmj.39302.509005.AE

Chambers D, Bagnall AM, Hempel S, Forbes C. Interventions for the treatment,

management and rehabilitation of patients with chronic fatigue

syndrome/myalgicencephalomyelitis:anupdatedsystematicreview.JRSocMed
2006;99:50620.

CleareAJ.Theneuroendocrinologyofchronicfatiguesyndrome.Endocr.Rev.24
(2003),23652.

Flachenecker P, Bihler I, Weber F, et al., Cytokine mRNA expression in patients

withmultiplesclerosisandfatigue.Mult.Scler.10(2004),1659.

FulcherKY,WhitePD.Strengthandphysiologicalresponsetoexerciseinpatients
with the chronic fatigue syndrome. J. Neurol. Neurosurg. Psychiatry 69 (2000),
3027.

JoyceJ,HotopfM,WesselyS.Theprognosisofchronicfatigueandchronicfatigue
syndrome:asystematicreview.Q.J.Med.90(1997),22333.

KroenckeDC,LynchSG,DenneyDR.Fatigueinmultiplesclerosis:relationshipto
depression,disability,anddiseasepattern.Mult.Scler.6(2000),1316.

LyallM,PeakmanM,WesselyS.Asystematicreviewandcriticalevaluationofthe
immunologyofchronicfatiguesyndrome.J.Psychosom.Res.55(2003),7990.

National Institute for Health and Clinical Excellence. Clinical guideline CG53.
Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy):
diagnosisandmanagement.London,NICE,2007.
http://guidance.nice.org.uk/CG53.

Reevesv WC et al. Identification of ambiguities in the 1994 chronic fatigue

syndrome research case definition and recommendations for resolution. BMC
HealthServRes3(2003),25.

Romani A, Bergamaschi R, Candeloro E, et al., Fatigue inmultiple sclerosis:

multidimensional assessment and response to symptomatic treatment. Mult.
Scler.10(2004),4628.

M.C.Tartaglia,S.Narayanan,S.J.Francis,etal.,Therelationshipbetweendiffuse
axonaldamageandfatigueinmultiplesclerosis.Arch.Neurol.61(2004),2017.

Wessely SC, Hotopf M, Sharpe M. Chronic Fatigue and its Syndromes (Oxford:
OxfordUniversityPress,1998).

WesselyS,NimnuanC,SharpeM.Functionalsomaticsyndromes:oneormany?
Lancet354(1999),9369.

WesselyS,WhitePD.Indebate:thereisonlyonefunctionalsomaticsyndrome.
Br.J.Psychiatry185(2004),956.

WhitePD,ThomasJM,KangroHO,etal.,Predictionsandassociationsoffatigue
syndromes and mood disorders that occur after infectious mononucleosis.

Lancet358(2001),194654.

WhitePD,SharpeMC,ChalderT,DeCesareJC,WalwynR;onbehalfofthePACE
trialgroup.ProtocolforthePACEtrial:arandomisedcontrolledtrialofadaptive
pacing, cognitive behaviour therapy, and graded exercise, as supplements to
standardisedspecialistmedicalcareversusstandardisedspecialistmedicalcare
aloneforpatientswiththechronicfatiguesyndrome/myalgicencephalomyelitis
orencephalopathy.BMCNeurol2007;7:6.

Cognitive and behavioural

treatments for functional somatic
syndromes

Peter White & Kate Harri

London 2012

Agenda

Do these treatments work?

Do treatments help occupation?
An example of CBT for pain
Predictors
Mediators

Risk markers for prolonged CFS

Fatigue, symptoms, mood disorders,
physical illness beliefs, pervasive
inactivity, sleep problems

Risk markers for prolonged whiplash

- Unexpectedness
- low education, female
Pain, symptoms, ROM, passivity,
psychol. Distress
SJ Kamper et al, 2007

Risk markers for musculoskeletal

pain in primary care
-

Pain, past history, multiple sites

Passivity, psychol. distress
ROM and disability
Social adversity

CD Mallen et al, 2007

Biopsychosocial model of CFS

Initial
infection
Beliefs
Rest or
boom & bust

Fatigue
Bodily
adaptation
Sleep
problems

CBT for pain disorders

Effect sizes versus waiting list controls
Pain
Depression
Activity
Social function
RTW

0.40
0.36
0.46
0.60
????

S Morley et al, Pain, 1999

CBT & GET for CFS

Effect sizes for function
CBT
GET
RTW

0.36
0.39
????

BD Castell et al, 2011

CBT for fibromyalgia

Effect sizes
Pain
Function
RTW

0.47
0.42
????

JA Glombiewski et al, 2010

GET for fibromyalgia

Effect sizes
Pain
HRQOL
RTW

0.31
0.40
????

W Hauser et al, 2010

RTW after MDT for CWP: women

JS Skouen et al, 2006

Main treatment phase

Follow up phase

50
40
30

Physical Function Score

60

70

Physical function

Time
SMC
APT

GET
CBT

Remission in PACE
%age
25
20
15
%age

10
5
0
APT

CBT

GET

SMC

Healthcare cost-effectiveness
1

Probability that intervention is most cost-effective

0.9

0.8

CBT

0.7

0.6

0.5

0.4

0.3

GET
0.2

0.1

APT
SMC

0
0

5000

10000

15000

20000

25000

30000

35000

QALY threshold ()

40000

45000

50000

55000

60000

Informal Care and Lost Employment in PACE

APT

CBT

GET

SMC

Informal care hours per week

11.0

8.0

7.7

11.4

Informal care cost (s)

6196

4008

4073

6507

86

84

86

89

Lost employment %
Lost employment cost (s)

P McCrone et al, 2012

14,865

13,958 14,638 14,157

Societal cost-effectiveness
1

Probability that intervention is most cost-effective

0.9

0.8

0.7

CBT
0.6

0.5

0.4

GET

0.3

0.2

0.1

SMC
0

APT
0

5000

10000

15000

20000

25000

30000

35000

QALY threshold ()

40000

45000

50000

55000

60000

CBT & GET have moderate

efficacy but only modest effects
in helping RTW after FSS

What moderates response to

behavioural treatments?

Moderators of non-response to GET or

CBT for CFS

Membership of a self-help group

Severity of fatigue
Sickness benefit
High combined mood score
Involvement in legal proceedings to achieve
disability benefits
Not duration of illness!
R Bentall et al, 2002

Moderators of non-response to CBT

for pain

More pain and pain sites

Depression
Rumination
Catastrophising
Life difficulties
JA Turner et al, 2007

Disability insurance claims:

return to work
Diagnosis

CFS/ME

14

Depression

18

Low back pain

22

Swiss Re, 2001

FSS insurance claims

1. Interpersonal clash at work
Domestic responsibilities

2. Never referred for treatment

No CBT/GET available locally
Already received CBT and/or GET

3. Dr X mitochondrial disease
Prof Y Fibro is incurable and [X] will never
return to work

Social risks
If you have to prove you are ill, you cant get
well. (N Hadler, 1996)
ME is an incurable disease.

What mediates response to

behavioural treatments?

Mediators of response to GET or CBT

for CFS
Treatment dose (number of sessions)
Reduction in symptom focusing
Reduction in fear avoidance
Not increased activity
Not increased fitness
Not change in cognitions
Not change in mood

Mediators of response to CBT for pain

Treatment dose
Increased perceived pain control
Reduction in serious pain beliefs
Reduced catastrophising
Increased self-efficacy

Conclusion
Biopsychosocial model best fit for FSS
Rehabilitation based treatments are
moderately helpful, but are not aimed to
help RTW
Their effect on occupation is mild to
moderate
Targets for more effective rehab include
attitudes & beliefs of doctors, employers,
and patients, as much as developing more
vocationally targeted treatments.

ME or CFS: Belief or science?

Peter White
Barts and the London
RCPsych Liaison Psychiatry Conference
29/02/12 - 02/03/12

My most recent new patient

50, single woman
Unwell since aged 21 mumps
Diagnosed ME aged 30
Classical ME aged 40
ME has ruined my life no career,
no relationship, no children

History of many years exhaustion,

poor sleep, low self-esteem, low
mood, anxiety, fear of falling when
away from home, brain fog (71
symptoms)
Serious suicide attempt aged 45
Treatments - B12, 5 sessions of
occupational therapy, 75 mg
venlafaxine, CAM

MSE - miserable, anxious, constant

suicidal thoughts, poor eye contact,
derealisation, depersonalisation
Pulse 100 bpm, tremor
Beck depression 51/63
HADS depression 18/21
HADS anxiety 18/21

Diagnosis of severe and chronic

major depressive disorder, with
panic attacks with agoraphobia,
with derealisation
But I need treatment for my ME; I
am not mad; I wont go and see a
psychiatrist.

Tragic tale of woman with

chronic fatigue syndrome 'too
tired' to eat
Derby Telegraph
Monday

She had battled for years with chronic

fatigue syndrome.. (no Rx 5 years)
A post mortem examination showed she
weighed 3st 2lbs when she died..
Mr O said L's loss of appetite was
caused by a lack of energy, but medics
said she had anorexia.
Why did they insist on the "anorexia"
label? It is well documented that people
with severe ME become too tired and
weak to eat..

The right diagnosis

40% of patients attending a CFS clinic did
not have CFS.
J Newton et al, 2010

49% of patients attending a CFS clinic did

not have CFS.
Devasahayam et al, 2012

Co-morbid medical conditions

CFS
(N=1,423)

Co-morbid depression
Co-morbid anxiety
Irritable Bowel Syndrome
Fibromyalgia/Chronic
Widespread Pain
Migraine
Chronic Regional Pain Disorder

32%
32%
29%
28%
21%
3%

RPE on a light cycle test (sedentary controls)

Perception of effort with exercise

Sleep disturbance
Mood (both depression and anxiety)
Aerobic fitness and strength
Somatic focusing
Introversion
Emotionality

Subjective more than objective

A global discrepancy between the subjective and
objective:
Effort with exercise versus work done
Reported disability versus physical activity
Cognition: symptoms versus tests
Insomnia versus polysomnography

Beliefs are associated with outcome

Physical illness
Viral illness
Exercise is dangerous or damaging
Family and partners beliefs

Predictions of non-response to GET

Membership of a self-help group
Sickness benefit
High combined HADS score
R Bentall et al, 2002

Prediction of non-response to CBT

Involvement in legal proceedings to achieve
disability benefits
J Prins et al, 2003

The effect of a doctors ME label on

prognosis
ME lasted longer than CFS.
ME patients had more consultations both in
general and specifically for fatigue.
No differences before diagnosis

Beliefs of doctors determine behaviour

32 single woman, attended with mother
Unwell with ME since 18
ME caused by Lyme disease

Beliefs of doctors determine behaviour

32 single woman, attended with mother

Unwell with ME since 18
ME caused by Lyme disease
Hearing voices since 18
Passivity experiences
Thought broadcast
Abulia

Beliefs of doctors determine behaviour

Spoke with mother
Confirmed voices, but also convinced of
Lyme disease

Beliefs of doctors determine behaviour

Spoke with mother
Confirmed voices, but also convinced of
Lyme disease
St Elsewheres week later for CSF and
antibiotics, in spite of my diagnosis of
schizophrenia
In spite of my calling GP urgently

Beliefs of doctors determine behaviour

One year later, I was copied into a letter from
a psychiatrist..

Beliefs of doctors determine behaviour

One year later, I was copied into a letter from
a psychiatrist..
I agree she has a schizophrenia like illness,
but I understand she has Lyme disease, which
is the likely underlying cause, and I would
advise re-referral to a Lyme disease specialist.

Doctors attitudes to MUS patients

188 GP patients
Rejecting (most common)
Colluding
Empowering (least common, most useful)
P Salmon et al, BMJ, 1999

Can the science help us?

CFS: What do we know?

Predisposition - female, childhood trauma, other FSS,
depression
Precipitated by various stressors especially infection
(glandular fever, meningitis etc), life events
Perpetuated by behavioural and psychological factors, and their
physiological consequences on fitness, sleep, and HPA axis

R Gracely et al, 2002

Brain activation in fibromyalgia - case

control

CBT is associated with increased grey

matter

De Lange F et al, 2008

Barts Pilot Study Results

*
White et al. 2004

CBT is associated with improved HPA

Roberts A et al, 2008

Yes, its the biopsychosocial model

Initial
infection
Beliefs
Rest or
boom & bust

Fatigue
Bodily
adaptation
Sleep
problems

Liaison psychiatrists to the rescue!

Liaison psychiatrists are what is left of general
physicians, physicians themselves being superspecialised.
We need to have the confidence to combine
the science with our therapeutic skills to
explain, empower and engage with our
patients.
Beliefs can change; science will help, since
knowledge is power.