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Date:    Tue, 20 Mar 2007 08:06:37 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM>
Subject: RES: CFS/ME & FM papers, published since February 2007

Source: NCBI PubMed
Date:   March 20, 2007
URL:    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
        Topic=((chronic fatigue) OR (myalgic encephalomyelitis)) OR fibromyalgia

Ref:    In the update, you will only find journals that are indexed by
        Medline (PubMed).

        All scientific papers 1938-today,
        http://www.me-net.combidom.com/library/literature.htm#publications

        Search scientific papers,
        http://www.me-net.combidom.com/library/literature.htm#catalogue

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        All popular papers 1900-today,
        http://www.me-net.combidom.com/library/literature.htm#popular


CFS/ME & FM papers, published since February 2007
-------------------------------------------------

___ Wallman KE, Sacco P.
       Sense of effort during a fatiguing exercise protocol in chronic
       fatigue syndrome.
       Res Sports Med. 2007 Jan-Mar;15(1):47-59.
___ Appel S, Chapman J, Shoenfeld Y.
       Infection and vaccination in chronic fatigue syndrome: Myth or
       reality?
       Autoimmunity. 2007 Feb;40(1):48-53.
___ Gulec H, Sayar K, Yazici Gulec M.
       The Relationship between Psychological Factors and Health Care-
       Seeking Behavior in Fibromyalgia Patients [Turkish].
       Turk Psikiyatri Derg. 2007 Spring;18(1):22-30.
___ Sierpina V, Levine R, Astin J, Tan A.
       Use of mind-body therapies in psychiatry and family medicine
       faculty and residents: attitudes, barriers, and gender differences.
       Explore (NY). 2007 Mar-Apr;3(2):129-35.
___ Takken T, Henneken T, van de Putte E, Helders P, Engelbert R.
       Exercise Testing in Children and Adolescents with Chronic Fatigue
       Syndrome.
       Int J Sports Med. 2007 Mar 15.
___ Van Geelen SM, Sinnema G, Hermans HJ, Kuis W.
       Personality and chronic fatigue syndrome: Methodological and
       conceptual issues.
       Clin Psychol Rev. 2007 Jan 27.
___ Yunus MB.
       Fibromyalgia and Overlapping Disorders: The Unifying Concept of
       Central Sensitivity Syndromes.
       Semin Arthritis Rheum. 2007 Mar 10.
___ Nijs J, Demol S, Wallman K.
       Can submaximal exercise variables predict peak exercise performance
       in women with chronic fatigue syndrome?
       Arch Med Res. 2007 Apr;38(3):350-3.
___ Rowe PC, Lucas KE.
       Orthostatic intolerance in chronic fatigue syndrome.
       Am J Med. 2007 Mar;120(3):e13.
___ Bennett RM, Jones J, Turk DC, Russel IJ, Matallana L.
       An internet survey of 2,596 people with fibromyalgia.
       BMC Musculoskelet Disord. 2007 Mar 9;8(1):27.
___ Nordahl HM, Stiles TC.
       Personality styles in patients with fibromyalgia, major depression
       and healthy controls.
       Ann Gen Psychiatry. 2007 Mar 9;6(1):9.
___ Kumor K, Pierzchala K.
       The problem of fatigue in neurological disorders [Polish].
       Wiad Lek. 2006;59(9-10):685-91.
___ Palomino RA, Nicassio PM, Greenberg MA, Medina EP Jr.
       Helplessness and loss as mediators between pain and depressive
       symptoms in fibromyalgia.
       Pain. 2007 Feb 28.
___ Baicus C, Baicus A.
       Spirulina did not ameliorate idiopathic chronic fatigue in four
       N-of-1 randomized controlled trials.
       Phytother Res. 2007 Mar 5.
___ Shorter E.
       Hysteria and catatonia as motor disorders in historical context.
       Hist Psychiatry. 2006 Dec;17(68 Pt 4):461-8.
___ Wigers SH, Finset A.
       Rehabilitation of chronic myofascial pain disorders [Norwegian].
       Tidsskr Nor Laegeforen. 2007 Mar 1;127(5):604-8.
___ Rimes KA, Goodman R, Hotopf M, Wessely S, Meltzer H, Chalder T.
       Incidence, prognosis, and risk factors for fatigue and chronic
       fatigue syndrome in adolescents: a prospective community study.
       Pediatrics. 2007 Mar;119(3):e603-9.
___ Hjollund NH, Andersen JH, Bech P.
       Assessment of fatigue in chronic disease: a bibliographic study of
       fatigue measurement scales.
       Health Qual Life Outcomes. 2007 Feb 27;5:12.
___ Busch A.
       Hydrotherapy improves pain, knee strength, and quality of life in
       women with fibromyalgia.
       Aust J Physiother. 2007;53(1):64.
___ Van Houdenhove B, Luyten P.
       Stress, depression and fibromyalgia.
       Acta Neurol Belg. 2006 Dec;106(4):149-56.
___ Kobelt A, Grosch E, Wasmus A, Ehlebracht-Konig I, Schwarze M, Krahling M,
       Gutenbrunner C.
       Is It Possible to Predict Approval of Medical Rehabilitation by the
       Extent of Fatigue and Subjective Need for Rehabilitation?
       Development, Results and Acceptance of a Short Screening [German].
       Rehabilitation (Stuttg). 2007 Feb;46(1):33-40.
___ Ang D, Kesavalu R, Lydon JR, Lane KA, Bigatti S.
       Exercise-based motivational interviewing for female patients with
       fibromyalgia: a case series.
       Clin Rheumatol. 2007 Feb 20.
___ Freedenfeld RN, Murray M, Fuchs PN, Kiser RS.
       Decreased pain and improved quality of life in fibromyalgia patients
       treated with olanzapine, an atypical neuroleptic.
       Pain Pract. 2006 Jun;6(2):112-8.
___ Harden RN, Revivo G, Song S, Nampiaparampil D, Golden G, Kirincic M,
       Houle TT.
       A critical analysis of the tender points in fibromyalgia.
       Pain Med. 2007 Mar-Apr;8(2):147-56.

--------
(c) 2007 NCBI PubMed

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Date:    Tue, 20 Mar 2007 12:12:35 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Does Thalidomide Have an Analgesic Effect? Current Status  and Future Directions

Does Thalidomide Have an Analgesic Effect? Current Status and Future
Directions

Current Pain and Headache Reports 2007, 11:109-114

Veeraindar Goli, MD, Duke University Medical Center, 932 Morreene Road,
Durham, NC 27705, USA. Email: goli0001 mc.duke.edu


Dramatic relief of pain and life-altering changes in quality of life in
some patients treated with immunomodulators such as thalidomide compel us
to look more closely at unconventional mechanisms that may be involved in
propagation of persistent pain.

Tumor necrosis factor (TNF)-a, interleukin (IL)-1b, IL-6, and IL-10 are the
cytokines with the most evidence in pain modulation. TNF-a and IL-1b seem
to initiate neuropathic pain, IL-6 maintains such pain, and IL-10 inhibits
this persistent pain.

Thalidomide was found to be effective in animal models by inhibiting TNF-a
production. Several case reports and case series in humans have
demonstrated mixed results, with some patients having dramatic responses,
especially in chronic intractable conditions such as complex regional pain
syndrome. Thalidomide may be an alternative for some patients with
intractable pain.

However, use of thalidomide is limited by its neurotoxic and teratogenic
effects. Newer analogues may significantly improve the risk/benefit of
using such immunomodulators.


Copyright © 2007 by Current Science, Inc.

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Date:    Tue, 20 Mar 2007 12:15:59 -0400
From:    "Bernice A. Melsky" <bernicemelsky@VERIZON.NET>
Subject: RES: Is There Genetic Polymorphism Evidence for Individual  Human Sensitivity to Opiates?

Is There Genetic Polymorphism Evidence for Individual Human Sensitivity to
Opiates?

Current Pain and Headache Reports 2007, 11:115-123

Makoto Nagashima, MD, PhD, Ryoji Katoh, MD, PhD, Yasuo Sato, MD, Megumi
Tagami, MD, PhD, Shinya Kasai, PhD, and Kazutaka Ikeda, PhD

Corresponding author: Kazutaka Ikeda, PhD, Department of Molecular
Psychiatry, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku,
Tokyo 156-8585, Japan. Email: ikedak prit.go.jp


Opiate analgesics have been widely used for severe acute pain and chronic
cancer-related pain. Individual differences in the effectiveness of opiates
and their side effects limit the clinical benefits and increase risks of
drug abuse.

Genetic factors might affect variations of opiate sensitivity. The mu
opioid peptide receptor (MOP) is the principal site of pharmacologic
actions for most clinically important opiate drugs. Recent studies using
various knockout mice and recombinant-inbred strain CXBK mice have
indicated that the analgesic effect of morphine is dependent on the amount
of the MOP.

There are more than 100 polymorphisms identified in the human MOP (OPRM1)
gene. These polymorphisms might be correlated with OPRM1 mRNA stability and
opiate sensitivity, including opiate analgesia, tolerance, and dependence.

More precise studies on the relationship between gene polymorphisms and
opiate sensitivity will enable realization of personalized pain treatment
by predicting opiate sensitivity and requirement for each patient.


Copyright © 2007 by Current Science, Inc.

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Date:    Wed, 21 Mar 2007 08:57:50 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: The effect of cognitive behaviour therapy for chronic  fatigue syndrome on self-reported cognitive impairments and  neuropsychological test performance

The effect of cognitive behaviour therapy for chronic fatigue syndrome on
self-reported cognitive impairments and neuropsychological test performance.

Journal: J Neurol Neurosurg Psychiatry. 2007 Apr;78(4):434-6.

Authors: Knoop H, Prins JB, Stulemeijer M, van der Meer JW, Bleijenberg G.

Affiliation: Expert Centre Chronic Fatigue, Radboud University Nijmegen
Medical Centre, P O Box 9011, 6525 EC Nijmegen, The Netherlands.
j.knoop nkcv.umcn.nl

NLM Citation: PMID: 17369597


BACKGROUND: Patients with chronic fatigue syndrome (CFS) often have
concentration and memory problems. Neuropsychological test performance is
impaired in at least a subgroup of patients with CFS. Cognitive behavioural
therapy (CBT) for CFS leads to a reduction in fatigue and disabilities.

AIM: To test the hypothesis that CBT results in a reduction of
self-reported cognitive impairment and in an improved neuropsychological
test performance.

METHODS: Data of two previous randomised controlled trials were used. One
study compared CBT for adult patients with CFS, with two control
conditions. The second study compared CBT for adolescent patients with a
waiting list condition. Self-reported cognitive impairment was assessed
with questionnaires. Information speed was measured with simple and choice
reaction time tasks. Adults also completed the symbol digit-modalities
task, a measure of complex attentional function.

RESULTS: In both studies, the level of self-reported cognitive impairment
decreased significantly more after CBT than in the control conditions.
Neuropsychological test performance did not improve.

CONCLUSIONS: CBT leads to a reduction in self-reported cognitive
impairment, but not to improved neuropsychological test performance. The
findings of this study support the idea that the distorted perception of
cognitive processes is more central to CFS than actual cognitive performance.

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Date:    Wed, 21 Mar 2007 09:34:44 -0400
From:    Co-Cure Moderator <ray CO-CURE.ORG>
Subject: RES: Cold pressor pain sensitivity in monozygotic twins discordant for chronic fatigue syndrome

Cold pressor pain sensitivity in monozygotic twins discordant for chronic
fatigue syndrome.

Journal: Pain Med. 2007 May-Jun;8(3):216-22.

Authors: Ullrich PM, Afari N, Jacobsen C, Goldberg J, Buchwald D.

Department of Rehabilitation Medicine, University of Washington, Seattle,
WA, USA.

NLM Citation: PMID: 17371408


Objective. Individuals with chronic fatigue syndrome (CFS) experience many
pain symptoms. The present study examined whether pain and fatigue ratings
and pain threshold and tolerance levels for cold pain differed between
twins with CFS and their cotwins without CFS.

Design. Cotwin control design to assess cold pain sensitivity, pain, and
fatigue in monozygotic twins discordant for CFS. Patients and Setting.
Fifteen monozygotic twin pairs discordant for CFS recruited from the
volunteer Chronic Fatigue Twin Registry at the University of Washington.

Results. Although cold pain threshold and tolerance levels were slightly
lower in twins with CFS than their cotwins without CFS, these differences
failed to reach statistical significance. Subjective ratings of pain and
fatigue at multiple time points during the experimental protocol among
twins with CFS were significantly higher than ratings of pain (P = 0.003)
and fatigue (P < 0.001) by their cotwins without CFS.

Conclusions. These results, while preliminary, highlight the perceptual and
cognitive components to the pain experience in CFS. Future studies should
focus on examining the heritability of pain sensitivity and the underlying
mechanisms involved in the perception of pain sensitivity in CFS.

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------------------------------

Date:    Wed, 21 Mar 2007 15:11:33 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM>
Subject: RES,NOT: CFS and personality

Source: Clinical Psychology Review
        Preprint
Date:   January 27, 2007
URL:                                                                   http://www.sciencedirect.com/science/journal/02727358


Personality and chronic fatigue syndrome: Methodological and conceptual issues
------------------------------------------------------------------------------
Stefan M. van Geelen(a), Gerben Sinnema(a), Hubert J.M. Hermans(b), Wietse
Kuis(c,*)
a Department of Psychology, Wilhelmina Children's Hospital, University Medical
  Center Utrecht, The Netherlands
b Faculty of Clinical Psychology and Personality, Radboud University Nijmegen,
  The Netherlands
c Department of Immunology, Wilhelmina Children's Hospital, University Medical
  Center Utrecht, The Netherlands
* Corresponding author. Division of Pediatrics, Wilhelmina Children's Hospital,
  University Medical Center Utrecht, P.O. Box 85090, KB.03.023.2,
  3508 AB, Utrecht, The Netherlands.
  E-mail address: W.Kuis umcutrecht.nl (W. Kuis).

Received 9 December 2005; received in revised form 29 November 2006; accepted
19 January 2007


Abstract

Among clinical psychologists, consulting physicians, scientific researchers
and society in general an image has emerged of patients with chronic fatigue
syndrome (CFS) as perfectionist, conscientious, hardworking, somewhat
neurotic and introverted individuals with high personal standards, a great
desire to be socially accepted and with a history of continuously pushing
themselves past their limits. The aim of this article is to (a) give a
concise review of the main recent studies on personality and CFS, (b) address
the major methodological problems in the study of personality in CFS and (c)
discuss some of the conceptual assumptions that seem to limit the research on
personality and CFS. The results of the reviewed studies range from no
evidence of major differences between the personalities of patients with CFS
and controls, to evidence of severe psychopathology and personality disorder
in patients with CFS. Although personality seems to play a role in CFS, it is
difficult to draw general conclusions on the relation between personality and
CFS. It is argued that this is partially due to the diversity and
heterogeneity in study methods, patient populations, control groups and CFS
case definitions. Personality should be regarded as an important factor to be
studied in CFS. However, additional studies are needed, not focusing
exclusively on personality disorder, or personality considered on a general
trait level. In recent developments in personality research, the continually
evolving life narrative that makes sense of, and gives direction to, an
individual's life is also regarded as an important aspect of personality. New
insights into personality and CFS might be gained by systematically studying
the self-narratives of patients with the syndrome.

Keywords: Chronic fatigue syndrome; Personality; Clinical psychology;
Narrative; Medicine


1. Introduction

This article's main concern is the study of personality in the chronic
fatigue syndrome (CFS). CFS is a syndrome of unknown origin. It is mainly
characterized by a severely disabling fatigue and it is commonly associated
with symptoms such as myalgias, headache, sleep disturbance, swollen lymph
nodes and cognitive impairment. In recent years CFS has become a growing
concern, not only for patients suffering from the illness and for their
families, but also for medical science, clinical psychology and society in
general.

Some of these concerns already become apparent in defining what CFS is. In
many cases, it is difficult to distinguish between idiopathic chronic
fatigue, CFS and other unexplained medical conditions such as fibromyalgia,
tension headache and irritable bowel syndrome, as these seem to be very
similar and substantially overlapping (Aaron & Buchwald, 2001; Wessely,
Nimnuan, & Sharpe, 1999). As no causes for CFS are found and definite markers
for the illness are absent, the diagnostic process is usually extended and
patients have to go through a whole battery of laboratory tests, physical
examinations and psychological investigations before they are diagnosed with
CFS. In 1988, the US Centers of Disease Control (CDC) proposed a set of
diagnostic criteria to facilitate scientific research into CFS (Holmes et
al., 1988). However, these criteria were criticized, not only because a large
number of symptoms had to be present for a diagnosis of CFS, which might bias
in favor of psychiatric morbidity (Katon & Russo, 1992), but also because it
excluded such conditions as anxiety and depression, which some propose to be
a result of the syndrome (Ray, 1991; Van Hoof, Cluydts, & De Meirleir, 2003).
Therefore, less restrictive criteria were developed, amongst others in the UK
by Sharpe et al. (1991). Consequently, the CDC criteria were also revised
(Fukuda et al., 1994). At present these criteria are generally accepted and
used for international research purposes. In Table 1 these criteria are
presented.

Estimations on the prevalence of CFS range from 37/100 000 (Lloyd, Hickie,
Boughton, Spencer, & Wakefield, 1990), to 75-267/100 000 (Buchwald et al.,
1995), and even 740/100 000 (Lawrie, Manders, Geddes, & Pelosi, 1997).
However, these numbers are difficult to compare as different populations were
studied and varying CFS case definitions were used. Estimations on the
incidence of CFS are rare but, based on their assumptions with regard to the
prevalence of CFS, Lawrie et al. (1997) estimated the annual incidence of CFS
to be 370/100 000.

Full recovery from CFS is unusual. In a recent review (Cairns & Hotopf, 2005)
of studies on the prognosis of CFS, it was found that the median full
recovery rate was only 5% and the median proportion of patients who had
improved during follow-up was 39.5%. The prognosis for children and
adolescents however, is generally somewhat better (Patel, Smith, Chalder, &
Wessely, 2003). In a recent follow-up study of adolescent patients with CFS
(Gill, Dosen, & Ziegler, 2004) it was found that, at a mean of 4.57 years
after initial examination, 25% of the patients showed near to complete
improvement and 31% showed partial improvement.

Etiological studies into the possible causes of CFS have been abundant.
Active viral infection has frequently been associated with the symptoms of
CFS, but evidence for this hypothesis has not consistently been found. There
appear to be no significant differences between patients with CFS and healthy
controls in the prevalence of human herpes viruses, Epstein-Barr virus,
cytomegalovirus, hepatitis C virus, adenovirus and parvovirus B19, amongst
many others. (Buchwald, Ashley, Pearlman, Kith, & Komaroff, 1996; Koelle et
al., 2003; Wallace, Natelson, Gause, & Hay, 1999).

Immune dysfunction is another possible etiological factor that has been
widely studied. Chronic lymphocyte overactivation with cytokine abnormalities
in patients with CFS, associations between T cell markers and CFS, and
associations between low natural killer cells and CFS have all been reported
(Patarca-Montero, Antoni, Fletcher, & Klimas, 2001; Straus, Fritz, Dale,
Gould, & Strober, 1993). However, in a recent systematic review of the
immunology of CFS, the authors noted that studies supporting almost any
conclusion regarding the presence, or absence of immunological abnormalities
in CFS could now be found, and concluded that no consistent pattern could be
identified (Lyall, Peakman, & Wessely, 2003).

The same holds true of studies on the role of the neuroendocrine system in
CFS. Disturbed neuroendocrine­immune system interactions, low circulating
cortisol, high nocturnal melatonin, abnormalities in the relationship between
cortisol and central neurotransmitter function, a disturbance of
neurotransmitters in HPA axis function, and alterations in adrenal function
in CFS have all been suggested and some evidence for these claims has been
found (Cleare, Blair, Chambers, & Wessely, 2001; Demitrack et al., 1991;
Kavelaars, Kuis, Knook, Sinnema, & Heijnen, 2000; Knook, Kavelaars, Sinnema,
Kuis, & Heijnen, 2000; Segal, Hindmarsh, & Viner, 2005). Again however, in an
extensive review on the neuroendocrinology of CFS, it was concluded that no
consistent evidence of abnormalities could be found and that it was unclear
whether neuroendocrine changes (if any) are primary or secondary to
behavioral changes in sleep or exercise (Parker, Wessely, & Cleare, 2001).

Along other lines of research, the psychiatric status of patients with CFS
has received much attention. Several studies have reported a high prevalence
of current psychiatric disorders in CFS, predominantly depression,
somatization disorder and hypochondria (Ciccone, Busichio, Vickroy, &
Natelson, 2003; Schweitzer, Robertson, Kelly, & Whiting, 1994). However,
while some studies concluded that psychiatric illness in many cases predated
the development of CFS (Katon, Buchwald, Simon, Russo, & Mease, 1991; Lane,
Manu, & Matthews, 1991), other studies concluded that psychiatric disorder
was concurrent with the onset of CFS and therefore more likely to be a
consequence of, rather than a risk factor to CFS (Axe & Satz, 2000; Hickie,
Lloyd, Wakefield, & Parker, 1990). In that case, CFS is not seen as a
manifestation of an underlying psychiatric disorder and more somatic causes
are presumed (Komaroff & Buchwald, 1998).

Neuropsychological deficits and impaired cognitive functioning in patients
with CFS have also received widespread attention, and have frequently been
implied to be an important explanatory factor for some of the symptoms of
CFS. People with CFS often complain of difficulties with memory and
concentration. Several studies have described an impaired cognitive
performance of patients with CFS on neuropsychological tests measuring speed
of information processing, memory, motor speed and executive functioning
(Busichio, Tiersky, Deluca, & Natelson, 2004; Cluydts & Michiels, 2001).
Problems with neuropsychological functioning were found to be unrelated to
depression, fatigue or anxiety (Short, McCabe, & Tooley, 2002) and have
instead been related to low levels of physical activity (Vercoulen et al.,
1998), a more extensive use of frontal and parietal brain regions (Lange et
al., 2005) and even genetic traits (Mahurin et al., 2004). In contrast with
this, many other studies have found no difference in cognitive performance
between patients with CFS and controls, and no evidence of any
neuropsychological deficits in CFS (Fry & Martin, 1996; Schmaling,
DiClementi, Cullum, & Jones, 1994). However, although in many studies
objectively no cognitive differences between patients with CFS and controls
are found, patients with CFS consistently report cognitive complaints and
underestimate their actual performance on neuropsychological tests. This
difference between the subjective perception of cognitive impairment and the
absence of any objective evidence has led some researchers to speculate that,
in contrast to laboratory cognitive tests, in CFS everyday cognitive tasks
may require excessive processing resources leaving patients with CFS
diminished spare attentional capacity (Wearden & Appleby, 1996), and other
researchers to suggest that patients with CFS set impossibly high standards
of personal performance (Metzger & Denney, 2002).


Other risk factors for the development of CFS that have been implied (and for
which some evidence has been found) are birth order (Brimacombe, Helmer, &
Natelson, 2002), family reinforcement of illness behavior (Brace,
Scott-Smith, McCauley, & Sherry, 2000), maternal overprotection in relation
to the formation of belief systems about activity avoidance (Fisher &
Chalder, 2003) and a family history of physical and mental illness (Endicott,
1999). However, as with all of the etiological studies that have been
discussed so far, the contrary conclusions can also be found. In a large
birth cohort study into childhood predictors of CFS in adulthood, in which
more than 11 000 people were followed up until the age of 30, no associations
between maternal or child psychological distress, parental illness or birth
order, and an increased risk of lifetime CFS were identified (Viner & Hotopf,
2004).

There have also been many studies into possibly effective treatment
strategies for CFS. However, presently there is no established, universally
beneficial intervention for the management and treatment of CFS (Whiting et
al., 2001). With regard to medical and pharmacological treatment, amongst
others, intramuscular dialyzable leukocyte extract (Lloyd et al., 1993),
intravenous immunoglobulin (Vollmer-Conna et al., 1997), hydrocortisone
(McKenzie et al., 1998) and antidepressants (Vercoulen et al., 1996; Natelson
et al., 1998) were investigated in placebo-controlled studies, without
proving their effectiveness. Recently, the effects of galantamine
hydrobromide (Blacker et al., 2004), polynutrient supplements (Brouwers, Van
der Werf, Bleijenberg, Van der Zee, & Van der Meer, 2002), homeopathic
treatment (Weatherley-Jones et al., 2004) and corticosteroids (Kakumanu,
Mende, Lehman, Hughes, & Craig, 2003) have been studied in randomized
controlled trials, but were also found to be ineffective. At the moment, only
cognitive behavior therapy (Price & Couper, 2000; Prins et al., 2001; Sharpe,
1998) and graded exercise therapy (Wallman, Morton, Goodman, Grove, &
Guilfoyle, 2004; Edmonds, McGuire, & Price, 2004) have shown some
effectiveness, for a proportion of patients, in randomized controlled trials.

So, CFS seems surrounded by controversy. Patients are confronted with a
highly ambiguous illness that severely incapacitates them. In addition to
this they suffer from the consequences of the unclear medical status of the
disease. Due to the uncertainties surrounding the etiology of CFS, its
symptomatology and the overall objective 'realness' of the syndrome, they are
likely to encounter disbelief concerning their medical condition (Friedberg &
Jason, 2001). At present it is being discussed whether the impact of labeling
patients with a diagnosis of CFS is enabling, or rather disabling (Huibers &
Wessely, 2006). In the absence of a clear biological marker for the illness,
which would permit a definite diagnosis instead of a descriptive one, based
almost solely on the exclusion of other disease entities, patients are often
faced with skepticism by their families, employers, insurance companies,
psychologists and physicians. In a recent study on illness experience in CFS
it was found that lack of illness recognition ranked high as a source of
dissatisfaction for patients and was thought to aggravate psychiatric
morbidity (Lehman, Lehman, Hemphill, Mandel, & Cooper, 2002). In contrast
with this, physicians participating in a study on their perspectives on
patients with CFS (Asbring & Narvanen, 2003) expressed the view that patients
seem to exaggerate the severity of their problems, and that there appears to
be a discrepancy between their reported health and the way they look and
behave.

Although it has been widely recognized that a positive and co-operative
caregiver-patient relationship is of the utmost importance in the successful
treatment of CFS (Sharpe, Chalder, Palmer, & Wessely, 1997), uncertainty and
conflicts about the causal attribution of the syndrome, in many cases, put
this relationship under pressure. Steven et al. (2000) showed that one-third
of a group of more than two-thousand general practitioners did not believe
that CFS was a distinct syndrome and thought the most likely cause was
depression. This finding was confirmed by another study in which it became
clear that while most of the doctors participating in the study believed CFS
to have a psychological cause, all of the patients attributed their illness
to a physical cause (Deale & Wessely, 2001). This disagreement over the
perceived origins of CFS was thought to largely account for the fact that
two-thirds of the patients in this study were dissatisfied with the quality
of the medical care they had received.

This same dispute about the etiology of the syndrome, in combination with
concerns about its nosological status, seems to have characterized and
dichotomized medical and psychological thought on CFS. In spite of the great
advances medical science has made in the explanation and treatment of
diseases with an evident organic cause, the causes for CFS remain unclear and
our understanding of the illness progresses only slowly. This "prototypical
mind/ body problem" (Johnson, DeLuca, & Natelson, 1999, p. 258) seems to
confront medicine with the limitations of the traditional paradigm, through
which it has made such progress in the understanding and treatment of
'classical' diseases. As is now widely acknowledged the debates on chronic
fatigue and immune dysfunction syndrome, neurasthenia, postviral fatigue
syndrome, myalgic encephalomyelitis, chronic mononucleosis and chronic
Epstein-Barr virus infection, as CFS was formerly known, were, and not
uncommonly still are, characterized by a mind/body dualism that seems
inherent to a biomedical model of thought, oriented towards monocausal
explanation (Lewis, 1996; Taerk & Gnam, 1994; Ware, 1994). On the one hand,
there are those who believe that CFS is initiated by a still unknown physical
cause such as a chronic or relapsing viral infection, immunological
deficiencies or abnormalities in the neuroendocrinological system. The
absence of a clear and objective organic cause, on the other hand, leads
others to relegate CFS to the realm of the mental and 'subjective' illnesses.
In that case CFS is mostly thought of as a psychiatric disorder (e.g. a
masked expression of depression, or a form of somatization), or a cognitive
phenomenon.

However, a more logical explanation of the variety of findings and opinions
on CFS would be that the illness is multifactorial. Social, mental and
somatic causes, and psychological and physical effects are not easily
discernible, but instead appear to be interrelated. In recent years, a more
biopsychosocial approach in the scientific research into CFS has become the
standard (Main, Richards, & Fortune, 2000). In line with this approach (and
in addition to the already mentioned studies) researchers have now also begun
to study the iatrogenic factors in CFS (Deale & Wessely, 2001), associations
in symptoms between patients with CFS and their parents (Van de Putte et al.,
2006), the illness beliefs and attributions of patients with CFS (Deale,
Chalder, & Wessely, 1998; Van Houdenhove, Neerinckx, Onghena, Lysens, &
Vertommen, 2000), the psychological adjustment of patients with CFS (Van
Middendorp, Geenen, Kuis, Heijnen, & Sinnema, 2001), the health-related
quality of life of patients with CFS (Hardt et al., 2001), the locus of
health control in patients with CFS (Van de Putte et al., 2005), the
relationship between ethnicity and CFS (Luthra & Wessely, 2004), the coping
strategies of patients with CFS (Ax, Gregg, & Jones, 2001), the influence of
family members in CFS (Gray et al., 2001), the cultural and historical
context of CFS (Abbey & Garfinkel, 1991; Ware, 1994; Ware & Kleinman, 1992;
Wessely 1990; Wessely, 1996) and the personalities of individuals who have
developed CFS (reviewed in this article).

So, within the biopsychosocial model of CFS one of the aspects studied, that
might have a perpetuating and even a predisposing role in the syndrome, is
the personality of people suffering from CFS. Among clinical psychologists,
consulting physicians, scientific researchers and in society in general, a
typical image has emerged of patients with CFS as perfectionist,
conscientious, hardworking, somewhat neurotic and introverted individuals
with high personal standards, a great desire to be socially accepted and with
a history of continuously pushing themselves past their limits. (Lewis,
Cooper, & Bennett, 1994; Surawy, Hackmann, Hawton, & Sharpe, 1995). In
addition to this, they are characterized as being particularly averse to any
psychological or psychiatric explanation of the syndrome and extremely
persistent in fixed beliefs concerning their illness, thereby reducing the
chance of successful treatment (Sharpe, 1998). However, this image of people
suffering from CFS was never really scrutinized, with most of the research
activity concerning the individual with CFS focusing on psychopathology and
possible psychiatric disorder.

The aim of this article is to (a) give a concise review of the main recent
studies on personality and CFS, (b) address the major methodological problems
in the study of personality in CFS and (c) discuss some of the conceptual
assumptions that seem to limit the research on personality and CFS.


2. Selection of studies

The PubMed and PsychINFO databases from 1988 (when the original Centers for
Disease Control criteria for CFS were first established) to November 2006
were searched using the keywords CFS and personality, CFS and psychology, CFS
and individual, CFS and identity. On PubMed this generated 623 hits and on
PsychINFO an additional 333 hits. All 956 abstracts were read. In addition
the reference lists of the retrieved articles were examined.

The intention in the selection of studies was to include all original
articles describing primary research on personality and CFS. Review articles,
articles describing studies without mentioning which CFS case definition
criteria were used, or without an appropriate control group, and articles
focusing exclusively on psychiatric morbidity, were all excluded. Using these
criteria led to the inclusion of a final 16 studies.1 This review might not
have captured all relevant studies. However, the discussed articles are the
most important ones and can be seen as representative of the current state of
affairs in the field. In Table 2 a concise overview of the main recent
studies on the role of personality in CFS is given.


3. Results

Studying these results, it soon becomes obvious that the findings regarding
the association of personality and CFS are not definitive. Although some
studies seem to confirm, for a proportion of patients, some of the aspects of
the aforementioned stereotype of people suffering from CFS, other studies
found no such evidence. Some findings however, seem to be more consistent
than others.


3.1. Neuroticism

All in all, there seems to be most empirical evidence for an increased level
of neuroticism in patients with CFS. Taillefer, Kirmayer, Robbins and Lasry
(2003) found significantly higher neuroticism scores in patients with CFS
compared to the general population. Chubb et al. (1999) found increased
scores in their CFS subjects with concurrent depression. Masuda, Munemoto,
Yamanaka, Takei, and Tei (2002) found elevated neuroticism scores in their
noninfectious CFS group, although not in their postinfectious CFS group.
Fiedler et al. (2000), Blakely et al. (1991), Buckley et al. (1999) and
Johnson, DeLuca and Natelson (1996) also found significant differences in
neuroticism scores between patients with CFS and healthy controls and Rangel,
Garralda, Levin, and Roberts (2000) found the related items of
conscientiousness, worthlessness and emotional lability to be significantly
more common in patients than in controls. However, most subjects in their
study were recovered and their mothers, instead of the patients themselves,
had been used as informants. Several other important limitations in the
interpretation of these findings regarding neuroticism should also be
mentioned. One study found elevated scores of neuroticism only in comparison
to non-study recruited norm values for a general population (Taillefer et
al., 2003). In addition, generally no differences in neuroticism between
patients with CFS and other patients suffering from a chronic disease were
found (Johnson et al., 1996; Taillefer et al., 2003; Wood & Wessely, 1999).
Other studies used the MMPI to detect neuroticism (Blakely et al., 1991;
Schmaling & Jones, 1996) which, due to its sensitivity to physical symptoms,
has been found to perform poorly in CFS and to overestimate psychopathology
in chronically ill populations (Johnson, De Luca, & Natelson, 1996) and
finally, many of the findings of high neuroticism were later accounted for by
co-morbid depression (Chubb et al., 1999; Fiedler et al., 2000; Johnson et
al., 1996; Taillefer et al., 2003).


3.2. Personality disorder

Furthermore, there also seems to be evidence for the prevalence of
personality disorder in a proportion of patients with CFS. In the first study
on personality and CFS, Millon et al. (1989) found elevated base rate means,
above those of a non-clinical population, on the histrionic, schizoid and
avoidant scales of the MCMI, measuring DSM axis II personality disorders.
Henderson and Tannock (2004) also found quite a high level of personality
disorder (39%), predominantly obsessive-compulsive personality disorders, in
their sample of patients with CFS. Similar rates and findings were reported
by Ciccone et al. (2003). In the study by Johnson et al. (1996), 37% of the
subjects with CFS met the criteria for at least one personality disorder,
predominantly histrionic and borderline personality disorders. So, there
certainly seems to be a somewhat higher rate of personality disorder within
the CFS population than in non-clinical populations, in which it is
estimated to be between 10-19% (Moran, Coffey, Carlin, & Patton, 2006;
Zimmerman & Corryell, 1990). However, personality disorder rates were similar
in patients with CFS and those with other medical conditions (Johnson et al.,
1996). Also, it should be noted that personality disorder was not found in
the majority of patients. Furthermore, again there are some important
confounding aspects and the generalizability of the findings in the
abovementioned studies can be questioned. For example, some studies did not
have a control group (Ciccone et al., 2003; Millon et al., 1989). Moreover,
the MCMI that Millon et al. used includes many items that tap somatic
concerns, thereby increasing the likelihood of a diagnosis of personality
disorder in chronically ill patients. Co-morbid depression accounted for
most personality pathology in one study (Johnson et al., 1996) and although
this was not the case in the study by Henderson and Tannock, they only
included patients attending a teaching hospital, who are likely to have a
more severe form of CFS.


3.3. Perfectionism, social desirability and extroversion/introversion

Although perfectionism, social desirability and introversion have commonly
been referred to as some of the most characteristic features of the
personalities of patients with CFS, the scientific evidence on this subject
is far less clear-cut. White and Schweitzer (2000) found higher
perfectionism scores in individuals with CFS than in their control group and
Christodoulou et al. (1999) found the only difference between their CFS and
MS groups to be an elevated persistence score, which they related to
perfectionism. However, in contrast to these findings Wood and Wessely
(1999), and Blenkiron, Edwards and Lynch (1999) did not find higher
perfectionism scores in patients than in controls.

There were three studies that specifically studied social desirability among
patients with CFS (Buckley et al., 1999; Chubb et al., 1999; Wood & Wessely,
1999), but these studies revealed no differences between patients and control
groups. With regard to extroversion and introversion, Masuda et al. (2002)
found the members of their postinfectious CFS group to score higher on
extroversion than controls, although the members of their noninfectious CFS
group were found to be more introspective. And finally, while Buckley et al.
found that patients with CFS scored significantly lower than their healthy
controls on extroversion, Chubb et al. found the scores on extroversion of
their CFS group not to be different from those of their healthy control
group.


3.4. Personality: predisposing, initiating or perpetuating?

So, the results vary from the uncovering of "evidence of severe personality
pathology and affective distress" (Millon et al., 1989, p. 131), to the
finding of "little evidence that any particular personality trait
discriminates CFS patients [...] from other patients suffering a physically
disabling condition" (Wood & Wessely, 1999, p. 395). However, even when
evidence of abnormalities in the personality profiles of patients with CFS is
found, there remains a considerable lack of clarity regarding the precise
role of personality in the syndrome, and this is reflected in the conclusions
these studies draw. For example, while Van Houdenhove, Neerinckx, Onghena,
Lysens, and Vertommen (2001) conclude that "high 'action-proneness' and an
associated 'overactive' lifestyle may be one of the factors playing a
predisposing, initiating as well as a perpetuating role in CFS" (p. 575),
Christodoulou et al. (1999) found no evidence to suggest that patients with
CFS had any particular personality traits that would have predisposed them to
develop their illness. Rangel et al. (2000) conclude that personality
difficulty might either be a contributory factor to CFS, or result from the
prolonged disease, and Buckley et al. (1999) and Blenkiron et al. (1999)
conclude that the personality of subjects with CFS might have changed as a
result of their disease.

Although the impression of many psychologists, physicians and researchers,
that the personality of patients is a factor in CFS, seems to be justified by
clinical experience and is supported somewhat by the available research,
decisive conclusions on this subject are difficult to draw on the basis of
the relevant scientific studies. Even though these studies have scrutinized
the aforementioned image of the 'typical' individual with CFS, no definitive
conclusions for the patients as a group can be drawn, and a general and
uniform answer to the question of the role of personality in CFS is hard to
formulate. A provisional conclusion might be that it is "difficult to
disentangle personality factors that may have contributed to the development
of the condition from emotional reactions that are consequences of the
debilitating symptoms and the mixed responses of others to the illness"
(Lewis, 1996, p. 237).

However, part of the reason for this opaqueness, seems to be due to a certain
heterogeneity of the reviewed studies with regard to study methods, patient
populations, control groups and CFS case definitions. Therefore, before
discussing what seem to be some shared conceptual assumptions of these
studies, in the next section some of the major methodological issues
concerning the study of personality in CFS will be addressed.


4. Methodological issues regarding the study of personality in CFS

4.1. Study methods

An obvious reason for the discrepancies in the conclusions of the studies
discussed might be the use of different methods to measure personality. This
diversity seems almost inevitable when we consider the variety and divergence
in health care settings and traditions of personality research. However, even
when using the same instruments there often was no uniformity in the
findings. In three studies, all using the Multidimensional Perfectionism
Scale (MPS) for example, a remarkable lack of consensus in the results
emerges. While White and Schweitzer (2000) demonstrated higher perfectionism
scores in individuals with CFS than in persons in their healthy control
group, Wood and Wessely (1999) using the same MPS, found no differences in
measures of perfectionism between the patients with CFS and the patients with
rheumatoid arthritis in their control group. This difference might be
explained by the fact that these studies used different control groups.
However, Blenkiron et al. (1999) also used a healthy control group and in
contrast with White and Schweitzer, they found the values for perfectionism
on the MPS to be lower in their CFS sample than in their healthy control
group. This example brings us to another issue in the possible explanation of
the lack of uniformity in the major findings of the studies.


4.2. Control groups

Another possible reason for a lack of consistency in the major findings could
be that not all studies used comparable control groups. Whereas many studies
used healthy individuals as (part of) their control group (Blakely et al.,
1991; Blenkiron et al., 1999; Buckley et al., 1999; Christodoulou et al.,
1999; Chubb et al., 1999; Fiedler et al., 2000; Johnson et al., 1996; Masuda
et al., 2002; Rangel et al., 2000; Schmaling & Jones, 1996; White &
Schweitzer, 2000), others used patients with fibromyalgia/chronic pain
(Blakely et al., 1991; Van Houdenhove et al., 2001), depressed patients
(Buckley et al., 1999; Chubb et al., 1999; Johnson et al., 1996), patients
with multiple sclerosis (Christodoulou et al., 1999; Johnson et al., 1996;
Taillefer et al., 2003), or patients with rheumatoid arthritis (Wood &
Wessely, 1999). As a consequence, the results of the studies can only be
interpreted relative to the specific control groups that were used. Certain
differences between patients with CFS and controls that might be obvious with
one control group, might become less significant, or even get completely lost
with another.


4.3. Patient populations and CFS case definitions

So, the results of a specific study can only be interpreted in the light of
the control group that was used. However, this is of course rather common in
medical and psychological research. Be that as it may, in the case of CFS the
same applies to the patient groups that were included, which is far less
usual. While most studies used adult patients with CFS, one study used
adolescent patients with CFS of whom most were recovered (Rangel et al.,
2000) and another study exclusively included combat exposed Gulf War veterans
with CFS (Fiedler et al., 2000). Nevertheless, this would seem to leave all
the studies using 'ordinary' adult individuals with CFS to be comparable.
However, as different CFS case definitions were used, this is not the case.
Some studies used the original CDC criteria of 1988 (Holmes et al., 1988),
others the revised CDC criteria of 1992 (Schluenderberg et al., 1992), others
the revised CDC criteria of 1994 (Fukuda et al., 1994), others the UK
operational criteria of 1991 (Sharpe et al., 1991) and one New Zealand's
McKenzie criteria of 1988 (McKenzie, 1988). To add to the confusion and
making the different findings even more difficult to compare, some studies
distinguished between noninfectious and postinfectious CFS patients (Masuda
et al., 2002), some studies distinguished between patients with CFS and
co-morbid psychiatric disorder/depression and patients with CFS without
co-morbid psychiatric disorder/depression (Chubb et al., 1999; Fiedler et
al., 2000), and one study only included non-depressed patients with CFS
(Buckley et al., 1999). This brings us to the next important problem, the
influence of depression on the study of CFS and personality.


4.4. CFS and depression

Several studies on the psychiatric status of patients with CFS were discussed
in the Introduction. However, as was mentioned there, depression is not an
exclusionary criterion for the diagnosis of CFS and therefore inevitably
plays an important role in the personality studies on CFS. As was noted by
Buchwald (1996) and Wessely, Chalder, Hirsch, Wallace, and Wright (1996),
amongst others, there is a considerable overlap between the criteria used for
several psychiatric DSM-diagnoses (most notably depression) and CFS. As a
consequence patients with symptoms required for a diagnosis of CFS, at the
same time have symptoms fitting into a diagnosis of depression.

When distinguishing between patients with or without depression, some found
that depression had a great impact on the major findings of their study. In
the study by Fiedler et al. (2000), the CFS with psychiatric co-morbidity
group scored significantly higher than the CFS without psychiatric
co-morbidity group on the neuroticism subscales of anxiety, hostility,
self-consciousness, impulsivity and vulnerability. Chubb et al. (1999) found
that the scores of patients with CFS were not different from those of healthy
controls, except for those subjects with CFS who were concurrently depressed,
where the scores resembled the scores of their depressed control
group.Johnson et al. (1996) also found that most of the personality disorders
in their CFS group were accounted for by the CFS group with concurrent
depressive disorder. However, in contrast with these findings, Henderson and
Tannock (2004) concluded that they were unable to account for the presence of
personality disorder in their assessment of patients with CFS, by co-morbid
depression. An additional problem is that the Beck Depression Inventory
(BDI), which three of the studies used (Blakely et al., 1991; Johnson et al.,
1996; Wood & Wessely, 1999), was found to perform poorly as a screener for
depression in subjects with CFS (Farmer et al., 1996).

All in all, the role of depression in CFS is extremely difficult to determine
as there are at least three plausible relationships. It could be that
depression is a predisposing, causative factor in CFS. On the other hand, it
might be that "CFS is no more than depression masquerading as a physical
illness" (Ray, 1991, p. 2), but it is also possible that depression is a
reaction to the illness and to the lack of clarity that surrounds CFS. In
this case it would be likely that depression is caused by the stress of being
diagnosed with a disease of unknown origin, in combination with the absence
of a standard treatment and the possible disbelief encountered in the health
care setting. As it seems to be the case with many of the findings of
abnormalities in CFS, the role of depression in the pathogenesis and
perpetuation of CFS remains unclear. These questions of causality and
nosology however, are somewhat beyond the reach of this article and will
therefore not be discussed further.2 Nevertheless, by raising these questions
we get to a more fundamental level of inquiry. In the next section some
conceptual issues regarding the study of personality in CFS will be
addressed.


5. Conceptual background of personality studies in CFS

As mentioned, the methods used to study personality in CFS are quite diverse.
Nonetheless, in the approach of the reviewed studies, a shared conceptual
model regarding the possible association of personality and CFS, and the
appropriate way to scientifically study it, seems to be reflected.

Firstly, these studies have focused much of their attention on personality
disorder. Psychological malfunctioning, rather than ordinary,
non-pathological and everyday aspects of personality, which are commonly seen
as a primary concern of personality psychology, has been a main interest of
personality research in CFS so far. By such a focus on, and an
overrepresentation of the psychopathological aspects of personality, it is
easy to provide only a one-sided and too stringent image of the personality
of individuals with CFS.

Secondly, on the whole these studies have tended to conceptualize personality
mainly in its most general and decontextualized structures. With the use of
psychological tests like the Tridimensional Personality Questionnaire, the
NEO Five-Factor Inventory and the Eysenk Personality Questionnaire, certain
characteristics of personality, such as extroversion, neuroticism and social
desirability can accurately be studied and compared. However, in this way
personality is approached primarily in its most basic and undifferentiated
structure, and only a limited understanding of personality is provided
(Block, 1995). Although personality traits can provide a kind of
dispositional signature of the person, few links have been made between
traits and actual contextualized behavior (Funder, 2001) and it seems
unlikely that the exclusive knowledge of such a basic structure of relatively
non-conditional and noncontingent dispositional traits, or psychopathological
personality profiles, is enough to wholly explain and account for the
behavioral consequences of CFS, or the complex association between
personality and the syndrome.

Within the humanities and the social sciences, especially personality
psychology, there has been an increasing awareness that persons do not merely
act and experience on the basis of quantifiable, general traits. They
primarily evaluate and motivate their behavior and beliefs in qualitative,
contextualized terms (Richardson, Rogers, & McCaroll, 1998; Taylor, 1989). On
the basis of these terms, persons assess their behavior, interpret
themselves, articulate what they believe to be important, try to make sense
of their past, give meaning to the present, direct their future projects and
provide their life with purpose and unity (McAdams, 1995). Personality is not
a static, independent, self-contained and decontextualized 'given', but is
always dynamically constructed in dialogue with others, and against a
'meaningful' background provided by social practices and culturally shared
moral values (Hermans, Kempen, & Van Loon, 1992; Taylor, 1995). In recent
decades, the idea of the 'narrative' has emerged as a new metaphor not only
within personality psychology (Hermans, 1996; Sarbin, 1986), but also within
clinical psychology (Guignon, 1998; Hermans & Dimaggio, 2004; McLeod, 1997).
>From this approach, persons are understood as the creators of meaning, and
narrative thought is seen as the process by which these meanings are
developed and changed (Bruner, 1991). The narrative is seen not only as a
novel way of conceptualizing human experience and identity, but also as a
useful clinical tool to help individuals understand why they act, and
organize their lives, in certain ways, and to aid them in retelling and
reorganizing their lifestory. In a broader concept of personality, than that
which was used so far in the research on CFS, the lifestory could be seen as
a special kind of psychosocial construction and individuals might be
understood as trying to coauthor a thematically coherent and meaningful
narrative with, and against the background of, their culture and social
world.

Dispositional traits and life narratives can be regarded as two different
levels of personality (McAdams et al., 2004), each with their own methods of
study, frameworks and taxonomies. In CFS, personality traits are usually
studied through the use of standardized questionnaires and (semi) structured
interviews in the search for abnormalities, or deviations from the average.
The benefit and attraction of studying personality in this way is not only
that it is rather time and cost effective, but also that it produces
objective, quantifiable and comparable data and as such seems to be in
accordance with the rigorous methods of the natural sciences. The downside to
this approach is that, to a considerable extent, it decontextualizes human
experience and behavior from its real life setting, and its social and
cultural background. The usefulness and attraction of studying personality on
the level of the life narrative, on the other hand, is that it can remain
much closer to the continually evolving and subjectively experienced reality
of the person. Starting from the assumption of normality, personality on this
level is usually studied through an open dialogue in which the subject
matters are decided, not primarily by the investigator, but in the first
place by the person him - or herself. Just as with personality considered on
a trait level however, the benefits to this approach also entail its main
drawbacks. Besides being rather time-consuming, the obtained data might be
difficult to compare and, because of their specific temporal and spatial
context, be of a contingent and subjective nature. This can lead to the
assumption that personality, considered as a developing lifestory changing
through time, cannot be categorized, quantified or systematically researched
(McAdams, 1995) and that it, because of this, cannot be studied in a proper
methodical way.

Within the scientific debates on CFS, some have tried to draw attention to
the fact that the lifestories of the patients seem to have been neglected.
Van Houdenhove (2002) for example, states that "much of the etiological and
therapeutic controversies about the so called chronic fatigue syndrome
(CFS)[...] may be due to the relative neglect of the patient's story - in
clinical practice as well as in research. More specifically I believe that
insufficient attention is being paid to the mostly significant context in
which the illness began, and the possible connection between the illness and
the patient's life history. [T]he patient's biography should be part of each
diagnostic evaluation and considered an important focus of psychological/
psychiatric research in CFS." (p. 495) At present, there have been few who
have addressed these concerns. Some qualitative studies have described, in
narrative terms, the experience of patients of the impact of CFS as a
disruption and disorganization of their pre-morbid lifestory and identity.
The transformation and rewriting of those stories is depicted as an
inescapable consequence of getting CFS and is usually followed by a
subsequent quest for the restoration and reorganization of a meaningful
autobiographical self-narrative (Bulow & Hyden, 2003; Clark & James, 2003;
Whitehead, 2006). Currently however, the biggest challenge for those wishing
to systematically study the association of personality, considered on the
narrative level, and CFS, will be to do so with methods that are firmly based
in psychological theories about personality and psychotherapy and that have
been specifically designed to analyze and categorize a person's narrative
into its most meaningful temporal constituents. Moreover, such methods should
be psychometrically validated and not only allow a study of the
idiosyncrasies of the single case, but these methods must also have been
developed in such a way that they can be generalized to a population and that
quantitative comparisons between different groups can be made (e.g. Baillio &
Lyddon, 2000; Hermans & Hermans-Jansen, 1995; Van Geel & De Mey, 2003).


6. Conclusion

Every science, whether it be psychology, medicine, physics or sociology, is
based on a set of conceptual assumptions. Usually, when these disciplines are
functioning satisfactory, these presuppositions remain implicit and there is
no need to make them explicit. However, when problems arise that seem
difficult to solve with the normal instruments of these sciences, we have to
focus our attention explicitly on these conceptual assumptions and ask
ourselves whether our understanding of the problem is not somehow obscured by
the commonly accepted model of thought. For psychology and medicine, CFS
poses exactly such a problem.

In this article the first aim was to give a concise review of the current
research on personality and CFS. There seems to be consistent evidence that
patients with CFS often score higher on some personality traits, most notably
neuroticism, than healthy controls. Furthermore, higher levels of DSM axis II
diagnoses, most notably obsessive­ compulsive, histrionic and borderline
personality disorders, within the CFS population, in comparison to healthy
populations are found. However, there are some important confounding elements
in these findings. When compared to patients with another chronic illness,
the finding of specific personality differences is far less common and
usually annulled. Additionally, the finding of divergence could often be
explained by co-morbid depression/ psychiatric disorder. Another limitation
is that, at times, instruments have been used to study certain aspects of
personality (e.g. the MMPI, the BDI and the MCMI) that have later been found
to perform inadequately for patients with CFS. And lastly, many studies
eventually conclude that the found personality differences are consequences
of the disease, rather than precipating factors and as such play no causal
role in CFS. All in all, under careful scrutiny the previously mentioned
stereotype of patients with CFS does not seem to be justified. Nonetheless,
at present there do seem to be at least three overarching conclusions that
can be drawn with regard to personality and CFS. Firstly, the heterogeneity
of findings within the CFS groups implies that, on the trait or
psychopathological level, there are no unique personality characteristics
that are either a necessary condition for, or an unavoidable consequence of
CFS. Secondly, although personality traits such as neuroticism and
perfectionism are generally considered to be stable, non-conditional and not
effected by life changes (Watson & Walker, 1996; Costa et al., 1986), most
studies seem to agree on the possibility that the pre-morbid personalities of
their subjects might have changed as a result of their condition. Diverse
forms of chronic illness seem to be able to alter personality in similar ways
and increased levels of neuroticism and introversion for example (not to
mention depression), could well be a feature of many different diseases. In
fact, the American Psychiatric Association acknowledges the possibility of
personality change as a result of chronic illness (American Psychiatric
Association, 1994). Thirdly, as a consequence of this, it can be concluded
that cross-sectional designs in the long run will probably not be able to
provide definitive answers to the question of the exact role of personality
in CFS.

In the section on the methodological problems of these personality studies it
was suggested that some of the confusion that remains regarding the
association between personality and CFS might be due to a variety in study
methods, control groups and CFS case definitions. This diversity seems almost
unavoidable. However, with regard to control groups, the substantial overlap
between CFS and some psychiatric diagnoses (e.g. depression), and other
unexplained medical conditions (e.g. fibromyalgia) is truly confusing in
research, and makes patients from these populations difficult to compare. Age
and sex matched healthy individuals, and patients with a somatic illness in
which fatigue is also a main complaint (e.g. rheumatoid arthritis, multiple
sclerosis) seem to be much better suited as control groups. With regard to
study methods, the exclusion of general psychopathology or shared problems on
a dispositional trait level in CFS has of course been essential and valuable
in the personality research on CFS. However, the cross-sectional designs of
the reviewed studies make inferences about causality very difficult. New
insights might be gained by longitudinal designs, studying the predictive
validity of certain personality traits as risk factors for the development of
CFS. Prospective studies in clinical populations of mood disorders and
emotional risk factors in relation to CFS for example, have already been able
to provide some evidence regarding their precipating role (Moss-Morris &
Spence, 2006; White et al., 2001). In addition, it will prove insightful to
follow-up a cohort of patients with a relatively short illness duration (i.e.
a recent diagnosis of CFS) in order to study whether certain personality
characteristics, and levels of depression, changed as a consequence of
prolonged illness duration.

Finally, in the section on the conceptual background of the study on
personality in CFS, it was argued that although the methods used so far were
diverse, the studies seemed to share some basic conceptual assumptions
regarding personality and the way to study it. Up to now, personality
research in CFS has either been in search for personality disorder and
psychological malfunctioning, or has been conducted on a general,
non-relational trait level. Nevertheless, the fact that to a large extent
personality is something that can only exist in, and develop through the
inherent relations and dialogues with family, peers, colleagues, media,
society and culture in general, must be taken in account. In previous issues
of this journal a similar perspective has been brought forward by Dwairy
(2002, 1997) with regard to the understanding of the personality and (mental)
health within collective cultures, but it also seems particularly true in the
study of CFS. Future personality research in CFS should not only take the
abovementioned methodological issues into account and be of a more
longitudinal nature, but should also be directed towards, and become aware of
the dialogically constructed, historically contextualized and indissoluble
relational terms by which persons understand, evaluate and articulate
themselves.

Modern individualized society, to a considerable degree, is focused on
achievement, consumption and success, and is characterized by a plurality of
rapid economical, political, religious, technological and cultural changes.
Against this background, modernity confronts people in a whole new fashion
with a multiplicity of problems and possible ways of life and the need, and
imperative, to find and develop a meaningful identity. New insights into the
possible difficulties and stumbling-blocks in the personality of individuals
with CFS might be gained, if research attention would also concentrate on
systematically and comparatively studying individuals with CFS, as
socioculturally embedded agents who are trying to construct a coherent and
intelligible self-narrative.

Notes

1 Millon et al. (1989), being the first to study the role of personality in
  CFS, was included although the study lacked an appropriate control group.
2 See, for example, Abbey and Garfinkel (1990), Moss-Morris and Petrie
  (2001), and Swartz (1988) for some of the articles concerned with the
  relation between CFS and depression, Wessely et al. (1999) and Aaron and
  Buchwald (2001) for a more general discussion concerning the nosological
  status of CFS, and Bolton (2001) and Borch-Jacobsen (2001) for a more
  philosophical and a historical discussion of nosological problems in the
  definition of psychiatric disorders.

The authors are grateful to Elise van de Putte, Coralie Fuchs, Gaston
Franssen, Marc Slors and anonymous reviewers of this journal for their
constructive remarks and suggestions on an earlier draft of this article.
Preparation of this manuscript was supported by a Netherlands Organization
for Scientific Research Grant (400-03-469).


Tables

Table 1. US Centers for Disease Control case definition of CFS, 1994
--------------------------------------------------------------------------------
Diagnostic criteria:
At least 6 months of persistent or recurring fatigue for which no physical
explanation has been found and which
 * is of new onset, that is to say it has not been lifelong
 * is not the result of ongoing exertion
 * is not substantially alleviated by rest
 * severely limits functioning

In combination with four or more of the following symptoms, persistent or
regularly recurring over a period of six months and which must not have
predated the fatigue:
 * self-reported impairment in memory or concentration
 * sore throat
 * tender cervical lymph nodes
 * muscle pain
 * multi-joint pains
 * headache
 * unrefreshing sleep
 * post-exertional malaise lasting 24 h or longer

Exclusionary criteria:
 * any medical condition that may explain the presence of chronic fatigue
 * a psychotic, major or bipolar depressive disorder (but not an uncomplicated
   depression)
 * dementia
 * anorexia or bulimia nervosa
 * alcohol abuse or the use of drugs
 * severe obesity
--------------------------------------------------------------------------------


Table 2 Primary research on personality in CFS
----------------------------------------------------------------------------------------------------------------------------------------------------
Study                Number of participants                Study methods                                Major findings
----------------------------------------------------------------------------------------------------------------------------------------------------
Henderson and        61 patients with CFS (CDC, 1994       Structured Clinical Interview for            39% of the CFS group, 73% of the
Tannock (2004)       (Fukuda et al., 1994))                DSM-III-R Diagnoses (SCID-II)                depressed group and 4% of the
                     40 psychiatric inpatients                                                          healthy group were diagnosed with
                     with depressive disorder                                                           personality disorders. Cluster C
                     45 healthy controls                                                                disorders (avoidant, dependent,
                                                                                                        obsessive-compulsive, self-defeating
                                                                                                        and passive-aggressive) were the most
                                                                                                        common in both the CFS and depressed
                                                                                                        group. Personality disorder in patient
                                                                                                        with CFS could not be accounted for by
                                                                                                        co-morbid depression.
Taillefer et al.,    45 patients with CFS (CDC, 1988       Illness Worry Scale, Neo Five-Factor         There was no difference between the
(2003)               (Holmes et al., 1988))                Inventory (NEO-FFI), SCL-90R                 groups on neuroticism, depressive
                     40 patients with multiple sclerosis   Depression Scale, Symptom                    symptoms, or on the SIQ. The CFS
                                                           Interpretation Questionnaire (SIQ)           group did have significantly higher
                                                                                                        scores than the MS group on the
                                                                                                        Illness Worry Scale. When the CFS
                                                                                                        group was divided into more and less
                                                                                                        depressed patients, the neuroticism
                                                                                                        scores were found to be significantly
                                                                                                        higher than the general population in
                                                                                                        the more depressed CFS group.
Masuda et al.,       16 patients with postinfectious       Holmes Social Readjustment Rating            The stress, maladjustment, marked
(2002)               CFS (CDC, 1992                        Scale, Cornell Medical Index (CMI),          anxiety, depressive tendency and
                     (Schluenderberg et al., 1992))        Maudsley Personality Inventory (MPI),        hypertense state scores of both CFS
                     20 patients with noninfectious        Yatabe-Guilford test, Self-rating            groups were significantly higher than in
                     CFS (CDC, 1992                        Depression Scale (SDS)                       the control group.
                     (Sharpe et al., 1992))                                                             No significant differences between
                     20 healthy controls                                                                both CFS groups on these scores
                                                                                                        were observed. However members
                                                                                                        of the postinfectious CFS group
                                                                                                        were diagnosed as social extroverts,
                                                                                                        while those in the noninfectious CFS
                                                                                                        group were neurotic and introspective.
Van Houdenhove       A randomized sample of a 100          Questionnaire for Habitual                   The patients and their significant others
et al., (2001)       patients out of 124 patients with     Action-proneness (HAB)                       scored the questionnaire similar. These
                     CFS (CDC, 1994                                                                     scores were higher than the norm values,
                     (Fukuda et al., 1994))                                                             suggesting that high "action-proneness"
                     68 patients with fibromyalgia                                                      and an associated "overactive" lifestyle
                     (FM)                                                                               may be one of the factors playing a
                                                                                                        predisposing, initiating as well as a
                                                                                                        perpetuating role in CFS and FM.
White and Schweitzer 44 patients with CFS (CDC, 1994       Multidimensional Perfectionism Scale         The study demonstrated higher
  (2000)             (Fukuda et al., 1994))                (MPS), Rosenberg Self-Esteem Scale           perfectionism scores and lower self-
                     44 healthy controls                   (RSE), Courtauld Emotional Scale             esteem in individuals with CFS, than in
                                                           (CECS), Marlowe-Crowne Social                individuals in the healthy control group.
                                                           Desirability Scale (MCS)                     The results suggest that individuals with
                                                                                                        CFS have a maladaptive perfectionist
                                                                                                        personality style.
Rangel et al.,       25 adolescent patients with CFS       Personality Assessment Schedule (PAS),       Subjects with CFS demonstrated
(2000)               (Oxford Criteria, 1991 (Sharpe et     Kiddie-SADS Psychiatric Interview            increased scores for introspection,
                     al., 1991)) At the time of the study  (K-SADS), Children's Global Assessment       sensitivity, conscientiousness,
                     two-thirds (n = 17) had recovered     Scale (CGAS), Child Behaviour                vulnerability, lability and worthlessness.
                     and the subject's mothers were used   Checklist (CBCL)                             Personality difficulty may either be a
                     as informants                                                                      contributory factor to CFS in children, or
                     15 healthy controls                                                                result from the prolonged disease.
Fiedler et al.       35 veterans with CFS (CDC, 1994       Combat Exposure Scale (CES), Operation       Measures of personality and negative
(2000)               (Fukuda et al., 1994)) and co-        Desert Storm Survey (ODS Survey),            coping strategies (as well as self-reported
                     morbid psychiatric disorder           Childhood Traumatic Events Scale,            combat and chemical exposures)
                     23 veterans with CFS and no co-       Psychiatric Epidemiology Research            significantly differentiated healthy
                     morbid psychiatric disorder           Interview-Life Events Scale (PERI),          veterans from those with CFS. On the
                     45 healthy veterans                   Neuroticism, Extroversion, Openness          neuroticism subscales of anxiety, hostility,
                                                           Personality Inventory (NEO-PI), Toronto      depression, self-consciousness,
                                                           Alexithymia Scale (TAS), Marlowe-            impulsivity and vulnerability the CFS/
                                                           Crowne Social Desirability Scale             psychiatric group scored significantly
                                                                                                        higher than the two other groups.
                                                                                                        Veterans with CFS reported a poorer
                                                                                                        ability to identify and communicate
                                                                                                        feelings than did healthy controls.
Chubb et al.         62 patients with CFS (CDC, 1994       Eysenck Personality Questionnaire            Patients with CFS and concurrent
(1999)               (Fukuda et al., 1994)) and 48         (EPQ), Attributional Style                   depression scored significantly higher
                     healthy controls completed the        Questionnaire (ASQ)                          than individuals with CFS without
                     EPQ.                                                                               concurrent depression or healthy
                     50 patients with CFS (CDC, 1994                                                    controls on the neuroticism subscale.
                     (Fukuda et al., 1994)), 100 healthy                                                On the social desirability subscale subjects
                     controls and 37 depressed patients                                                 with CFS did not differ from the controls.
                     completed the ASQ.                                                                 Scores on both questionnaires show no
                                                                                                        difference between patients with CFS and
                                                                                                        healthy controls except for those subjects
                                                                                                        with CFS who are also concurrently
                                                                                                        depressed. In these cases the scores
                                                                                                        resemble patients with depression.
Buckley et al.       30 non-depressed patients with        Revised NEO Five-Factor                      Higher scores on neuroticism and
(1999)               CFS (CDC, 1994 (Fukuda et al.,        Inventory, Eysenk                            introversion in patients with CFS than
                     1994))                                Personality Questionnaire                    in healthy controls. Lower neuroticism in
                     20 patients with major depressive                                                  CFS than MDD patients. Patients with
                     disorder (MDD)                                                                     CFS reported increased postmorbid
                     15 healthy controls                                                                neuroticism and introversion,
                                                                                                        suggesting that personality may have
                                                                                                        changed as a result of the illness.
Christodoulou et al. 38 patients with CFS (CDC,1994        Diagnostic Interview Schedule                Personality profiles of CFS and MS
(1999)               (Fukuda et al., 1994))                (Q-DIS), Tridimensional                      subjects were generally similar. Both
                     40 patients with multiple sclerosis   Personality Questionnaire (TPQ)              the MS and the CFS groups showed
                     40 healthy controls                                                                elevated levels of Harm Avoidance and
                                                                                                        lower levels of Reward Dependence in
                                                                                                        comparison to healthy subjects. The
                                                                                                        only difference was on the dimension of
                                                                                                        persistence, where the CFS group
                                                                                                        displayed preserved persistence and
                                                                                                        the MS group showed a reduction.
                                                                                                        There was no evidence to suggest that
                                                                                                        patients with CFS possessed an unusual
                                                                                                        level of negativity that would have
                                                                                                        predisposed them to develop their illness.
Wood and Wessely     101 patients with CFS (Oxford         MacLean's questionnaire on attitudes         Alexithymia scores were greater in the
(1999)               Criteria, 1991 (Sharpe et al., 1991)  towards mental illness, Social Desirability  RA patient group and social adjustment
                     and CDC, 1994 (Fukuda et al.,         Questionnaire, Defensiveness Scale of        was poorer in the CFS group. No
                     1994))                                Adjective Check List, Twenty-Item            differences were found between CFS
                     45 patients with rheumatoid           Toronto Alexithymia Scale,                   and RA patients in measures of
                     arthritis (RA)                        Tridimensional Personality Questionnaire,    perfectionism, attitudes towards mental
                                                           Multidimensional Perfectionism Scale,        illness, defensiveness, social desirability,
                                                           Beck Depression Inventory (BDI) Social       or sensitivity to punishment. There was
                                                           Adjustment Scale (SAS)                       no evidence from this study of major
                                                                                                        differences between the personalities of
                                                                                                        patients with CFS and patients with RA.
Blenkiron et al.,    40 patients with CFS (CDC, 1994       Multidimensional Perfectionism Scale,        Women more than men with CFS tend
(1999)               (Fukuda et al., 1994))                Chalder Fatigue Questionnaire, Hospital      to set lower expectations and standards
                     31 healthy controls                   Anxiety and Depression Scale (HAD)           for others. The values for perfectionism
                                                                                                        found on the MPS were lower in the CFS
                                                                                                        sample (reflecting fewer perfectionist
                                                                                                        traits) than in the control group. This
                                                                                                        may indicate that the CFS respondents in
                                                                                                        this survey had already moderated their
                                                                                                        perfectionist tendencies and reset their
                                                                                                        standards to cope with the
                                                                                                        unpredictabilities of the disorder.
Schmaling and Jones  53 patients with CFS                  Minnesota Multiphasic Personality            The aggregate MMPI profile of
(1996)               (Approximately CDC,                   Inventory (MMPI)                             patients with CFS suggests that they
                     1988/ 1994 (Holmes et al., 1988;                                                   have significant physical complaints
                     Fukuda et al., 1994))                                                              and difficulties with cognitive
                     43 healthy controls                                                                functioning, are concerned about their
                                                                                                        symptoms, and are emotionally
                                                                                                        distressed. Their profile is similar to
                                                                                                        that of patients with chronic pain.
Johnson et al.,      35 patients with CFS (CDC, 1988/      The NEO Neuroticism Scale, Personality       The study found progressively higher
(1996)               1992 (Holmes et al., 1988; Sharpe     Diagnostic Questionnaire-Revised (PDQ-       rates of personality disorders (PD) and
                     et al., 1992))                        R), Beck Depression Inventory                neuroticism from healthy controls
                     20 patients with multiple sclerosis                                                through CFS and MS (who did not
                     24 depressed patients                                                              differ) to the depressed group. The
                     40 healthy controls                                                                most common PD's among subjects with
                                                                                                        CFS were histrionic (23%) and
                                                                                                        borderline (17%). The CFS group with
                                                                                                        concurrent depressive disorder (34% of
                                                                                                        the CFS group) was found to account for
                                                                                                        most of the personality disorder.
Blakely et al.       58 patients with CFS (McKenzie        Minnesota Multiphasic Personality            Progressively more elevated scores on
(1991)               (New Zealand) criteria, 1988)         Inventory, Beck Depression Inventory,        most scales from healthy controls
                     81 patients with chronic pain (CP)    General Health Questionnaire (GHQ)           through chronic pain to patients with
                     104 healthy controls                  Lazarus ways of Coping (WoC)                 CFS were found. The individuals with
                                                                                                        CFS showed more deviant personality
                                                                                                        traits reflecting emotionality or
                                                                                                        neuroticism, inward hostility, self-
                                                                                                        criticism and guilt, although
                                                                                                        personality profiles fell into different
                                                                                                        groups. The hypothesis is brought
                                                                                                        forward that in CFS we are dealing
                                                                                                        with a particular subpopulation of
                                                                                                        patients with CP, who are particularly
                                                                                                        extreme and relatively homogenous in
                                                                                                        their endorsement of CFS symptoms.
Millon et al.        24 patients with CFS (CDC, 1988       Millon Clinical Multiaxial Inventory         Evidence of severe personality
(1989)               (Holmes et al., 1988))                (MCMI-II), Profile of Mood States            pathology and affective distress was
                     No appropriate control group          Hamilton Rating Scale of Depression          found. Anxiety, somatic disorder and
                                                           (HAM-D), Folstein Mini-Mental                depression were particularly prominent.
                                                           Examination The Wechsler Memory Scale        Histrionic (33%), schizoid (29%) and
                                                           (WMS)                                        avoidant, narcissistic and aggressive/
                                                                                                        sadistic (each 25%) personality scales
                                                                                                        were pathologically elevated.
----------------------------------------------------------------------------------------------------------------------------------------------------


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(c) 2007 Elsevier/ScienceDirect B.V.

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------------------------------

Date:    Wed, 21 Mar 2007 15:33:19 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Normal cerebrospinal fluid levels of hypocretin-1 (orexin  A) in patients with fibromyalgia syndrome

Normal cerebrospinal fluid levels of hypocretin-1 (orexin A) in patients
with fibromyalgia syndrome.

Sleep Med. 2007 Mar 16; [Epub ahead of print]

Taiwo OB, Russell IJ, Mignot E, Lin L, Michalek JE, Haynes W, Xiao Y,
Zeitzer JM, Larson AA.

University of Minnesota, Department of Veterinary and Biomedical Sciences,
Rm 295, Animal Science/Veterinary Medicine Building, 1988 Fitch Avenue, St.
Paul, MN 55113, USA.

PMID: 17369087


BACKGROUND: The hypothalamic neuropeptide hypocretin (orexin) modulates
sleep-wake, feeding and endocrine functions. Cerebrospinal fluid (CSF)
hypocretin-1 (Hcrt-1) concentrations are low in patients with
narcolepsy-cataplexy, a sleep disorder characterized by hypersomnolence and
rapid eye movement (REM) sleep abnormalities.

METHODS: We determined CSF Hcrt-1 concentrations of patients with the
fibromyalgia syndrome (FMS), a condition characterized by fatigue, insomnia
and in some cases daytime hypersomnolence.

RESULTS: Basal CSF levels of Hcrt-1 in FMS did not differ from those in
healthy normal controls.

CONCLUSIONS: These findings suggest that abnormally low Hcrt-1 is not a
likely cause of fatigue in FMS.

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------------------------------

Date:    Wed, 21 Mar 2007 15:37:31 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Long-term opioid contract use for chronic pain management  in primary care practice. A five year experience.

Long-term opioid contract use for chronic pain management in primary care
practice. A five year experience.

J Gen Intern Med. 2007 Apr;22(4):485-90.

Hariharan J, Lamb GC, Neuner JM.

Division of General Internal Medicine, Medical College of Wisconsin,
Froedtert East Clinic Bldg., Suite E4200, 9200 West Wisconsin Avenue,
Milwaukee, WI, 53226, USA, jharihar@mcw.edu.

PMID: 17372797


BACKGROUND: The use of opioid medications to manage chronic pain is complex
and challenging, especially in primary care settings. Medication contracts
are increasingly being used to monitor patient adherence, but little is
known about the long-term outcomes of such contracts.

OBJECTIVE: To describe the long-term outcomes of a medication contract
agreement for patients receiving opioid medications in a primary care setting.

DESIGN: Retrospective cohort study.

SUBJECTS: All patients placed on a contract for opioid medication between
1998 and 2003 in an academic General Internal Medicine teaching clinic.

MEASUREMENTS: Demographics, diagnoses, opiates prescribed, urine drug
screens, and reasons for contract cancellation were recorded. The
association of physician contract cancellation with patient factors and
medication types were examined using the Chi-square test and multivariate
logistic regression.

RESULTS: A total of 330 patients constituting 4% of the clinic population
were placed on contracts during the study period. Seventy percent were on
indigent care programs. The majority had low back pain (38%) or
fibromyalgia (23%). Contracts were discontinued in 37%. Only 17% were
cancelled for substance abuse and noncompliance. Twenty percent
discontinued contract voluntarily. Urine toxicology screens were obtained
in 42% of patients of whom 38% were positive for illicit substances.

CONCLUSIONS: Over 60% of patients adhered to the contract agreement for
opioids with a median follow-up of 22.5 months. Our experience provides
insight into establishing a systematic approach to opioid administration
and monitoring in primary care practices. A more structured drug testing
strategy is needed to identify nonadherent patients.

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------------------------------

Date:    Fri, 23 Mar 2007 15:36:45 +0100
From:    Jan van Roijen <j.van.roijen CHELLO.NL>
Subject: res: FMS -pivotal trial for chronic pain

~~~~~~~~~~~~~~~~~~~~~~~~~~~~


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http://www.pipelinereview.com/joomla/content/view/10541/106/


Pipeline Review



Fralex Therapeutics Inc. initiates pivotal
trial for chronic pain associated with fibromyalgia
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

22 Mar 2007


Announced the initiation of RELIEF, its pivotal study for the
treatment of chronic pain associated with fibromyalgia. The trial
will evaluate the safety and effectiveness of the Company's
non-drug, in-home therapy, Complex Neural Pulse(TM)
(CNP(TM)). The first clinical trial site in Ottawa, Ontario, has
been initiated and patient screening and recruitment will begin
shortly.

TORONTO, Canada | Mar 22, 2007 | Fralex Therapeutics Inc.
(TSX: FXI) ("Fralex" or the "Company"), a medical technology
company developing neuromodulation therapy, today announced
the initiation of RELIEF, its pivotal study for the treatment of
chronic pain associated with fibromyalgia. The trial will evaluate
the safety and effectiveness of the Company's non-drug,
in-home therapy, Complex Neural Pulse(TM) (CNP(TM)). The
first clinical trial site in Ottawa, Ontario, has been initiated and
patient screening and recruitment will begin shortly.

"We are pleased that we have achieved our milestone of
initiating the RELIEF trial within the first quarter of 2007 and look
forward to initiating further clinical sites in Canada and the U.S.
in the coming weeks," said Avi Grewal, President and CEO of
Fralex. "We believe that CNP will significantly advance the
practice of medicine in the treatment of various chronic,
debilitating conditions by offering a non-invasive, relatively
low-cost treatment option. Patients can regain control of their
lives without having to deal with possible addiction issues, or
other side effects that themselves seriously affect quality of life."

The RELIEF trial will enrol between 200 and 300 subjects
across 13 centres in the U.S. and Canada, and is being
conducted under an Investigational Device Exemption (IDE)
from the U.S. Food and Drug Administration (FDA) and an
Investigational Testing Authorization (ITA) from Health Canada.

Subjects will be randomized on a one-to-one basis to receive
CNP or placebo for 12 weeks. The primary efficacy endpoint will
be a statistically and clinically significant difference between the
active and placebo groups in the proportion of the subjects who
achieve a 30% or greater reduction in their NRS pain scores.


About Fibromyalgia

Fibromyalgia is a chronic, debilitating condition characterized by
widespread musculoskeletal (MSK) pain, disturbed sleep, and
fatigue along with multiple painful tender points, which are widely
and symmetrically distributed. According to the American Pain
Society, fibromyalgia is estimated to affect eight to twelve million
people in the United States. Fibromyalgia is one of the most
commonly diagnosed conditions in pain clinics in the United
States. No treatments have been specifically approved for
fibromyalgia in the United States or Canada.

About FRALEX:

FRALEX is a medical technology company focused on
developing and commercializing Complex Neural Pulse(TM) or
CNP(TM), a novel neuromodulation therapeutic technology for
chronic pain, which utilizes specifically designed, low-frequency
electromagnetic pulses. FRALEX is proceeding with its
FDA-approved pivotal clinical trial (the "RELIEF" trial) to
evaluate the safety and effectiveness of this technology in the
treatment of chronic pain associated with fibromyalgia. The trial
is to be conducted in 2007 and 2008 at leading medical centres
within the US and Canada. For more information on FRALEX,
please visit www.fralex.com; further details on the RELIEF trial
will be posted on www.clinicaltrials.gov.

Certain statements contained in this release containing words
like "believe", "intend", "may", "expect", and other similar
expressions, are forward-looking statements that involve a
number of risks and uncertainties.
Factors that could cause actual results to differ materially from
those projected in the Company's forward-looking statements
include the following: market acceptance of Company's
technologies and products; the ability to obtain financing;
Company's financial and technical resources relative to those of
its competitors; Company's ability to keep up with rapid
technological change; government regulation of therapeutic
technologies; the Company's ability to enforce its intellectual
property rights and protect its proprietary technologies; the
ability to obtain and develop partnership opportunities; the
timing of commercial product launches; the ability to achieve key
technical milestones in key products and other risk factors
identified from time to time in the Company's filings.


SOURCE: Fralex Therapeutics Inc

[Return to top]

------------------------------

Date:    Fri, 23 Mar 2007 16:23:50 +0100
From:    Jan van Roijen <j.van.roijen CHELLO.NL>
Subject: not,med: clinical guidelines often influenced by industry

~~~~~~~~~~~~~~~~~~~~~~~~~~~~


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http://www.bmj.com/cgi/content/extract/334/7586/171


BMJ  2007;334:171 (27 January),
doi:10.1136/bmj.39104.406065.DB

News


US clinical guidelines often influenced by industry, NEJM says
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Janice Hopkins Tanne

1 New York

Many clinical guidelines for doctors in the United States are
influenced by the pharmaceutical industry and special interest
groups, said an article in the New England Journal of Medicine
last week (2007;356:331-3).

"The quality of guidelines varies considerably," and some are
controversial, says a commentary by the journal's national
correspondent, Robert Steinbrook.

Meanwhile, the National Institutes of Health (NIH) cancelled a
conference that it had planned on guidelines for screening
pregnant women for herpes, after it received a protest letter from
the Center for Science in the Public Interest. The organisation's
letter said that four out of five of the speakers had undisclosed
ties to drug firms that made antiviral drugs (BMJ
2007;334:115).

The letter was signed by Richard Horton, editor of the Lancet;
two former editors of the New England Journal of Medicine,
Marcia Angell and Jerome Kassirer; 41 other physicians and
scientists, including the head . . . [Full text of this article]
http://www.bmj.com/cgi/content/full/334/7586/171

``````

Related Article
Who should call the tune?
James R Philp
BMJ 2007 334: 491. [Extract]
http://www.bmj.com/cgi/content/extract/334/7592/491-c


This article has been cited by other articles:
(Search Google Scholar for Other Citing Articles)

Philp, J. R (2007). Who should call the tune?. BMJ 334: 491-491
[Full text]
http://www.bmj.com/cgi/content/full/334/7592/491-c

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Read all Rapid Responses
http://www.bmj.com/cgi/eletters/334/7586/171


An additional hazard of clinical guidelines.
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bmj.com, 27 Jan 2007 [Full text]
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US clinical guidelines often influenced by industry-referral
to NICE in UK
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bmj.com, 28 Jan 2007 [Full text]
http://www.bmj.com/cgi/eletters/334/7586/171#155522

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Date:    Fri, 23 Mar 2007 12:36:26 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: The pain of fibromyalgia syndrome is due to muscle  hypoperfusion induced by regional vasomotor dysregulation

The pain of fibromyalgia syndrome is due to muscle hypoperfusion induced by
regional vasomotor dysregulation.

Med Hypotheses. 2007 Mar 19; [Epub ahead of print]

Katz DL, Greene L, Ali A, Faridi Z.

Yale Prevention Research Center, Yale University School of Medicine, 130
Division Street, Derby, CT 06418, USA; Yale University School of Public
Health, Yale University School of Medicine, 60 College Street, New Haven,
CT 06520, USA.

PMID: 17376601


Fibromyalgia syndrome (FMS) is a condition of chronic muscle pain and
fatigue of unknown etiology and pathogenesis. There is limited support for
the various hypotheses espoused to account for the manifestations of FMS,
including immunogenic, endocrine, and neurological mechanisms.

Treatment, partially effective at best, is directed toward symptomatic
relief without the benefit of targeting known, underlying pathology. A
noteworthy commonality among partially effective therapies is a
vasodilatory effect. This is true both of conventional treatments,
unconventional treatments such as intravenous micronutrient therapy, and
lifestyle treatments, specifically graduated exercise.

The pain of fibromyalgia is described in terms suggestive of the pain in
muscles following extreme exertion and anaerobic metabolism. Taken
together, these characteristics suggest that the pain could be induced by
vasomotor dysregulation, and vasoconstriction in muscle, leading to
low-level ischemia and its metabolic sequelae.

Vasodilatory influences, including physical activity, relieve the pain of
FMS by increasing muscle perfusion. There are some preliminary data
consistent with this hypothesis, and nothing known about FMS that refutes it.

The hypothesis that the downstream cause of FMS symptoms is muscle
hypoperfusion due to regional vasomotor dysregulation has clear
implications for treatment; is testable with current technology; and should
be investigated.

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Date:    Sun, 25 Mar 2007 16:08:09 +0200
From:    "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM>
Subject: RES,NOT: CFS and CBT

Source: Journal of Neurology, Neurosurgery, and Psychiatry
        Vol. 78, #4, pp 434-436
Date:   March 21, 2007
URL:    http://jnnp.bmj.com/cgi/content/full/78/4/434

        http://www.jnnp.com


[Short report]

The effect of cognitive behaviour therapy for chronic fatigue syndrome on
self-reported cognitive impairments and neuropsychological test performance
---------------------------------------------------------------------------
Hans Knoop, Judith B Prins, Maja Stulemeijer, Jos W M van der Meer, Gijs
Bleijenberg
Hans Knoop, Gijs Bleijenberg, Expert Centre Chronic Fatigue, Radboud
  University Nijmegen Medical Centre, Nijmegen, The Netherlands
Judith B Prins, Maja Stulemeijer, Department of Medical Psychology, Radboud
  University Nijmegen Medical Centre, Nijmegen, The Netherlands
Jos W M van der Meer, Department of Internal Medicine, Radboud University
  Nijmegen Medical Centre, Nijmegen, The Netherlands
Correspondence to: H Knoop, Expert Centre Chronic Fatigue, Radboud University
  Nijmegen Medical Centre, P O Box 9011, 6525 EC Nijmegen, The Netherlands;
j.knoop nkcv.umcn.nl

Received 26 June 2006
Revised 14 November 2006
Accepted 15 November 2006


Abstract

Background
Patients with chronic fatigue syndrome (CFS) often have concentration and
memory problems. Neuropsychological test performance is impaired in at least
a subgroup of patients with CFS. Cognitive behavioural therapy (CBT) for CFS
leads to a reduction in fatigue and disabilities.

Aim
To test the hypothesis that CBT results in a reduction of self-reported
cognitive impairment and in an improved neuropsychological test performance.

Methods
Data of two previous randomised controlled trials were used. One study
compared CBT for adult patients with CFS, with two control conditions. The
second study compared CBT for adolescent patients with a waiting list
condition. Self-reported cognitive impairment was assessed with
questionnaires. Information speed was measured with simple and choice
reaction time tasks. Adults also completed the symbol digit-modalities task,
a measure of complex attentional function.

Results
In both studies, the level of self-reported cognitive impairment decreased
significantly more after CBT than in the control conditions. Neuropsychological
test performance did not improve.

Conclusions
CBT leads to a reduction in self-reported cognitive impairment, but not to
improved neuropsychological test performance. The findings of this study
support the idea that the distorted perception of cognitive processes is more
central to CFS than actual cognitive performance.

Abbreviations: CBT, cognitive behavioural therapy; CFS, chronic fatigue
syndrome; CIS, checklist individual strength; CIS-conc, checklist individual
strength-concentration; SDMT, symbol digit modalities task; SIP-ab, sickness
impact profile-alertness behaviour; SOCI, self-observation of cognitive
impairment

--------------------------------------------------------------------------------

Chronic fatigue syndrome (CFS) is characterised by severe fatigue, lasting
longer than 6 months and leading to functional impairment. The fatigue is not
the result of a known organic disease or ongoing exertion, and not alleviated
by rest. According to the Centre for Disease Control definition of CFS,
impaired concentration and/or memory is an additional symptom criterion.1 The
level of self-reported cognitive impairments in CFS is high2 and contributes
to the social and occupational dysfunctions of patients with CFS.3

Studies evaluating neuropsychological functioning in patients with CFS with
neuropsychological tests yielded conflicting results.4 Reduced speed of
(complex) information processing is the most consistently found impairment.3
5 6 However, several studies found no cognitive impairments7 and other
studies identified a subset of patients with defective performance.8 9

Fatigue-related cognitions and behaviour can perpetuate CFS.10 Several
controlled trials have shown that cognitive behavioural therapy (CBT) aimed
at these perpetuating factors leads to a reduction in fatigue and
disabilities.11

The first hypothesis tested was that CBT for CFS also results in a reduction
of self-reported cognitive impairments. The second hypothesis was that the
neuropsychological test performance of patients with CFS improves after CBT.
Data of two previous CBT trials12 13 were used to test the hypotheses.


MATERIALS AND METHODS

Patients

The first study from which data were used compared the effects of CBT for
adults with CFS with natural course and support groups12 in a multicentre
randomised controlled trial. Assessments were done at baseline, and at 8 and
14 months. An intention-to-treat analysis showed a reduction in fatigue and
functional impairment after CBT. In two of the three participating treatment
centres, neuropsychological tests were part of the assessments. Consequently,
data from neuropsychological test performance were available for a subset of
233 (78 CBT; 76 natural course; 79 support group) of the total group of 278
patients. The mean (SD) age of this group was 36.8 (10.2) years, 182 (78%)
were female and median illness duration was 41 months. The second study was a
randomised controlled trial comparing CBT for adolescents with CFS13 with a
waiting list condition. A total of 69 patients were randomly assigned to the
conditions. Assessments were done at baseline and at 5 months. The results
showed a greater decrease in fatigue and functional impairment in the CBT
group. Neuropsychological data of 67 patients were available (33 CBT; 34
waiting list). The mean (SD) age of the group was 15.6 (1.3) years, 59 (88%)
were female and median illness duration was 18 months.


Questionnaires assessing self-reported cognitive impairments

Checklist individual strength-concentration

In both studies, the severity of concentration problems over the past 2 weeks
was assessed with the subscale concentration of the checklist individual
strength (CIS) that consists of five items on a seven-point scale. The score
can range between 5 and 35.3 12 13


Sickness impact profile-alertness behaviour

In adults, the self-observed effect of cognitive impairments on daily
functioning was assessed with the subscale sickness impact profile-alertness
behaviour (SIP-ab) of the sickness impact profile.14 The subscale has 10
items, each item is weighed and the score can range between 0 and 777. No
such instrument was available for adolescents.


Self-observation of cognitive impairment

In adolescents, the frequency of cognitive impairments was determined with a
structured diary. Patients rated both concentration and memory impairment
separately on a daily self-observation list four times a day for 12 days
(0=no impairment; 1=impaired). The percentage of concentration problems and
memory problems (both number of assessments with a problem divided by 48
times 100) were added and then divided by two to calculate the mean
percentage of incidents of cognitive impairment.


Neuropsychological tests

Reaction time task

The reaction time task consisted of two subtests, simple and choice reaction
time tasks. Both are described in detail elsewhere.8 15 In a previous study,
the reaction times of patients with CFS were slower than that of healthy
controls on both tasks.8


Symbol digit modalities task

The symbol digit modalities task (SDMT)16 was used in the adult study as a
measure of complex attention. In previous studies, patients with CFS scored
lower than a matched healthy control group.8 9


Statistical analysis

Statistical analysis was performed using SPSS V.12.01. Significance was
assumed at p,0.05. A multivariate analysis of variance was performed with
self-reported cognitive impairment and reaction time as dependent variables
and treatment as fixed factor. Univariate tests and post hoc analysis are
reported if the multivariate test was significant. For the SDMT, a univariate
analysis was performed, as data were available for a subset of 174 patients
as the SDMT was added later to the test battery. In the adult study, the
dependent variables were the change scores at 14 months from baseline and in
the adolescent study, it was at 5 months from baseline. Reaction times were
transformed by a logarithm transformation. For adults, if data at 14 months
were missing and data 8-months post-treatment were available, the second were
used. In all other cases, missing data were replaced with estimates derived
by single imputation (missing variable analysis regression in SPSS with
baseline value as predictor). For significant treatment effects, effect sizes
were calculated.


RESULTS

Nineteen adult patients (8%) had missing checklist individual
strength-concentration (CIS-conc) and SIP-ab post-treatment data. One patient
had missing data on both reaction time tasks at baseline, for 44 (19%)
patients only baseline data and for 30 (17%) patients only a baseline SDMT
score was available. Two adolescent patients had no SOCI scores at baseline.
For 4 (6%) patients the CIS-conc and SOCI at second assessment were missing.
Two patients had no baseline reaction time and for 13 (20%) adolescents the
reaction times at the second assessment were missing.

In both studies, there were more data missing from neuropsychological tests
than from questionnaires as some patients were willing to mail the
questionnaires, but refused to undergo a second neuropsychological
assessment.


Self-reported cognitive impairments

Adults

The multivariate test (Pillai's trace) showed a significant change in
self-reported cognitive impairments (F(4,460)=4.76; p=0.001). The univariate
tests showed a significant effect of treatment on the change in CIS-conc and
SIP-ab (F(2,230)=8.94; p<0.001 and F(2,230)=4.42; p=0.013). Following CBT,
the decrease in CIS was significantly greater than in both the natural course
(p,0.001) and the support group (p=0.001; table 1). There was a significantly
greater decrease in SIP-ab score after CBT compared with natural course
(p=0.004). The difference between CBT and support group failed to reach
significance (p=0.055).


Adolescents

The multivariate test showed a significant treatment effect on self-reported
cognitive impairments (F2,62=5.03; p=0.009). Univariate tests showed that the
decrease in the CIS-conc and SOCI score was significantly larger in the CBT
group (F(1,63)=6.4; p=0.014 and F(1,63)=6.28; p=0.015).


Neuropsychological test performance

Adults

There was no significant effect of treatment on either reaction time task
(F(4,458)=0.44; p=0.783). There was no significant treatment effect on the
SDMT (F(2,171)=0.73; p=0.484).


Adolescents Multivariate tests showed no significant treatment effect on
either reaction time task (F(2,62)=0.34; p=0.714).


DISCUSSION

The hypothesis that self-reported cognitive impairments decrease after CBT in
patients with CFS was confirmed. Only one comparison in the adult study,
measuring cognitive impairments more indirectly, showed an effect in the
expected direction without reaching significance. The results of the original
adolescent study13 already indicated that concentration problems decrease
after CBT. In that study, the concentration problems were assessed with a
single item evaluating these problems retrospectively over a period of 6
months. This assessment can be easily influenced by situational circumstances
and memory biases, which can be prevented by the use of a diary as in the
present study. No support could be found for the hypothesis that
neuropsychological test performance improves after CBT.

A methodological problem is that in a substantial part of the patients the
neuropsychological data of the second assessment were missing. Furthermore,
in our analysis we assumed that dropout occurred at random, whereas patients
may drop out for non-random reasons. We repeated the analyses, but only on
patients who completed both assessments. Again, there was no significant
treatment effect. Our interpretation is that this indicates that improvement
in self-reported cognitive impairments after CBT is independent of the change
in neuropsychological test performance.

A discrepancy between subjectively reported disabilities versus objectively
measured performance is not limited to the current study. Mahurin et al17
found that the objective cognitive functioning of monozygotic twins
discordant for CFS did not differ, whereas the twin with CFS reported more
cognitive impairments. Metzger and Denney18 showed that patients with CFS
underestimated their cognitive performance. In the study by Vercoulen et al,8
most patients with CFS reported concentration and memory problems, whereas
only a small percentage showed an impaired performance. Given the fact that
patients with CFS perceive their cognitive processes as impaired but
underestimate their actual performance, one would expect that an effective
treatment of CFS would lead to a more accurate perception of one's
performance. The results of the present study are consistent with this
prediction. CBT resulted in decreased complaints about cognitive functioning,
but not in a change in performance. This is also in line with the hypothesis
that a distorted perception of symptoms and performance is a crucial element
of CFS.10


ACKNOWLEDGEMENTS

The authors thank Theo Fiselier for contributing to the selection of
adolescent patients with CFS, Lammy Elving for contributing to the selection
of adult patients and Ria te Winkel and Lida Nabuurs for assisting in data
collection.

Funding: The Health Insurance Council (College van Zorgverzekeraars) funded
the adult CBT study. The Children's Welfare Stamps Netherlands (Stichting
Kinderpostzegels Nederland) and the ME Foundation (ME Stichting) funded the
adolescent CBT study.

Competing interests: none.


TABLE

Table 1 Estimated treatment effect in change score (95% CI) on the dependent variables
------------------------------------------------------------------------------------------------------
Self-reported cognitive impairments
  Adults                          CBT                      Natural course        Support group
    CIS-conc                      -7.4 (-9.1 to -5.7)+     -2.7 (-4.4 to -1.0)** -3.4 (-5.1 to -1.8)**
    SIP-ab                        -116 (-156 to -76)++     -31 (-72 to -10)**    -61 (-100 to -21)
  Adolescents                     CBT                      Waiting list
    CIS-conc                      -6.8 (-10.5 to -3.5)+++  -0.9 (-4.2 to +2.5)*
    SOCI                          -7.9 (-12.8 to -2.9)1    0.9 (-4.1 to +6.0)*
------------------------------------------------------------------------------------------------------
Neuropsychological test performance
  Adults                          CBT                      Natural course        Support group
    Simple reaction time (ms)      9 (-9 to 27)            -5 (-23 to 14)        6 (-12 to 24)
    Choice reaction time (ms)     -24 (-51 to 3)           -27 (-54 to 1)        -26 (-53 to 1)
    SDMT                           2.8 (0.8 to 4.8)        2.3 (0.2 to 4.4)      4 (2 to 6)
  Adolescents                     CBT                      Waiting list
    Simple reaction time (ms)     -30 (-53 to -8)          -18 (-41 to 4)
    Choice reaction time (ms)     -12 (-29 to 6)           -10 (-28 to 8)
------------------------------------------------------------------------------------------------------
CBT, cognitive behavioural therapy; CIS-conc, checklist individual strength-concentration; SDMT,
symbol digit modalities task; SIP-ab, sickness impact profile-alertness behaviour; SOCI, self-
observation of cognitive impairment.
 *  Significantly different from the CBT condition, p,0.05.
**  Significantly different from the CBT condition, p,0.01.
+   Cohen's d based on change within treatment condition=1.3.
++  Cohen's d=0.6.
+++ Cohen's d=0.4.


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--------
(c) 2007 BMJ Publishing Group Ltd.


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