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Date:    Tue, 31 Oct 2006 15:14:22 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks@xxx.xx>
Subject: RES,NOT: Immunity, cognitive dysfunction, and symptoms in CFS

Source: Journal of Psychosomatic Research
         Vol. 60, #6, pp 559-566
Date:   June 2006
URL:    http://www.sciencedirect.com/science/journal/00223999


Impaired natural immunity, cognitive dysfunction, and physical symptoms in
patients with chronic fatigue syndrome: preliminary evidence for a subgroup?^*
------------------------------------------------------------------------------
Scott D. Siegel, Michael H. Antoni^**, Mary Ann Fletcher, Kevin Maher, Mary
Catherine Segota, Nancy Klimas
Behavioral Medicine Research Center, Department of Psychology, University of
Miami, Miami, FL, USA
*  This work was supported by research grant 1U01AI45940.
** Corresponding author. Department of Psychology, University of Miami, 5665
    Ponce DeLeon Blvd, Coral Gables, FL, USA. Tel.: +1 305 284 5466;
    fax: +1 305 284 1366. E-mail address: mantoni@miami.edu (M.H. Antoni).

Abbreviations: CFS, chronic fatigue syndrome; NKCA, natural killer
    cell activity; POMS-V, Profile of Mood States-Vigor; POMS-F, Profile of
    Mood States-Fatigue; FSI-I, Fatigue Severity Inventory-Intensity;
    MFSI-M, Multidimensional Fatigue Symptom Inventory-Mental; PASAT,
    Paced Auditory Serial Addition Test; FSI-D, Fatigue Severity Inventory-
    Disruption; PSQI, Pittsburgh Sleep Quality Index; SF-36, Medical Out-
    comes Study 36-Item Short Form Health Survey; BDI, Beck Depression
    Inventory; PSS, Perceived Stress Scale; MANOVA, multivariate analysis of
    variance; MANCOVA, multivariate analysis of covariance.

Received 15 August 2005


Abstract

Objective
The diagnostic criteria of chronic fatigue syndrome (CFS) define a
heterogeneous population composed of several subgroups. Past efforts to
identify subgroup markers have met with mixed success. This study was
designed to examine natural killer cell activity (NKCA) as a potential
subgroup marker by comparing the clinical presentations of CFS patients with
and without clinically reduced NKCA.

Methods
Forty-one female CFS patients were classified into having either low or
normal NKCA levels. These subgroups were then compared on objective measures
of cognitive functioning and subjective assessments of fatigue, vigor,
cognitive impairment, and daytime dysfunction.

Results
Relative to CFS patients in the normal-NKCA subgroup, low-NKCA patients
reported less vigor, more daytime dysfunction, and more cognitive
impairment. In addition, low-NKCA patients performed less on objective
measures of cognitive functioning relative to normal-NKCA patients.

Conclusions
The results are offered as preliminary evidence in support of using NKCA as
an immunological subgroup marker in CFS. Findings are also discussed in
terms of known associations between dysregulated immune functions, somatic
symptoms, and psychological stress.

Keywords
Chronic fatigue syndrome; Natural killer cell activity; Subgroups; Sickness 
behavior


Introduction

Chronic fatigue syndrome (CFS) has been labeled a 'controversial illness,'
with no known diagnostic markers or pathophysiology [1]. However, CFS
afflicts approximately 800,000 people in the United States, approximately
80% of whom are women [2]. It is characterized by great variability in
clinical presentation, including flu-like symptoms, cognitive impairment,
neurological symptoms, and pain [3,4]. CFS is frequently associated with
comorbidities, ranging from other chronic illnesses with heterogeneous sets
of symptoms (such as fibromyalgia and multiple chemical sensitivities) to
atopic disease and psychiatric illness (e.g., depression) [1]. CFS patients
experience substantial reductions in occupational, educational, and social
functioning, which collectively contribute to decrements in quality of life
[1]. CFS may also represent an economic burden for society (e.g., high rates
of unemployment due to disability) and health care institutions [5,6].
Several etiologies have been proposed - immunological, neuroendocrine, and
autonomic - and yet no physiological mechanism has been consistently and
uniquely related to CFS [7-13]. As a result, current CFS treatments are
symptom-focused and relatively ineffective [14]. Improved treatment options
for CFS will likely only come with a better understanding of the syndrome's
underlying pathophysiology.

The present study sought to improve the understanding of CFS pathophysiology
by investigating the existence of patient subgroups. It has been proposed
[3,15,16] that CFS may have multiple causes, with a different underlying
pathophysiology for each subgroup of patients. Evidence in support of this
subgroup hypothesis begins with CFS diagnostic criteria [3], which are
thought to define a heterogeneous population composed of several relatively
homogenous subgroups. First, CFS diagnostic criteria are polythetic,
allowing for patients with wide-ranging clinical presentations to receive
the same diagnosis. Second, the diagnostic criteria were not derived
empirically, but were developed by consensus among a panel of investigators
based on anecdotal evidence. Third, CFS has no diagnostic laboratory test,
but is rather a diagnosis of exclusion. Calls have been made to identify CFS
subgroup markers, including recommendations from the authors of the
diagnostic criteria [3].

Past attempts to identify patient subgroups have typically focused on
clinical presentation without considering underlying physiology. For
example, one study found that CFS patients who described a gradual onset of
physical symptoms had higher rates of psychiatric illness relative to
patients who reported an acute onset [15], but this finding has been
difficult to replicate (e.g., Buchwald et al. [17]). Other investigations
have relied on factor analysis to identify symptom clusters such as
flu-like, cognitive, and neurologic symptoms [18]. In contrast to these
symptom-focused approaches, Buchwald et al. [17] investigated several
markers of inflammation (e.g., C-reactive protein) in attempting to describe
an immune activation subgroup of CFS patients. However, because the
magnitude of the associations among the inflammatory markers was small, and
because absolute blood levels of inflammatory markers were of questionable
clinical significance, Buchwald et al. recommended against the use of these
criteria for differentiating CFS subgroups.

The present study specifically investigated the existence of an
immunological subgroup of CFS patients. It has been suggested that CFS
clinical presentation may implicate an immunological pathophysiology
[19-21]. However, reviews of research on potential immunological
abnormalities (e.g., lymphocyte count and proliferation, cytokine
production, and neopterin) in CFS patients have shown the literature to be
inconsistent and often contradictory [22,23]. In the present investigation,
natural killer cell activity (NKCA) was chosen as the criterion by which CFS
patients were categorized into 'immunological' and 'nonimmunological'
subgroups. NKCA is an in vitro measure of NK effector functions and is
presumed to correspond to NK cells' ability, in vivo, to eliminate virally
infected and cancerous somatic cells. Unlike other immunological variables,
research has reliably shown NKCA to be reduced in CFS patients compared to
healthy controls [22,24,25]. Furthermore, although CFS samples as a whole
have been characterized by reduced NKCA, closer examination has demonstrated
that only subgroups of CFS patients manifest with reduced NKCA (e.g.,
Whiteside and Friberg [26] and Levine et al. [27]).

Evidence has shown that immune dysregulation is associated with fatigue and
cognitive impairment in both CFS [20,28] and non-CFS populations [29-31]
(for reviews, see Dantzer [32] and Larson and Dunn [33]). For example, an
increased production of proinflammatory cytokines has been associated with a
constellation of symptoms known as sickness behavior, including fatigue,
cognitive impairment, and reduced activity. Reduced NKCA may contribute to
enhanced cytokine production. In addition to its role in antiviral immunity,
NK cells down-regulate immunological activity following microbial clearance
of pathogens by eliminating antigen-presenting cells [34]. For example,
animal research has shown that mice deficient in perforin (a mediator of NK
effector functions) exhibit prolonged and enhanced production of the
cytokine interferon-g. Based on these reported findings, we hypothesized in
this study that patients in the immunological group, characterized by
reduced NKCA, would demonstrate greater fatigue, cognitive impairment, and
disability than patients in the nonimmunological group.



Methods

Participants

CFS participants were recruited from a tertiary care clinic at the Veterans
Affairs Medical Center, University of Miami (Miami, FL) and through
distribution of recruitment brochures, local newspaper advertising, and
internet advertising. Because of the poor recruitment of male participants,
which is attributable to the low prevalence of diagnosed CFS among men
relative to women and/or known gender differences in health-care-seeking
behaviors, we included only female participants in this study. Participants
for this report come from a larger, longitudinal study; only baseline data
from the larger study are reported here. We recruited individuals aged 18­
60 years with a preexisting diagnosis of CFS based on the Centers for
Disease Control and Prevention diagnostic criteria [3]. Participants also
needed to be English-speaking, with at least an eighth-grade education, to
ensure that they were capable of reading and completing questionnaires.
Exclusion criteria included any active medical condition that could explain
the presence of chronic fatigue (including an active infection), current use
of immunomodulatory or antibiotic medications, and a past or present
psychiatric diagnosis of psychosis (e.g., schizophrenia), dementia, major
depressive disorder with psychotic or melancholic features, bipolar
disorder, anorexia or bulimia nervosa, or alcohol/substance abuse within 2
years of the onset of the fatigue or anytime thereafter.

Prospective participants went through a two-stage screening process before
being enrolled into the study. First, prospective participants were
interviewed by telephone to collect demographic information and symptom,
medical, and psychiatric histories. If initial eligibility requirements were
met, they were invited for in-person screening, at which point informed
consent was obtained. Next, physical examination was performed, blood was
drawn to rule out exclusionary medical conditions (e.g., elevated Lyme
titer), and the Structured Clinical Interview for DSM-IV Axis I Disorders
was administered [35]. All participants received usual care from their
treating physician throughout the study.


NKCA

NKCA was determined using the whole blood chromium release assay described
by Baron et al. [36] and Patarca et al. [37]. The NK-sensitive
erythroleukemic K562 cell line was used as target cells. The assay was
performed in triplicate at four target/effector cell ratios with 4-h
incubation. Results are expressed as the mean of three measures of percent
cytotoxicity at a target/effector cell ratio of 1:1.

CFS participants were subgrouped by NKCA cutoff values obtained from local
laboratory norms. The choice to use local norms was based on Whiteside and
Friberg [26], who stated that, for the purpose of defining low NKCA,
controls should be of the same geographic location and should be tested in
the same assays as CFS patients. These norms were based on a sample of
healthy controls recruited during the same years the CFS participants were
being recruited. Inclusion/exclusion criteria included: (a) ages 18 ­75
years; (b) no active acute or chronic illness; and (c) no history of drug
use within the last 6 months. Healthy controls were assessed through
self-report measures and physical examination. The healthy controls used for
establishing the laboratory norms were 26 healthy men and women, with a mean
age of 43 years (S.D.=13). CFS participants were characterized as blow NKCAQ
if their NKCA value fell below 23.7%, the lower limit of the normal range
(mean control NKCA-1 S.D.). Participants with NKCA values above 23.7% were
characterized as 'normal NKCA.'^1


Physical symptom and psychosocial measures

Fatigue and vigor
Profile of Mood States-Vigor (POMS-V) and Profile of Mood States-Fatigue
(POMS-F) [38] were used to assess self-reported energy levels. High scores
on the POMS-V are indicative of high levels of vigor, whereas high scores on
the POMS-F are indicative of high levels of fatigue. Energy was also
assessed with the self-report Fatigue Severity Inventory-Intensity (FSI-I)
[39]. High scores on the FSI-I are indicative of high levels of fatigue.

Cognitive impairment
Cognitive impairment was assessed with a self-report measure and two
objective measures. The self-report measure was the short form version of
Multidimensional Fatigue Symptom Inventory-Mental (MFSI-M) [40]. The MFSI-M
assesses a wide range of cognitive symptoms, including difficulties with
concentration, confusion, and memory. The short form version of the MFSI was
empirically derived from a larger 83-item measure that has shown sufficient
psychometric properties. High scores on the MFSI-M indicate greater
cognitive impairment. The two objective measures used were the Paced
Auditory Serial Addition Task (PASAT) [41] and the Digit Span subtest of the
Wechsler Adult Intelligence Scale-Third Edition [42]. The PASAT measures the
rates of information processing, sustained attention, and divided attention.
The total number of correct answers from the first of two trials was used
for this study. The Digit Span task measures both auditory attention and
working memory, but only auditory attention (assessed by the number of
forward digits correct) was examined in this study. High scores on the PASAT
and Digit Span indicate good information processing and attentional
abilities.

Daily functioning
Fatigue Severity Inventory-Disruption (FSI-D), the physical functioning
subscale of Medical Outcomes Study 36-Item Short Form Health Survey (SF-36)
[43], and the daytime dysfunction subscale of the Pittsburgh Sleep Quality
Index (PSQI) [44] were used to assess the selfreport degree of daily
functioning. The FSI-D specifically asks participants to consider the degree
to which fatigue interferes with activities of daily living, the SF-36 asks
participants to consider the role of their overall health (including
comorbidities) on daily functioning, and the PSQI-Daytime Dysfunction
subscale asks participants to consider only the role of their sleep quality
on daily functioning. High scores on the FSI-D and the daytime dysfunction
subscale of the PSQI, but low scores on the physical functioning subscale of
the SF-36, indicate a low degree of daily functioning.

Control variables
Information on age, ethnicity, education, marital status, and illness
duration (i.e., years since symptom onset) were collected during the phone
interview and used as potential control variables. Additionally, because the
symptoms of CFS are similar to symptoms associated with stress and
depression, the Beck Depression Inventory (BDI) II [45] and the Perceived
Stress Scale (PSS) [46] were also included as potential control variables.
To address the issue of multicollinearity (i.e., overlap between measures of
fatigue and depression), somatic items from the BDI were not included in the
total score.


Statistical analyses

Sample demographic variables of low- and normal-NKCA CFS participants were
compared using chi-square or independent-samples t tests, as appropriate. In
this sample, zero-order correlations among dependent variables within each
set of symptoms (but not necessarily across sets) revealed small to moderate
relationships (.20<r<.55), making multiple multivariate analyses of variance
(MAN- OVA) preferable to other statistical tests (e.g., confirmatory factor
analysis). To determine whether there were differences between NKCA groups
on measures of energy, cognitive impairment, and daily functioning, a series
of multivariate analyses of covariance (MANCOVA) was conducted, with NKCA
subgroup as independent factor and with measures of psychosocial and
physical functioning as dependent variables. Additionally, potential control
variables that correlated with the dependent variables at r>=.20 were
included as covariates in the analyses. When statistical significance was
found with the omnibus MANCOVA, post hoc descriptive discriminant analyses
were conducted to better understand the effect. For illustrative purposes,
the results of univariate tests are also presented.


Sociodemographic characteristics

Forty-one women diagnosed with CFS, with a mean age of 44.5 years
(S.D.=9.21), were enrolled in this study. Participants designated as low
NKCA (n=22) did not differ significantly from their normal-NKCA counterparts
(n=19) on demographic or psychosocial variables, with the exception of
marital status (see Table 1). Unless otherwise noted, values are reported as
M (S.D.). Low-NKCA participants were more likely to be either separated or
divorced. Qualitative descriptors on effect sizes are based on guidelines
suggested by Cohen [47].


Fatigue and vigor

Low- and normal-NKCA groups were compared on the following measures of
energy: POMS-V, POMS-F, and FSI-I. Controlling for BDI scores (excluding
somatic items), a MANCOVA demonstrated a significant difference between
groups [Lambda=.775, F(3,36)=3.49, P=.025], a large effect size (eta^2=.23).
Inclusion of other control variables did not affect the results. Descriptive
discriminant analyses (see Table 2) indicate that relative to the
normal-NKCA group, low-NKCA group members reported lower levels of vigor on
the POMS and greater levels of fatigue on the FSI. Overall, 65.7% of the
participants were correctly classified based on the fatigue and vigor
variables. Consistent with descriptive discriminant analysis, illustrative
univariate analyses indicated that relative to the normal-NKCA group,
low-NKCA group members reported significantly less vigor on the POMS
[F(1,38)=5.95, P=.019] and a trend towards more fatigue on the FSI-I
[F(1,38)=3.60, P=.065]. No significant differences were found on the POMS-F
(see Table 3 for group means adjusted for BDI).


Cognitive impairment

Low- and normal-NKCA groups were compared on the following measures of
cognitive functioning: MFSI-M, PASAT, and Digit Span. Controlling for
illness duration, MANCOVA demonstrated a significant difference between
groups [Lambda=.543, F(3,36)=10.09, P<.001], a large effect size
(eta^2=.46). Inclusion of other control variables did not affect the
results. Descriptive discriminant analysis (see Table 2) indicates that,
relative to the normal-NKCA group, low-NKCA group members reported
significantly more cognitive symptoms on the MFSI and performed less on the
PASAT and the Digit Span. Overall, 68.8% of the participants were correctly
classified based on cognitive impairment variables. Consistent with
descriptive discriminant analyses, univariate analyses indicated that,
relative to the normal-NKCA group, low-NKCA group members reported
significantly more cognitive symptoms on the MFSI [F(1,38)=15.32, P<.001]
and performed significantly less on both the PASAT [F(1,38)=19.45, P<.001]
and the Digit Span [F(1,38)=8.57, P=.006] (see Table 3 for group means,
which have been adjusted for illness duration).

Performance on the Digit Span was also compared to national age-referenced
norms. Collapsing across NKCA groups, CFS participants did not differ from
their age-referenced norms ( PN.10). In contrast, the difference between CFS
participants in the low-NKCA group and age-referenced norms was marginally
significant [t(21)=-1.86, P=.076], whereas participants in the normal-NKCA
group performed better than their age-referenced norms [t(18)=3.31, P<.01].


Daily functioning

Low- and normal-NKCA groups were compared on the following measures of
daily functioning: FSI-D, PSQI- Daytime Dysfunction, and SF-36-Physical
Functioning. MANOVA (no potential control variables correlated with
dependent variables) demonstrated a significant difference between groups
[Lambda=.728, F(3,36)=4.47, P<.01], a large effect size (eta^2=.27).
Descriptive discriminant analyses (see Table 2) indicate that, relative to
the normal-NKCA group, low-NKCA group members reported more daily disruption
due to fatigue on the FSI, more daytime dysfunction due to sleep
difficulties, and less overall ability to function physically on the SF-36.
Overall, 59.1% of the participants were correctly classified based on daily
functioning variables. Consistent with descriptive discriminant analysis,
univariate analyses indicated that, relative to the normal-NKCA group,
low-NKCA group members reported significantly more daily disruption due to
fatigue on the FSI-D [F(1,38)=7.0, P=.012], less ability to function
physically on the SF-36 [F(1,38)=9.75, P=.003], and a trend toward reporting
more daytime dysfunction because of sleep difficulties ([F(1,38)=2.96
P=.094] (see Table 3 for group means).


Discussion

The clinical presentation associated with CFS - fatigue, flu-like symptoms,
and cognitive impairment - implicates an immunological-based
pathophysiology. Indeed, there are empirical findings to support this
hypothesis, but, taken as a whole, the literature is both inconsistent and
contradictory [22]. Therefore, the main focus of this investigation was to
test the hypothesis that CFS patients can be categorized into subgroups that
differ with respect to the underlying physiology and clinical presentation.

NKCA was used to classify CFS patients into low- and normal-NKCA subgroups.
This variable was chosen because, unlike other immune variables studied in
CFS patients, it is reliably reduced in CFS patients compared to healthy
controls [22,24-27]. However, NKCA values for CFS patients ranged from
clinically reduced to normal levels [25]. The present study showed that when
the low- and normal-NKCA groups were compared on multiple indicators of
fatigue/vigor, cognitive impairment, and daily functioning, clear
differences emerged. Compared to patients with normal NKCA, patients with
reduced NKCA reported less vigor, more cognitive difficulty, poorer daily
functioning, and performed less well on objective measures of cognitive
abilities.

It should be kept in mind that patients in this study performed at expected
levels on the Digit Span task when compared to national age-referenced
norms, although when comparisons to these norms were made with the low-NKCA
group only, a marginally significant lower performance emerged. In contrast,
the normal-NKCA group outperformed age-referenced norms. The literature on
cognitive impairment in CFS patients, like the immunology literature, is
inconsistent. Although many CFS patients report a decline in their memory,
attention, and concentration, assessment with objective instruments (e.g.,
PASAT) has failed to document a true cognitive deficit in samples of CFS
patients [48]. In the present study, differences on self- report and
objective measures of cognitive impairment between the low- and normal-NKCA
groups highlighted the advantage of conducting analyses with subgroups.
Future research will be needed to clarify the clinical significance of these
cognitive differences.

What were the possible mediators of the relationship between reduced NKCA
and clinical symptoms in this study? Two initial hypotheses are proposed
here. One, given the role NK cells play in targeting virally infected cells,
a clinically significant reduction in NKCA may lead to a nonspecific
activation of latent viruses and new viral infections [49,50]. Glaser and
Kiecolt-Glaser [51] have advanced the hypothesis of bpartial reactivation,Q
which proposes that replication of specific viral proteins without
activation of the complete virus may be capable of inducing a 'chronic'
inflammatory response. It is plausible that reduced NKCA can lead to either
partial or complete activation of latent viruses, and possibly increased
rates of new viral infections, which collectively may induce a response
similar to sickness behavior [32]. Sickness behavior, a constellation of
symptoms that includes fatigue, cognitive impairment, and reduced activity,
is a well-conserved behavioral repertoire that human and nonhuman animals
demonstrate in response to illness [32]. Clear evidence now shows that
mediators of peripheral inflammation make their way to the central nervous
system, where they are capable of inducing these behavioral changes [33].
Unlike early CFS reports, which sought to identify a specific viral cause of
CFS [52], the partial activation hypothesis proposes that a nonspecific
increase in viral activation may contribute to CFS symptomatology through a
common immunological pathway.

Our second potential hypothesis focuses on the immunoregulatory functions of
NK cells. Following microbial clearance of a pathogen, NK cells are
responsible for the lysis of antigen-presenting cells, which has a
down-regulatory effect on the immune response. For example, animal research
has shown that mice deficient in perforin, a mediator of NK effector
functions, show enhanced and protracted proinflammatory cytokine production
in response to viral antigens [34]. This cytokine production may induce a
sickness behavior response. Using a sickness behavior theoretical framework
may also help explain why, in this study, certain measures of clinical
presentation differentiated the low- and normal-NKCA groups better than
other measures. For example, the POMS-V, which clearly differentiated the
groups, may be a proxy for anhedonia, a central component of sickness
behavior [32,33]. In contrast, measures of fatigue (POMS-F and FSI-I) failed
to discriminate between groups. Although fatigue is also considered part of
the sickness behavior response, it is, by definition, the one symptom shared
by all CFS patients. Thus, patients in the low-NKCA group may be described
as having both fatigue and low vigor.

The present study is limited by its cross-sectional design, raising the
possibility that the relationship observed between NKCA and clinical
symptoms may be spurious. For example, compared to healthier patients,
patients with significant symptom profiles may experience greater distress,
and it may be this distress that causes reductions in NKCA [51]. Although
the low- and normal-NKCA groups did not report significant differences in
depression (BDI) or perceived stress (PSS), a statistically larger
percentage of the low-NKCA patients, compared with the normal-NKCA patients,
were divorced or separated. This may point to a history of
marital/relationship discord, which may have had long-lasting effects on
NKCA. Furthermore, low-NKCA patients may have premorbid personality styles
that predispose toward distress (e.g., depressive), and this may account for
the reduced levels of NKCA and perhaps a greater symptom reporting. To
further understand these relationships, the patients included in this
investigation are currently being followed longitudinally. This will allow
us to test the stability of our proposed NKCA subgroups independent of
ongoing stressors and distress levels. As this study only included women,
future investigations should include men. Furthermore, future research can
objectively assess subgroup differences in levels of activity (e.g., with
the actigraph) [53] as a proxy for fatigue and dysfunction. Finally,
examination of potential mediators, such as plasma cytokine levels, markers
of NK effector functions (e.g., perforin content) [54], or markers of viral
activation (e.g., antibody to viral capsid antigens) [51], is warranted to
test the hypotheses presented above. Preliminary studies from our laboratory
indicate a decreased level of intracellular perforin in NK cells from CFS
patients [54].

CFS is a misunderstood, debilitating condition of unknown etiology. Despite
some initial enthusiasm, research in the last two decades has produced
little advancement in the understanding of the pathophysiology of CFS.
Unfortunately, this lack of progress seems to have only further contributed
to the belief among members of the medical community (and lay public) that
CFS is not an actual organic condition. Determining whether CFS symptoms are
caused by an organic condition is certainly a fair empirical question. As a
first step, reconciling inconsistencies in the CFS literature may be
advanced by conducting subgroup analyses. This was the first known study to
use NKCA as a criterion by which to group CFS patients. Additional research
is needed to test the utility of this subgroup strategy in prospective
designs that incorporate repeated indicators of CFS symptom severity and
disease status.


Note

^1 This system of designating low NKCA is similar to the approach used by
Whiteside and Friberg, who described low NKCA as falling in the lowest 10%
of control NKCA values, which would correspond to 1.28 S.D. below the mean.


Tables

Table 1. Demographic and psychosocial characteristics of participants
-------------------------------------------------------------------------
                        Low NKCA       Normal NKCA     Statistical
Variables              (n=22)         (n=19)          comparison
-------------------------------------------------------------------------
Age                    45.3 (9.59)    43.5 (8.90)     t=0.617,    P>.10
Time (years) since
  Symptom onset         10.0 (6.82)     9.9 (7.52)     t=0.027,    P>.10
  Diagnosis              5.7 (4.29)     6.3 (4.4)      t=-0.459,   P>.10
Ethnicity (%)                                         chi^2=1.44, P>.10
  Caucasian             68.2           84.2
  Hispanic              22.7           10.5
  Other                  9.1            5.3
Education (%)                                         chi^2=2.91, P>.10
  >=College degree      59.1           63.2
  Some college/trade    27.3           36.8
  HS diploma/            9.1           0
   general
   educational
   development
  <HS diploma            4.5           0
Marital status (%)                                    chi^2=7.55, P=.023
  Married               40.9           68.4
   or equivalent
  Divorced/separated    31.8           0
  Single                27.3           31.6
Duration (years)       10.1 (6.28)     9.8 (8.35)     t=0.129,    P>.10
BDI                    14.8 (8.05)    14.5 (5.10)     t=0.172,    P>.10
PSS                    27.6 (8.66)    27.0 (8.97)     t=0.220,    P>.10
-------------------------------------------------------------------------


Table 2. Descriptive discriminant analysis results
-------------------------------------------------------------------------
Variables       Standardized coefficients        Structure weights
-------------------------------------------------------------------------
Vigor/fatigue^a
POMS-V                  -.664                         -.734
POMS-F                   .767                         -.230
FSI-I                    .589                          .571

Cognitive^b
MFSI-M                   .526                          .692
PASAT                   -.603                         -.780
Digit Span              -.319                         -.518

Daily functioning^c
FSI-D                   -.356                         -.703
PSQI                    -.345                         -.457
SF-36                    .713                          .830
-------------------------------------------------------------------------
^a Centroid values: low NKCA=.485, normal NKCA=-.561.
^b Centroid values: low NKCA=.832, normal NKCA=-.963.
^c Centroid values: low NKCA=-.566, normal NKCA=.626.


Table 3. Adjusted group means and S.D. for CFS patients in the low- and
          normal-NKCA groups
-------------------------------------------------------------------------
Variables              Low NKCA            Normal NKCA         P
-------------------------------------------------------------------------
POMS-V                  5.77 (3.38)         8.54 (4.32)         .019
POMS-F                 17.55 (5.94)        18.76 (6.23)         .065
FSI-I                   6.89 (1.39)         6.39 (1.13)         .36
MFSI-M                 14.18 (5.22)         8.58 (3.52)        <.001
PASAT                  29.05 (12.16)       43.64 (13.16)       <.001
Digit Span              9.40 (2.15)        11.12 (1.61)         .006
FSI-D                   6.61 (1.89)         5.07 (1.78)         .012
PSQI                    2.00 (0.95)         1.53 (0.77)         .094
SF-36                  31.67 (17.27)       50.26 (20.38)        .003
-------------------------------------------------------------------------


References

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      and Sons, 2003. p. 1-38.
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      Interview for DSM-IV (SCID). Washington (DC): American Psychiatric
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      143-52.
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      (SF-36): I Conceptual framework and item selection. Med Care 1992;
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      Pittsburgh Sleep Quality Index: a new instrument for psychiatric
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      studies demonstrating the antiviral effect of natural killer cells in
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      abnormalities of chronic fatigue syndrome. J Clin Microbiol 1990;28:
      1403-10.
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      responses to Epstein­Barr virus, human herpesvirus 6 and human
      herpesvirus 7 in patients with chronic fatigue syndrome. Intervirology
      1995;38:269-73.
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      JLF. Self-reported sleep quality and fatigue correlates with
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      52:140-7.
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      Quantitative fluorescence measures for determination of intracellular
      perforin content. Clin Diagn Lab Immunol 2002;9:1248-52.

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(c) 2006 Elsevier/ScienceDirect

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Date:    Tue, 31 Oct 2006 15:14:58 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks@xxx.xx>
Subject: RES,NOT: 'Action-proneness'in CFS

Source: Journal of Psychosomatic Research
         Vol. 60, #6, pp 623-625
Date:   June 2006
URL:    http://www.sciencedirect.com/science/journal/00223999


[Short communication]

In search of a new balance. Can high 'action-proneness' in patients with
chronic fatigue syndrome be changed by a multidisciplinary group treatment?
---------------------------------------------------------------------------
Boudewijn Van Houdenhovea(a,*), Karolien Bruyninckx(b), Patrick Luyten(b,c)
a Chronic Fatigue Reference Centre, University Hospitals, K.U. Leuven,
   Leuven, Belgium
b Department of Psychology, K.U. Leuven, Leuven, Belgium
c Postdoctoral Fellow Research Fund, K.U. Leuven, Leuven, Belgium
* Corresponding author. University Hospital Gasthuisberg, Herestraat
   49, B-3000 Leuven, Belgium.
   E-mail address: boudewijn.vanhoudenhove@uz.xxxxx.xx.xx

Received 21 June 2005; received in revised form 28 November 2005; accepted
13 December 2005


Abstract

Objective
The purpose of this study is to investigate changes in 'action-proneness'
(a cognitive and behavioral tendency toward direct action) after a
multidisciplinary group intervention, including cognitive behaviour therapy
(CBT) and graded exercise therapy (GET).

Methods
Patients with chronic fatigue syndrome (n=62) completed three versions of a
Dutch self-report questionnaire evaluating action-proneness retrospec-
tively that is (1) before illness onset, (2) before treatment and (3) after
treatment. Significant others (n=62) also gave their opinion about the
patients' action-proneness at time points 1 and 2.

Results
Premorbid action-proneness levels considerably dropped after illness onset.
After treatment, action-proneness levels significantly increased again,
although levels remained below premorbid levels.

Conclusion
High action-proneness retrospectively reported by CFS patients can be
adaptively modified by a multidisciplinary group treatment including CBT and
GET.

Keywords
Action-proneness; Chronic fatigue syndrome; Lifestyle; Multidisciplinary
treatment; Outcome study; Overactivity


Introduction

Chronic fatigue syndrome (CFS) is a distressing and potentially disabling
illness characterized by persistent medically unexplained fatigue, muscular
and articular pains, postexertional malaise, and other nonspecific symptoms
[1]. A clear cause of the condition is not established, although the
pathophysiology of CFS (and the largely overlapping fibromyalgia syndrome)
may be based on subtle stress system malfunctions [2].

Many authors believe that since a direct curative treatment for CFS is not
available, recovery may be facilitated when patients realistically adapt to
their current limitations, at the same time, trying to progressively
increase their physical and mental effort tolerance [2]. In a systematic
review, both cognitive behavior therapy (CBT) and graded exercise therapy
(GET) have been considered evidencebased methods to obtain these goals [3].

In our previous research, we investigated the possible etiopathogenetic role
of an 'overactive' lifestyle in CFS, which we operationalized as high
'action-proneness,' that is, a cognitive and behavioral tendency toward
direct action [4]. Maladaptive overactivity patterns may not only precede
the illness but may persist after illness onset (e.g., periodic outbursts of
activity followed by prolonged periods of rest), constituting an important
perpetuating factor [5].

The aim of the present study was to investigate whether, and to which
degree, adaptive changes in beliefs, attitudes, and intentions concerning
(over)activity occur in CFS patients participating in a multidisciplinary
CBT- and GET-based treatment program. The study was part of a larger outcome
study, the results of which are reported elsewhere [6].


Methods

Participants

Sixty-two consecutively admitted patients (55 female and 7 male, mean
age=39.03 years, S.D.=8.61) participated in the study. The majority (87%)
had at least higher secondary education, and 80% were married or living
together. Only two patients dropped out before the end of the treatment.

Each patient was sent to our CFS Reference Centre at the University
Hospitals Leuven by his/her general practitioner. At the end of the
multidisciplinary diagnostic screening, a CFS diagnosis was based on the CDC
criteria [1] and the patient was informed about our therapeutic approach. It
was notably explained that amelioration could be obtained by 'the search for
a new physical and mental equilibrium' - implying an optimal balance between
doing too little and doing too much - as a basic condition for long-term
recovery [7].

When the patient agreed with this approach, he/she gave written consent and
entered the program. No other selection criterion was used, except the
impossibility of attending an outpatient setting (e.g., because of
geographical reasons).

Besides the CFS group, the patients' significant others (SO) (n=62, in 70%
the partners) also participated in the study.


Therapeutic intervention

The treatment lasted 6 months. During the first month, it took 2 days a week
(4h a day) and was then gradually reduced to 1 day in a month. For an
extensive description of the therapeutic program, see Ref. [6].

In line with the therapeutic rationale, the cognitive-behavioral therapist
placed much emphasis on discussing concrete modalities of activity pacing,
while at the same time, encouraging patients to improve their physical
condition as much as possible.

Graded exercise therapy consisted of 1-h sessions, with an initial training
intensity corresponding to the work load at 60% of the heart rate reserve,
calculated on the basis of a maximum exercise test. Starting from Week 3,
all participants were asked to exercise three times a week (including at
home). The training program was adjusted to a slower pace when deemed
necessary, after discussion with the patient.


Instruments

The 'Vragenlijst voor Habituele Actiebereidheid' (Questionnaire for Habitual
Action-proneness) (HAB) was used to measure the degree of action-proneness
[8]. This is a well-validated Dutch questionnaire consisting of 50 items (to
be answered as 'correct' or 'incorrect'), capturing beliefs, attitudes, and
tendencies with respect to physical as well as mental activity.

To evaluate possible changes in action-proneness, we administered the HAB
questionnaire to the patients in three different forms at different time
points. HAB1 items retrospectively focused on premorbid action-proneness,
for example, 'Before I got ill... I didn't need much time to think before
making a decision.' HAB2 items focused on current (i.e., pretreatment)
action-proneness, for example, 'I enjoy exerting myself to the limit.'
Finally, HAB3 items focused on posttreatment action-proneness (or activity-
related intentions), for example, 'From now on... no effort is too much for
me.'

The SOs were also instructed to give their opinion about the patient's
action-proneness, for example, 'Before he/she got ill... he/she took any
job, if only to have something to do' (premorbid HAB-SO1), and, 'If he/she
had a choice, he/she would sleep far into the day' (pretreatment HAB-SO2).


Procedure

A naturalistic pre/post design was used. At the start of the program,
patients were asked to fill in HAB1 and HAB2. The SOs were asked to fill
in HAB-SO1 and HAB-SO2 at the same time point. Immediately after the last
treatment session, patients filled in HAB3. Full anonymity and
confidentiality were guaranteed to both patients and SOs.


Statistical analyses

To compare premorbid, pretreatment and posttreatment action-proneness
scores, we used paired t tests. All statistics were carried out with the
software program Statistica [9].


Results

As shown in Tables 1 and 2, the patients' pretreatment action-proneness
levels (M=17.75, S.D.=6.21) were significantly lower than premorbid levels
(M=38.27, S.D.=6.65, P<.001). On the other hand, posttreatment action-
proneness levels (M=20.23, S.D.=4.65) were significantly higher than
pretreatment levels (P=.03) but still significantly lower than premorbid levels
(P<.001).

The SOs scored the patients' pretreatment action-proneness also as lower
(M=19.95, S.D.=6.97) than the patients' premorbid action-proneness
(M=35.03, S.D.=7.80, P<.001).


Discussion

First, the results of this study are in line with our previous findings
that CFS patients describe themselves, before illness onset, as highly
'action-prone' [4]. Moreover, as in our former research [5], patients'
self-descriptions were paralleled by the opinion of their SOs.

Second, after illness onset, patients' reported action-proneness levels
strongly decreased - an expected finding that could be considered a
consequence of symptoms and illness-related functional limitations.

Third, when at the end of the treatment patients were asked to describe
their activity-related intentions, their action-proneness levels increased
again, but without reaching retrospectively reported premorbid levels.

Together with the fact that our treatment program led to a significant
amelioration of the patients' reported global physical and mental
functioning, and an increase of their psychological attributions and
self-efficacy (see Ref. [6] for more details), the results of the present
study may be interpreted as the patients' readiness for adaptive activity
management and realistic adjustment of lifestyle and life goals.

However, the following methodological limitations should be taken into
account. Both patients' and SOs' reports might be retrospectively biased
[10]. In addition, we cannot be sure that the patients' intentions would
lead to actual changes in their daily life. Also, our multidisciplinary
setting does not indicate which therapeutic ingredients are necessary or
sufficient for the desired behavior modifications. Finally, the present
study was uncontrolled - although the results of our larger outcome study
[6] make it plausible that action-proneness changes were due to the
therapeutic intervention.

Taken together, controlled prospective research using objective measures of
physical and psychosocial functioning is necessary to ascertain whether
these preliminary therapeutic findings in CFS patients reflect a real shift
'toward a new balance.'


Acknowledgment

The authors thank the team members of the CFS Reference Centre of the
University Hospitals Leuven for their help in the collection of data.


Tables

Table 1. Means and S.D.'s for the HAB questionnaires at different time
          points in CFS patients and SOs
------------------------------------------------------------------------
             CFS patients                        SOs
             ------------------------------      ------------------------
             HAB1        HAB2        HAB3        HAB-SO1       HAB-SO2
             (n=62)      (n=58)      (n=56)      (n=62)        (n=62)
------------------------------------------------------------------------
Mean        38.27       17.75       20.23       35.03         19.95
S.D.         6.65        6.21        4.65        7.80          6.97
------------------------------------------------------------------------
HAB1: patients, premorbid; HAB2: patients, pretreatment; HAB3: patients,
posttreatment; HAB-SO1: SOs, premorbid; HAB-SO2: SOs, pretreatment.


Table 2. Paired sample statistics for the HAB questionnaires at different
          time points in CFS patients and SOs
------------------------------------------------------------------------
HAB1 vs.            HAB2 vs.             HAB1 vs.            HAB-SO1 vs.
HAB2                HAB3                 HAB3                HAB-SO2
------------------------------------------------------------------------
t=19.22             t=-2.19              t=17.09             t=10.89
P<.001              P=.03                P<.001              P<.001
------------------------------------------------------------------------
HAB1: patients, premorbid; HAB2: patients, pretreatment; HAB3: patients,
posttreatment; HAB-SO1: SOs, premorbid; HAB-SO2: SOs, pretreatment.


References

  [1] Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A.
      The chronic fatigue syndrome: a comprehensive approach to its
      definition and study. Ann Intern Med 1994;121:953-9.
  [2] Van Houdenhove B, Egle UT. Fibromyalgia: a stress disorder? Piecing
      the biopsychosocial puzzle together. Psychother Psychosom
      2004;73:267-75.
  [3] Whiting P, Bagnall AM, Sowden AL, Cornell JE, Mulrow CD,
      Ramirez G. Interventions for the treatment and management of
      chronic fatigue syndrome: a systematic review. JAMA 2002;286:
      1360-8.
  [4] Van Houdenhove B, Onghena P, Neerinckx E, Hellin J. Does high
      'action proneness' make people more vulnerable to chronic fatigue
      syndrome? A controlled psychometric study. J Psychosom Res 1995;
      39:633-40.
  [5] Van Houdenhove B, Neerinckx E, Onghena P, Lysens R, Vertommen
      H. Premorbid 'overactive' lifestyle in chronic fatigue syndrome and
      fibromyalgia. An etiological factor or proof of good citizenship? J
      Psychosom Res 2001;51:571-6.
  [6] Pardaens K, Haagdorens L, Van Wambeke P, Van den Broeck A, Van
      Houdenhove B, How relevant are exercise capacity measures for
      evaluating treatment effects in chronic fatigue syndrome? Results
      from a prospective, multidisciplinary outcome study. Clin Rehabil
      2006;20:56-66.
  [7] Van Houdenhove B, Egle UT, Luyten P. The role of life stress in
      fibromyalgia. Curr Rheumatol Rep 2005;7:365-70.
  [8] Dirken J. Vragenlijst voor Habituele Actiebereidheid [Questionnaire
      for Habitual Action-proneness]. Groningen: Swets & Zeitlinger, 1979.
  [9] Statistica for Windows [Computer Program Manual]. Tulsa, OK, 2001.
[10] Riley MS, O'Brien CJ, McCluskey DR, Bell NP, Nicholls DP.
      Aerobic work capacity in patients with chronic fatigue syndrome.
      BMJ 1990;301:953-6.

--------
(c) 2006 Elsevier/ScienceDirect

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

Date:    Tue, 31 Oct 2006 15:47:20 -0500
From:    Fred Springfield <fredspringfield@xxxxx.xxx>
Subject: RES: Neuropsychiatric symptoms related to interferon alpha

[Neuropsychiatric symptoms related to interferon alpha]
[Article in Polish]

Journal: Psychiatr Pol. 2006 Jul-Aug;40(4):787-97.

Authors: Malyszczak K, Inglot M, Pawlowski T, Czarnecki M, Rymer W, Kiejna A.

Katedra i Klinika Psychiatrii Akademii Medycznej we Wroclawiu.

PMID: 17068950


Neuropsychiatric symptoms are commonly related to interferon alpha
treatment. The paper summarises the current knowledge about their
aetiology, course, and treatment.

Interferon alpha is a cytokine with antiviral and antineoplasmatic
activity. It is commonly used in the treatment of chronic hepatitis C and
B, malignant melanoma, Kaposi sarcoma, renal cancers, and some
haematological malignancies. Treatment with interferon alpha is associated
with depressive symptoms, cognitive disturbances, chronic fatigue syndrome,
dysphoria, anxiety symptoms, anorexia, mania and psychotic states.

Up to a half of the patients need psychiatric consultations, 10-25% of them
need psychiatric treatment. Neuropsychiatric symptoms are the results of
direct affection of CNS by interferon and induced cytokines. They increase
hypothalamic-pituitary-adrenal (HPA) activity, alter thyroid function and
lead to a behavioural syndrome called 'sickness behaviour'. Moreover
interferon induces the activity of 2, 3 indoloamine dioxygenase, the enzyme
which converts tryptophan into kynurenine, leads to a reduced level of
tryptophan, and thus to a reduced level of central serotonin and to an
increased level of neurotoxic kynurenine metabolites.

Interferon also affects central opioid receptors and changes dopaminergic
and noradrenergic neurotransmission. Serotonin selective reuptake
inhibitors (SSRI), other antidepressants i.e. nortriptyline,
benzodiazepines, naltrexone, and neuroleptics (for maniac and psychotic
states) are used to treat interferon associated psychiatric symptoms.
Psychological therapy may also be useful, as well as psychoeducation and
behavioural interventions.

[Return to top]

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

Date:    Tue, 31 Oct 2006 15:52:58 -0500
From:    "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx>
Subject: RES: Fibromyalgia, infection and vaccination: Two more parts  in the etiological puzzle

Fibromyalgia, infection and vaccination: Two more parts in the etiological
puzzle.

J Autoimmun. 2006 Oct 27; [Epub ahead of print]

Ablin JN, Shoenfeld Y, Buskila D.

Department of Rheumatology, Tel-Aviv Sourasky Medical Center and Sackler
Faculty of Medicine, Tel-Aviv University, 6 Weizman St., 64239 Tel-Aviv,
Israel.

PMID: 17071055


As the pathogenesis of fibromyalgia continues to raise debate, multiple
putative triggers have been implicated. The current review summarizes the
available data linking fibromyalgia to either infection or vaccination.

Multiple infectious agents have been associated with the development of
either full-blown fibromyalgia (e.g. hepatits C), or with symptom complexes
extensively overlapping with that syndrome (e.g. chronic Lyme disease). The
cases of Lyme disease, mycoplasma, hepatits C and HIV are detailed. Despite
the described associations, no evidence is available demonstrating the
utility of antibiotic or anti-viral treatment in the management of
fibromyalgia. Possible mechanistic links between fibromyalgia and HIV are
reviewed.

Associations have been described between various vaccinations and symptom
complexes including fibromyalgia and chronic fatigue syndrome. The case of
Gulf War syndrome, a functional multisystem entity sharing many clinical
characteristics with fibromyalgia is discussed, with emphasis on the
possibility of association with administration of multiple vaccinations
during deployment in the Persian Gulf and the interaction with stress and
trauma.

Based on this example a model is proposed, wherein vaccinations function as
co-triggers for the development of functional disorders including
fibromyalgia, in conjunction with additional contributing factors.

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Date:    Wed, 1 Nov 2006 15:41:59 -0500
From:    Fred Springfield <fredspringfield@xxxxx.xxx>
Subject: RES: Cognitive-behaviour therapy for chronic fatigue syndrome: Comparison of outcomes within and outside the confines of a randomised controlled trial

Cognitive-behaviour therapy for chronic fatigue syndrome: Comparison of
outcomes within and outside the confines of a randomised controlled trial.

Journal: Behav Res Ther. 2006 Oct 27; [Epub ahead of print]

Authors: Louise Quarmbya, Katharine A. Rimesa, Alicia Dealea, Simon
Wessely,  and Trudie Chalder [*]

Affiliation: King's College London, Academic Department of Psychological
Medicine, Weston Education Centre, Cutcombe Road, London SE5 9RJ, UK
[*]Corresponding author. Tel.: +44 2078480406; fax: +44 2078485408. E-Mail:
sphatrc@iop.xxx.xx.xx

Received 16 February 2006;
revised 16 August 2006;
accepted 29 August 2006.
Available online 30 October 2006.

NLM Citation: PMID: 17074300


Outcomes for cognitive-behaviour therapy (CBT) in randomised controlled
trials (RCTs) have rarely been compared to those in routine clinical
practice. Taking the case of CBT for chronic fatigue syndrome (CFS), we
evaluated the results of a successful RCT against those of the same
treatment given in the same setting as part of routine practice.

Fatigue and social adjustment scores were compared for patients who
received CBT for CFS as part of a RCT (N=30) and patients who received CBT
as part of everyday clinical practice (N=384). The results in the RCT were
superior to those in routine clinical practice. Between pre-treatment and
6-month follow-up, the RCT showed a larger reduction in fatigue and greater
improvement in social adjustment than those in routine treatment. The
changes in fatigue scores were similar for both groups during treatment but
were greater in the RCT between post-treatment and follow-up.

Potential reasons for the superior results of the RCT include patient
selection, therapist factors and the use of a manualised treatment protocol.

Practitioners need to pay particular attention to relapse prevention and
ensuring adequate follow-up in addition to encouraging patients to continue
with cognitive-behavioural strategies once treatment has ended.

[Return to top]

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

Date:    Wed, 1 Nov 2006 16:29:33 -0500
From:    "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx>
Subject: RES: Interdisciplinary rehabilitation in fibromyalgia and  chronic back pain: a prospective outcome study

Interdisciplinary rehabilitation in fibromyalgia and chronic back pain: a
prospective outcome study.

J Pain. 2006 Nov;7(11):807-15.

Angst F, Brioschi R, Main CJ, Lehmann S, Aeschlimann A.

Rehaclinic Zurzach, Zurzach, Switzerland.

PMID: 17074622


This study aimed to examine short-term and mid-term course of health,
biopsychosocial functional ability, and coping performance of patients with
fibromyalgia (FM) or chronic back pain (BP) after participation in a
standardized 4-week inpatient, interdisciplinary pain rehabilitation program.

In a prospective cohort study, assessments were made by using a set of
standardized, well-tested self-rating instruments and other parameters
before and after the intervention up to the 6-month follow-up with
standardized effect sizes (ES) and comparison to population norms. The
effects of improvements in health and coping domains on pain reduction were
examined by linear regression modeling.

The health of the 65 FM and the 60 BP patients at baseline was far worse
than expected from the norms. Improvements included ES up to 1.09 for pain,
physical role performance, and mental/affective health dimensions and 0.50
in coping at discharge from the clinic. At the 6-month follow-up, all
effects were consistently lower but still up to ES = 0.75. Improvements of
FM and BP were equal at discharge but slightly better for the FM's mood
scales at the 6-month follow-up. Physical and social function, mood, and
coping were significantly associated with pain reduction.

PERSPECTIVE: Inpatient, structured interdisciplinary rehabilitation
covering elements of cognitive and operant behavioral therapy, graded
activity exercise, and adapted drug therapy revealed moderate to large
short-term and mid-term improvements in physical and mental health and in
the major coping dimensions as captured by comprehensive and specific
assessment.

[Return to top]

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

Date:    Thu, 2 Nov 2006 13:42:19 -0500
From:    Fred Springfield <fredspringfield@xxxxx.xxx>
Subject: RES: Well-being in patients with chronic fatigue syndrome: The  role of acceptance

Original article
Well-being in patients with chronic fatigue syndrome: The role of acceptance

Journal: Journal of Psychosomatic Research, Volume 61, Issue 5 , November
2006, Pages 595-599
doi:10.1016/j.jpsychores.2006.04.015

Authors: Stefaan Van Damme [a], Geert Crombez [a], Boudewijn Van Houdenhove
[b], An Mariman [c], and Walter Michielsen [c]

Affiliations:
[a] Department of Experimental-Clinical and Health Psychology, Ghent
University, Ghent, Belgium
[b] University Hospital, Leuven, Belgium
[c] University Hospital, Ghent, Belgium

Received 6 December 2005;
revised 6 April 2006;
accepted 25 April 2006.
Available online 1 November 2006.



Abstract
Objective: Research in chronic pain patients has shown that accepting the
chronic nature of their illness is positively related to quality of life.
The aim of this study was to investigate whether acceptance is also
associated with better well-being in patients suffering from chronic
fatigue syndrome (CFS).

Methods: Ninety-seven patients completed a battery of questionnaires
measuring fatigue, functional impairment, psychological distress, and
acceptance.

Results: Results indicated that acceptance has a positive effect upon
fatigue and psychological aspects of well-being. More specifically,
acceptance was related to more emotional stability and less psychological
distress, beyond the effects of demographic variables, and fatigue severity.

Conclusion: We suggest that promoting acceptance in patients with CFS may
often be more beneficial than trying to control largely uncontrollable
symptoms.


Keywords: Chronic fatigue syndrome; Quality of life; Acceptance; Illness
cognitions


Copyright © 2006 Elsevier Inc. All rights reserved.

[Return to top]

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

Date:    Fri, 3 Nov 2006 03:04:11 +0100
From:    Jan van Roijen <j.van.roijen@xxxxx.xx>
Subject: med: ME/CFS is a real illness, gov't says

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


Send an Email for free membership
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~
       >>>> Help ME Circle  <<<<
 >>>>    3 November 2006     <<<<
Editorship : j.van.roijen@xxxxx.xx
Outgoing mail scanned by Norton AV
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~

http://www.msnbc.msn.com/id/15535705/

NBC News


Chronic fatigue is a real illness, gov't says
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
The long-controversial diagnosis finally gets recognized


Robert Bazell
Chief science and health correspondent


NEW YORK - Jennie Spotilla was embarking on a successful
career as a lawyer when she was struck down.

"It felt like someone took a ton of bricks and just dumped it on
my head," Spotilla says. "The worst flu I could possibly imagine."

But it has lasted 12 years. She long ago was forced to stop
working.


"An average day, if it's a good day, I'm able to get up, take a
shower, take care of my dog," she says.

Doctors could not find a simple cause for her illness. They
diagnosed it as chronic fatigue syndrome. That's been a
controversial topic in medicine for decades, with some doctors
insisting there is no such thing.

But now the top federal public heath agency is declaring that it is
real, and that it affects more than 1 million Americans - four
times as many women as men.

"People genuinely are suffering and there are things we can do
to genuinely help them," says Dr. Julie Gerberding, who heads
the Centers for Disease Control (CDC). "And we need to take
this seriously as a real illness for a lot of people."

Jennie Spotilla, like many sufferers, often encounters skepticism
from doctors and others.

"Even strangers who, if I told them I had chronic fatigue
syndrome, they would think it was a joke, that I was just being
lazy or making it up," she says.

The new CDC effort includes Internet tools and public service
announcements to teach doctors to better cope with chronic
fatigue.

And coping can be difficult, because while some symptoms can
be treated, there is for now nothing close to a cure.


© 2006 MSNBC Interactive

[Return to top]

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

Date:    Wed, 1 Nov 2006 13:09:56 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks@xxx.xx>
Subject: RES,NOT: Beta-Alanine and GABA in CFS

Source: Clinica Chimica Acta
         Preprint
Date:   July 14, 2006
URL:    http://www.sciencedirect.com/science/journal/00098981


Beta-Alanine and gamma-aminobutyric acid in chronic fatigue syndrome
--------------------------------------------------------------------
Ulf Hannestad (a,*), Elvar Theodorsson(a), Birgitta Evengard(b)
a Faculty of Health Science, Division of Clinical Chemistry, Linkoping
   University, SE-581 85 Linkoping, Sweden
b Department of Laboratory Medicine, Karolinska Institutet at Karolinska
   University Hospital, Huddinge, SE-141 86 Stockholm, Sweden
* Corresponding author. Tel.: +46 13 223246; fax: +46 13 223240.
   E-mail address: ulf.hannes tad@ibk.liu.se (U. Hannestad).

Received 7 June 2006; received in revised form 7 July 2006; accepted 7 July
2006


Abstract

Background
Due to the occurrence of sleep disturbances and fatigue in chronic fatigue
syndrome (CFS), an investigation was performed to examine if there is an
abnormal excretion of gamma-aminobutyric acid (GABA) and/or its structural
analogue beta-alanine in the urine from CFS patients. Both GABA and beta-
lanine are inhibitory neurotransmitters in the mammalian central nervous 
system.

Methods
The 24 h urine excretion of GABA and beta-alanine was determined by isotope
dilution gas chromatography mass spectrometry in 33 CFS patients and 43
healthy controls. The degree of symptoms in both patients and controls was
measured by grading of three typical CFS symptoms using a Visual Analogue
Scale.

Results
Men had a significantly higher excretion of both beta-alanine and GABA than
women. Comparing CFS patients with healthy controls showed no significant
difference in excretion of neither beta-alanine nor GABA. No correlation
was found between the excretion of beta-alanine or GABA and any of the
three characteristic CFS symptoms measured. However, two female and two
male CFS patients excreted considerably higher amounts of beta-alanine in
their 24 h urine samples than control subjects.

Conclusions
Increased excretion of beta-alanine was found in a subgroup of CFS patients,
indicating that there may be a link between CFS and beta-alanine in some CFS
patients.

Keywords
Chronic fatigue syndrome; beta-Alanine; gamma-Aminobutyric acid; Polyamines;
Ornithine decarboxylase; Immunosuppression


1. Introduction

Chronic fatigue syndrome (CFS) is a disabling illness, with major impact on
quality of life. No single pathogenetic factor has as yet been convincingly
demonstrated [1]. In the majority of CFS patients, the symptoms of fatigue
and neurocognitive dysfunctions start after a flu-like illness, indicating
that viral infections may play a pathogenic role [2].

Disabling fatigue is the most characteristic symptom of CFS. One of the
neurotransmitters involved in regulating sleep and which also likely has a
potential of evoking fatigue is gamma-aminobutyric acid (GABA) by activating
GABA_A receptors [3-5]. GABA is the major inhibitory neurotransmitter of the
central nervous system (CNS), and GABA receptors can be found on 60-75% of
its neurones [6]. Many hypnotics, including barbiturates and benzodiazepines,
act by stimulating GABA receptors. Beta-Alanine is an amino acid and a
structural analogue of GABA, differing only by having one less methylene
group.

Beta-Alanine found in the CNS originates in part from the metabolism of the
polyamines putrescine, spermidine and spermine [7,8].

In cases of elevated concentrations of beta-alanine or GABA in CNS one can
expect to find increased excretion of these amines in urine as there is an
active transport of both beta-alanine and GABA from CNS to blood over the
blood-brain barrier. Studies by Komura et al. [9,10] and Kakee et al. [11]
have demonstrated the active transfer of beta-amino acids, including GABA and
beta-alanine, from CNS to blood. Patients with decreased levels of
4-aminobutyrate aminotransferase, also called GABA-transaminase, have
extremely high CNS concentrations of beta-alanine and GABA, which results in
excretion of large amounts of the two substances in the urine [12,13].
GABA-transaminase deficiency also results in very high concentrations of
beta-alanine and GABA in the cerebrospinal fluid and plasma [12,13]. Among
the most pronounced symptoms observed in these patients were lethargy,
somnolence, seizures and retarded psychomotor development.

Interestingly, McGregor et al. have shown that there is a positive correlation
between typical CFS symptoms and an increased excretion of beta-alanine in the 
urine of CFS patients [14]. In contrast, Jones et al. did not find such a 
connection [15].

The aim of the present study was to investigate, using state-of-the-art
methodology, if increased amounts of beta-alanine and/or GABA are found in
the urine from CFS patients compared to healthy controls. The rational for
this approach was that GABA is an inhibitory neurotransmitter in CNS involved
in sleep regulation [3,4]. Beta-Alanine, also activating GABA_A receptors
[16,17], could likewise be involved in sleep regulation. Indeed, it has been
demonstrated that intracerebroventricular injections of beta-alanine in
chicks strongly diminish spontaneous activity and induce sleep-like behaviour
[18]. It has furthermore been shown that the same administration of
beta-alanine to rats causes inhibition of exploratory behaviour and of
motility [19]. These animal model studies agree with our hypothesis that
increased extracellular concentrations of beta-alanine in the CNS may be
among the pathogenic factors in CFS.

Using an isotope dilution gas chromatography mass spectrometry (ID GC-MS)
method, we measured the excretion of beta-alanine and GABA in the urine of 33
CFS patients (22 female and 11 male) and compared with a group of 42 healthy
controls (24 female and 19 male). Typical CFS symptoms of all subjects were
recorded and eventual relation between symptoms and excretion of beta-alanine/
GABA was determined.


2. Study cohort and materials

This study was approved by the local Ethics Committees at the Karolinska
University Hospital, Huddinge (Stockholm, Sweden) and at the University
Hospital in Linkoping (Sweden) with approval number 03-379. The CFS patients
included in the study, 22 women and 11 men, fulfilled the 1994 case
definition for CFS [20]. They were recruited from an outpatient clinic
specialised for CFS patients at the Karolinska University Hospital, Huddinge.
Age and sex matched healthy subjects were recruited among hospital staff as a
control group, and consisted of 24 women and 19 men. All patients and healthy
subjects gave informed consent before participating in the study. Patients
and controls had similar age distribution (Table 1).

The patients and the healthy controls collected urine during a 24 h period in
a plastic bottle containing 15 ml of hydrochloric acid (6.0 mol/l) for
stabilisation of amines and preservation. All samples except five were
collected during May to June 2004. Five of the patients participated in a
pilot study and collected their samples during September to October 2002. The
participating subjects, except for the five pilot study patients, were also
asked to fill out a questionnaire where any medication was noted together
with grading of typical CFS symptoms. Three different symptoms, fatigue,
muscle pain and cognitive difficulties, were recorded on a continuous Visual
Analogue Scale (VAS), 0-10. Among these patients, 10 (36%) had a sudden
onset, whereas 18 (64%) had gradual onset of their CFS. The mean duration of
the illness was 7.4 years with a range of 1.5 to 25 years. In 14 (50%) of the
patients the symptoms of CFS started after a flu-like infection.

All chemicals used were of analytical grade. GABA and beta-alanine were
purchased from Fluka Chemie (Buchs SG, Switzerland). Beta-Alanine (U-13C3;
15N) was from Cambridge Isotope Laboratories, Inc (MA, USA), and GABA-
2,2,3,3,4,4-D6 from CDN Isotopes (Quebec, Canada). All chemicals used for 
derivatization, ethyl acetate, 1-hexanol, acetylchloride and heptaflour-
obutyric anhydride, were obtained from Fluka Chemie (Buchs SG, Switzerland).


3. Methods

The volume of the collected urine was determined. A portion of the urine was
frozen and stored at -20 C until analysed. The concentration of creatinine
was assayed by an enzymatic method on a Bayer Advia 1650 instrument,
according to the manufacturer's instructions. For the determination of the
concentration of beta-alanine and GABA, 25 l urine was hydrolysed for 20 h
at 120 C in hydrochloric acid, 6.0 mol/l. All urine samples were analysed
blinded. The derivatization method used was a modification of the method
described by MacKenzie and Tenaschuk [21,22]. After hydrolysis, 100 l of an
internal standard solution was added and the samples were taken to dryness
under a stream of compressed air. Esterification was done by treating the
samples with acetyl chloride, 1.5 mol/l, in 1-hexanol at 120 C for 15 min.
After blowing air over the samples, the dry residues were dissolved in 200 l
of ethyl acetate and 50 l of heptaflourobutyric anhydride was added. After 15
min at 90 C, the reagent in the samples was taken to dryness with compressed
air. Ethyl acetate, 200 l, was added and the samples were analysed on a mass
spectrometer. Isotope dilution technique was used for quantification of
beta-alanine and GABA. Beta-Alanine (U-13C3; 15N) and gamma-aminobutyric-2,
2,3,3,4,4-D6 acid were used as internal standards for beta-alanine and GABA.

To determine the between-run variation, three different urine samples with
low, medium and high concentrations of beta-alanine and GABA were used as
controls and were included in each urine analysis. The mass spectrum of
beta-alanine, GABA and the two internal standards were determined (Fig. 1)
and quantification was done using a Hewlett Packard 5970 MSD mass
spectrometer coupled to a HP 5890 gas chromatograph using a HP 1-MS column,
30 m x 0.25 mm with a film thickness of 0.25 m. After sample injection, the
oven temperature was held at 100 C for 1 min and then ramped to 285 C at 3
C/min. Under these conditions, the derivatives of beta-alanine and its
internal standard eluted after around 17 min. GABA and its internal standard
eluted after about 22 min. The analyses and quantification on the mass
spectrometer were carried out by selected ion monitoring, with acquisition of
ions m/z 268.1 and m/z 282.1 for beta-alanine and GABA, respectively.
Acquisition of the internal standards beta-alanine (U-13C3; 15N) and
gamma-aminobutyric-2,2,3,3,4,4-D6 acid was done with m/z 272.1 and m/z 288.1,
respectively. All these four fragments are the result from loss of the
neutral fragment O (CH_2)_5CH_3 from the molecular ion. Standard solutions
with five different concentration levels, between 10 and 400 mol/l for
beta-alanine and between 5.0 and 200 mol/l for GABA, were used for
quantification. To establish the proportion between free and conjugated
beta-alanine and GABA in urine, samples from twelve healthy controls were
analysed both with and without acid hydrolysis.

Both beta-alanine and GABA were quantified by ID GC-MS. This is an accurate
and precise technique often used to establish reference or definitive methods
for different analytes, as is done for example for glucose by National
Institute of Standards and Technology (Gaithersburg, MD, USA). Data were
analysed using the GLM-module of Systat 11 for Windows (http://www.systat.com)
using the urinary excretion of beta-alanine and GABA as dependent variables
and sex, age and measures of tiredness, muscle ache and cognitive problems as
independent variables. The analysis was performed both using non-transformed
values for the 24 h amounts and the natural logarithm of the same values (to
correct for skewness).


4. Results

The results from grading of symptoms using VAS showed that the patients - as
expected - had significantly more of the CFS related symptoms including
fatigue, muscle problems and cognition/memory complaints, compared to the
healthy controls (Table 1). The symptoms of fatigue and cognition/memory
problems were most pronounced. All CFS patients and healthy controls except
two (not included in the study) collected a full 24 h urine sample. One of
the subjects admitted uncomplete urine collection and the other was excluded
because of unreasonably small amounts of creatinine excreted. The between-day
variation of the ID GC-MS method for the three concentration levels of the
control samples is shown in Table 2. The between-run coefficient of variation
ranged from 1.98-2.60% for beta-alanine and 3.69-4.74% for GABA.

When measuring the 24 h excretion of beta-alanine and GABA for the patients
and control subjects, we found that men, as seen among the control subjects,
excreted a significantly larger amount of both beta-alanine and GABA during
24 h than women (p<0.05). The mean excretion of beta-alanine in the control
group was for men 356 mumol/24 h (133-772 mumol/24 h, n=19), and for women
261 mumol/24 h (55-652 mumol/24 h, n=24). The mean excretion of GABA in the
control group was 98 mumol/24 h (38-143 mumol/24 h, n=19) for men and 83
mumol/24 h (52-121 mumol/24 h, n=24) for women. Male patients had a mean
excretion of beta-alanine of 512 mumol/24 h (155-2107 mumol/24 h, n=11) while
the corresponding excretion for female patients was 228 mumol/24 h (103-652
mumol/24 h, n=22). The mean excretion of GABA among CFS patients was 85
mumol/24 h (67-111 mumol/24 h, n=11) for men and 69 mumol/24 h (38-114
mumol/24 h, n=22) for women. When comparing male and female CFS patients with
male and female controls respectively, no significant difference (p>0.05) in
excretion of neither beta-alanine nor GABA was found. However, as can be seen
in Fig. 2, two of the female and two of the male CFS patients excreted more
of beta-alanine than the healthy controls and other CFS patients. In contrast
to beta-alanine, no extraordinary high excretion of GABA could be seen among
the patients compared to the controls (Fig. 3).

The concentration of the free forms of beta-alanine and GABA, together with
the concentration of total beta-alanine and GABA in urine was determined by
analysis of twelve urine samples from healthy controls, both with and without
acid hydrolysis. We found that about 30% of these amines existed in their
free form and that about 70% were conjugated. The mean proportion of free
beta-alanine in urine was 35.2% (3.4-47.5%) and for GABA the mean was 29.4%
(14.1-52.9%).


5. Discussion

We were unable to demonstrate significantly higher amounts of beta-alanine
and/or GABA excreted in the urine of CFS patients as a group compared to a
group of healthy controls. However, two of the female and two of the male CFS
patients excreted considerably more (250%, 239% and 580%, 306%, respectively
more than the mean for healthy controls) of beta-alanine compared to the
healthy controls, indicating a possible link between high beta-alanine
excretion and CFS in a subgroup of patients. The mean duration of the illness
in these four patients was 3.1 years (range 1.5-5.5 years). Three of these
four patients had a gradual onset of CFS, the fourth a sudden onset. The
symptoms of the four patients did not deviate significantly from the rest of
the patients. Two of them had a flu-like onset of their CFS, two had not.
However, the increased excretion of beta-alanine in these patients supports
the results of McGregor et al. [14], who found a relation between excretion
of beta-alanine and CFS symptoms. In contrast Jones et al. [15] found no
abnormal excretion of beta-alanine among CFS patients. In agreement with
Jones et al., we were unable to detect the two substances CFSUM1 and CFSUM2,
described by McGregor et al. [14], in the urine of patients or controls.
Chalmers et al. [23] claim that CFSUM1 and CFSUM2 are artefacts from
derivatization and not true endogenous metabolites.

Given its pronounced biological effects, it is possible that even a small
increase in the concentration of beta-alanine, in parallel with GABA, in the
extracellular fluid of the CNS can result in symptoms of CFS [24]. This is
analogous to the pronounced clinical effects of antidepressants despite the
modest increases in the extracellular concentrations of monoamines they
induce [25]. In the earlier studies, mentioned above, two patients with
GABA-transaminase deficiency [12,13] had 5-fold elevated levels of beta-
alanine in cerebrospinal fluid and urine. Some of the CNS symptoms, i.e.
pronounced somnolence and lethargy, seen in these patients resemble those
seen in CFS. This is in accordance with the hypothesis that in a subset of
CFS patients the typical symptoms may be caused by high concentrations of
beta-alanine and possibly GABA in extracellular fluid of the CNS.

However, it is likely that minor elevations of the concentration of beta-
alanine in extracellular fluid of the CNS are difficult to detect by measuring 
urine excretion. The normal excretion of beta-alanine is about
100-300 mumol/24 h, suggesting that a minor increased excretion caused by CFS
can be masked by the normal variations in excretion of beta-alanine. Thus
periods of sufficiently high concentration of beta-alanine in CNS to be
reflected in urine are probably transient and difficult to capture, which
might explain why we found so few patients with increased urinary excretion
of beta-alanine. Likewise this could explain the discrepancy in the findings
of McGregor et al. [14] and Jones et al. [15] discussed above. There are
differences in the protocols between these two studies and the present study,
making it difficult to compare the results. In the current study the patients
and healthy controls collected a 24 h urine sample and the concentration of
beta-alanine and GABA, including conjugated forms, was determined after acid
hydrolysis of the urine samples. In the two other studies the study subjects
did not collect a full 24 h urine sample, no hydrolysis was performed, and
thus only the free form of beta-alanine was determined. Also, the two
previous studies did not report the results separately according to gender.

A possible source of the increased urine excretion of beta-alanine seen in
some CFS patients may be a low grade catabolic process (e.g. an ongoing virus
infection in CNS), producing increased amounts of polyamines. Ornithine
decarboxylase (ODC) is a highly inducible and strongly regulated enzyme that
is rate-limiting in the production of polyamines [26­28]. Hence, an induction
of ODC by an exogenous agent could result in enhanced levels of polyamines
and beta-alanine. Polyamines, and especially spermine, are known to be
immunosuppressants. Spermine inhibits monocyte activation and natural killer
cell activity [29-32], and therefore increased levels of spermine in the CNS
could locally affect the immune system.

GABA and beta-alanine also play a role in the effect of special drugs. There
are antiepileptic drugs (e.g. vigabatrin) that inhibit GABA-transaminase and
increase the amounts of these two inhibitory neurotransmitters in CNS [33,34]
whereas the benzodia-zepines act by stimulating GABA receptors [35]. The side
effects of these drugs resemble the typical symptoms of CFS, including
fatigue, headache, dizziness and memory disturbances.

A phenomenon sometimes found in CFS, which also could be related to beta-
alanine/GABA, is the disturbance of the hypothalamo-pituitary-adrenal (HPA)
axis [36-38]. Recently, mutations in 3 genes have been found which are
involved in the HPA-axis activity [39]. It has also been shown that there is
a connection between the activity of the GABA receptors and the function of
the HPA axis. Indeed, benzodiazepines, which enhance the activity of beta-
alanine give HPA axis dysregulation as a side effect [40-44].

The sex difference observed in the present study was the finding that men
excreted significantly more of both beta-alanine and GABA than women. This
difference has to our knowledge not been reported before and the reason for
this difference is unclear.

Previous studies of the possible involvement of beta-alanine in CFS have
resulted in conflicting evidence. This may be due to a lack of standardisation
in sampling and methodological inadequacies. Our study of patients with CFS
and controls using standardised sampling procedures and an ID GC-MS analysis
method, showed no overall difference between the groups regarding excretion
of beta-alanine and/or GABA. However, 2 female and 2 male patients of 33 CFS
patients had markedly elevated excretion of beta-alanine, suggesting a
possible involvement of this inhibitory neurotransmitter in CFS.

These findings indicate that beta-alanine, possibly derived from polyamines,
may play a role in the pathogenesis of CFS in a subgroup of patients.


Acknowledgements

We wish to thank Elisabeth Wahlund for her professional help in organising
the collection of samples.


Figure captions

Fig. 1. Mass spectra of the heptafluorobutyryl-n-hexyl derivatives together
with the mass fragment used for quantification: A) beta-alanine; m/z 268, B) 
beta-alanine (U-13C3; 15N), used as internal standard; m/z 282, C) gamma-
aminobutyric acid (GABA); m/z 272, D) gamma-aminobutyric-2,2,3,3,4,4-D6 acid, 
used as internal standard; m/z 288.

Fig. 2. Excretion of beta-alanine in 24 h urine for female and male CFS 
patients and healthy controls.

Fig. 3. Excretion of GABA in 24 h urine for female and male CFS patients and
healthy controls.


Tables

Table 1. Symptoms recorded by CFS patients and healthy controls on a 0-10 
Visual Analogue
          Scale (VAS)
-------------------------------------------------------------------------------------------
Group        Number     Age, years        Symptoms (VAS), mean (range)
              ---------  ---------------- 
-------------------------------------------------
              F=female   mean (range)      Fatigue          Muscle Cognition/
              M=male memory
-------------------------------------------------------------------------------------------
CFS patients 20 F       39.6 (25.5-53.5)  7.1^a (2.2-9.6)  4.8^a (0.0-7.5) 
5.7^a (0.4-9.2)
               8 M       40.4 (30.1-53.3)  6.3^a (0.7-9.7)  4.0^a (0.0-8.0) 
4.5^a (0.0-9.6)
Controls     24 F       41.9 (28.9-54.1)  1.6   (0.0-5.7)  0.7   (0.0-4.7)  0.9 
(0.0-3.2)
              19 M       40.6 (32.2-48.3)  1.4   (0.0-5.0)  0.9   (0.0-4.8)  1.0 
(0.0-4.5)
-------------------------------------------------------------------------------------------
^a Significantly more symptoms in patients than in controls (p<0.001).


Table 2. Between-run variation in determination of total beta-alanine and GABA 
in three
          different control urine samples
-------------------------------------------------------------------------------------------
                   beta-Alanine (mol/l)                  GABA (mol/l)
                   Control sample no.                    Control sample no.
                   ------------------------------- -----------------------------
                   1           2            3            1           2 3
-------------------------------------------------------------------------------------------
Mean              71.9        125          350          28.3        43.7 117
Minimum           68.9        120          338          26.7        39.8 110
Maximum           75.4        129          360          30.3        46.0 123
SD                 1.87         2.93         6.91        1.34        2.05 4.32
CV (%)             2.60         2.35         1.98        4.74        4.68 3.69
-------------------------------------------------------------------------------------------
Number of analysis of each control sample = 9.
SD = standard deviation. CV = coefficient of variation.


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(c) 2006 Elsevier/ScienceDirect B.V.
[Return to top] ------------------------------ Date: Fri, 3 Nov 2006 12:26:14 -0500 From: Fred Springfield <fredspringfield@xxxxx.xxx> Subject: RES: Screening for psychological distress using internet administration of the Hospital Anxiety and Depression Scale (HADS) in individuals with chronic fatigue syndrome Screening for psychological distress using internet administration of the Hospital Anxiety and Depression Scale (HADS) in individuals with chronic fatigue syndrome. Journal: Br J Clin Psychol. 2006 Nov;45(Pt 4):483-98. McCue P, Buchanan T, Martin CR. Department of Psychology, Northumbria University, UK. NLM Citation: PMID: 17076959 OBJECTIVES: To investigate the factor structure and internal consistency of the Hospital Anxiety and Depression Scale (HADS) in individuals with Chronic Fatigue Syndrome (CFS) using an Internet administered version of the instrument. DESIGN: Between subjects. METHOD: Confirmatory factor analysis (CFA) and internal consistency analysis of the HADS was used to determine the psychometric characteristics of the instrument in individuals with CFS and a control group with data captured via an Internet data collection protocol. RESULTS: CFA revealed that a 3-factor solution offered the most parsimonious account of the data. Internal consistency estimations of the anxiety and depression subscales were found to be acceptable for both groups. The CFS group was found to have significantly higher HADS-assessed anxiety and depression scores compared with controls, however, there was also evidence found that Internet administration of the instrument may inflate HADS subscale scores as an artifact of testing medium. CONCLUSIONS: The HADS is suitable for use for screening individuals with CFS in terms of the factor structure of the instrument, however, clinicians should be aware that this instrument assesses 3 domains of affective disturbance rather than 2 as is interpreted within the current HADS anxiety and depression subscale scoring system. Researchers need also be aware that Internet administration of negative affective state measures such as the HADS is likely to inflate scores and need to ensure that comparisons between clinical groups are made with control group data gathered using the same collection methodology. [Return to top] ------------------------------ Date: Fri, 3 Nov 2006 14:26:45 -0500 From: Fred Springfield <fredspringfield@xxxxx.xxx> Subject: RES: The therapeutic effects of electrical acupuncture and auricular-plaster in 32 cases of chronic fatigue syndrome The therapeutic effects of electrical acupuncture and auricular-plaster in 32 cases of chronic fatigue syndrome. Journal: J Tradit Chin Med. 2006 Sep;26(3):163-4. Authors: Yuemei L, Hongping L, Shulan F, Dongfang G. Affiliation: First Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, China. NLM Citation: PMID: 17078435 OBJECTIVE: To observe the therapeutic effects of electrical acupuncture and auricular-plaster therapy for chronic fatigue syndrome (CFS). METHOD: 64 CFS patients were randomly divided into two groups. 32 cases in the treatment group were treated by the electrical acupuncture and auricular-plaster therapy, and 32 cases in the control group with oral hydrocortisone. RESULTS: The total effective rates were respectively 93.75% in the treatment group and 75.00% in the control group, with a statistically significant difference between the two groups (P < 0.05). CONCLUSION: Electrical acupuncture and auricular-plaster therapy may show a better anti-fatigue effect than that of routine Western drugs. [Return to top] ------------------------------ Date: Fri, 3 Nov 2006 14:42:00 -0500 From: Fred Springfield <fredspringfield@xxxxx.xxx> Subject: RES: Differential diagnosis of chronic fatigue syndrome and major depressive disorder Differential diagnosis of chronic fatigue syndrome and major depressive disorder. Journal: Int J Behav Med. 2006;13(3):244-51. Authors: Hawk C [a], Jason LA [b], Torres-Harding S [b]. Affiliations: [a] Hines VA Hospital, Hines, Illinois, USA [b] DePaul University, Chicago, Illinois, USA NLM Citation: PMID: 17078775 The goal of this study was to identify variables that successfully differentiated patients with chronic fatigue syndrome, major depressive disorder, and controls. Fifteen participants were recruited for each of these three groups, and discriminant function analyses were conducted. Using symptom occurrence and severity data from the Fukuda et al. (1994) definitional criteria, the best predictors were postexertional malaise, unrefreshing sleep, and impaired memory-concentration. Symptom occurrence variables only correctly classified 84.4% of cases, whereas 91.1% were correctly classified when using symptom severity ratings. Finally, when using percentage of time fatigue reported, postexertional malaise severity, unrefreshing sleep severity, confusion-disorientation severity, shortness of breath severity, and self-reproach to predict group membership, 100% were classified correctly. [Return to top] ------------------------------ Date: Fri, 3 Nov 2006 21:26:10 +0100 From: Jan van Roijen <j.van.roijen@xxxxx.xx> Subject: res: CFS 'not just for women' ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Send an Email for free membership ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ >>>> Help ME Circle <<<< >>>> 3 November 2006 <<<< Editorship : j.van.roijen@xxxxx.xx Outgoing mail scanned by Norton AV ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ From: "johnherd@xxxxx.xxx" <johnherd@xxxxxx.xxx> http://www.theage.com.au/news/National/Chronic-fatigue-not-just-for-women/2006/11/03/1162340044569.html Chronic fatigue 'not just for women ' ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ November 3, 2006 - 6:54PM Women are no more likely to get chronic fatigue syndrome than men, nor are neurotic types more prone, according to new myth-debunking Australian research. Scientists from the University of Sydney and the University of NSW (UNSW) have discovered who is most likely to get the debilitating condition and it has nothing to do with age, sex, personality traits or mental health as many people thought. Chronic fatigue syndrome is most commonly triggered by an acute illness, like glandular fever, and it is the severity of this illness that decides whether you will develop the syndrome, the research found. "The sicker you are at the beginning of the infection, the more likely it is to result in a prolonged illness," said UNSW infectious diseases specialist Andrew Lloyd. "As far as we can see this is the only determinant of who is likely to get it." The research team made its discovery by tracking the long-term health of individuals infected by three infections - the mosquito borne Ross River virus, Q fever bacterial infection and Epstein-Barr virus, which causes glandular fever - in the NSW city of Dubbo. Of the first 253 people investigated, about 10 percent developed chronic fatigue, a state affecting 100,000 Australians only diagnosed when the disabling tiredness persists for more than six months. In these people, the acute infection has a hit and run effect on the brain that takes some time to repair. "These three different bugs trigger this fatigue in 10 percent of people from moment one, of day one, of the acute infection," Prof Lloyd said. After a year only five per had the condition, and about 99 per cent were better within two years without medical intervention. "While that's still not good, there's a notion in the community that people with chronic fatigue never get better," he said. The scientist said the research, published in the prestigious British Medical Journal, also dispels several other myths surrounding the condition. "We looked at age, sex, education, personality style, and psychiatric health and it turns out that none of those things predict the outcome," he said. "It's commonly believed that more women get it than men and that these people are neurotic, obsessive and unduly focused on symptoms and this is their problem, not chronic fatigue. "We found no evidence to support any of this." He said the syndrome was misunderstood because sufferers commonly delayed seeking help for a year, by which time several other secondary problems like weight gain, depression and marital difficulties had set in. © 2006 AAP [Return to top] ------------------------------ Date: Fri, 3 Nov 2006 23:56:08 +0100 From: Jan van Roijen <j.van.roijen@xxxxx.xx> Subject: res: Differential Diagnosis of CFS & MMD ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Send an Email for free membership ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ >>>> Help ME Circle <<<< >>>> 3 November 2006 <<<< Editorship : j.van.roijen@xxxxx.xx Outgoing mail scanned by Norton AV ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ Fri, 3 Nov 2006, Fred Springfield posted the abstract on Co-Cure of: *Differential Diagnosis of Chronic Fatigue Syndrome and Major Depressive Disorder* - Journal: International Journal of Behavioral Medicine 2006, Vol. 13, No. 3, 244-251; Authors: Caroline Hawk, Leonard A. Jason, and Susan Torres-Harding: http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind0611a&L=co-cure&T=0&P=4403 ```````````````````````````````````````````````````````````````````````` ~jvr: as 'fair use' I add the *discussion * section from this study ```````````````````````````````````````````````````````````````````````` Discussion In the first stepwise discriminant function analysis, symptom occurrence data for the eight symptoms of the U.S. diagnostic criteria for CFS reveal that postexertional malaise, unrefreshing sleep, and impaired memory-concentration were the best predictors (i.e., 84.4% correct classification). A second discriminant function analyses was performed using severity ratings for the eight symptoms of the current CFS diagnostic criteria, and results reveal that once again, postexertional malaise, unrefreshing sleep, and impaired memory-concentration were the best predictors of group membership. In this analysis, there was a 91.1% correct classification. These findings indicate that the use of severity ratings for the eight symptoms of the CFS diagnostic criteria led to fewer misclassifications. A final stepwise discriminant function analysis was performed in which 6 of the 24 variables were found to be the best predictors of group membership: percentage of time fatigue was experienced, self-reproach, postexertional malaise, unrefreshing sleep, confusion- disorientation, and shortness of breath. Using these 6 predictors, 100% of the study participants were correctly classified. In the first two stepwise discriminant function analyses using symptom occurrence data and severity data, postexertional malaise, memory-concentration difficulties, and unrefreshing sleep were the only variables kept in the analyses. This suggests these variables are good discriminators of CFS, MDD, and controls. Exercise intolerance, sleep difficulties, and cognitive difficulties have been repeatedly demonstrated to be prominent features of CFS (Jason, Taylor, et al., 2001; Jason & Taylor, 2002). In the final stepwise discriminant function analysis, fatigue, postexertional malaise, unrefreshing sleep, and confusion-disorientation were 4 of the 6 variables kept in the equation out of a total of 24 predictor variables initially entered. These findings are also consistent with those of Jason, Taylor, et al. Taken together, the findings of Jason, Taylor, et al. and the results of our study suggest that fatigue, unrefreshing sleep, postexertional malaise, and cognitive functioning represent important markers in the assessment of CFS. The best results in classification were achieved when a wide variety of measures was used and new symptoms found to distinguish cases of CFS from MDD and controls were included. For example, the inclusion of self-reproach in the final equation was not surprising in light of the findings of Johnson et al. (1996). Self-reproach appears to be a crucial variable for discriminating between people who have CFS and MDD. As noted before, self-reproach is much less commonly present in people with CFS when compared to people with MDD. The inclusion of shortness of breath in the final equation is of interest as well because this symptom is not currently included in the Fukuda et al. (1994) case definition. A study by Jason, Torres-Harding, Taylor, and Carrico (2001) with a different sample also found shortness of breath to be a good discriminator among CFS, melancholic depression, and healthy controls. Jason, Torres-Harding, et al. suggested that this finding may be indicative of neurally mediated hypotension in people with CFS. Neurally mediated hypotension is defined as a 30-mm Hg drop in systolic, or a 15-mm Hg drop in diastolic, blood pressure occurring in response to an orthostatic challenge (e.g., standing upright after sitting or laying down; Rowe & Calkins, 1998). Included within the predictors entered into the final stepwise analysis were two measures of fatigue: One was a simple severity rating of fatigue on a 100-point scale ranging from 0 (no problem) to 100 (most severe problem possible), and the other was the percentage of time fatigue was reported on the ACTRE. Results of the analysis reveal that only one of these measures was a good predictor of group membership: percentage of time fatigue was reported on the ACTRE. This may suggest that fatigue is best measured by a daily log over a 2-day period of time versus a one-item severity rating score. Assessing fatigue over the span of 2 days may be more valid than assessment at one point in time because fatigue levels are variable for many people. Furthermore, the fluctuating nature of fatigue and the other symptoms of CFS are a commonly reported feature of this illness. Finally, as Stouten (2005) correctly mentioned, many frequently used fatigue scales do not accurately represent the severe fatigue that is characteristics of CFS (although this problem is avoided with the Profile of Fatigue-Related Symptoms; Ray, Weir, Phillips, & Cullen, 1992). There are several limitations in this study. The sample sizes were relatively small; thus, the study needs to be replicated with larger samples. With such a small sample, there are methodological problems that are encountered, particularly when multiple predictor variables are employed. In addition, the use of stepwise discriminant function analysis can be problematic in general because it capitalizes on chance for the order of variable inclusion. Also, data may be over-fitted because the equation derived from a single sample is too close to the sample and may not generalize to the population. CFS is a difficult condition to diagnose, because the signs and symptoms of this illness overlap with other medical and psychiatric condition (Taylor, Jason, & Schoeny, 2001). Several key symptoms and their severity ratings may assist the accurate diagnosis of CFS and differentiate it from MDD. The current definitional symptoms of postexertional malaise, unrefreshing sleep, and impaired memory-concentration appear to be particularly important in distinguishing CFS from MDD. In addition, self-reproach items on the BDI appear useful to indicate the presence of MDD rather than CFS. Finally, using symptoms that are not currently part of the CFS case definition, such as activity levels and shortness of breath, and measuring fatigue over the course of 2 days, might also increase the ability to differentiate people with CFS from those with solely depressive disorders. [Return to top] ------------------------------ Date: Fri, 3 Nov 2006 21:16:42 -0500 From: Fred Springfield <fredspringfield@xxxxx.xxx> Subject: RES: Probing the Working Memory System in Chronic Fatigue Syndrome: A Functional Magnetic Resonance Imaging Study Using the n-Back Task Probing the Working Memory System in Chronic Fatigue Syndrome: A Functional Magnetic Resonance Imaging Study Using the n-Back Task. Journal: Psychosom Med. 2006 Nov 1; [Epub ahead of print] Authors: Caseras X, Mataix-Cols D, Giampietro V, Rimes KA, Brammer M, Zelaya F, Chalder T, Godfrey EL. Affiliations: Unitat de Psicologia Medica, Institut de Neurociencies, Universitat Autonoma de Barcelona, Barcelona, Spain (X.C.); the Division of Psychological Medicine and Psychiatry (X.C., D.M.-C., K.A.M., T.C.), the Department of Psychology (D.M.-C., E.L.G.), and the Centre for Neuroimaging Sciences (V.G., M.B., F.Z.), King's College London, Institute of Psychiatry, London, UK. NLM Citation: PMID: 17079703 Objective: Up to 90% of patients with chronic fatigue syndrome (CFS) report substantial cognitive difficulties. However, objective evidence supporting these claims is inconsistent. The present functional magnetic resonance imaging study examined the neural correlates of working memory in patients with CFS compared with controls. Methods: Seventeen patients with CFS and 12 healthy control subjects were scanned while performing a parametric version of the n-back task (0-, 1-, 2-, and 3-back). Results: Both groups performed comparably well and activated the verbal working memory network during all task levels. However, during the 1-back condition, patients with CFS showed greater activation than control subjects in medial prefrontal regions, including the anterior cingulate gyrus. Conversely, on the more challenging conditions, patients with CFS demonstrated reduced activation in dorsolateral prefrontal and parietal cortices. Furthermore, on the 2- and 3-back conditions, patients but not control subjects significantly activated a large cluster in the right inferior/medial temporal cortex. Trend analyses of task load demonstrated statistically significant differences in brain activation between the two groups as the demands of the task increased. Conclusions: These results suggest that patients with CFS show both quantitative and qualitative differences in activation of the working memory network compared with healthy control subjects. It remains to be determined whether these findings stay stable after successful treatment. [Return to top] ------------------------------ Date: Fri, 3 Nov 2006 21:34:39 -0500 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: Sex hormones and pain in regularly menstruating women with fibromyalgia syndrome Sex hormones and pain in regularly menstruating women with fibromyalgia syndrome. J Pain. 2006 Nov;7(11):851-9. Okifuji A, Turk DC. Pain Research Center, Department of Anesthesiology, University of Utah, Salt Lake City, Utah.; Pain Management Center, University of Utah Health Science Center, Salt Lake City, Utah. PMID: 17074627 Fibromyalgia syndrome (FMS) is more prevalent in women than in men. The skewed sex distribution in the prevalence has prompted questions of if and how sex hormones may be involved in the pathophysiology of FMS. In this study, we evaluated the levels of sex hormones and pain sensitivity at different phases of a menstrual cycle in regularly menstruating women with FMS relative to age-matched healthy women. Participants (n = 74 in each group) underwent a 9-day urine test to identify the date of ovulation. Three laboratory visits were scheduled to ascertain the varying levels of estrogen (E) and progesterone (P): Late-follicular phase (high E, low P); mid-luteal phase (high E, high P); and perimenstrual phase (low E, low P). At each visit, blood was drawn and ischemic pain testing was performed. The groups did not differ in the fluctuation of luteal hormone, follicular-stimulating hormone, E, and testosterone across a menstrual cycle. FMS patients showed slightly elevated P levels during the mid-luteal phase relative to healthy women but levels were within the normal range. Women with FMS showed consistently lower pain thresholds and tolerance relative to healthy women throughout the menstrual cycle. Pain threshold at the late follicular phase was modestly related to the P level. The results suggest that the disproportionate prevalence of females with FMS is not likely to be attributable to hormonal factors. Furthermore, the role of sex hormones in pain sensitivity for both FMS and healthy women seems to be limited. PERSPECTIVE: Normally menstruating women with FMS and healthy women do not seem to show fluctuating threshold and tolerance to the ischemic pain test. The role of sex hormones in the hyperalgesia of FMS appears limited. [Return to top] ------------------------------ Date: Sat, 4 Nov 2006 11:03:40 -0500 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: Exploring the altered daily geographies and lifeworlds of women living with fibromyalgia syndrome: A mixed-method approach Exploring the altered daily geographies and lifeworlds of women living with fibromyalgia syndrome: A mixed-method approach. Soc Sci Med. 2006 Oct 30; [Epub ahead of print] Crooks VA. Department of Geography, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6. PMID: 17079063 In this paper I employ data triangulation in order to investigate the complex nature of the altered lifeworlds and daily geographies of women living with fibromyalgia syndrome (FMS). More specifically, I use the findings of in-depth interviews and a standardized test (the Sickness Impact Profile [SIP]) in a mixed-method approach to understanding how women's lives change after the onset of FMS and how their changing bodies and locations in society and space shape such altered lifeworlds. These data were collected from 55 women living with FMS in Ontario, Canada. The experiential evidence shared during the interviews is used to qualify or explain certain phenomena observed within the SIP dataset. I focus on four specific experiences in the women's lives; these are the: (1) onset of mental haziness and fatigue; (2) development of disrupted sleep/sleep disorders; (3) removal from paid labour; and (4) withdrawal from social and recreational activities. It is found that changes in the women's bodies precipitated some of the most significant life changes experienced, including altered identities and diminished incomes, and that altered bodily realities facilitated or denied access to socio-spatial life. At the same time, the women's changing locations in society and space also played a role in bringing about such changes. [Return to top] ------------------------------ Date: Sat, 4 Nov 2006 11:30:37 -0500 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: A comparison of physical functional performance and strength in women with fibromyalgia, age- and weight-matched controls, and older women who are healthy A comparison of physical functional performance and strength in women with fibromyalgia, age- and weight-matched controls, and older women who are healthy. Phys Ther. 2006 Nov;86(11):1479-88. Panton LB, Kingsley JD, Toole T, Cress ME, Abboud G, Sirithienthad P, Mathis R, McMillan V. Department of Nutrition, Food and Exercise Sciences, College of Human Sciences, Florida State University, 436 Sandels Building, Tallahassee, FL 32306 (USA). PMID: 17079747 BACKGROUND AND PURPOSE: The purpose of this study was to compare functionality and strength among women with fibromyalgia (FM), women without FM, and older women. SUBJECTS: Twenty-nine women with FM (age [X+/-SD]=46+/-7 years), 12 age- and weight-matched women without FM (age=44+/-8 years), and 38 older women who were healthy (age=71+/-7 years) participated. METHODS: The Continuous Scale-Physical Functional Performance Test (CS-PFP) was used to assess functionality. Isokinetic leg strength was measured at 60 degrees /s, and handgrip strength was measured using a handgrip dynamometer. RESULTS: The women without FM had significantly higher functionality scores compared with women with FM and older women. There were no differences in functionality between women with FM and older women. Strength measures for the leg were higher in women without FM compared with women with FM and older women, and both women with and without FM had higher grip strengths compared with older women. DISCUSSION AND CONCLUSION: This study demonstrated that women with FM and older women who are healthy have similar lower-body strength and functionality, potentially enhancing the risk for premature age-associated disability. [Return to top] ------------------------------ Date: Sat, 4 Nov 2006 21:25:47 +0100 From: Jan van Roijen <j.van.roijen@xxxxx.xx> Subject: not,med: Dr. Elinor Stein -FM-CFS Canada ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Send an Email for free membership ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ >>>> Help ME Circle <<<< >>>> 4 November 2006 <<<< Editorship : j.van.roijen@xxxxx.xx Outgoing mail scanned by Norton AV ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ From: "FM-CFS Canada, John Ernst" <hope@xxxxxx.xx> At our request, the respected Dr. Elinor Stein in Calgary, Alberta, Canada, wrote a guide to differentiate CFS from both depression and anxiety. It is freely available. *Assessment and Treatment of Patients with ME/CFS: Clinical Guidelines for Psychiatrists* http://fm-cfs.ca/Psychiatry-overview.pdf Dr. (Ellie) Stein has also provided general advice through our online Question and Answer sessions, answering nine questions. http://fm-cfs.ca/QAStein.html As to who we are, we are FM-CFS Canada, a national charity devoted to the promotion of awareness, education, research, and treatment. Our web site freely shares all of our information, and we've invited a variety of medical experts to write educational guides for their peers, and all of the results will be posted, at fm-cfs.ca. fyi, while we're a national group and have online resources to share with groups, we've also been promoting most of our awareness in Ottawa, Canada, trying to make our nation's capital and leaders more aware. Here's a page about the campaign: http://fm-cfs.ca/Ottawa.html Cheers, John Ernst Executive Director FM-CFS Canada 412 - 99 Fifth Avenue Ottawa, Ontario Canada, K1S 5P5 hope@xxxxx.xx http://fm-cfs.ca Toll-Free: 1-877-437-HOPE (4673) Direct - 1-613.565.2423 Charitable Registration No. 89241 7742 RR0001 [Return to top] ------------------------------ Date: Sun, 5 Nov 2006 13:22:21 -0500 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: Posttraumatic stress disorder, tenderness, and fibromyalgia syndrome: are they different entities? Original article Posttraumatic stress disorder, tenderness, and fibromyalgia syndrome: are they different entities? Journal of Psychosomatic Research, Volume 61, Issue 5 , November 2006, Pages 663-66 doi:10.1016/j.jpsychores.2006.07.003 Daniella Amital [a], Leah Fostick [b], Michael L. Polliack [b], Shlomo Segev [c], Joseph Zohar [b], Alan Rubinow [d],and Howard Amital [e] [a] Department of Psychiatry "B," Ness-Ziona Mental Health Center, Hadassah-Hebrew University School of Medicine, Jerusalem, Israel [b] Department of Psychiatry "A," Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel [c] Medical Surveillance Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel [d] Rheumatology Unit, Division of Internal Medicine, Hadassah-Hebrew University School of Medicine, Jerusalem, Israel [e] Department of Medicine "D," Meir Medical Center (affiliated with Sackler Faculty of Medicine, Tel-Aviv University), Kfar-Saba, Israel Received 11 April 2006; revised 4 July 2006; accepted 11 July 2006. Available online 1 November 2006. Abstract Objectives: Many features of fibromyalgia syndrome (FMS) resemble those of posttraumatic stress disorder (PTSD). The goal of this study was to investigate the comorbidity of FMS and PTSD in a cohort of men following an intensive, initial, defined traumatic event. Methods: One hundred twenty-four males (55 patients with PTSD, 20 patients with major depression, and 49 controls) were evaluated for the presence of FMS. The major traumatic events in all PTSD patients were combat-related. Each individual completed questionnaires characterizing his disease, disabilities, and quality of life. Results: Forty-nine percent of PTSD patients, compared to 5% of major depression patients and none of normal controls, fulfilled the American College of Rheumatology criteria for FMS (P<.0001). Significant correlations were detected between tender points and measured parameters in the PTSD group. Conclusions: In male patients, PTSD is highly associated with FMS. The degree and impact of these disorders are also highly related. Keywords: Fibromyalgia syndrome; Posttraumatic stress disorder; Pain; Depression; Gender; Tenderness [Return to top] ------------------------------ Date: Mon, 6 Nov 2006 12:34:00 -0500 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: Psychophysiological responses in patients with fibromyalgia syndrome Original article Psychophysiological responses in patients with fibromyalgia syndrome Journal of Psychosomatic Research, Volume 61, Issue 5, November 2006, Pages 671-679 doi:10.1016/j.jpsychores.2006.07.004 Kati Thieme [a, b, *], Ulrike Rose [c], Thomas Pinkpank [c], Claudia Spies [d], Dennis C. Turk [b] and Herta Flor [a] [a] Department of Clinical and Cognitive Neuroscience, University of Heidelberg, Central Institute of Mental Health, Mannheim, Germany [b] Department of Anesthesiology, University of Washington, Seattle, WA, USA [c] Department of Clinical Psychology, Humboldt-University Berlin, Germany [d] Department of Anesthesiology and Intensive Care, Campus Charite, University Medicine, Berlin, Germany [*] Corresponding author. Department of Clinical and Cognitive Neuroscience, University of Heidelberg, Central Institute of Mental Health, J5, 68169 Mannheim, Germany. Tel.: +49 621 17036339; fax: +49 621 17036305. Received 14 December 2005. Available online 1 November 2006. Abstract Physical and emotional stress and altered reactivity of the autonomic nervous system have been implicated in the development and maintenance of fibromyalgia syndrome (FMS). This study investigated blood pressure, heart rate (HR), skin conductance levels (SCL), and surface electromyograms (EMG) from the trapezius muscle in 30 FMS patients and 30 age- and sex-matched healthy controls (HCs). All measures were continuously recorded during baseline (BL), social conflict, mental arithmetic, and relaxation tasks. The FMS patients showed significantly higher stress ratings and self-reported stress responses. Baseline EMG levels were significantly lower, and BL HR was significantly elevated. During both stress tasks, HR reactivity was significantly lower, and SCL reactivity was significantly higher in the FMS group. This pattern of low BL muscle tension and high BL HR, along with low HR and high SCL reactivity to stress, is discrepant to other chronic pain syndromes and suggests unique psychophysiological features associated with FMS. Several potential mechanisms for these psychophysiological responses are discussed. Keywords: Fibromyalgia syndrome; Psychophysiology; Electromyography; Stress-reactivity Copyright © 2006 Published by Elsevier Inc. [Return to top] ------------------------------ Date: Mon, 6 Nov 2006 18:10:09 -0500 From: Fred Springfield <fredspringfield@xxxxx.xxx> Subject: RES: Early Adverse Experience and Risk for Chronic Fatigue Syndrome: Results From a Population-Based Study Early Adverse Experience and Risk for Chronic Fatigue Syndrome: Results From a Population-Based Study Journal: Arch Gen Psychiatry. 2006;63:1258-1266. Authors: Christine Heim, PhD; Dieter Wagner, PhD; Elizabeth Maloney, MS, DrPH; Dimitris A. Papanicolaou, MD; Laura Solomon, MPH; James F. Jones, MD; Elizabeth R. Unger, MD, PhD; William C. Reeves, MD, MSc Author Affiliations: Viral Exanthems and Herpesvirus Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention (Drs Heim, Wagner, Maloney, Jones, Unger, and Reeves and Ms Solomon), and Departments of Psychiatry and Behavioral Sciences (Dr Heim) and Medicine (Dr Papanicolaou), Emory University School of Medicine, Atlanta, Ga. Dr Papanicolaou is now with Merck & Co, Inc, Rahway, NJ; Ms Solomon is now with the Human Research Protection Office, Office of the Chief Science Officer, Centers for Disease Control and Prevention. Context Chronic fatigue syndrome (CFS) is an important public health problem. The causes of CFS are unknown and effective prevention strategies remain elusive. A growing literature suggests that early adverse experience increases the risk for a range of negative health outcomes, including fatiguing illnesses. Identification of developmental risk factors for CFS is critical to inform pathophysiological research and devise targets for primary prevention. Objective To examine the relationship between early adverse experience and risk for CFS in a population-based sample of clinically confirmed CFS cases and nonfatigued control subjects. Design, Setting, and Participants A case-control study of 43 cases with current CFS and 60 nonfatigued controls identified from a general population sample of 56 146 adult residents from Wichita, Kan. Main Outcome Measures Self-reported childhood trauma (sexual, physical, and emotional abuse and emotional and physical neglect) and psychopathology (depression, anxiety, and posttraumatic stress disorder) by CFS status. Results The CFS cases reported significantly higher levels of childhood trauma and psychopathology compared with the controls. Exposure to childhood trauma was associated with a 3- to 8-fold increased risk for CFS across different trauma types. There was a graded relationship between the degree of trauma exposure and CFS risk. Childhood trauma was associated with greater CFS symptom severity and with symptoms of depression, anxiety, and posttraumatic stress disorder. The risk for CFS conveyed by childhood trauma increased with the presence of concurrent psychopathology. Conclusions This study provides evidence of increased levels of multiple types of childhood trauma in a population-based sample of clinically confirmed CFS cases compared with nonfatigued controls. Our results suggest that childhood trauma is an important risk factor for CFS. This risk was in part associated with altered emotional state. Studies scrutinizing the psychological and neurobiological mechanisms that translate childhood adversity into CFS risk may provide direct targets for the early prevention of CFS. [Return to top] ------------------------------ Date: Mon, 6 Nov 2006 18:33:24 -0500 From: Fred Springfield <fredspringfield@xxxxx.xxx> Subject: RES: Premorbid Predictors of Chronic Fatigue Premorbid Predictors of Chronic Fatigue Journal: Arch Gen Psychiatry. 2006;63:1267-1272. Authors: Kenji Kato, PhD; Patrick F. Sullivan, MD, FRANZCP; Birgitta Evengård, MD, PhD; Nancy L. Pedersen, PhD Author Affiliations: Department of Medical Epidemiology and Biostatistics (Drs Kato, Sullivan, and Pedersen) and Department of Laboratory Medicine, Karolinska University Hospital Huddinge (Dr Evengård), Karolinska Institutet, Stockholm, Sweden; Departments of Genetics, Psychiatry, and Epidemiology, University of North Carolina at Chapel Hill (Dr Sullivan); and Department of Psychology, University of Southern California, Los Angeles (Dr Pedersen). Context Chronic fatigue syndrome is a disabling problem characterized by persistent fatigue lasting at least 6 months with a number of ancillary symptoms. Although the etiology of chronic fatiguing illness is unknown, some evidence suggests that stress may confer increased risk for development of the disorder. Moreover, subjects with chronic fatiguing illness may have distinctive personality traits, although this finding could reflect confounding by other mechanisms. Objective To assess the prospective association of premorbid self-reported stress and personality with chronic fatiguelike illness. Design Prospective nested case-control study in a population-based sample. Setting General community. Participants From the Swedish Twin Registry, 19 192 twins born between January 1, 1935, and December 31, 1958. Main Outcome Measures Information about current chronic fatiguing illnesses was obtained from computer-assisted telephone interviews conducted between 1998 and 2002. Self-reported stress (based on a single question) and personality scales (emotional instability and extraversion in the Eysenck Personality Inventory) were measured from 1972 to 1973 by a mailed questionnaire. Relative risks were estimated with case-control analyses (matched for age and sex) and co-twin control analyses (comparing discordant pairs). Results Higher emotional instability and self-reported stress in the premorbid period were associated with higher risk for chronic fatiguelike illness in matched case-control analyses (odds ratios, 1.72 and 1.64, respectively). In co-twin control analyses, relative risk of emotional instability decreased to 1.02 whereas that of stress increased considerably to 5.81. There was no association between extraversion and fatigue. Conclusions Elevated premorbid stress is a significant risk factor for chronic fatiguelike illness, the effect of which may be buffered by genetic influences. Emotional instability assessed 25 years earlier is associated with chronic fatigue through genetic mechanisms contributing to both personality style and expression of the disorder. These findings suggest plausible mechanisms for chronic fatiguing illness. [Return to top] ------------------------------

End of CO-CURE Medical & Research Posts Only Digest - 30 Oct 2006 to 6 Nov 2006 (#2006-50)

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