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Stress management and the role of Rhodiola rosea : a review

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Objective: Stress describes the physiological reaction to threat or pressure, which manifests as physical symptoms of exhaustion or energy loss and psychological symptoms, including irritability or tension. If untreated, chronic stress or burnout may develop, both are areas of unmet medical need. Evidence-based treatment and prevention measures are needed. Methods: Prevention strategies and existing treatment options for stress-related symptoms were evaluated to establish criteria for an adequate pharmacological approach to stress. The authors reviewed the literature to reach a clinically meaningful strategy for prevention and treatment of persistent stress symptoms and their consequences, including burnout and secondary diseases. Results: Current medication reveals a treatment gap. Most drugs target only psychological or physical stress symptoms. Furthermore, psychotropic medications sometimes prescribed for stress often have unacceptable side effects and bear a risk of overtreatment. Ideally pharmacological therapy should afford comprehensive treatment of all stress symptoms with a favourable safety profile. Conclusions: Rhodiola rosea extract (RRE) fulfils important requirements. It is the main adaptogen approved by the HMPC/EMA for the indication ‘stress’ and influences the release of stress hormones while boosting energy metabolism as revealed in animal literature. RRE offers comprehensive treatment of stress symptoms and can prevent chronic stress and stress-related complications.
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International Journal of Psychiatry in Clinical Practice
ISSN: 1365-1501 (Print) 1471-1788 (Online) Journal homepage:
Stress management and the role of Rhodiola
rosea: a review
Ion-George Anghelescu, David Edwards, Erich Seifritz & Siegfried Kasper
To cite this article: Ion-George Anghelescu, David Edwards, Erich Seifritz & Siegfried Kasper
(2018): Stress management and the role of Rhodiola rosea: a review, International Journal of
Psychiatry in Clinical Practice, DOI: 10.1080/13651501.2017.1417442
To link to this article:
© 2018 The Author(s). Published by Informa
UK Limited, trading as Taylor & Francis
Published online: 11 Jan 2018.
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Stress management and the role of Rhodiola rosea: a review
Ion-George Anghelescu
, David Edwards
, Erich Seifritz
and Siegfried Kasper
Department of Psychiatry and Psychotherapy, Clinic Dr. Fontheim, Liebenburg, Germany;
Claridges Barn, Oxfordshire, UK;
Department of
Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland;
Department of Psychiatry and
Psychotherapy, Medical University of Vienna, Vienna, Austria
Objective: Stress describes the physiological reaction to threat or pressure, which manifests as physical
symptoms of exhaustion or energy loss and psychological symptoms, including irritability or tension. If
untreated, chronic stress or burnout may develop, both are areas of unmet medical need. Evidence-based
treatment and prevention measures are needed.
Methods: Prevention strategies and existing treatment options for stress-related symptoms were eval-
uated to establish criteria for an adequate pharmacological approach to stress. The authors reviewed the
literature to reach a clinically meaningful strategy for prevention and treatment of persistent stress symp-
toms and their consequences, including burnout and secondary diseases.
Results: Current medication reveals a treatment gap. Most drugs target only psychological or physical
stress symptoms. Furthermore, psychotropic medications sometimes prescribed for stress often have
unacceptable side effects and bear a risk of overtreatment. Ideally pharmacological therapy should afford
comprehensive treatment of all stress symptoms with a favourable safety profile.
Conclusions: Rhodiola rosea extract (RRE) fulfils important requirements. It is the main adaptogen
approved by the HMPC/EMA for the indication stressand influences the release of stress hormones while
boosting energy metabolism as revealed in animal literature. RRE offers comprehensive treatment of stress
symptoms and can prevent chronic stress and stress-related complications.
Received 27 October 2017
Revised 1 December 2017
Accepted 12 December 2017
Rhodiola rosea; stress;
Stress describes the physiological reaction to environmental
threats or pressures, which can be self-driven e.g., striving for per-
fection, high ambition or external such as social pressures, exces-
sive demands or workloads. Although the body may initially adapt
to perform under stress, it soon becomes dysfunctional if stress
persists and has a too high intensity. Stress manifests itself in a
wide variety of both physical and psychological symptoms, has a
negative impact on performance and leads to absence from work.
Work-related stress occurs across all groups of society and affects
22% of the European workforce. It is a crucial factor in 5060% of
all lost working days (Milczarek, Schneider, & Gonz
alez, 2009) with
a rising trend. In 2016, a survey of a large German health insur-
ance company revealed that over 60% of survey participants are
now more stressed than in 2013 (Techniker Krankenkasse, 2016).
The World Health Organization (WHO) has called stress the health
epidemic of the 21st century.
If stress persists and is left untreated, it can result in serious
health problems including burnout and secondary conditions, e.g.,
depression, anxiety, cardiovascular, gastrointestinal, neurological
or musculoskeletal disease or diabetes consequently with higher
costs to the community and a higher impact on individualslives.
The main implications for individuals related to health impairment
are lower income and reduced quality of life. However, stress has
not only individual, but also social and economic consequences.
Organisations are affected by rising costs related to sick leave,
reduced productivity and higher staff turnover (European Agency
for Safety and Health at Work [EU-OSHA], 2014).
The authors reviewed the current literature to identify and assess
prevention strategies and treatment options for stress-related
symptoms and thus established criteria for an adequate and holistic
pharmacological approach to stress. The aim of this process was to
propose a consensus for prevention and treatment of symptoms of
persistent stress as well as for prevention of health consequences of
stress such as burnout and secondary diseases. In this review article
we have outlined current understanding of the pathophysiology of
stress and identified the areas of greatest clinical need for interven-
tion, which occurs at two stages: as a preventive treatment for a
patient with stress to avoid the development of chronic stress and
for those already suffering from persistent stress, an appropriate
therapy to avoid burnout and secondary diseases. Assessment of
prevention and treatment strategies identified some non-pharma-
cological approaches and some pharmacological approaches which
have shown limited efficacy targeting the symptoms of stress and
these are outlined below. The literature review process identified a
significant amount of data on the clinical effects of Rhodiola rosea
extract (RRE) on stress and stress-related disorders and mechanistic
studies allude to the ability of RRE to normalise stress and boost
energy levels. Thus, in the latter part of this review article we have
focused our attention on RRE as a specific pharmacological
approach to stress management.
Stress, allostatic state and allostatic (over)load
In 1936 Hans Selye postulated the so-called general adaptation
syndrome which describes the stereotyped response of an
CONTACT Ion-George Anghelescu Department of Psychiatry and Psychotherapy, Clinic Dr. Fontheim, 38704 Liebenburg, Germany
ß2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (,
which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
organism in reaction to a stressor. This syndrome consists of three
stages. The first stage is the alarm reaction (fight or flight
response) in which resources are mobilised to maintain homeosta-
sis. This has subsequently been termed as allostasis, which
describes the biological response to stressors to promote stability
through change (McEwen, 2000). Primary mediators of allostasis
include, but are not confined to, hormones of the hypothalamic-
pituitary-adrenal (HPA) axis, catecholamines and cytokines.
Restoration of allostasis leads to the second stage of resistance,
in which defence and adaptation are sustained and optimal.
However, many current stressors are persistent and can lead an
organism into stage three where the bodys capacity to withstand
them is surpassed by the consequences of exhaustion and
depleted reserves. Extreme psychological stress impacts on the
complex regulation of emotion by the brain and on human psy-
chological resilience and vulnerability to psychopathology
(Charney, 2004).
The concepts of allostasis and allostatic load link the protective
and survival values of the acute response to stress to the adverse
consequences that result if the acute response persists and
becomes chronic (McEwen & Wingfield, 2003). An allostatic state
may result from an imbalance of the primary mediators, reflecting
excessive production of some and inadequate production of
others (McEwen, 2005). In some cases, the stress mediators them-
selves can turn on the body and cause problems. If recovery from
the acute event is not accompanied by an adequate homeostatic
response to terminate the acute adaptive response of stress medi-
ators, the deleterious effects on psychological and physiological
function termed allostatic load occur. The allostatic load is the
burden borne by a brain and body adapting to challenges, both
physiological and psychological. A sustained allostatic state may
ensue, termed allostatic overload. The tipping point for allostatic
overload will vary among individuals. It manifests as disease e.g.,
chronic hypertension and the generation of atherosclerotic pla-
ques, elevated glucocorticoids leading to insulin resistance and
increased risk for cardiovascular disease, immunosuppression or
elevation of inflammatory cytokines (see below).
Pathomechanism, symptoms and health consequences
of chronic stress
The symptoms of stress can be multiple and affect many organ
systems. The physiological stress response involves stimulation of
the autonomic nervous system (ANS) and the hormonal system,
with potentially negative impact on the cardiovascular system, the
musculoskeletal system, the immunological system and others
(Figure 1).
Fatigue and exhaustion manifest as key physical stress symp-
toms. Others can be gastrointestinal symptoms, headache, back-
ache or sexual dysfunction. Psychological and emotional
symptoms of stress include e.g., tension, irritability, anxious or
depressive mood, bad temper and the feeling of losing control.
Concomitantly, changes in cognition, including forgetfulness and
inability to concentrate may occur. Behavioural symptoms of
stress include social withdrawal, alcohol and cigarette abuse, eat-
ing disorders, proneness to mistakes and work absence (Edwards,
Heufelder, & Zimmermann, 2012; Milczarek et al., 2009).
These symptoms result from several postulated pathomechan-
isms. The HPA axis is one of the main stress response pathways.
Stress induces the release of corticotropin releasing hormone
(CRH) in the hypothalamus. This activates the pituitary gland to
release adrenocorticotropic hormone (ACTH). The latter stimulates
the release of adrenaline, noradrenaline and cortisol in the adrenal
gland. The actions of this hormone system are tightly regulated
normally to ensure that the organism can respond quickly and
adequately to stress, via negative feedback mechanisms, levels of
hormones e.g., cortisol return to normal values.
Chronic stress, however, results in persistently elevated levels
e.g., of cortisol, as demonstrated in animal and cell models.
Studies of rabbits under immobilisation stress revealed an
Figure 1. Multi-faceted symptoms of stress.
activation of e.g., stress-activated protein kinase/Jun N-terminal
protein kinase (SAPK/JNK) (Panossian, Hambardzumyan,
Hovhanissyan, & Wikman, 2007). Previous studies, e.g., with mouse
hippocampal (HT22) cells, indicate that JNK leads to an inhibition
of glucocorticoid receptor function. This again results in a block-
ade of the negative feedback mechanism of cortisol release (see
Figure 2(A); Panossian, 2013; Panossian et al., 2007; Wang et al.,
2005). Consequently, cortisol levels in the blood remain high
which may lead to fatigue, depression, impaired cognitive per-
formance, hyperglycaemia, high blood pressure and other health
problems as a long-term consequence.
At the intracellular level, high cortisol levels impact on the
balance between trophic and atrophic factors within neurones,
thus affecting neurogenesis and brain plasticity in the hippo-
campus and frontal cortex, which results in neurodegenerative
changes involved in mood regulation (Gould & Tanapat,
Investigations with rat cells showed that the release of SAPK
leads to an increase in nitric oxide (NO) release (Guan, Buckman,
Springer, & Morrison, 1999). The latter impairs both glycolysis and
mitochondrial function which results in a decrease in adenosine
triphosphate (ATP) synthesis (see Figure 2(B); Brown, 2001; Giulivi,
1998). Low ATP levels are associated with symptoms such as loss
of energy, fatigue and exhaustion (Panossian, 2013; Panossian &
Wikman, 2009).
A role of inflammatory mechanisms involving cytokines has
also been hypothesised in chronic stress-related mental diseases,
such as depression, anxiety or dementia (Bagyinszky et al., 2017;
Kim et al., 2017).
An association between type 2 diabetes and depression has
recently been explained, to some extent, by unspecific patho-
physiological mechanisms involved in the stress response (Berge
& Riise, 2015). Chronic stress is also associated with an increased
risk of cardiovascular disease (CVD) (Bot & Kuiper, 2017; Nabi
et al., 2013). Long-term work stress accounts for an estimated
16% of male and 22% of female CVD in the EU (Houtman, 2005).
Recent studies report that the activity of the amygdala, a key
component of the brain involved in emotion and stress, is of pre-
dictive value for the incidence of acute cardiovascular events dur-
ing a median follow up period of 3.7 years among nearly 300
individuals with no prior history of CVD (Tawakol et al., 2017).
Burnout is a stress disorder of unspecific risk stage which is char-
acterised by symptoms of mental exhaustion and physical fatigue,
Figure 2 (A) Postulated pathomechanisms of stress: persistent stress leads to a blockade of the negative feedback of cortisol. (Adapted from Panossian, 2013;
Panossian et al., 2007). (B) Postulated pathomechanisms of stress: persistent stress leads to a disruption of ATP synthesis. (Adapted from Panossian & Wikman, 2009).
cynicism or depersonalisation and reduced personal accomplish-
ment (Hochstrasser et al., 2016). It represents a risk factor not only
for psychiatric diseases such as depression and anxiety, but also
for cardiovascular, metabolic and other somatic diseases. Work-
related burnout has been associated with an increased 10-year
mortality risk (Ahola, V
anen, Koskinen, Kouvonen, & Shirom,
2010). Thus, the prevention of burnout deserves special attention.
The usual non-pharmacological treatment is cognitive behav-
ioural therapy or psychotherapy and there is currently no specific
pharmacological treatment for burnout. Several biomarkers have
been tested for association with burnout, but the results are
contradictory and there are currently no established biochemical
markers which can be considered as reliable indicators for burn-
out (Danhof-Pont, van Veen, & Zitman, 2011).
Stress-vulnerability and resilience, respectively, play an import-
ant role in the predisposition for, or resistance against, burnout
and are an area of focus in stress research. The stress-vulnerability
model was first hypothesised by Zubin and Spring (1977) to iden-
tify and treat relapses of mental illness. It suggests that people
inherit a genetic predisposition to mental illness. This vulnerability
in itself is not sufficient to manifest the disorder and requires
interaction with bio-pyscho-social stressors (Goh & Agius, 2010).
Increased vulnerability is potentially influenced by genetic factors
and/or individual stress experience and may lead to decreased
resilience to stress. Conversely, stress overload and burnout may
be prevented by enhancing resilience. Hence, the prevention of
burnout and exhaustion by enhancement of resilience on the one
hand and by the adequate treatment of stress symptoms on the
other is very important and appears to be an area of a consider-
able unmet medical need.
Stress management strategies
Popular coping strategies, such as distraction, physical activities,
relaxation, socialising and healthy food, may be employed in order
to get out of the stressful situation with the aim of regaining
inner calm and strength. The usual form of care for work-related
chronic stress is coaching, using a cognitive-behavioural approach
whose primary aim is to reduce symptoms and improve function-
ing (Schoutens, Frings-Dresen, & Sluiter, 2016). As an alternative
non-pharmacological approach, mindfulness-based stress reduc-
tion is a clinically standardized meditation technique that has
demonstrated an effect on stress reduction in healthy people,
with benefit similar to that of standard relaxation training (Chiesa
& Serretti, 2009).
However, many modern stressors are persistent and the bodys
capacity to withstand them is surpassed by the consequences of
exhaustion and depleted reserves, leading to burnout (German
Association for Psychiatry, Psychotherapy and Psychosomatics
[DGPPN], 2012). Thus, as mentioned above, the areas of unmet
clinical need for intervention may be identified in two stages: as a
preventive treatment in a patient with stress or a lack of vitality
to avoid the development of chronic stress or exhaustion, and
secondly, as a first-line treatment when persistent stress and
exhaustion are present, to avoid burnout and secondary diseases.
It should not be the goal of a treatment strategy to make one
keep going while neglecting the signs and symptoms of exhaus-
tion, but rather to assist in coping with temporary unusual
demands, allowing for rapid readaption to normal states once the
stressful situation has subsided.
Pharmacological interventions
If stress symptoms persist, together with continuously demanding
life circumstances that cannot easily be avoided, pharmacological
intervention may become necessary to prevent serious mental
and social sequelae. However, current pharmacotherapy reveals a
treatment gap. Many herbals, vitamin combinations or prescrip-
tion medicines tend to focus only on single symptoms, rather
than comprehensively on all aspects of stress or burnout. Besides,
psychiatric prescription drugs like antidepressants, anxiolytics or
b-blockers are mostly indicated for more severe diseases, such as
depression or anxiety and there is a risk of overtreatment includ-
ing severe side effects and/or risk of dependency.
Herbal treatment options or other drugs available over-the-
counter (OTC) tend to focus either on increasing/preserving
energy reserves (treatment of physical symptoms) or on promot-
ing relaxation (treatment of psychological symptoms). For
example: those acting as energisers, including vitamins/minerals
and tonics; and those acting on mood, relaxation and sleep, such
as St. Johns wort, valerian, passion flower, lavender and antihist-
amines. An ideal pharmacological therapy should offer a compre-
hensive treatment of all relevant stress symptoms combined with
a favourable safety profile.
Figure 3. Proposed model for the mode of action of Rhodiola rosea extract (RRE): normalisation of stress hormone release and activation of ATP synthesis.
The term adaptogenis used to describe medicinal plants that
have the capacity to normalise body functions and strengthen
systems compromised by stress and are able to enhance the
state of non-specific resistanceof an organism to stress
described above as allostasis. The Committee on Herbal Medicinal
Products (HMPC) which is the European Medicines Agencys
(EMA) committee responsible for compiling and assessing scien-
tific data on herbal substances, preparations and combinations
developed the reflection paper on the adaptogenic concept (EMA,
In this paper, adaptogens are defined as virtually non-toxic to
the recipient. They are non-specific in pharmacological properties
and act by increasing the resistance of an organism to a broad
spectrum of adverse biological, chemical and physical factors.
Adaptogens act as regulators with a normalising effect on the
various organ systems and their effect is the more pronounced
the deeper the pathologic changes in the organism are.
As such, adaptogens should be differentiated from traditional
herbal medicinal products of related action, such as tonics and
stimulants. The EMA has established HMPC monographs on many
herbals including some adaptogens, i.e., preparations deriving
from Eleutherococcus senticosus, Panax ginseng and Rhodiola rosea.
These monographs cover their therapeutic use and safety as regis-
tered drugs.
Rhodiola rosea extract (RRE)
Extract from the roots and rhizomes of Rhodiola rosea (RRE) is an
adaptogen that acts to increase the bodys resistance to stress,
exhaustion and fatigue. It is the main adaptogen given the indica-
tion stressby the HMPC (European Medicines Agencys [EMA],
2011,2012). A wide variety of preclinical in vivo and ex vivo stud-
ies conducted in cell lines and animal models have elucidated
the presence of several biochemical and pharmacological stress-
reducing actions of RRE. It possesses a unique mechanism of
action: it normalises the release of stress hormones while simul-
taneously boosting energy metabolism via activation of ATP syn-
thesis in mitochondria (Figure 3; Abidov, Crendal, Grachev,
Seifulla, & Ziegenfuss, 2003; Olsson, von Sch
eele, & Panossian,
2009; Panossian et al., 2007). Blood levels of several stress media-
tors (e.g., p-SAPK/p-JNK, NO, cortisol) were assessed in rabbits
under immobilisation stress; in the animals under stress that
received placebo the levels of the above-mentioned markers
were significantly elevated while in animals which received RRE
(1 mg/kg for seven days) the stress mediators remained virtually
unchanged (Panossian et al., 2007). In other studies, rats treated
with RRE (50 mg/kg) exhibited a significantly prolonged duration
of exhaustive swimming in comparison with untreated rats.
Furthermore, RRE induced the (re)synthesis of ATP in rat mito-
chondria from skeletal muscles and stimulated recovery after exer-
cise (Abidov et al., 2003).
Table 1. Clinical studies with Rhodiola rosea extract (RRE) in subjects with stress symptoms.
Reference Study design Patient population Treatment Duration Outcome measures Results
Heldmann et al.
Single centre, open-
label pilot study
50 healthy male and
female computer work-
ers (3050 years)
1375; Rosalin
200 mg BID
12 weeks Effects on attention
and task performance
(reaction time and
error rate). Event-
related brain potentials
were measured.
Treatment led to an
increase of attention
resources under a
strong attention bur-
den (simulated multi-
Treatment also led to
an increase in both
working speed and
working quality.
Cropley et al.
Open-label, rando-
mised (vs. control),
repeated measures
n¼80 mildly anxious
participants (1835
years), with score >30
on Spielberger State-
Trait Anxiety Inventory
1375, Rosalin
200 mg BID
2 weeks STAI; Perceived Stress
Scale; Profile of Mood
States Inventory;
Milford Epworth
Sleepiness Scale; Leeds
Sleep Evaluation
Questionnaire (LSEQ);
Cognitive function
Significant reduction in
self-reported anxiety,
stress, anger, confusion
and depression;
significant improve-
ment in total mood;
no impairment in cog-
nitive performance ver-
sus control.
Edwards et al.
Open, multicentre,
n¼101: male (n¼33)
and female (n¼68)
outpatients (44.5 ± 7.5
years), with distinct
stress symptoms
treated in general
1375, Rosalin
200 mg BID
4 weeks Seven Numerical
Analogue Scales (NAS)
of subjective stress
symptoms measures;
Perceived Stress
Questionnaire (PSQ);
Fatigue Inventory 20
(MFI-20); Numbers
Connecting Test (NCT);
Sheehan Disability
Scale (SDS);
Multidimensional Mood
State Questionnaire
(MDMQ); Clinical Global
All outcome variables
showed clinically rele-
vant improvement in
stress symptoms,
fatigue, quality of life,
mood, concentration,
disability, functional
impairment and overall
therapeutic effect.
Significant improve-
ments were observed
after three days of
treatment and contin-
ued for four weeks.
Darbinyan et al.
Randomised, pla-
double-blind, cross-
n¼56 healthy physi-
cians (2435 years)
Standardised SHR-5
RRE (4.5 mg salidro-
170 mg OD
32 weeks Anti-fatigue effect dur-
ing night duty using
five different tests.
Less fatigue in medical
doctors on night duty
with treatment versus
placebo after two
weeks of treatment.
RRE acts to normalise cortisol synthesis potentially through
inhibition of the SAPK pathway involved in the pathogenesis
of glucocorticoid resistance, which is also found in certain
chronic immune/inflammatory diseases and in some patients
with depression (Panossian, 2013; Panossian et al., 2007). At
the same time, through inhibition of the SAPK/JNK pathway,
RRE potentially prevents the formation of NO and the associ-
ated decline in ATP synthesis (Guan et al., 1999; Panossian &
Wikman 2009).
Stress leads to a damage of the mitochondrial function and
the excessive production of reactive oxidative species (ROS) in
mitochondria, which may cause damage e.g., to proteins, nucleic
acids, and membranes, which in turn can lead to activation of cell
death processes such as apoptosis (Zhang, Wu, Lu, Guo, & Ma,
2006). RRE may also offer potential protection against heart and
brain diseases (e.g., heart attack, stroke, depression and
Alzheimers disease) through anti-oxidative/anti-inflammatory
mechanisms (Lee et al., 2013; Olpe & Seifritz, 2014; Zhang et al.,
RRE products with medicinal drug status must fulfil high
pharmaceutical requirements with regard to their quality and
safety, e.g., products containing RRE WS
1375 (Rosalin
). It should
also be noted that there are many dietary supplements available
which contain Rhodiola rosea drug or extracts that do not comply
with the high standards set by the HMPC and pharmaceutical
quality requirements for registered medicinal drugs.
Clinical studies with RRE
In several clinical studies of stress, burnout and chronic fatigue,
RRE was found to be effective, safe and well tolerated.
Stress symptoms
In clinical studies, mental work capacity, attention, task perform-
ance and overall mood improved during the course of treatment
with RRE and stress and self-reported mild anxiety were reduced
(Table 1; e.g., Cropley, Banks, & Boyle, 2015; Darbinyan et al.,
2000; Edwards et al., 2012; Heldmann, Roth, Dienel, & M
Among people suffering from life-stress symptoms, clinically
relevant improvement in stress symptoms, stress-related disabil-
ities in work, social and family life, functional impairment and
overall therapeutic effect were observed with RRE treatment over
four weeks (Figure 4; Edwards et al., 2012). In this single-arm
study, adult subjects with life-stress symptoms (n¼101) treated in
general practice received open-label RRE (200 mg, twice-daily).
Seven widely recognised questionnaires to cover various aspects
of stress symptoms and psychological well-being were employed
to assess the outcome of treatment. Invariably, all outcome varia-
bles showed significant, consistent and steady improvement in
stress symptoms, fatigue, quality of life, mood, concentration, dis-
ability, functional impairment and overall therapeutic effect. The
improvements were observed as early as after three days of treat-
ment and continued throughout the whole study duration of
28 days.
RRE has also demonstrated positive effects in the treatment of
symptoms of mild anxiety associated with stress. Among students
with self-reported anxiety and stress (n¼81) who were rando-
mised to receive either RRE or a control (no treatment), the RRE
group reported a significant reduction in self-reported anxiety,
anger, confusion, stress and vigour at 14 days and a significant
improvement in total mood as compared with the no treatment
group (Cropley et al., 2015).
The effect of RRE on neuropsychological and neurophysio-
logical measures of attention and mental resource allocation has
recently been studied (Heldmann et al., 2016). The results of this
trial of 50 healthy volunteers (aged 3050 years) at risk for stress
symptomatology showed increased performance under multi-task-
ing conditions over the course of RRE administration for 12 weeks.
Overall, RRE had a positive influence on attention and mental
resource allocation and thus on speed and quality of performance
under conditions of high cognitive demand.
In an earlier study, the effect of RRE on healthy physicians on
night duty (n¼56) was evaluated using a combination of tests
that measured overall level of mental fatigue, involving complex
perceptive and cognitive cerebral functions, such as associative
thinking, short-term memory, calculation and ability of concentra-
tion and speed of audio-visual perception. A significant improve-
ment in these test results was observed in the RRE group during
Figure 4. Efficacy of Rhodiola rosea extract (RRE) in management of life stress symptoms. NAS: Numerical Analogue Scales-rating of symptoms from 0 (not at all) to
10 (severely impaired). (Adapted from Edwards et al., 2012).
the two-week treatment period, suggesting that RRE can reduce
general fatigue under certain stressful conditions (Darbinyan et al.,
Chronic fatigue symptoms and exhaustion
Unexplained chronic fatigue is a widespread healthcare problem
that significantly affects the working population (Jackson &
Macleod, 2017) and which is often associated with stress. First-line
treatments are cognitive behavioural or graded exercise therapy
(Daniels & Loades, 2017). However, these treatments yield only
moderate effect sizes. RRE is shown to improve mental perform-
ance in people with stress-related fatigue and further to improve
all dimensions of chronic fatigue symptoms (Table 2; Lekomtseva,
Zhukova, & Tartakovsky, 2013; Olsson et al., 2009).
In a double-blind study, participants (n¼60) selected accord-
ing to diagnostic criteria for fatigue syndrome were randomised
to receive RRE (576 mg extract/day) or placebo for four weeks.
Significant effects of RRE in comparison with placebo were
observed for symptoms of fatigue (Pines burnout scale) and in
tests of attention (Connors computerised continuous performance
test II [CCPT II]). Pre- versus post-treatment cortisol responses to
awakening were significantly different in the treatment group
compared with the control group. Thus, RRE is found to exert an
anti-fatigue effect that increases mental performance, particularly
the ability to concentrate and decreases cortisol response to
awakening stress in burnout patients with fatigue syndrome
(Olsson et al., 2009).
Significant improvements in specific chronic fatigue outcomes
(e.g., multi-dimensional fatigue inventory 20 [MFI-20], recent per-
ceived stress questionnaire [PSQ-R], Sheehan disability scale
[SDS]) have been demonstrated with RRE treatment among 101
patients with chronic fatigue treated in an open-label, single-arm
study for up to eight weeks (p<.001). Furthermore, the results
of the trial supported the therapeutic effect on concomitant con-
ditions related to chronic fatigue such as mood, concentration,
quality of life and general well-being which was demonstrated
with RRE treatment (200 mg, twice-daily; Lekomtseva et al.,
Burnout symptoms
The aim of the treatment of stress and burnout with an adapto-
gen is to increase stress resistance, thus addressing the source
rather than the symptoms of the syndrome and preventing sub-
sequent diseases associated with a history of burnout. The core
indicators of burnout are subjective perceptions of chronic
demand-related stress with subsequent emotional exhaustion and
decreased performance in work-related or self-set tasks. Reported
symptoms of burnout comprise not only psychiatric or mood dis-
orders such as fatigue, cynicism, impaired sexual life, lack of con-
centration or a generally negative attitude toward work, but also
somatic symptoms such as headaches, hypertension or irritable
stomach. Treatment with RRE for eight and 12 weeks, respectively,
was accompanied by a clear improvement in burnout symptoms
(Table 3; Goyvaerts & Bruhn, 2012; Kasper & Dienel, 2017).
Investigating the effects of RRE on burnout-related symptoms,
a German non-interventional study was conducted in 128 primary
care practices and included 330 patients with two or more burn-
out indicator symptoms (exhaustion, depression, insomnia, fatigue
or drop in performance). A considerable alleviation of these symp-
toms after the administration of RRE for eight weeks was reported
based on the results of the self-rating questionnaires used in this
trial (Goyvaerts & Bruhn, 2012).
An exploratory single-arm, multi-centre study investigated the
clinical outcomes in burnout patients (n¼118) treated with RRE
Table 2. Clinical studies with Rhodiola rosea extract (RRE) in subjects with chronic fatigue.
Reference Study design Patient population Treatment Duration Outcome measures Results
Lekomtseva et al.
Open, multicentre,
One hundred male and
female outpatients
(1860 years) with
chronic fatigue
1375, Rosalin
200 mg BID
8 weeks Multidimensional Fatigue
lnventory 20 (MFI-20)
measures; three
Numerical Analogue
Scales (NAS) of chronic
fatigue symptoms;
Sheehan Disability Scale
(SDS); Number
Connecting Test (NCT);
Pittsburgh Sleep Quality
Index (PSQI); Recent
Perceived Stress
Questionnaire (PSQ-R);
Beck's Depression lnven-
tory (BDI-II); Clinical
Global Impression (CGI).
Statistically significant
improvement in all
dimensions of chronic
fatigue symptoms (MFI-
20 and NAS) from week
18(p<.001) and con-
comitant conditions
related to CF comorbid-
ity and general well-
being (PSQI, PSQ-R, BDI-
II, SDS and NCT).
Olsson et al.
Randomised, placebo-
controlled, double-
blind, parallel-group
Sixty adult (2055
years) burnout patients
experiencing difficulties
equivalent to the crite-
ria of fatigue syndrome
Proprietary SHR-5
RRE 288 mg BID
4 weeks Quality of life (SF-36
questionnaire); symp-
toms of fatigue (Pines
burnout scale); depres-
sion (Montgomery -
Asberg depression rating
scale - MADRS); atten-
tion (Conners computer-
ised continuous
performance test II -
CCPT II) and saliva
cortisol response to
awakening were
assessed on day 1 and
after 28 days of
Anti-fatigue effect that
increased mental per-
formance, particularly
the ability to concen-
trate, and decreased cor-
tisol response to
awakening stress.
Significant effects of
SHR-5 RRE in comparison
with placebo were
observed in Pines burn-
out scale and the CCPT
II indices omissions, Hit
RT SE, and variability.
(200 mg, twice-daily) over 12 weeks. The aim of the treatment
with RRE was to increase stress resistance and thus to aim at the
source rather than at the symptoms of the syndrome and to fur-
ther prevent subsequent diseases associated with a history of
burnout. A broad spectrum of rating scales was employed to
evaluate the therapeutic effect of RRE in the treatment of burnout
symptoms, such as fatigue, cynicism, difficulties to concentrate,
impaired sexual life and also somatic symptoms. A wide range of
the evaluated outcome measures improved considerably over the
course of treatment. Some of these changes were already
Table 3. Clinical studies with Rhodiola rosea extract (RRE) in subjects with burnout symptoms.
Reference Study design Patient population Treatment Duration Outcome measures Results
Kasper and Dienel
Open, multicentre,
n¼118 male (n¼49)
and female (n¼68)
outpatients (44 ± 8
years) with burnout
1375, Rosalin
200 mg BID
12 weeks Seven Numerical
Analogue Scales (NAS) of
subjective stress symp-
toms; Burnout-Screening-
Scales BOSS I and BOSS II;
(MBI); Perceived Stress
Questionnaire (PSQ);
Numbers Connecting Test
(NCT); Sheehan Disability
Scale (SDS); Clinical Global
Impression (CGI);
Multidimensional Mood
State Questionnaire
(MDMQ); Patient question-
naire for sexual function
(PSFQ); Numerical
Analogue Scales of
Subjective Stress
Symptoms (NAS).
Treatment caused a
significant and clinic-
ally relevant improve-
ment in burnout
symptoms from week
1 to week 12 (NAS,
Goyvaerts and Bruhn
Open, multicentreand
330 patients (>18
years) with at least
two of the following
symptoms: exhaustion,
depression, insomnia,
fatigue and drop in
Proprietary SHR-5
RRE 288 mg BID
8 weeks Burnout total score. Significant improve-
ment in burnout symp-
toms total score after
48 weeks.
Figure 5. Intervention stages for treatment of physical/psychological stress and exhaustion. Patients with medical conditions that may result in symptoms of stress
and exhaustion such as anaemia, migraine, IBS (irritable bowel syndrome), cancer and hormonal disturbances, may also receive RRE after assessment and management
of the medical condition. Controlin this context means: normal functioning in daily life.
significant after the first week of RRE administration (Kasper &
Dienel, 2017).
The trials to date, although limited in participant numbers and
often exploratory in design, nonetheless provide promising results
and an encouraging basis for future randomised controlled trials
further investigating the clinical outcomes of RRE in patients with
high symptom load of chronic stress, chronic fatigue and burnout.
Clinical experience of sexual problems in individuals that were
predominately due to stress have been helped by RRE and recent
studies involving male and female stressed rats have confirmed
this finding (Edwards, Eltbogen, & N
oldner, 2017; Edwards, Kumar,
oldner, 2016). RRE has also shown encouraging data in
exploratory studies of diseases that can occur as a consequence
of stress, including depression (Darbinyan et al., 2007) and anxiety
(Bystritsky, Kerwin, & Feusner, 2008).
Safety and tolerability of RRE
RRE presents a very favourable safety profile. In clinical studies, no
serious side effects that could be attributed to RRE were reported
(e.g., Cropley et al., 2015; Edwards et al., 2012; Kasper & Dienel,
2017; Lekomtseva, Zhukova, & Wacker, 2017).
The HMPC monograph on Rhodiola rosea roots and rhizomes
states that there are no known side effects (EMA, 2012). In add-
ition, to date no drug-drug interactions have been reported for
RRE (EMA, 2012).
Treatment recommendation
RRE has the potential to close the treatment gap for clinically rele-
vant stress symptoms, which is due to its dual mode of action
providing both physical and psychological symptom relief, normal-
ising stress hormone levels and increasing energy and its excellent
safety profile. RRE potentially addresses multiple aspects in the
management of stress and burnout:
Prevention of stress symptoms from becoming chronic.
Treatment of stress symptoms.
Prevention of stress-related complications (burnout) and
secondary diseases.
Figure 5 summarises the authorstreatment recommendations
for the use of RRE in various stages of stress.
There is still much to learn about the pathophysiology of stress,
resilience and stress vulnerability, including cellular and cerebral
network mechanisms which are the focus of current research
interests. In parallel to increasing knowledge of these phenom-
ena, additional investigations are needed to further elucidate
the impact of RRE on mechanisms that play a significant role
in stress in the human body. Clinical evidence for the effect of
RRE on stress and stress-related symptoms to date may be lim-
ited to studies of exploratory design; appropriate study popula-
tions are sometimes difficult to define. However, the studies so
far provide promising results, especially in frequently difficult to
treat populations. Further randomised controlled trials are
needed to confirm the promising results of the existing studies
with RRE in patients with symptoms of chronic stress, chronic
fatigue and burnout.
Editorial assistance was provided by H þO communications Ltd.
Disclosure statement
Ion-George Anghelescu has received consulting fees and/or hono-
raria from Schwabe, Boehringer Ingelheim, Otsuka, Janssen,
Lundbeck, Lilly, Medice, Servier and Trommsdorf (I.G. A.).
David Edwards reports honoraria and support within the last
three years from Bayer, Besins, Pfizer and Schwabe.
Erich Seifritz has received consulting fees and/or honoraria
from Schwabe, Otsuka, Janssen, Lundbeck, Eli Lilly, Servier,
Hoffmann La Roche, Vifor, Takeda, Sunovion, Pfizer, Astra Zeneca
and Angelini.
Siegfried Kasper has received grants/research support, consult-
ing fees and/or honoraria within the last three years from
Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly,
Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre
Fabre, Schwabe and Servier.
Funding for this publication was provided by Dr. Willmar Schwabe
GmbH & Co. KG.
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... R. rosea L. is widely used in Chinese traditional medicine to activate blood circulation, unblock blood vessels and enhance mental function (China, 2005), while roots and rhizomes extract increases the body's resistance to stress and exhaustion (Anghelescu et al., 2018). This is mostly attributed to its ability to normalize the release of stress hormones combined with an increase in energy metabolism through the activation of ATP mitochondria synthesis (Abidov et al., 2003;Anghelescu et al., 2018). ...
... R. rosea L. is widely used in Chinese traditional medicine to activate blood circulation, unblock blood vessels and enhance mental function (China, 2005), while roots and rhizomes extract increases the body's resistance to stress and exhaustion (Anghelescu et al., 2018). This is mostly attributed to its ability to normalize the release of stress hormones combined with an increase in energy metabolism through the activation of ATP mitochondria synthesis (Abidov et al., 2003;Anghelescu et al., 2018). ...
... R. rosea L. also raises the levels of dopamine, serotonin, and norepinephrine, and inhibits the AchE activity (Amsterdam & Panossian, 2016;Sharma et al., 2015), so having a great potential for stress management, namely to prevent chronic stress and stress-related complications. (Amsterdam & Panossian, 2016;Anghelescu et al., 2018). Indeed, R. rosea L. extracts are effective, safe, and welltolerated in clinical studies on stress, burnout, and chronic fatigue (Anghelescu et al., 2018). ...
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Objective: To evaluate the effect of salidroside on oxygen and glucose deprivation (OGD)-treated NT2 cells and its underlying mechanisms of action. Methods: Retinoic acid was used to induce the differentiation of NT2 cells into neurons. The effects of salidroside on survival, apoptosis, inflammatory response, and oxidative stress of neurons undergoing OGD were evaluated. Using precursor cells as controls, the effect of salidroside on the differentiation progression of OGD-treated cells was evaluated. In addition, the effect of erastin, a ferroptosis inducer, on NT2 cells was examined to investigate the underlying mechanisms of neuroprotective action of salidroside. Results: Salidroside alleviated the effects of OGD on neuronal survival, apoptosis, inflammation, and oxidative stress, and promoted NT2 cell differentiation. Moreover, salidroside prevented ferroptosis of OGD-treated cells, which was abolished following erastin treatment, indicating that ferroptosis mediated the regulatory pathway of salidroside. Conclusions: Salidroside attenuates OGD-induced neuronal injury by inhibiting ferroptosis and promotes neuronal differentiation.
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The roots and rhizomes of Rhodiola rosea L. (Crassulaceae), which is widely growing in Northern Europe, North America, and Siberia, have been used since ancient times to alleviate stress, fatigue, and mental and physical disorders. Phenolic compounds: phenylpropanoids rosavin, rosarin, and rosin, tyrosol glucoside salidroside, and tyrosol, are responsible for the biological action of R. rosea, exerting antioxidant, immunomodulatory, anti-aging, anti-fatigue activities. R. rosea extract formulations are used as alternative remedies to enhance mental and cognitive functions and protect the central nervous system and heart during stress. Recent studies indicate that R. rosea may be used to treat diabetes, cancer, and a variety of cardiovascular and neurological disorders such as Alzheimer’s and Parkinson’s diseases. This paper reviews the beneficial effects of the extract of R. rosea, its key active components, and their possible use in the treatment of chronic diseases. R. rosea represents an excellent natural remedy to address situations involving decreased performance, such as fatigue and a sense of weakness, particularly in the context of chronic diseases. Given the significance of mitochondria in cellular energy metabolism and their vulnerability to reactive oxygen species, future research should prioritize investigating the potential effects of R. rosea main bioactive phenolic compounds on mitochondria, thus targeting cellular energy supply and countering oxidative stress-related effects.
Background Emergency nurses are experienced specific stress factors. To evaluate stressors of emergency nurses effectively is useful to improve quality of nursing care. This study aimed to translate the stressor scale for emergency nurses into Chinese (C-SSEN) and carry out the reliability and validity test among Chinese emergency nurses. Methods A total of 358 emergency nurses from four hospitals in Tianjin, Henan, and Shandong province of China are recruited through a convenience sampling. The C-SSEN was translated into Chinese applying a classic ‘forward-backward’ translation method. Reliability (internal consistency, test-retest reliability) and validity (content validity, construct validity) were assessed. Results The final version of C-SSEN was rated by the expert panel, indicating good content validity (I-CVI ≥ 0.83, S-CVI = 0.96). The scale had satisfactory content validity, internal consistency (Cronbach’s α coefficient = 0.958), and test-retest reliability (intra-class correlation coefficient = 0.824). Conclusion The C-SSEN is a useful and reliable scale to evaluate stressors among emergency nurses.
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Purpose: This study is the first clinical trial aiming to explore the clinical outcomes in burnout patients treated with Rhodiola rosea. The reported capacity of R. rosea to strengthen the organism against stress and its good tolerability offer a promising approach in the treatment of stress-related burnout. The aim of the treatment was to increase stress resistance, thus addressing the source rather than the symptoms of the syndrome and preventing subsequent diseases associated with a history of burnout. The objective of the trial was to provide the exploratory data required for planning future randomized trials in burnout patients in order to investigate the clinical outcomes of treatment with R. rosea dry extract in this target group. Methods: The study was planned as an exploratory, open-label, multicenter, single-arm trial. A wide range of rating scales were assessed and evaluated in an exploratory data analysis to generate hypotheses regarding clinical courses and to provide a basis for the planning of subsequent studies. A total of 118 outpatients were enrolled. A daily dose of 400 mg R. rosea extract (WS(®) 1375, Rosalin) was administered over 12 weeks. Clinical outcomes were assessed by the German version of the Maslach Burnout Inventory, Burnout Screening Scales I and II, Sheehan Disability Scale, Perceived Stress Questionnaire, Number Connection Test, Multidimensional Mood State Questionnaire, Numerical Analogue Scales for different stress symptoms and impairment of sexual life, Patient Sexual Function Questionnaire, and the Clinical Global Impression Scales. Results: The majority of the outcome measures showed clear improvement over time. Several parameters had already improved after 1 week of treatment and continued to improve further up to the end of the study. The incidence of adverse events was low with 0.015 events per observation day. Discussion: The trial reported here was the first to investigate clinical outcomes in patients suffering from burnout symptoms when treated with R. rosea. During administration of the study drug over the course of 12 weeks, a wide range of outcome measures associated with the syndrome clearly improved. Conclusion: The results presented provide an encouraging basis for clinical trials further investigating the clinical outcomes of R. rosea extract in patients with the burnout syndrome.
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Background: Rhodiola rosea roots and rhizomes are a herbal medicine for temporary relief of stress symptoms such as fatigue and sensed weakness. A daily dosage of 400 mg is recommended. Methods: A dry ethanolic extract of R. rosea (WS® 1375) was studied in 100 subjects with prolonged or chronic fatigue symptoms. In an uncontrolled, open-label multicenter clinical trial, the subjects were administered 2 × 200 mg WS® 1375 over 8 weeks. Outcome measures were scales and tests related to fatigue. They were evaluated in an exploratory data analysis to generate hypotheses regarding efficacy. The pilot character of the trial is marked by its broad focus on subjects suffering from fatigue in general and by its comparatively long duration. Results: The greatest change was observed after 1 week of treatment. The fatigue symptoms continued to decline further, with statistically significant improvement at week 8. The safety assessments of WS® 1375 during the trial proved to be favorable, with most adverse events being of mild intensity and not related to the study drug. Conclusions: The results indicate that 2 × 200 mg WS® 1375 may be an effective treatment in subjects suffering from prolonged or chronic fatigue. The safety and tolerability of WS® 1375 also presented a favorable profile.
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Background: Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic activity predicts risk of subsequent cardiovascular events. Methods: Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent (18)F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally. Amygdalar activity, bone-marrow activity, and arterial inflammation were assessed with validated methods. In a separate cross-sectional study we analysed the relation between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. Image analyses and cardiovascular disease event adjudication were done by mutually blinded researchers. Relations between amygdalar activity and cardiovascular disease events were assessed with Cox models, log-rank tests, and mediation (path) analyses. Findings: 293 patients (median age 55 years [IQR 45·0-65·5]) were included in the longitudinal study, 22 of whom had a cardiovascular disease event during median follow-up of 3·7 years (IQR 2·7-4·8). Amygdalar activity was associated with increased bone-marrow activity (r=0·47; p<0·0001), arterial inflammation (r=0·49; p<0·0001), and risk of cardiovascular disease events (standardised hazard ratio 1·59, 95% CI 1·27-1·98; p<0·0001), a finding that remained significant after multivariate adjustments. The association between amygdalar activity and cardiovascular disease events seemed to be mediated by increased bone-marrow activity and arterial inflammation in series. In the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation (r=0·70; p=0·0083). Perceived stress was associated with amygdalar activity (r=0·56; p=0·0485), arterial inflammation (r=0·59; p=0·0345), and C-reactive protein (r=0·83; p=0·0210). Interpretation: In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings. Funding: None.
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Interleukin-18 (IL18) is a multifunctional cytokine that has been implicated in increased susceptibility to depression; however, the underlying mechanism remains unknown. We found that the IL18 system in the basolateral amygdala (BLA) determined susceptibility to chronic stress. Mice subjected to chronic restraint stress or chronic foot-shock stress demonstrated increased expression of IL18 in the BLA, and exhibited depression-like behaviors, whereas IL18 knockout (KO) mice were resilient to these chronic stresses. IL18 and IL18 receptors in the BLA were expressed in glutamatergic and GABAergic neurons in addition to glial cells. Local inhibition of IL18 and IL18 receptors in the BLA by stereotaxic injection of siRNA-IL18 or siRNA-IL18 receptor-1α was sufficient to suppress stress-induced depression-like behaviors. Following chronic stress, the downstream mediator of IL18 receptor activation, phospho-NF-kB, was increased in BLA neurons expressing IL18 receptors. Furthermore, siRNA-mediated inhibition of NF-kB in the BLA significantly suppressed stress-induced depression-like behaviors, and NF-kB KO mice were resilient to chronic stress. The siRNA-mediated inhibition of NF-kB in the BLA downregulated stress-induced increased expression of Hcrt, MCH, OXT, AVP, and TRH, the neuropeptides that were induced by chronic stress in the BLA and promoted depression-like behaviors. These results suggest that the local IL18 and its receptor system in the BLA function as molecular regulators promoting susceptibility to chronic stress.
Alzheimer's disease (AD) is a complex disorder and the most common form of neurodegenerative dementia. Several genetic, environmental, and physiological factors, including inflammations and metabolic influences, are involved in the progression of AD. Inflammations are composed of complicated networks of many chemokines and cytokines with diverse cells. Inflammatory molecules are needed for the protection against pathogens, and maintaining their balances is important for normal physiological function. Recent studies demonstrated that inflammation may be involved in neurodegenerative dementia. Cellular immune components, such as microglia or astrocytes, mediate the release of inflammatory molecules, including tumor necrosis factor, growth factors, adhesion molecules, or chemokines. Over- and underexpression of pro- and anti-inflammatory molecules, respectively, may result in neuroinflammation and thus disease initiation and progression. In addition, levels of several inflammatory factors were reported to be altered in the brain or bodily fluids of patients with AD, reflecting their neuropathological changes. Therefore, simultaneous detection of several inflammatory molecules in the early or pre-symptomatic stage may improve the early diagnosis of AD. Further studies are needed to determine, how induction or inhibition of inflammatory factors could be used for AD therapies. This review summarizes the role or possible role of immune cells and inflammatory molecules in disease progression or prevention.
Objective There is growing recognition in psychology that wellness is more than the absence of disease and distress. Well‐being has been defined in numerous ways. Two dominant models include Diener, Eunkook, Suh, Lucas and Smith's (1999) model of subjective well‐being (SWB) and Ryff's (1989) model of psychological well‐being (PWB). In contrast to the abundance of research investigating negative constructs and psychopathology in chronic fatigue syndrome (CFS), there has been a paucity of positive psychology studies. This study had two aims: to examine PWB and SWB and their relationship to symptoms in CFS and to compare PWB scores in a subgroup of the CFS sample to a matched control group. Method Chronic fatigue syndrome participants (n = 60) completed self‐report scales of PWB, SWB, fatigue, anxiety and depression. PWB scores in a subgroup of the CFS sample (n = 42) were compared with those of a matched nonclinical control group (n = 42). Results Correlations between scales of symptoms and well‐being were complex. Well‐being dimensions were largely independent of physical components of fatigue but strongly related to psychological components of fatigue and psychological distress. Multiple regression indicated that five dimensions of well‐being uniquely predicted symptomatology. Compared with the control group, the CFS group scored significantly lower on five of Ryff's six PWB dimensions, with particularly marked deficits in personal growth, environmental mastery and self‐acceptance. Conclusion This multidimensional assessment of well‐being advances our understanding of CFS and offers new treatment targets. Future research must investigate whether interventions targeting theses well‐being deficits can boost the efficacy of symptom‐focused treatments. Copyright © 2016 John Wiley & Sons, Ltd. Key Practitioner Messages • Previous psychological research into CFS has largely focused on the identification of negative constructs and CBT, a treatment that targets evidenced‐based negative constructs, has demonstrated efficacy in reducing levels of fatigue and disability. However, the majority of people continue to experience psychiatric symptoms and excessive levels of fatigue post‐treatment. Finding ways to enhance the efficacy of existing treatments is a clinical priority. • There is evidence to suggest that in clinical populations, standard CBT is effective at reducing negative affect and thinking but fails to enhance low levels of positive affect and thinking, implying treatments may be more effective if they promote positive functioning alongside a reduction of negative functioning. • Multidimensional models of well‐being suggest that well‐being is not a single phenomenon, and different psychological disorders may be characterized by varying well‐being deficit profiles. • Psychological well‐being was found to be diminished in CFS participants compared with controls, with particularly marked deficits in personal growth, environmental mastery and self‐acceptance, suggesting that these may be particularly important treatment targets. • Well‐being dimensions within the CFS group were largely independent of physical symptoms but strongly related to psychological symptoms, suggesting what may be causing low levels of well‐being in CFS is largely psychological factors and the general impact of living with a chronic illness rather than symptom levels per se.
Objectives: Chronic Fatigue Syndrome (CFS) is a debilitating condition that affects 0.2-0.4% of the population. First-line treatments are Cognitive Behaviour Therapy or graded exercise therapy; however, these treatments yield only moderate effect sizes. Emerging research suggests that anxiety about health may be common in CFS. Health anxiety treatment models demonstrate good therapeutic outcomes; however, these models have yet to be applied to CFS. This paper describes the application of a novel cognitive behavioural approach to the treatment of both physical and anxiety related symptoms in a patient with CFS and, furthermore, presents a conceptual hypothesis regarding the mutually maintaining relationship between these two co-occurring conditions. Design: A single-case design was used, with pre-data, post-data and follow-up data. The cognitive behavioural model of health anxiety was adapted and delivered as an eight-session intervention. The intervention was driven by an individualized formulation developed collaboratively with the patient. Results: The application of this approach generated reliable and clinically significant reductions in physical and psychological symptoms, which were maintained at 12-month follow-up. The participant no longer fulfilled the criteria for CFS or health anxiety following eight treatment sessions. The treatment approach was found to be agreeable to the patient. All treatment hypotheses were supported. Conclusions: An adapted cognitive behavioural approach to treating CFS and health anxiety yields positive results and shows promise for application to the broader CFS population. Copyright © 2016 John Wiley & Sons, Ltd. Key practitioner messages: Chronic Fatigue Syndrome (CFS) is a debilitating condition that is difficult to treat successfully; first-line recommended treatments achieve only moderate effect sizes. Anxiety, particularly about health, is reported to be common in CFS. However, anxiety is not specifically targeted within treatment and may negatively influence outcome due to the potentially mutually maintaining nature of these complex conditions. The present study demonstrates that an integrated treatment approach designed to encompass physical and psychological symptoms yields reliable and clinically significant outcomes in 50% of time recommend for first line treatments. Results reflected non-case level status for both CFS and health anxiety at end of treatment, in addition to reductions across all clinical measures. This study demonstrates the fundamental importance of an individualized, rather than generic, treatment approach to complex cases; the 'meaning' of experience is a central tenet within a cognitive approach that should be reflected in treatment.