Article

The relationships of working conditions, recent stressors and childhood trauma with salivary cortisol levels

Research Department of Arkin Mental Health Institute, Amsterdam, The Netherlands.
Psychoneuroendocrinology (Impact Factor: 4.94). 10/2011; 37(6):801-9. DOI: 10.1016/j.psyneuen.2011.09.012
Source: PubMed
ABSTRACT
An etiological model has been suggested where stress leads to high cortisol levels and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, resulting in somatic diseases and psychopathology. To evaluate this model we examined the association of different stressors (working conditions, recent life events and childhood trauma) with various cortisol indicators in a large cohort study.
Data are from 1995 participants of the Netherlands Study of Depression and Anxiety (NESDA). Most of the selected participants had a current or remitted anxiety and/or depressive disorder. Working conditions were assessed with self-report questionnaires, life-events and childhood trauma were assessed with interview questionnaires. Cortisol levels were measured in seven saliva samples, determining the 1-h cortisol awakening response (CAR), evening cortisol levels and cortisol suppression after a 0.5mg dexamethasone suppression test (DST).
Regression analyses--adjusted for covariates--showed two significant associations: low social support at work and high job strain were associated with more cortisol suppression after the DST. No other associations were found with any of the cortisol variables.
Working conditions, recent stressors and childhood trauma were not convincingly associated with cortisol levels.

Full-text

Available from: Jack Dekker, Oct 30, 2014
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Models
PNEC-2061;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
Holleman,
M.,
et
al.,
The
relationships
of
working
conditions,
recent
stressors
and
childhood
trauma
with
salivary
cortisol
levels.
Psychoneuroendocrinology
(2011),
doi:10.1016/j.psyneuen.2011.09.012
The
relationships
of
working
conditions,
recent
stressors
and
childhood
trauma
with
salivary
cortisol
levels
Michiel
Holleman
a,
*
,
Sophie
A.
Vreeburg
b
,
Jack
J.M.
Dekker
a,c
,
Brenda
W.J.H.
Penninx
b,d,e
a
Research
Department
of
Arkin
Mental
Health
Institute,
Amsterdam,
The
Netherlands
b
Department
of
Psychiatry,
VU
University
Medical
Center,
Amsterdam,
The
Netherlands
c
Department
of
Clinical
Psychology,
VU,
Amsterdam,
The
Netherlands
d
Department
of
Psychiatry,
Leiden
University
Medical
Center,
Leiden,
The
Netherlands
e
Department
of
Psychiatry,
University
Medical
Center
Groningen,
Groningen,
The
Netherlands
Received
8
March
2011;
received
in
revised
form
19
September
2011;
accepted
21
September
2011
Psychoneuroendocrinology
(2011)
xxx,
xxx—xxx
KEYWORDS
HPA
axis;
Cortisol;
Cortisol
awakening
response;
Dexamethasone
suppression
test;
Stress;
Demand
control
model;
Job
strain;
Life
events;
Childhood
trauma
Summary
Background:
An
etiological
model
has
been
suggested
where
stress
leads
to
high
cortisol
levels
and
hypothalamic—pituitary—adrenal
(HPA)
axis
dysregulation,
resulting
in
somatic
diseases
and
psychopathology.
To
evaluate
this
model
we
examined
the
association
of
different
stressors
(working
conditions,
recent
life
events
and
childhood
trauma)
with
various
cortisol
indicators
in
a
large
cohort
study.
Methods:
Data
are
from
1995
participants
of
the
Netherlands
Study
of
Depression
and
Anxiety
(NESDA).
Most
of
the
selected
participants
had
a
current
or
remitted
anxiety
and/or
depressive
disorder.
Working
conditions
were
assessed
with
self-report
questionnaires,
life-events
and
childhood
trauma
were
assessed
with
interview
questionnaires.
Cortisol
levels
were
measured
in
seven
saliva
samples,
determining
the
1-h
cortisol
awakening
response
(CAR),
evening
cortisol
levels
and
cortisol
suppression
after
a
0.5
mg
dexamethasone
suppression
test
(DST).
Results:
Regression
analyses
adjusted
for
covariates
showed
two
significant
associations:
low
social
support
at
work
and
high
job
strain
were
associated
with
more
cortisol
suppression
after
the
DST.
No
other
associations
were
found
with
any
of
the
cortisol
variables.
Conclusions:
Working
conditions,
recent
stressors
and
childhood
trauma
were
not
convincingly
associated
with
cortisol
levels.
#
2011
Elsevier
Ltd.
All
rights
reserved.
*
Corresponding
author
at:
Research
Department
of
Arkin
Mental
Health
Institute
Amsterdam,
Strekkerweg
77,
1033
DA
Amsterdam,
The
Netherlands.
Tel.:
+31
20
5905295.
E-mail
address:
michiel.holleman@arkin.nl
(M.
Holleman).
Available
online
at
www.sciencedirect.com
j
our
na
l
h
omepa
g
e:
www.e
lse
vie
r.c
om/l
oca
te/
psyne
ue
n
0306-4530/$
see
front
matter
#
2011
Elsevier
Ltd.
All
rights
reserved.
doi:10.1016/j.psyneuen.2011.09.012
Page 1
1.
Introduction
Stress
is
thought
to
lead
to
a
hyperactive
hypothalamus—
pituitary—adrenal
(HPA)
axis
and,
when
chronic,
the
resulting
high
cortisol
levels
may
contribute
to
somatic
diseases
and
psychopathology
(Sapolsky,
1998).
Evidence
for
elevated
cortisol
levels
are
for
example
found
among
persons
with
obesity
or
ischemic
heart
disease
(Reynolds
et
al.,
2010),
hypertension
or
diabetes
mellitus
(Schoorlemmer
et
al.,
2009)
and
atherosclerosis
(Eller
et
al.,
2005;
Dekker
et
al.,
2008).
In
addition,
hyperactivity
of
the
HPA-axis
was
found
among
persons
with
depression
(Vreeburg
et
al.,
2009a)
and
anxiety
disorders
(Vreeburg
et
al.,
2010a).
A
central
assump-
tion
is
that
underlying
stress
exposure
and
experience
are
related
to
altered
HPA
axis
activity.
To
assess
basal
HPA-axis
activity,
salivary
cortisol
mea-
sures
are
often
used.
The
cortisol
awakening
response
(CAR)
reflects
the
natural
response
of
the
HPA-axis
on
awakening
(Wilhelm
et
al.,
2007),
is
associated
with
the
circadian
rhythm
of
cortisol
secretion
and
is
considered
to
be
regulated
in
anticipation
of
demands
of
the
upcoming
day
(Fries
et
al.,
2009).
The
CAR
is
preferable
to
single
morning
cortisol
measurements
since
it
has
a
greater
intra-personal
stability
(Coste
et
al.,
1994;
Wu¨st
et
al.,
2000)
and
is
considered
to
be
a
more
reliable
measure
for
the
acute
reagibility
of
the
HPA-
axis
(Schmidt-Reinwald
et
al.,
1999).
Evening
cortisol
levels
reflect
basal
activity,
whereas
the
dexamethasone
suppres-
sion
test
(DST)
examines
the
reactivity
to
a
pharmacological
challenge
of
the
stress
system.
Prior
studies
have
examined
the
impact
of
various
differ-
ent
types
of
stressors
on
HPA-axis
functioning
in
adulthood.
Stressors
examined
so
far
differ
in
their
recency
and
timing
across
the
lifespan
(e.g.
recent
stressors
versus
stressors
that
occurred
in
early
life)
and
in
their
severity
(traumatic
versus
more
normative),
which
make
research
findings
not
easily
comparable
across
studies.
Moreover,
some
studies
have
indicated
that
chronic
hyperactivity
of
the
HPA-axis
in
response
to
early
chronic
or
traumatic
stressors
results
in
a
possible
adaptational
pattern
of
decreased
cortisol
levels
in
later
life.
This
may
explain
why
also
lower
cortisol
levels
have
been
found
among
persons
with
stress-related
conditions
like
chronic
fatigue
syndrome,
fibromyalgia
and
posttraumatic
stress
disorder
(Heim
et
al.,
2000a;
Fries
et
al.,
2005;
Miller
et
al.,
2007;
Pervanidou,
2008)
and
would
suggest
that
the
impact
of
early-life
stressors
(such
as
childhood
trauma)
may
even
be
reversed
as
compared
to
recent
stressors
that
take
place
in
later
life
(such
as
job
stressors
or
recent
life
stres-
sors)
(Gerritsen
et
al.,
2010).
To
assess
the
negative
effects
of
work
stressors,
the
job
demand-control
model
is
frequently
used.
This
model
assumes
that
job
strain
is
the
combination
of
high
job
demands
with
low
job
control,
also
called
decision
latitude.
Job
strain
has
been
positively
associated
with
morning
corti-
sol
(Steptoe
et
al.,
2000;
Alderling
et
al.,
2006)
and
CAR
levels
(Maina
et
al.,
2009a,b).
The
CAR
also
has
been
posi-
tively
associated
with
high
job
demands
in
men
and
with
low
decision
latitude
in
women
(Maina
et
al.,
2008).
Further-
more,
higher
evening
saliva
cortisol
levels
were
associated
with
high
job
strain
(Rystedt
et
al.,
2008).
In
contrary,
others
found
higher
saliva
cortisol
levels
among
subjects
reporting
low
job
strain
(Steptoe
et
al.,
1998;
Fujiwara
et
al.,
2004).
Also
when
considering
other
theoretical
concepts
for
job
stress
such
as
the
effort—reward
imbalance
model,
overall
results
for
HPA-axis
activity
are
conflicting
(Chandola
et
al.,
2010).
The
clearest
evidence
for
job
characteristics
on
HPA-
axis
activity
in
a
recent
meta-analysis
appeared
to
exist
between
high
job
stressor
levels
and
a
high
CAR
(Chida
and
Steptoe,
2009).
Studies
on
recent
life
events
and
HPA-activity
are
difficult
to
compare,
since
the
assessment
of
life
events
vary
in
time.
Associations
have
been
found
between
increased
morning
cortisol
and
life
events
during
the
last
three
years
(Gerritsen
et
al.,
2010)
and
between
increased
evening
cortisol
and
life
events
within
a
month
but
not
within
six
months
(Strickland
et
al.,
2002).
In
contrast,
another
study
found
no
associations
between
morning
or
evening
cortisol
and
life
events
within
one
to
six
months
(Harris
et
al.,
2000).
It
has
also
been
hypothesized
that
particularly
childhood
trauma
leads
to
alterations
in
HPA-axis
regulation
(Nemeroff,
2004;
Carpenter
et
al.,
2007).
However,
results
are
conflict-
ing.
Some
studies
have
indicated
that
persons
exposed
to
childhood
trauma
in
the
past
have
indications
of
higher
basal
or
reactive
cortisol
levels
later
in
life
(Heim
et
al.,
2001,
2000b,
2008;
Rinne
et
al.,
2002;
Faravelli
et
al.,
2010).
On
the
contrary,
others
showed
negative
childhood
events
to
be
associated
with
lower
morning
or
reactive
cortisol
levels
(Elzinga
et
al.,
2008;
Gerritsen
et
al.,
2010),
which
could
be
explained
by
the
fact
that
adaptational
processes
result
in
hypocortisolism
later
in
life.
These
inconsistent
findings
have
not
been
clearly
explained
yet,
but
it
has
been
hypothesized
that
exact
timing,
severity
of
trauma,
or
co-occurring
psy-
chopathology
such
as
PTSD
or
depressive
disorder
might
play
a
moderating
role
in
the
link
between
trauma
and
HPA-axis
functioning
(Heim
et
al.,
2000b,
2008;
Elzinga
et
al.,
2008).
Taken
together,
there
is
evidence
that
different
types
of
stressors
generally
are
associated
with
HPA-axis
functioning.
Mainly
higher
HPA-axis
activity
has
been
observed
for
recent
stressors
such
as
job
stressors
and
recent
life
events,
but
for
childhood
trauma
both
higher
and
lower
HPA-axis
functioning
have
been
observed.
Since
results
have
not
always
been
consistent,
there
is
a
need
for
further
research.
Studies
on
the
association
of
stressors
and
HPA-activity
with
a
large
cohort
are
scarce,
especially
with
a
broad
set
of
stressors
and
cortisol
measurements
and
covariates.
Therefore,
we
examined
the
relationship
between
work
stressors,
impor-
tant
life
events
and
childhood
trauma
with
various
salivary
cortisol
measures
(cortisol
awakening
response,
evening
level
and
suppression
after
dexamethasone),
correcting
for
detailed
covariates.
2.
Methods
2.1.
Study
sample
Data
are
from
the
Netherlands
Study
of
Depression
and
Anxiety
(NESDA),
a
large
cohort
study
on
the
course
of
depressive
and
anxiety
disorders.
In
total
2981
respondents
participated
in
the
study.
Included
were
652
subjects
with
no
current
or
past
psychiatric
disorders
(‘healthy
controls’)
obtained
through
a
screening
approach
conducted
among
65
general
practitioners,
as
well
as
628
subjects
with
earlier
and
1701
subjects
with
current
episodes
of
depressive
or
+
Models
PNEC-2061;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
Holleman,
M.,
et
al.,
The
relationships
of
working
conditions,
recent
stressors
and
childhood
trauma
with
salivary
cortisol
levels.
Psychoneuroendocrinology
(2011),
doi:10.1016/j.psyneuen.2011.09.012
2
M.
Holleman
et
al.
Page 2
anxiety
disorder.
The
latter
group
was
recruited
through
the
community,
the
general
practitioner
practices
using
a
screening
approach
as
well
as
through
outpatient
mental
health
care
settings
in
order
to
recruit
a
representative
cohort
of
patients
reflecting
all
treatment
settings.
Psychia-
tric
diagnoses
were
established
by
using
the
lifetime
version
2.1
of
the
Composite
Interview
Diagnostic
Instrument
(CIDI,
Wittchen,
1994).
Across
recruitment
setting,
uniform
in-
and
exclusion
criteria
were
used.
A
general
inclusion
criterion
was
an
age
of
18
through
65
years.
In
order
to
maintain
representativity,
only
two
exclusion
criteria
used:
(1)
a
primary
clinical
diagnosis
of
a
psychiatric
disorder
not
sub-
ject
of
NESDA
which
will
largely
affect
course
trajectory
such
as
psychotic
disorder,
obsessive
compulsive
disorder,
bipolar
disorder,
or
severe
addiction
disorder,
and
(2)
not
being
fluent
in
Dutch
since
language
problems
would
harm
the
validity
and
reliability
of
collected
data.
For
objectives
and
more
on
methods
of
NESDA
see
Penninx
et
al.
(2008).
The
research
protocol
was
approved
by
the
Ethical
Commit-
tee
of
participating
universities
and
all
respondents
provided
written
informed
consent.
We
subsequently
excluded
a
total
of
19
pregnant
or
breast-
feeding
women,
113
participants
on
corticosteroids
and
71
participants
on
tricyclic
antidepressants
because
of
their
demonstrated
effects
on
the
HPA-axis,
leaving
a
sample
of
2778
participants.
Of
these
2000
(72.0%)
returned
saliva
sam-
ples,
of
whom
1829
(90.6%)
returned
all
seven
samples,
131
(6.5%)
six,
24
(1.2%)
five
and
16
(0.7%)
four
samples
or
less.
Responders
on
saliva
collection
did
not
differ
from
non-respon-
ders
in
gender,
job
stressors
and
childhood
trauma
exposure,
but
were
older
(43.6
versus
38.3
years,
p
<
.001),
more
edu-
cated
(12.3
versus
11.8
years,
p
<
.001),
had
less
negative
life
events
the
past
year
(0.59
versus
0.74,
p
<
.001)
and
were
less
likely
to
have
an
anxiety
disorder
(41.0%
versus
49.7%, p
<
.001)
or
depressive
disorder
(38.6%
versus
46.0%,
p
<
.001).
2.2.
Measurements
2.2.1.
Stressors
2.2.1.1.
Working
conditions
and
work
stress.
Only
partici-
pants
currently
working
at
least
8
h
a
week
(63.2%)
were
included
for
analysis
on
working
conditions.
Based
on
Kar-
asek’s
demands/control
model,
perceived
working
condi-
tions
were
measured
with
a
Dutch
questionnaire
based
on
the
Job
Content
Questionnaire
(Houtman,
1995).
The
ques-
tionnaire
consisted
of
29
dichotomous
items,
forming
five
scales:
job
demands
(5
items;
Cronbach’s
a
=
.77),
decision
latitude
or
job
control
(13
items;
Cronbach’s
a
=
.78),
social
support
at
work
(8
items;
Cronbach’s
a
=
.83)
and
job
inse-
curity
(3
items;
Cronbach’s
a
=
.78).
Job
strain
is
based
on
the
median
split
of
job
demands
and
decision
latitude.
Conform
the
‘quadrant’
definition,
participants
perceiving
high
job
strain
(high
demands
combined
with
low
decision
latitude)
were
distinguished
from
the
others,
forming
a
dichotomous
variable
(Landsbergis
et
al.,
1994).
2.2.1.2.
Important
life
events.
The
number
of
important
life
events
during
the
past
year,
were
recorded
by
an
inter-
view
with
the
list
of
threatening
experiences
containing
12
life
event
categories
with
long-term
contextual
threat
plus
the
possibility
to
declare
an
‘other’
category
(Brugha
et
al.,
1985).
Defined
categories
were
a
serious
illness
or
injury
to
subject;
serious
illness
or
injury
to
a
close
relative;
death
of
first-degree
relative;
death
of
close
family
friend
ore
second-
degree
relative;
separation
due
to
marital
difficulties;
broke
off
a
steady
relationship;
serious
problem
with
a
close
friend,
neighbor
or
relative;
unemployed
or
seeking
work
for
more
than
one
month;
subject
sacked
from
job;
major
financial
crisis;
problems
with
police
and
court
appearance;
something
valuable
lost
or
stolen.
2.2.1.3.
Childhood
trauma.
Traumas
during
childhood
were
inventoried
by
a
structured
interview
using
the
NEMESIS
questionnaire
(de
Graaf
et
al.,
2002).
Respondents
were
asked
whether
they
had
experienced
emotional
neglect,
psychological
abuse,
physical
abuse
or
sexual
abuse
on
one
or
more
occasions
before
the
age
of
16.
Respondents
were
asked
to
report
these
adversities
with
the
questions:
‘Do
you
consider
that
in
your
case
you
can
speak
of
emotional
neglect?
psychological
abuse?
physical
abuse?
sexual
abuse?’
Emotional
neglect
was
described
to
respondents
as:
‘At
home
one
did
not
listen
to
you,
your
experiences
or
problems
were
ignored,
you
felt
that
you
could
not
get
your
parent’s
attention
and
support.’
Psychological
abuse
was
described
as:
‘‘You
were
cursed,
unjustly
punished,
your
brothers
and
sisters
were
favored
or
you
were
cheated
on.’
Physical
abuse
was
described
as:
‘‘You
were
kicked,
hit
with
or
without
an
object,
or
you
were
physically
mal-
treated
in
any
other
way.’
Sexual
abuse
was
defined
as:
‘‘You
were
sexually
touched
against
your
will,
or
you
were
forced
to
sexually
touch
the
other.’
On
each
category
participant
were
also
asked
how
often
these
adversities
occurred
by
choosing
between:
‘once,
sometimes,
regularly,
often
and
very
often’’.
We
considered
the
experience
of
an
adversity
more
than
once
(i.e.
sometimes
or
more
often)
as
an
indica-
tion
for
the
presence
of
a
childhood
trauma
as
compared
to
no
abuse
or
once.
In
line
with
van
Harmelen
et
al.
(2010),
we
defined
childhood
emotional
abuse
as
the
presence
of
emo-
tional
neglect
or
psychological
abuse
more
than
once
(i.e.
sometimes
or
more
often)
as
compared
to
no
abuse.
Besides
considering
the
types
of
childhood
trauma
as
described
above,
also
a
cumulative
index,
called
childhood
trauma
index,
was
calculated
as
the
sum
of
experienced
number
and
frequency
(0
never,
1
once
or
sometimes,
2
regularly
to
very
often)
of
childhood
trauma
for
each
parti-
cipant
ranging
from
0
to
8
(Wiersma
et
al.,
2009).
In
our
earlier
studies,
we
described
associations
between
childhood
abuse
with
anxiety
and
depression,
(Hovens
et
al.,
2010)
chronicity
of
depression
(Wiersma
et
al.,
2009)
and
inde-
pendent
of
psychopathology
reduced
medial
prefrontal
cortex
volume
(van
Harmelen
et
al.,
2010).
2.2.2.
Salivary
cortisol
As
described
in
more
detail
elsewhere
(Vreeburg
et
al.,
2009a),
respondents
were
instructed
to
collect
saliva
sam-
ples
at
home
on
a
regular
(working)
day
shortly
after
the
interview.
The
median
time
between
the
interview
and
saliva
sampling
was
9
days
(25th—75th
percentile:
5—23).
The
median
time
between
saliva
sampling
and
the
job
content
questionnaire
was
2
days
(25th—75th
percentile:
0—10).
Saliva
samples
were
obtained
using
Salivettes
(Sarstedt,
Germany)
at
seven
time
points;
at
awakening
(T1)
and
30
(T2),
45
(T3)
and
60
(T4)
min
later,
at
2200
h
(T5)
and
2300
h
(T6),
and
the
next
morning
at
awakening
(T7)
after
ingestion
+
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PNEC-2061;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
Holleman,
M.,
et
al.,
The
relationships
of
working
conditions,
recent
stressors
and
childhood
trauma
with
salivary
cortisol
levels.
Psychoneuroendocrinology
(2011),
doi:10.1016/j.psyneuen.2011.09.012
Work,
recent
stress,
childhood
trauma
and
salivary
cortisol
3
Page 3
of
0.5
mg
dexamethasone,
taken
directly
after
the
saliva
sample
at
2300
h
(T6).
After
return
by
mail,
samples
were
stored
at
80
8C.
Cortisol
analysis
was
performed
by
com-
petitive
electrochemiluminescence
immunoassay
(E170
Roche,
Switzerland).
The
functional
detection
limit
was
2.0
nmol/l
and
the
intra-
and
interassay
variability
coeffi-
cients
in
the
measuring
range
were
less
than
10%.
In
data
cleaning,
missings
were
assigned
to
cortisol
values
>2
SDs
above
the
mean.
This
way
we
eliminated
respectively
12
(0.6%),
24
(1.2%),
31
(1.6%),
23
(1.2%),
16
(0.8%),
12
(0.6%)
and
13
(0.7%)
samples
from
T1
to
T7.
2.2.2.1.
1-h
awakening
cortisol.
We
calculated
the
area
under
the
curve
with
respect
to
the
increase
(AUCi)
and
with
respect
to
the
ground
(AUCg)
(Pruessner
et
al.,
2003).
The
AUCg
is
an
estimate
of
the
total
cortisol
secretion
and
predicts
mean
cortisol
levels
throughout
the
day,
whereas
the
AUCi
is
a
measu re
of
the
dynamic
of
the
cortisol
awaken-
ing
response
(CAR),
more
related
to
the
sensitivity
of
the
system,
emphasizing
changes
over
time
(Schmidt-Reinwald
et
al.,
1999;
Edwards
et
al.,
2001;
Pr uess ner
et
al.,
2003;
Fekedulegn
et
al.,
2007).
Morning
cortisol
analyses
included
all
persons
with
four
valid
morni ng
cortisol
values
(n
=
1680).
2.2.2.2.
Evening
cortisol.
Since
cortisol
levels
at
22h00
and
23h00
strongly
correlated
(r
=
0.74,
p
<
.01),
we
used
the
mean
of
both
cortisol
levels
(n
=
1984).
2.2.2.3.
Dexamethasone
suppression
test
(DST).
This
test
provides
information
on
the
negative
feedback
system
of
the
HPA-axis,
since
dexamethasone
reduces
cortisol
level
by
acting
on
the
pituitary
(Carroll
et
al.,
1981).
Sample
T7
was
provided
by
1916
subjects.
Of
these,
1870
subjects
reported
they
had
taken
the
0.5
mg
dexamethasone.
As
an
indicator
for
suppression
a
cortisol
suppression
ratio
(T1/T7)
was
calculated
(n
=
1845).
In
sum,
1995
respondents
provided
at
least
one
usable
saliva
measurement
and
constitute
the
present
study
sample.
2.2.3.
Covariates
Effects
of
sociodemographics
(sex,
age),
sampling
factors
(awakening
time,
working,
season,
sleep
duration)
and
health
indicators
(cardiovascular
disease,
physical
activity
and
smoking)
on
salivary
cortisol
variables
are
found
in
former
analyses
of
our
data
(Vreeburg
et
al.,
2009a).
These
identified
determinants
are
considered
as
covariates.
Respondents
reported
time
of
awakening
and
working
status
(yes/no)
on
the
sampling
day.
Season
was
categorized
in
less
(October
through
February)
and
more
daylight
(March
through
September)
months.
Average
sleep
duration
during
the
past
four
weeks
was
dichotomized
as
<
=
6
or
>
6
h/
night,
and
smoking
status
as
current
versus
no
smoker.
Physical
activity
was
assessed
using
the
International
Physical
Activity
Questionnaire
and
expressed
in
1000
MET-minutes
(metabolic
energy
turnover
per
minute)
a
week
(Craig
et
al.,
2003).
Cardiovascular
disease
(CVD)
included
stroke,
angina
pectoris,
myocardial
infarction,
percutaneous
transluminal
coronary
angioplasty
and
coronary
artery
bypass
grafting
and
was
adjudicated
using
standardized
algorithms
considering
self-report
and
medication
use
(based
on
drug
container
inspection
and
ATC
coding).
3.
Statistical
analyses
AUCg
and
AUCi
showed
normal
distributions.
The
distribution
of
evening
cortisol
and
DST
were
skewed
and
therefore
log-
transformed
for
analyses.
Multivariable
linear
regression
analyses
were
performed;
each
stressor
was
entered
in
separate
analyses
without
and
with
adjustment
for
covari-
ates.
Since
we
earlier
described
increased
CAR
and
evening
cortisol
levels
among
persons
with
depressive
and
anxiety
disorders
(Vreeburg
et
al.,
2009b,
2010a)
we
verified
whether
adding
psychopathology
as
covariate
(yes
or
no
having
a
current
diagnosis
of
depressive
or
anxiety
disorder)
or
adding
an
interaction
term
of
psychopathology
*
stressor
made
a
difference.
Analyses
were
conducted
using
SPSS
version
15.0.
4.
Results
Sample
characteristics
of
the
1995
respondents
are
pre-
sented
in
Table
1.
The
mean
age
was
43.1
years
(SD
=
13.1,
range
18—65)
and
65.1%
was
female.
1261
persons
(63.2%)
were
employed
during
the
period
of
the
interview
and
1234
worked
on
the
day
of
cortisol
sampling.
1516
persons
(76%)
had
a
current
or
remitted
depression
and/or
anxiety
disorder.
In
Table
2
the
results
of
the
multivariable
regression
analyses
are
presented.
Unadjusted
and
adjusted
analyses
yielded
largely
similar
results.
Adjusted
analyses
found
sig-
nificant
associations
for
social
support
at
work
and
cortisol
suppression
after
dexamethasone
ingestion
(b
=
.06,
p
=
.05)
suggesting
that
persons
with
more
social
support
are
less
likely
to
suppress
cortisol
after
dexamethasone
ingestion.
A
similar
type
of
association
was
found
for
job
strain
with
cortisol
suppression
(b
=
.06,
p
=
.03),
suggesting
that
persons
with
more
job
strain
are
more
likely
to
suppress
cortisol
after
dexamethasone
ingestion.
None
of
the
other
stressors
showed
any
association
with
cortisol
variables.
We
checked
whether
adding
a
variable
for
depressive
or
anxiety
disorders
(which
we
previously
associated
with
higher
CAR
and
evening
cortisol
levels
(Vreeburg
et
al.,
2009a,
2010a))
changed
any
of
our
reported
findings
in
Table
2.
However,
no
different
associations
emerged.
In
addition,
we
could
not
demonstrate
the
presence
of
moderation
by
psychopathology
since
entering
stressor
*
psychopathology
interaction
terms
did
not
yield
any
significant
interaction
terms
for
the
four
cortisol
outcomes.
4.1.
Post
hoc
analyses
We
checked
whether
the
impact
of
job
strain
would
be
stron-
ger
when
this
variable
was
calculated
as
a
continuous
variable
by
using
the
quotient
method
that
divides
job
demands
by
decision
latitude.
For
this
continuous
indicator,
we
could
not
confirm
any
significant
associations
with
cortisol
variables.
Since
it
has
been
shown
that
age
and
gender
may
have
an
impact
on
the
relation
between
stress
and
cortisol
(Kudielka
et
al.,
2004;
Otte
et
al.,
2005)
we
systematically
tested
for
potential
gender
and
age
interactions
in
our
results.
We
added
gender
*
stressor
and
age
*
stressor
interaction
terms
for
all
stressor
variables
examined
(n
=
10)
for
each
of
the
four
main
cortisol
variables
(AUCg,
AUCi,
Evening,
DST).
Only
four
of
the
80
interaction
terms
yielded
significant
findings,
+
Models
PNEC-2061;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
Holleman,
M.,
et
al.,
The
relationships
of
working
conditions,
recent
stressors
and
childhood
trauma
with
salivary
cortisol
levels.
Psychoneuroendocrinology
(2011),
doi:10.1016/j.psyneuen.2011.09.012
4
M.
Holleman
et
al.
Page 4
which
is
what
can
be
expected
on
the
basis
of
statistical
chance
alone.
Consequently,
we
conclude
that
there
was
no
convincing
evidence
for
gender
or
age
interaction
in
the
impact
of
stressors
on
HPA-axis
functioning.
Subsequently,
we
tested
whether
the
impact
of
early
life
adversity
could
have
created
vulnerability
for
later
stressor
exposures
as
suggested
by
Heim
et
al.
(2002)
and
Elzinga
et
al.
(2008).
For
this
purpose,
we
tested
six
interaction
terms
for
the
childhood
trauma
index
with
5
job
stressor
variables
and
the
recent
life
event
variable.
Significant
interactions
were
found
for
childhood
trauma
index
with
decision
latitude
on
evening
cortisol
(b
=
.25,
p
=
.004),
the
AUCi
(b
=
.23,
p
=
.02)
and
AUCg
(b
=
.21,
p
=
.03),
of
the
childhood
trauma
index
with
social
support
on
AUCi
(b
=
.19,
p
=
.01)
and
AUCg
(b
=
.21,
p
=
.001)
and
of
the
childhood
trauma
index
with
job
demands
on
AUCi
(b
=
.13,
p
=
.03).
Those
with
more
childhood
trauma
had
lower
cortisol
values
when
reporting
more
job
demands
and
higher
cortisol
values
when
experiencing
job
control
or
social
support
at
work.
5.
Discussion
This
study
examined
the
association
of
working
conditions
and
stressors
with
HPA
axis
activity,
while
adjusting
for
important
covariates.
Overall,
we
observed
few
significant
associations,
suggesting
that
the
stressors
examined
were
not
convincingly
related
to
salivary
cortisol
levels.
The
only
significant
associations
after
adjustment
for
covariates
were
found
for
low
social
support
at
work
and
high
job
strain
with
more
cortisol
suppression
after
dexamethasone
ingestion.
However,
in
this
large
cohort
study
where
we
examined
ten
stressors
on
four
cortisol
outcomes,
two
results
with
a
p-value
under
the
significance
threshold
of
.05
is
what
can
be
expected
on
the
basis
of
chance.
Consequently,
this
study
could
not
convincingly
confirm
associations
between
various
types
of
stressors
with
HPA-axis
functioning.
Earlier
results
of
studies
on
the
association
of
work
stres-
sors
with
HPA
axis
activity
have
not
been
consistent,
but
associations
of
high
job
strain
have
been
found
with
an
elevated
CAR,
higher
morning
cortisol
or
evening
cortisol
(Steptoe
et
al.,
2000;
Alderling
et
al.,
2006;
Rystedt
et
al.,
2008;
Maina
et
al.,
2009a,
2009b).
Others
found
inverse
associations
(Steptoe
et
al.,
1998;
Fujiwara
et
al.,
2004).
Most
of
these
studies
were
not
based
on
a
large
population
but
had
specific
populations
(e.g.
only
call-center
employ-
ees),
which
makes
them
hard
to
compare
to
our
study
sample.
Also,
most
studies
did
not
consider
such
a
broad
spectrum
of
covariates,
although
we
also
could
not
reveal
many
associations
in
unadjusted
analyses.
In
a
meta-analysis
of
the
CAR
and
psychosocial
factors,
Chida
and
Steptoe
(2009)
found
a
positive
association
between
job
stressor
level
and
the
CAR.
They
also
observed
a
negative
association
between
the
CAR
and
fatigue,
burn
out
and
exhaustion,
which
could
explain
our
null
finding
since
we
did
not
include
these
factors
in
our
study.
We
should
acknowledge
that
a
reason
for
our
null
findings
might
also
be
that
retrospective
measurements
of
work
stressor
may
not
be
very
reliable,
since
in
a
study
of
Metzenthin
et
al.
(2009)
salivary
cortisol
levels
seemed
to
be
more
related
to
subjective
work
stress
when
rated
at
the
time
of
salivary
sampling
than
when
rated
retrospectively.
With
respect
to
aberrant
HPA
axis
activity
reflected
by
differences
in
the
amount
of
suppression
after
dexametha-
sone
ingestion,
we
did
find
two
significant
associations
with
persons
reporting
less
social
support
and
reporting
high
job
strain
showed
more
cortisol
suppression.
In
light
of
the
many
associations
we
explored,
these
associations
should
be
con-
sidered
as
null
findings.
Nevertheless,
it
is
interesting
to
relate
them
to
earlier
literature.
Hypersuppression
after
dexamethasone
ingestion
suggests
increased
sensitivity
of
the
HPA
axis
to
negative
feedback
and
is
hypothesized
to
be
a
mechanism
behind
hypocortisolism,
possibly
after
chronic
stress
(Heim
et
al.,
2000a).
Although
to
our
knowledge
there
is
no
comparable
study
on
the
relationship
of
job
+
Models
PNEC-2061;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
Holleman,
M.,
et
al.,
The
relationships
of
working
conditions,
recent
stressors
and
childhood
trauma
with
salivary
cortisol
levels.
Psychoneuroendocrinology
(2011),
doi:10.1016/j.psyneuen.2011.09.012
Table
1
Sample
characteristics;
N
=
1995.
%
Female
65.1
Age
(mean
years,
SD)
43.2
(13.1)
Years
of
education
(mean,
SD)
12.4
(3.3)
Time
of
awakening
(mean,
SD)
7h30
(1h12)
%
Employed
63.2
%
Working
on
a
day
of
sampling
59.1
%
sampling
in
month
with
more
daylight
55.0
%
6
h
of
sleep
30.1
%
Smoking
33.1
Physical
activity
(mean
MET-minutes
1000,
SD)
3.7
(3.1)
%
Cardiovascular
disease
5.2
Psychopathology
%
Lifetime
depression
and/or
anxiety
76.0
%
Current
depression
and/or
anxiety
a
54.7
Dystymia
8.7
MDD
33.8
Social
phobia
21.3
Panic
disorder
20.1
GAD
13.2
Stress
indicators
Number
of
negative
life
events
in
the
past
year
%
One
event
22.6
%
Tw o
or
more
events
4.7
%
Job
strain
(high
demands
with
low
control)
b
25.5
%
Childhood
emotional
abuse
39.1
%
Childhood
physical
abuse
11.8
%
Childhood
sexual
abuse
9.6
Cortisol
characteristics
Cortisol
awakening
response
(CAR)
AUCg
(mean,
SD)
19.1
(7.0)
AUCi
(mean,
SD)
2.3
(6.3)
Evening
cortisol
Mean
evening
cortisol
(mean,
SD)
5.4
(3.4)
Dexamethasone
suppression
test
Cortisol
suppression
ratio
(mean,
SD)
c
2.8
(1.7)
Abbreviations:
SD
=
standard
deviation,
MET-minutes
=
meta-
bolic
energy
turnover
per
minute,
AUCg
=
area
under
the
morning
curve
with
respect
to
the
ground,
AUCi
=
area
under
the
morning
curve
with
respect
to
the
increase.
a
Current
depression
and/or
anxiety
during
the
past
six
months.
b
Percentage
of
employed
participants
N
=
1261.
c
Cortisol
suppression
ratio
=
cortisol
at
awakening/cortisol
at
awakening
after
dexamethasone
ingestion.
Work,
recent
stress,
childhood
trauma
and
salivary
cortisol
5
Page 5
characteristics
and
DST,
Pruessner
et
al.
(1999)
did
find
an
association
of
burnout
with
more
suppression.
Burnout
might
be
seen
as
a
consequence
of
chronic
work
stressors
(Maslach
and
Jackson,
1981).
It
is
likely
that
a
considerable
part
of
the
persons
in
our
study
with
low
social
support
and
high
job
strain
might
have
suffered
from
chronic
burnout
feelings,
and
therefore
the
two
significant
associations
we
found
could
be
in
line
with
earlier
findings
that
especially
chronic
work
stressors
are
associated
with
more
suppression
after
DST
(Miller
et
al.,
2007).
Despite
all
this,
we
have
to
acknowledge
that
in
line
with
our
overall
interpretation
of
null
findings
a
recent
review
could
not
show
evidence
that
work
stress
measured
longitudinally
was
associated
with
lower
cortisol
reactivity
(Chandola
et
al.,
2010).
With
respect
to
recent
life
events
we
did
not
find
any
associations
with
the
cortisol
measurements.
This
is
in
con-
cordance
with
another
study
(Harris
et
al.,
2000),
but
others
did
find
associations
for
morning
cortisol
or
evening
cortisol
(Strickland
et
al.,
2002;
Gerritsen
et
al.,
2010).
Results
with
former
studies
are
difficult
to
compare
since
they
all
use
different
criteria
for
the
recency
definition
of
life
events,
ranging
from
one
month
to
three
years,
which
may
add
to
heterogeneity
of
findings.
Cortisol
levels
might
be
heigh-
tened
during
a
stressful
episode
and
with
the
passage
of
time
the
body
might
counter-regulate,
resulting
in
cortisol
levels
below
normal
(Miller
et
al.,
2007).
It
could
theoreti-
cally
be
that
higher
cortisol
levels
of
persons
with
very
recent
life
events
(e.g.
one
month
ago)
are
mixed
with
low
to
normal
cortisol
levels
of
persons
who
experienced
less
recent
events
(e.g.
eleven
months
ago),
leaving
no
overall
correlation
between
cortisol
levels
and
life
events.
This
idea
can
be
supported
by
Strickland
et
al.
(2002)
who
found
increased
evening
cortisol
with
life-events
within
the
past
month
and
not
with
life-events
that
occurred
longer
than
six
months
ago.
Another
explanation
for
our
null
findings
for
recent
life
events,
may
be
that
the
life
events
considered
were
either
too
diffuse
or
integrating
life
events
that
had
not
resulted
in
high
enough
levels
of
stress
experience.
Finally,
we
could
also
not
confirm
that
recent
life
events
become
more
important
for
HPA-axis
functioning
when
a
person
has
been
exposed
to
childhood
trauma,
since
no
convincing
evidence
for
interac-
tions
between
childhood
and
recent
stressors
were
found.
For
the
relationship
of
childhood
trauma
with
HPA
axis
activity
we
did
not
find
any
significant
results
while
others
found
higher
basal
or
reactive
cortisol
levels
later
in
life
(Heim
et
al.,
2000b,
2001;
Rinne
et
al.,
2002;
Heim
et
al.,
2008;
Faravelli
et
al.,
2010)
or
lower
morning
or
reactive
cortisol
levels
(Elzinga
et
al.,
2008;
Gerritsen
et
al.,
2010).
Also,
here
the
outcomes
of
earlier
studies
are
conflicting,
not
based
on
large
populations
and
furthermore
difficult
to
compare
since
various
studies
were
based
on
specific
psy-
chiatric
populations
(e.g.
PTSD).
In
our
earlier
studies,
we
described
associations
between
childhood
abuse
with
anxiety
and
depression
(Hovens
et
al.,
2010),
chronicity
of
depres-
sion
(Wiersma
et
al.,
2009)
and
independent
of
psycho-
pathology
reduced
medial
prefrontal
cortex
volume
(van
Harmelen
et
al.,
2010).
Considering
these
findings,
we
do
not
have
reasons
to
doubt
the
childhood
trauma
assessment
validity.
Also
considering
that
unadjusted
analyses
did
not
reveal
associations
either,
we
believe
that
childhood
trauma
in
our
study
truly
did
not
impact
on
HPA-axis
functioning.
However,
it
remains
to
be
determined
in
other
studies
+
Models
PNEC-2061;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
Holleman,
M.,
et
al.,
The
relationships
of
working
conditions,
recent
stressors
and
childhood
trauma
with
salivary
cortisol
levels.
Psychoneuroendocrinology
(2011),
doi:10.1016/j.psyneuen.2011.09.012
Table 2 Results of multivariable analyses associating stress measurements with cortisol indicators
a
: regression coefficients (b) and p-values.
AUCg AUCi Evening DST
Unadjusted Adjusted
a
Unadjusted Adjusted
a
Unadjusted Adjusted
a
Unadjusted Adjusted
a
Working conditions b p b p b p b p b p b p b p b p
N = 1048 N = 1048 N = 1252 N = 1174
Job demands .05 .09 .02 .49 .00 .95 .03 .33 .05 .08 .03 .21 .04 .13 .05 .08
Social support .04 .14 .03 .27 .01 .80 .01 .75 .04 .19 .01 .78 .04 .17 .06 .05
Job insecurity .04 .15 .00 .95 .04 .17 .03 .42 .00 1.00 .01 .78 .02 .49 .03 .34
Decision latitude .00 .96 .05 .14 .04 .14 .05 .11 .01 .66 .00 .94 .04 .18 .04 .12
Job strain .02 .45 .01 .76 .00 .92 .01 .80 .04 .17 .03 .31 .05 .07 .06 .03
N = 1680 N = 1680 N = 1984 N = 1845
No. negative life events .00 .98 .02 .49 .02 .51 .02 .36 .00 .88 .00 .87 .01 .56 .01 .62
Emotional abuse .05 .04 .04 .09 .01 .56 .01 .61 .03 .18 .01 .68 .01 .61 .00 .85
Physical abuse .00 .92 .01 .75 .02 .38 .02 .42 .04 .11 .01 .53 .03 .25 .02 .40
Sexual abuse .02 .42 .00 .96 .01 .79 .01 .60 .04 .07 .00 .84 .02 .34 .03 .19
Trauma index .04 .08 .02 .43 .01 .64 .00 .87 .05 .03 .01 .72 .01 .63 .00 .96
Abbreviations: AUCg = area under the morning curve with respect to the ground, AUCi = area under the morning curve with respect to the increase, Evening = mean cortisol at 22h00 and/or
23h00, DST = cortisol suppression ratio (salivary cortisol T1/salivary cortisol T7).
a
Adjusted for sex, age, education, working, time of awakening, sleep, month with more daylight, smoking, physical activity, and cardiovascular disease.
6
M.
Holleman
et
al.
Page 6
whether
exact
timing
and
severity
of
childhood
trauma,
or
co-occurring
psychopathology
such
as
PTSD
might
play
a
moderating
role
(Heim
et
al.,
2000a,
2002,
2008;
Elzinga
et
al.,
2008).
It
has
also
been
hypothesized
that
particularly
the
inter-
action
of
childhood
trauma
with
recent
stressors
is
important
for
the
reactivity
of
the
HPA-axis
(Heim
et
al.,
2002;
Elzinga
et
al.,
2008).
Based
on
earlier
findings,
higher
as
well
as
lower
cortisol
levels
might
be
expected
when
persons
with
child-
hood
trauma
are
exposed
to
recent
stressors.
Our
post-hoc
analyses
suggested
that
persons
with
more
occurrence
of
childhood
trauma
had
a
lower
CAR
or
evening
cortisol
levels
when
reporting
more
demands
or
less
decision
latitude
or
less
social
support
at
work.
The
presence
of
five
out
of
24
sig-
nificant
interactions
although
slightly
more
than
to
be
expected
could
still
implicate
null
findings.
Alternative
explanations
that
deserve
further
future
exploration
could
be
that
these
blunted
associations
are
due
to
underlying
genetic
or
psychological
interactions
since
genetic
factors
and
personality
or
coping
styles
may
play
a
role
in
the
individual
sensitivity
to
life
events
(Bet
et
al.,
2009).
Also,
a
blunted
association
might
reflect
consequences
of
chronic
stress
exposure
since
childhood
trauma
is
associated
with
a
variety
of
psychosocial
stressors
later
in
life
(Kendall-Tack-
ett,
2002).
In
a
previous
study
with
the
same
sample,
we
observed
a
higher
CAR
in
persons
with
remitted
as
well
as
current
MDD
and
panic
disorder
(Vreeburg
et
al.,
2009b,
2010a).
There-
fore,
a
higher
cortisol
awakening
curve
might
represent
a
trait
indicator
for
affective
disorders
potentially
already
present
before
the
onset
of
these
disorders.
This
would
suggest
that
underlying
genetic
vulnerability
could
be
responsible
for
these
earlier
observations,
which
is
in
line
with
the
finding
that
also
healthy
controls
with
a
family
history
of
affective
disorders
already
showed
an
elevated
CAR
similar
to
patients
(Vreeburg
et
al.,
2010b).
The
present
findings
suggest
that
exposure
to
stressors
does
not
further
differentiate
HPA-axis
function
in
our
sample.
It
could
be
that
stressors
have
more
impact
on
HPA-axis
functioning
in
healthy
controls
who
do
not
have
the
same
underlying
increased
genetic
vulnerability.
The
absence
of
significant
psychopathology
*
stressor
interaction
terms
in
our
study
does
not
provide
evidence
for
this
suggestion.
Also
earlier
findings
are
inconsistent
with
this
suggestion
since
Strickland
et
al.
(2002)
did
not
find
different
association
in
depressed
or
non-depressed
persons,
and
both
Heim
et
al.
(2000b,
2008)
and
Yehuda
et
al.
(2004)
found
stronger
effects
among
depressed
patients.
To
our
knowledge,
our
study
is
unique
with
respect
to
its
large
cohort
and
our
extensive
assessment
of
stressors
and
cortisol
variables
as
well
as
covariates.
However,
our
study
also
had
some
limitations.
First,
non-compliance
with
the
sampling
instructions
or
dexamethasone
ingestion
could
have
resulted
in
measurement
error,
which
may
have
led
to
under-
estimation
of
associations.
However,
it
should
be
noted
that
even
when
awakening
is
closely
monitored,
still
at
least
15%
of
all
persons
do
not
respond
with
a
cortisol
rise
(Dockray
et
al.,
2008).
We
checked
for
compliance
to
the
DST
test
in
a
subset
of
our
cohort
by
measuring
dexamethasone
levels
with
a
radioimmunoassay
using
the
anti-dexamethasone
antibody
from
IgG
Corporation
(Nashville,
TN,
functional
detection
limit
is
0.4
nmol/l
and
reported
cross-reactivity
for
cortisol
is
.04%
(Weijtens
et
al.,
1997)).
Among
47
respondents
with
a
T1/T7
ratio
<
1.5
(indicative
of
non-suppression)
who
reported
dexamethasone
ingestion,
we
found
detectable
dexamethasone
levels
(>0.4
nmol/l)
in
the
T7
saliva
samples
among
90%,
indicating
that
non-compliance
with
dexametha-
sone
ingestion
is
not
likely
to
be
frequent.
Second,
the
responsiveness
of
the
HPA
axis
might
be
associated
with
the
severity,
duration,
and
exact
timing
of
onset
of
the
stressor
(Heim
et
al.,
2008)
which
we
could
not
further
consider.
Third,
retrospective
measurements
of
stressors
might
not
be
reliable
and
mix
up
chronic
and
acute
stressors.
However,
our
assessments
of
stressors
were
based
on
widely
used
and
validated
assessments,
and
were
earlier
found
to
be
associated
with
the
development
and
chronicity
of
psycho-
pathology
(Wiersma
et
al.,
2009;
Hovens
et
al.,
2010;
Spin-
hoven
et
al.,
2011).
Fourth,
the
group
of
healthy
persons
might
be
undersized
in
our
sample
and
therefore
our
results
might
not
be
representative
for
the
general
population.
All
in
all,
we
conclude
that
in
this
large
cohort
study
the
relationship
between
childhood
trauma,
recent
negative
life
events
and
work
stressors
with
different
indicators
of
saliva
cortisol
could
not
be
convincingly
established
in
a
mixed
population
of
depressed/anxious
and
healthy
individuals.
These
null
findings
could
indicate
that
the
impact
of
stressors
on
HPA-axis
functioning
becomes
visible
only
when
more
detailed
aspects
of
severity,
chronicity
and
timing
of
stres-
sors
are
considered.
Role
of
funding
source
The
infrastructure
for
the
NESDA
study
is
funded
through
the
Geestkracht
program
of
the
Netherlands
Organisation
for
Health
Research
and
Development;
this
organisation
has
no
further
role
in
study
design;
in
the
collection,
analysis
and
interpretation
of
data;
in
the
writing
of
the
report;
and
in
the
decision
to
submit
the
paper
for
publication.
Conflict
of
interest
All
authors
reported
no
conflict
or
financial
competing
interests.
Acknowledgements
The
infrastructure
for
the
NESDA
study
(www.nesda.nl)
is
funded
through
the
Geestkracht
program
of
the
Netherlands
Organisation
for
Health
Research
and
Development
(Zon-Mw,
grant
number
10-000-1002)
and
is
supported
by
participating
universities
and
mental
health
care
organisations
(VU
Uni-
versity
Medical
Center,
GGZ
inGeest,
Arkin,
Leiden
University
Medical
Center,
GGZ
Rivierduinen,
University
Medical
Center
Groningen,
Lentis,
GGZ
Friesland,
GGZ
Drenthe,
IQ
Health-
care,
Netherlands
Institute
for
Health
Services
Research
(NIVEL)
and
Netherlands
Institute
of
Mental
Health
and
Addiction
(Trimbos).
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press
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Holleman,
M.,
et
al.,
The
relationships
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working
conditions,
recent
stressors
and
childhood
trauma
with
salivary
cortisol
levels.
Psychoneuroendocrinology
(2011),
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