Molecular Psychiatry,
Год журнала:
2020,
Номер
26(8), С. 3672 - 3683
Опубликована: Сен. 1, 2020
Abstract
Depression
is
one
of
the
global
leading
causes
disability,
but
treatments
remain
limited
and
classical
antidepressants
were
found
to
be
ineffective
in
a
substantial
proportion
patients.
Thus,
novel
effective
therapies
for
treatment
depression
are
urgently
needed.
Given
emerging
role
inflammation
etiology
pathophysiology
affective
disorders,
we
herein
illustrate
how
experimental
endotoxemia,
translational
model
systemic
inflammation,
could
used
as
tool
develop
test
new
therapeutic
options
against
depression.
Our
concept
based
on
striking
overlap
inflammatory,
neural,
characteristics
patients
with
inflammation-associated
endotoxin-challenged
healthy
subjects.
Experimental
administration
endotoxin
volunteers
safe,
well-tolerated,
without
known
long-term
health
risks.
It
offers
highly
standardized
approach
characterize
potential
targets
depression,
well
identify
that
would
benefit
from
these
interventions,
and,
therefore,
contribute
improve
personalization
increase
overall
rate
responders.
Siloed
or
singular
system
approach
to
disease
management
is
common
practice,
developing
out
of
traditional
medical
school
education.
Textbooks
medicine
describe
a
huge
number
discrete
diseases,
usually
in
systematic
fashion
following
headings
like
etiology,
pathology,
investigations,
differential
diagnoses,
and
management.
This
suggests
that
the
body
has
multitude
ways
respond
harmful
incidences.
However,
physiology
systems
biology
provide
evidence
there
simple
mechanism
behind
this
phenotypical
variability.
Regardless
if
an
injury
change
was
caused
by
trauma,
infection,
non-communicable
disease,
autoimmune
disorders,
stress,
typical
physiological
response
is:
increase
blood
supply
area,
white
cells
into
affected
tissue,
phagocytic
activity
remove
offending
agent,
followed
down-regulation
these
mechanisms
resulting
healing.
The
cascade
inflammation
body's
unique
maintain
its
integrity
macroscopic
as
well
microscopic
injuries.
We
hypothesize
chronic
development
progression
are
linked
uncontrolled
dysfunctional
injuries
regardless
their
nature,
physical,
environmental,
psychological.
Thus,
we
aim
reframe
prevailing
individual
diseases
more
integrated
systemic
treating
"person
whole,"
enhancing
patient
experience,
ability
make
necessary
changes,
maximize
overall
health
well-being.
first
part
paper
reviews
local
immune
cascades
pro-
anti-inflammatory
regulation
interconnected
feedback
loops
with
neural
psychological
pathways.
second
emphasizes
one
nature's
principles
at
work-system
design
efficiency.
Continually
overwhelming
finely
tuned
will
result
allowing
emerge;
pathways
several
conditions
described
detail.
final
considers
implications
understandings
for
clinical
care
explore
how
lens
could
shape
physician-patient
encounter
redesign.
conclude
healthcare
professionals
must
advocate
lifestyle
level
national
levels
enhance
population
Molecular Psychiatry,
Год журнала:
2021,
Номер
26(12), С. 7393 - 7402
Опубликована: Июнь 16, 2021
Abstract
We
examined
whether
inflammation
is
uniformly
associated
with
all
depressive
and
anxiety
symptoms,
these
associations
are
potentially
causal.
Data
was
from
147,478
individuals
the
UK
Biobank
(UKB)
2,905
Netherlands
Study
of
Depression
Anxiety
(NESDA).
Circulating
C-reactive
protein
(CRP)
measured
in
both
cohorts
interleukin-6
(IL-6)
NESDA.
Genetic
instruments
for
proteins
were
obtained
published
GWAS
UKB.
Depressive
symptoms
assessed
self-report
questionnaires.
In
NESDA,
neurovegetative
(appetite,
sleep,
psychomotor)
disaggregated
as
increased
vs.
decreased.
joint
analyses,
higher
CRP
depressed
mood
(OR
=
1.06,
95%
CI
1.05–1.08),
altered
appetite
1.25,
95%CI
1.23–1.28),
sleep
problems
1.05,
1.04–1.06),
fatigue
1.12,
1.11–1.14),
irritability
1.05–1.08)
worrying
control
1.03,
1.02–1.04).
IL-6
additionally
anhedonia
1.30,
1.12–1.52).
Higher
levels
1.27,
1.13–1.43)
1.26,
1.07–1.49)
sleep.
1.21,
1.08–1.35)
while
decreased
1.45,
1.18–1.79).
Mendelian
Randomisation
genetically
predicted
activity
risk
(estimate
0.25,
SE
0.08)
0.19,
0.07).
Inflammation
core
low
somatic/neurovegetative
fatigue,
changes.
Less
consistent
found
anxiety.
The
IL-6/IL-6R
pathway
could
be
causally
linked
to
depression.
Experimental
studies
required
further
evaluate
causality,
mechanisms,
usefulness
immunotherapies
symptoms.
JAMA Psychiatry,
Год журнала:
2020,
Номер
78(2), С. 161 - 161
Опубликована: Окт. 20, 2020
Importance
Observational
studies
highlight
associations
of
C-reactive
protein
(CRP),
a
general
marker
inflammation,
and
interleukin
6
(IL-6),
cytokine-stimulating
CRP
production,
with
individual
depressive
symptoms.
However,
it
is
unclear
whether
inflammatory
activity
associated
symptoms
to
what
extent
metabolic
dysregulation
underlies
the
reported
associations.
Objective
To
explore
genetic
overlap
between
activity,
dysregulation,
GWAS
Data
Sources
Genome-wide
association
study
(GWAS)
summary
data
European
individuals,
including
following:
levels
(204
402
individuals);
9
(3
which
did
not
differentiate
underlying
diametrically
opposite
[eg,
insomnia
hypersomnia])
as
measured
Patient
Health
Questionnaire
(up
117
907
statistics
for
major
depression,
excluding
UK
Biobank
participants,
resulting
in
sample
sizes
500
199
up
230
214
respectively;
386
533
body
mass
index
(BMI)
322
154
height
253
280
individuals).
Design
In
this
correlation
2-sample
mendelian
randomization
(MR)
study,
linkage
disequilibrium
score
(LDSC)
regression
was
applied
infer
single-nucleotide
variant–based
heritability
estimates.
Two-sample
MR
tested
potential
causal
variants
levels,
IL-6
signaling,
BMI
The
dates
were
November
2019
April
2020.
Results
Based
on
large
GWAS
sources,
analyses
revealed
consistent
false
discovery
rate
(FDR)–controlled
(genetic
range,
0.152-0.362;
FDRP
=
.006
toP
<
.001)
that
similar
size
correlations
suggested
upregulation
signaling
suicidality
(estimate
[SE],
0.035
[0.010];
FDR
plus
Bonferroni
correctionP
.01),
finding
remained
stable
across
statistical
models
sensitivity
using
alternative
instrument
selection
strategies.
Mendelian
consistently
show
higher
or
other
symptoms,
but
anhedonia,
tiredness,
changes
appetite,
feelings
inadequacy.
Conclusions
Relevance
This
reports
coheritability
may
result
from
potentially
also
found
suicidality.
These
findings
have
clinical
implications,
highlighting
anti-inflammatory
approaches,
especially
blockade,
putative
strategy
suicide
prevention.
Psychological Medicine,
Год журнала:
2019,
Номер
50(16), С. 2682 - 2690
Опубликована: Окт. 16, 2019
Abstract
Background
Studies
investigating
the
link
between
depressive
symptoms
and
inflammation
have
yielded
inconsistent
results,
which
may
be
due
to
two
factors.
First,
studies
differed
regarding
specific
inflammatory
markers
studied
covariates
accounted
for.
Second,
differentially
related
inflammation.
We
address
both
challenges
using
network
psychometrics.
Methods
estimated
seven
regularized
Mixed
Graphical
Models
in
Netherlands
Study
of
Depression
Anxiety
(NESDA)
data
(
N
=
2321)
explore
shared
variances
among
(1)
depression
severity,
modeled
via
sum-score,
nine
DSM-5
symptoms,
or
28
individual
symptoms;
(2)
C-reactive
protein
(CRP),
interleukin
6
(IL-6),
tumor
necrosis
factor
α
(TNF-
);
(3)
before
after
adjusting
for
sex,
age,
body
mass
index
(BMI),
exercise,
smoking,
alcohol,
chronic
diseases.
Results
The
sum-score
was
IL-6
CRP
before,
only
covariate
adjustment.
When
modeling
a
conceptual
replication
Jokela
et
al
.,
associated
with
‘sleep
problems’,
‘energy
level’,
‘weight/appetite
changes’;
first
links
survived
In
conservative
model
all
38
variables,
were
unrelated.
Following
recent
psychometric
work,
we
re-estimated
full
without
regularization:
‘insomnia’,
‘hypersomnia’,
‘aches
pain’
showed
unique
positive
relations
markers.
Conclusions
found
evidence
differential
markers,
covariates.
Associations
attenuated
adjustment;
BMI
sex
consistently
strong
Depression and Anxiety,
Год журнала:
2018,
Номер
35(11), С. 1081 - 1094
Опубликована: Сен. 10, 2018
Background
Anxiety
is
characterized
by
prolonged
preparation
for
real
or
perceived
threat.
This
may
manifest
both
as
psychological
and
physiological
activation,
ultimately
leading
to
greater
risk
poor
health.
Chronic
inflammation
play
an
integral
role
in
this
relationship,
given
the
influential
that
it
has
chronic
illness.
The
aim
of
meta-analysis
examine
levels
inflammation,
measured
inflammatory
cytokines
C-reactive
protein,
people
with
anxiety
disorders,
PTSD
(posttraumatic
stress
disorder),
obsessive–compulsive
disorder
compared
healthy
controls.
Several
moderating
variables,
including
specific
diagnosis
depression
comorbidity,
were
also
assessed.
Methods
Seventy
six
full-text
articles
screened
eligibility
41
studies
included
analysis.
Results
demonstrated
a
significant
overall
difference
between
controls
(HCs)
disorders
pro-inflammatory
(P
=
0.013,
Hedge's
g
–0.39),
which
appears
be
largely
driven
interleukin-1β
(IL-1β;
P
0.009,
–0.50),
IL-6
<
0.001,
–0.93),
tumor
necrosis
factor-α
0.030,
–0.56).
Moderation
analyses
revealed
effect
0.050),
only
individuals
differences
HCs
0.004,
–0.68).
Conclusions
These
data
demonstrate
association
dysregulation
diagnoses
associated
chronic,
impactful,
severe
provides
insight
into
way
anxiety,
particular
PTSD,
related
certain
markers.
In
doing
so,
these
findings
provide
initial
step
disentangling
relationship
basic
health
processes.
