Diagnosis
and
treatment
of
circadian
rhythm
sleep-wake
disorders
both
require
assessment
phase
the
brain’s
pacemaker.
The
gold-standard
univariate
method
is
based
on
collection
a
24-hr
time
series
plasma
melatonin,
suprachiasmatic
nucleus-driven
pineal
hormone.
We
developed
validated
multivariate
whole-blood
mRNA-based
predictor
melatonin
which
requires
few
samples.
Transcriptome
data
were
collected
under
normal,
sleep-deprivation
abnormal
sleep-timing
conditions
to
assess
robustness
predictor.
Partial
least
square
regression
(PLSR),
applied
transcriptome,
identified
set
100
biomarkers
primarily
related
glucocorticoid
signaling
immune
function.
Validation
showed
that
PLSR-based
predictors
outperform
published
blood-derived
predictors.
When
given
one
sample
as
input,
R2
predicted
vs
observed
was
0.74,
whereas
for
two
samples
taken
12
hr
apart,
0.90.
This
blood
transcriptome-based
model
enables
from
Science Translational Medicine,
Journal Year:
2023,
Volume and Issue:
15(701)
Published: June 21, 2023
Rhythms
are
intrinsic
to
endocrine
systems,
and
disruption
of
these
hormone
oscillations
occurs
at
very
early
stages
the
disease.
Because
adrenal
hormones
secreted
with
both
circadian
ultradian
periods,
conventional
single–time
point
measurements
provide
limited
information
about
rhythmicity
and,
crucially,
do
not
during
sleep,
when
many
fluctuate
from
nadir
peak
concentrations.
If
blood
sampling
is
attempted
overnight,
then
this
necessitates
admission
a
clinical
research
unit,
can
be
stressful,
disturbs
sleep.
To
overcome
problem
measure
free
within
their
target
tissues,
we
used
microdialysis,
an
ambulatory
fraction
collector,
liquid
chromatography–tandem
mass
spectrometry
obtain
high-resolution
profiles
tissue
steroids
over
24
hours
in
214
healthy
volunteers.
For
validation,
compared
against
plasma
further
seven
Sample
collection
subcutaneous
was
safe,
well
tolerated,
allowed
most
normal
activities
continue.
In
addition
cortisol,
identified
daily
variation
cortisone,
corticosterone,
18-hydroxycortisol,
aldosterone,
tetrahydrocortisol
allo-tetrahydrocortisol,
presence
dehydroepiandrosterone
sulfate.
We
mathematical
computational
methods
quantify
interindividual
variability
different
times
day
develop
“dynamic
markers”
normality
individuals
stratified
by
sex,
age,
body
index.
Our
results
insight
into
dynamics
real-world
settings
may
serve
as
normative
reference
for
biomarkers
disorders
(ULTRADIAN,
NCT02934399).
Naunyn-Schmiedeberg s Archives of Pharmacology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 10, 2025
Abstract
One
of
the
goals
clinical
pharmacology
is
to
optimize
patient
treatment
by
adopting
new
strategies
which
will
increase
efficacy
and
decrease
adverse
effects
drugs.
In
literature,
it
has
shown
that
effectiveness
toxicity
medications
can
vary
significantly
based
on
when
they
are
administered,
making
timing
a
crucial
factor
in
plans.
Chronopharmacology
relatively
branch
focuses
adjusting
drug
administration
times
enhance
outcomes.
largely
influenced
an
individual’s
circadian
rhythm
refers
periodic
changes
biological
processes
depending
time
day.
The
chronopharmacology
influences
practice,
accumulating
knowledge
this
field
likely
lead
healthcare
providers
adopt
for
regimens.
This
review
aims
summarize
impact
particularly
current
practices
highlight
latest
findings
related
chronophysiological
mechanisms.
Chronobiology International,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 23
Published: Jan. 22, 2025
The
intricate
relationship
between
circadian
rhythms
and
mood
is
well-established.
Disturbances
in
sleep
often
precede
the
development
of
disorders,
such
as
major
depressive
disorder
(MDD),
bipolar
(BD),
seasonal
affective
(SAD).
Two
primary
factors,
intrinsic
clocks
light,
drive
natural
fluctuations
throughout
day,
mirroring
patterns
sleepiness
wakefulness.
Nearly
all
organisms
possess
that
coordinate
daily
rhythms,
with
light
serving
environmental
cue
to
synchronize
these
internal
timekeepers
24-hour
cycle.
Additionally,
directly
influences
states.
Disruptions
those
caused
by
jet
lag,
shift
work,
or
reduced
daylight
hours,
can
trigger
exacerbate
symptoms.
complex
subtle
connections
disruptions
dysregulation
suggest
focusing
solely
on
individual
clock
genes
insufficient
fully
understand
their
etiology
progression.
Instead,
instability
may
arise
from
systemic
misalignments
external
cycles
synchronization
clocks.
Here,
we
synthesize
past
research
independent
contributions
regulation,
drawing
particularly
insights
animal
studies
illuminate
fundamental
mechanisms
relevant
human
health.
Diagnosis
and
treatment
of
circadian
rhythm
sleep-wake
disorders
both
require
assessment
phase
the
brain’s
pacemaker.
The
gold-standard
univariate
method
is
based
on
collection
a
24-hr
time
series
plasma
melatonin,
suprachiasmatic
nucleus-driven
pineal
hormone.
We
developed
validated
multivariate
whole-blood
mRNA-based
predictor
melatonin
which
requires
few
samples.
Transcriptome
data
were
collected
under
normal,
sleep-deprivation
abnormal
sleep-timing
conditions
to
assess
robustness
predictor.
Partial
least
square
regression
(PLSR),
applied
transcriptome,
identified
set
100
biomarkers
primarily
related
glucocorticoid
signaling
immune
function.
Validation
showed
that
PLSR-based
predictors
outperform
published
blood-derived
predictors.
When
given
one
sample
as
input,
R2
predicted
vs
observed
was
0.74,
whereas
for
two
samples
taken
12
hr
apart,
0.90.
This
blood
transcriptome-based
model
enables
from
