Translational Psychiatry,
Journal Year:
2023,
Volume and Issue:
13(1)
Published: April 19, 2023
Abstract
Major
depressive
disorder
(MDD)
is
a
complex
and
heterogeneous
psychiatric
syndrome
with
genetic
environmental
influences.
In
addition
to
neuroanatomical
circuit-level
disturbances,
dysregulation
of
the
brain
transcriptome
key
phenotypic
signature
MDD.
Postmortem
gene
expression
data
are
uniquely
valuable
resources
for
identifying
this
genomic
drivers
in
human
depression;
however,
scarcity
tissue
limits
our
capacity
observe
dynamic
transcriptional
landscape
It
therefore
crucial
explore
integrate
depression
stress
transcriptomic
from
numerous,
complementary
perspectives
construct
richer
understanding
pathophysiology
depression.
review,
we
discuss
multiple
approaches
exploring
reflecting
stages
MDD:
predisposition,
onset,
illness.
We
next
highlight
bioinformatic
hypothesis-free,
genome-wide
analyses
their
integration.
Last,
summarize
findings
recent
studies
within
conceptual
framework.
Cancer Letters,
Journal Year:
2023,
Volume and Issue:
562, P. 216180 - 216180
Published: April 13, 2023
Patient-derived
organoids
(PDO)
are
a
new
biomedical
research
model
that
can
reconstruct
phenotypic
and
genetic
characteristics
of
the
original
tissue
useful
for
on
pathogenesis
drug
screening.
To
introduce
progression
in
this
field,
we
review
key
factors
constructing
derived
from
epithelial
tissues
cancers,
covering
culture
medium
matrix,
morphological
characteristics,
profiles,
high-throughput
screening,
application
potential.
We
also
discuss
co-culture
system
cancer
with
tumor
microenvironment
(TME)
associated
cells.
The
is
widely
used
evaluating
crosstalk
cells
TME
components,
such
as
fibroblasts,
endothelial
cells,
immune
microorganisms.
article
provides
prospective
standardized
cultivation
mode,
automatic
evaluation,
sensitivity
screening
using
methods.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(2), P. 864 - 864
Published: Jan. 10, 2024
Fear
extinction
is
a
phenomenon
that
involves
gradual
reduction
in
conditioned
fear
responses
through
repeated
exposure
to
fear-inducing
cues.
Functional
brain
connectivity
assessments,
such
as
functional
magnetic
resonance
imaging
(fMRI),
provide
valuable
insights
into
how
regions
communicate
during
these
processes.
Stress,
ubiquitous
aspect
of
life,
influences
learning
and
by
changing
the
activity
amygdala,
prefrontal
cortex,
hippocampus,
leading
enhanced
and/or
impaired
extinction.
Glucocorticoid
receptors
(GRs)
are
key
stress
response
show
dual
function
regulation:
while
they
enhance
consolidation
memories,
also
facilitate
Accordingly,
GR
dysregulation
associated
with
anxiety
mood
disorders.
Recent
advancements
cognitive
neuroscience
underscore
need
for
comprehensive
understanding
integrates
perspectives
from
molecular,
cellular,
systems
levels.
In
particular,
neuropharmacology
provides
neurotransmitter
receptor
systems,
aiding
investigation
mechanisms
underlying
regulation
potential
therapeutic
targets.
A
notable
player
this
context
cortisol,
hormone,
which
significantly
both
memory
reconsolidation
Gaining
thorough
intricate
interactions
has
implications
terms
addressing
psychiatric
disorders
related
stress.
This
review
sheds
light
on
complex
between
processes,
emotions,
their
neural
bases.
endeavor,
our
aim
reshape
comprehension
fear,
stress,
emotional
well-being,
ultimately
development
interventions.
Science,
Journal Year:
2024,
Volume and Issue:
384(6698)
Published: May 23, 2024
The
molecular
pathology
of
stress-related
disorders
remains
elusive.
Our
brain
multiregion,
multiomic
study
posttraumatic
stress
disorder
(PTSD)
and
major
depressive
(MDD)
included
the
central
nucleus
amygdala,
hippocampal
dentate
gyrus,
medial
prefrontal
cortex
(mPFC).
Genes
exons
within
mPFC
carried
most
disease
signals
replicated
across
two
independent
cohorts.
Pathways
pointed
to
immune
function,
neuronal
synaptic
regulation,
hormones.
Multiomic
factor
gene
network
analyses
provided
underlying
genomic
structure.
Single
RNA
sequencing
in
dorsolateral
PFC
revealed
dysregulated
(stress-related)
non-neuronal
cell
types.
Analyses
brain-blood
intersections
>50,000
UK
Biobank
participants
were
conducted
along
with
fine-mapping
results
PTSD
MDD
genome-wide
association
studies
distinguish
risk
from
processes.
data
suggest
shared
distinct
both
propose
potential
therapeutic
targets
biomarkers.
Nature Neuroscience,
Journal Year:
2022,
Volume and Issue:
25(11), P. 1434 - 1445
Published: Oct. 20, 2022
Abstract
Post-traumatic
stress
disorder
(PTSD)
can
develop
following
severe
trauma,
but
the
extent
to
which
genetic
and
environmental
risk
factors
contribute
individual
clinical
outcomes
is
unknown.
Here,
we
compared
transcriptional
responses
hydrocortisone
exposure
in
human
induced
pluripotent
stem
cell
(hiPSC)-derived
glutamatergic
neurons
peripheral
blood
mononuclear
cells
(PBMCs)
from
combat
veterans
with
PTSD
(
n
=
19
hiPSC
20
PBMC
donors)
controls
donors).
In
only,
observed
diagnosis-specific
glucocorticoid-induced
changes
gene
expression
corresponding
PTSD-specific
transcriptomic
patterns
found
postmortem
brains.
We
glucocorticoid
hypersensitivity
neurons,
identified
genes
that
this
PTSD-dependent
response.
find
evidence
of
a
coregulated
network
transcription
mediates
hyper-responsivity
PTSD.
These
findings
suggest
represent
platform
for
examining
molecular
mechanisms
underlying
PTSD,
identifying
biomarkers
response,
conducting
drug
screening
identify
new
therapeutics.
Cambridge Quarterly of Healthcare Ethics,
Journal Year:
2023,
Volume and Issue:
32(4), P. 529 - 541
Published: Feb. 17, 2023
Abstract
The
generation
of
three-dimensional
cerebral
organoids
from
human-induced
pluripotent
stem
cells
(hPSC)
has
facilitated
the
investigation
mechanisms
underlying
several
neuropsychiatric
disorders,
including
stress-related
namely
major
depressive
disorder
and
post-traumatic
stress
disorder.
Generating
hPSC-derived
neurons,
organoids,
even
assembloids
(or
multi-organoid
complexes)
can
facilitate
research
into
biomarkers
for
susceptibility
or
resilience
may
bring
about
advances
in
personalized
medicine
biomarker
psychiatric
disorders.
Nevertheless,
organoid
does
not
come
without
its
own
set
ethical
considerations.
With
increased
complexity
resemblance
to
vivo
conditions,
discussions
moral
status
these
models
are
ongoing,
questions
sentience,
consciousness,
status,
donor
protection,
chimeras.
There
are,
however,
unique
considerations
that
arise
worth
looking
context
disorders
using
organoids.
This
paper
provides
research-specific
use
purposes.
as
a
case
study
here
help
inform
other
practices
vitro
studies
brain
with
high
American Journal of Psychiatry,
Journal Year:
2023,
Volume and Issue:
180(10), P. 739 - 754
Published: July 26, 2023
Objective:
Multidisciplinary
studies
of
posttraumatic
stress
disorder
(PTSD)
and
major
depressive
(MDD)
implicate
the
dorsolateral
prefrontal
cortex
(DLPFC)
in
disease
risk
pathophysiology.
Postmortem
brain
have
relied
on
bulk-tissue
RNA
sequencing
(RNA-seq),
but
single-cell
RNA-seq
is
needed
to
dissect
cell-type-specific
mechanisms.
The
authors
conducted
first
single-nucleus
postmortem
study
PTSD
elucidate
transcriptomic
pathology
with
resolution.
Method:
Profiling
32
DLPFC
samples
from
11
individuals
PTSD,
10
MDD,
control
subjects
was
(∼415K
nuclei;
>13K
cells
per
sample).
A
replication
sample
included
15
(∼160K
>11K
Results:
Differential
gene
expression
analyses
identified
significant
differentially
expressed
genes
(snDEGs)
excitatory
(EX)
inhibitory
(IN)
neurons
astrocytes,
not
other
cell
types
or
bulk
tissue.
MDD
had
more
false
discovery
rate–corrected
snDEGs,
a
greater
rate.
In
EX
IN
neurons,
biological
pathways
that
were
enriched
compared
glucocorticoid
signaling.
Furthermore,
signaling
induced
pluripotent
stem
(iPSC)–derived
cortical
demonstrated
relevance
opposite
direction
regulation
especially
neurons.
Many
snDEGs
17q21.31
locus
are
particularly
interesting
given
causal
roles
pathogenesis
DLPFC-based
neuroimaging
(PTSD:
ARL17B,
LINC02210-CRHR1,
LRRC37A2;
MDD:
LRRC37A
LRP4),
while
others
regulated
by
glucocorticoids
iPSC-derived
SLC16A6,
TAF1C;
CDH3).
Conclusions:
findings
point
mechanisms
response
highlighting
importance
examining
indicating
promising
novel
biomarkers
therapeutic
targets.
Neuron,
Journal Year:
2024,
Volume and Issue:
112(9), P. 1426 - 1443.e11
Published: March 4, 2024
Glucocorticoids
are
important
for
proper
organ
maturation,
and
their
levels
tightly
regulated
during
development.
Here,
we
use
human
cerebral
organoids
mice
to
study
the
cell-type-specific
effects
of
glucocorticoids
on
neurogenesis.
We
show
that
increase
a
specific
type
basal
progenitors
(co-expressing
PAX6
EOMES)
has
been
shown
contribute
cortical
expansion
in
gyrified
species.
This
effect
is
mediated
via
transcription
factor
ZBTB16
leads
increased
production
neurons.
A
phenome-wide
Mendelian
randomization
analysis
an
enhancer
variant
moderates
glucocorticoid-induced
reveals
causal
relationships
with
higher
educational
attainment
altered
brain
structure.
The
relationship
postnatal
cognition
also
supported
by
data
from
prospective
pregnancy
cohort
study.
work
provides
cellular
molecular
pathway
neurogenesis
relates
lasting
phenotypes.
Neurobiology of Stress,
Journal Year:
2023,
Volume and Issue:
23, P. 100530 - 100530
Published: Feb. 23, 2023
Hypothalamic-pituitary
adrenal
(HPA)axis
dysregulation
has
long
been
implicated
in
stress-related
disorders
such
as
major
depression
and
post-traumatic
stress
disorder.
Glucocorticoids
(GCs)
are
released
from
the
glands
a
result
of
HPA-axis
activation.
The
release
GCs
is
with
several
neurobiological
changes
that
associated
negative
consequences
chronic
onset
course
psychiatric
disorders.
Investigating
underlying
effects
may
help
to
better
understand
pathophysiology
impact
plethora
neuronal
processes
at
genetic,
epigenetic,
cellular,
molecular
levels.
Given
scarcity
difficulty
accessing
human
brain
samples,
2D
3D
vitro
cultures
becoming
increasingly
useful
studying
GC
effects.
In
this
review,
we
provide
an
overview
studies
investigating
on
key
proliferation
survival
progenitor
cells,
neurogenesis,
synaptic
plasticity,
activity,
inflammation,
genetic
vulnerability,
epigenetic
alterations.
Finally,
discuss
challenges
field
offer
suggestions
for
improving
use
models
investigate