Psychological
trauma
has
profound
effects
on
brain
function
and
precipitates
psychiatric
disorders
in
vulnerable
individuals,
however,
the
molecular
mechanisms
linking
with
risk
remain
incompletely
understood.
Using
RNA-seq
data
postmortem
tissue
of
a
cohort
304
donors
(N=136
exposure),
we
investigated
transcriptional
signatures
exposures
two
cortical
regions
(dorsolateral
prefrontal
cortex,
dorsal
anterior
cingulate
cortex)
amygdala
(medial
basolateral
amygdala)
associated
stress
processing
regulation.
We
focused
dissecting
heterogeneity
traumatic
experiences
these
by
investigating
exposure
to
several
types
(childhood,
adulthood,
complex,
single
acute,
combat,
interpersonal
traumas)
interactions
sex.
Overall,
were
more
childhood
traumas,
whereas
adulthood
(regardless
experience).
cell-type-specific
expression
imputation,
identified
strong
response
medial
excitatory
neurons
trauma,
which
coincided
dysregulation
observed
human
induced
pluripotent
stem
cell
(hiPSC)-derived
glutamatergic
exposed
hydrocortisone.
resolved
multiscale
coexpression
networks
for
each
region
modules
enriched
whose
connectivity
was
altered
trauma.
Trauma-associated
provide
insight
into
coordinated
functional
different
traumas
point
potential
gene
targets
further
dissection.
Together,
characterization
long-lasting
encoding
corticolimbic
brain.
The
molecular
organization
of
the
human
neocortex
historically
has
been
studied
in
context
its
histological
layers.
However,
emerging
spatial
transcriptomic
technologies
have
enabled
unbiased
identification
transcriptionally
defined
domains
that
move
beyond
classic
cytoarchitecture.
We
used
Visium
gene
expression
platform
to
generate
a
data-driven
neuroanatomical
atlas
across
anterior-posterior
axis
dorsolateral
prefrontal
cortex.
Integration
with
paired
single-nucleus
RNA-sequencing
data
revealed
distinct
cell
type
compositions
and
cell-cell
interactions
domains.
Using
PsychENCODE
publicly
available
data,
we
mapped
enrichment
types
genes
associated
neuropsychiatric
disorders
discrete
This
Viewpoint
discusses
the
opportunity
to
include
inflammatory
biomarkers
as
specifiers
for
major
depression
in
upcoming
Sixth
Edition
of
Diagnostic
and
Statistical
Manual
Mental
Disorders
(
DSM-6
).
Biology,
Год журнала:
2025,
Номер
14(1), С. 76 - 76
Опубликована: Янв. 15, 2025
Understanding
the
regulatory
mechanisms
of
stress-induced
immunosuppression
and
developing
reliable
diagnostic
methods
are
important
tasks
in
clinical
medicine.
This
will
allow
for
development
effective
strategies
prevention
treatment
conditions
associated
with
immune
system
dysfunction
induced
by
chronic
stress.
The
purpose
this
review
is
to
conduct
a
comprehensive
analysis
synthesis
existing
data
on
immunosuppression.
aimed
at
identifying
key
neuroendocrine,
cytokine,
cellular
processes
underlying
suppression
response
under
study
involved
search
scientific
literature
covering
cellular,
molecular
regulation,
as
well
modern
its
diagnosis.
Major
international
bibliographic
databases
publications
biomedicine,
psychophysiology,
immunology
were
selected
search.
results
identified
regulating
reviewed
provided
detailed
descriptions
neuroendocrine
cytokine
A
significant
portion
confirms
that
activation
hypothalamic-pituitary-adrenal
(HPA)
axis
subsequent
elevation
cortisol
levels
exert
substantial
immunosuppressive
effects
cells,
particularly
macrophages
lymphocytes,
leading
innate
adaptive
responses.
also
highlight
crucial
role
catecholamines
(adrenaline
noradrenaline)
initiating
Egyptian Journal of Medical Human Genetics,
Год журнала:
2025,
Номер
26(1)
Опубликована: Март 20, 2025
Abstract
Background
Posttraumatic
stress
disorder
(PTSD)
affects
approximately
8%
of
the
US
population,
with
varying
susceptibility
among
individuals
exposed
to
trauma.
While
genetic
factors
contribute
PTSD
risk,
emerging
evidence
suggests
that
epigenetic
mechanisms
play
a
crucial
role
in
translating
environmental
exposures
into
lasting
neurobiological
changes.
Purpose
This
review
provides
comprehensive
analysis
cutting-edge
research
on
PTSD,
particular
emphasis
novel
findings
regarding
resilience
and
mechanisms.
We
explore
recent
technological
advances
their
applications
understanding
pathophysiology.
Main
body
Advanced
epigenomic
approaches
have
revealed
complex
interactions
between
DNA
methylation,
histone
modifications,
non-coding
RNAs
PTSD.
Novel
highlight
cell
type-specific
signatures
temporal
dynamics
following
trauma
exposure.
Single-cell
studies
identified
previously
unknown
cellular
heterogeneity
responses.
Recent
data
modifications
not
only
influence
individual
but
may
also
transgenerational
transmission
effects.
Integrative
multi-omics
new
insights
molecular
networks
underlying
vulnerability.
Conclusion
unprecedented
complexity
These
open
avenues
for
personalized
interventions
based
profiles
suggest
therapeutic
strategies
targeting
modifications.
enhanced
has
significant
implications
risk
assessment,
prevention,
treatment.
Graphical
abstract
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 27, 2024
Abstract
Pathophysiology
of
many
neuropsychiatric
disorders,
including
schizophrenia
(SCZD),
is
linked
to
habenula
(Hb)
function.
While
pharmacotherapies
and
deep
brain
stimulation
targeting
the
Hb
are
emerging
as
promising
therapeutic
treatments,
little
known
about
cell
type-specific
transcriptomic
organization
human
or
how
it
altered
in
SCZD.
Here
we
define
molecular
neuroanatomy
identify
changes
individuals
with
SCZD
compared
neurotypical
controls.
Utilizing
Hb-enriched
postmortem
tissue,
performed
single
nucleus
RNA-sequencing
(snRNA-seq;
n=7
donors)
identified
17
molecularly
defined
types
across
16,437
nuclei,
3
medial
7
lateral
populations,
several
which
were
conserved
between
rodents
humans.
Single
molecule
fluorescent
situ
hybridization
(smFISH;
n=3
validated
snRNA-seq
mapped
their
spatial
locations.
Bulk
type
deconvolution
tissue
from
35
33
controls
yielded
45
SCZD-associated
differentially
expressed
genes
(DEGs,
FDR
<
0.05),
32
(71%)
unique
tissue.
eQTL
analysis
717
independent
SNP-gene
pairs
(FDR
where
either
SNP
a
risk
variant
(16
pairs)
gene
DEG
(7
pairs).
colocalization
16
colocalized
genes.
These
results
topographically
organized
distinct
signatures
demonstrate
genetic
associated
SCZD,
thereby
providing
novel
insights
into
role
disorders.
One
Sentence
Summary
Transcriptomic
identification
illness
state.
