Journal of Psychiatry and Neuroscience,
Journal Year:
2024,
Volume and Issue:
49(1), P. E35 - E44
Published: Feb. 1, 2024
Susceptibility
to
schizophrenia
is
determined
by
interactions
between
genes
and
environment,
possibly
via
epigenetic
mechanisms.
Schizophrenia
has
been
associated
with
a
restrictive
epigenome,
histone
deacetylase
(HDAC)
inhibitors
have
postulated
as
coadjuvant
agents
potentiate
the
efficacy
of
current
antipsychotic
drugs.
We
aimed
evaluate
global
posttranslational
modifications
(HPTMs)
HDAC
expression
activity
in
dorsolateral
prefrontal
cortex
(DLPFC)
individuals
schizophrenia.
Molecular Psychiatry,
Journal Year:
2021,
Volume and Issue:
27(4), P. 1886 - 1897
Published: Nov. 10, 2021
Abstract
A
growing
body
of
evidence
has
emerged
demonstrating
a
pathological
link
between
oxidative
stress
and
schizophrenia.
This
identifies
as
convergence
point
or
“central
hub”
for
schizophrenia
genetic
environmental
risk
factors.
Here
we
review
the
existing
experimental
translational
research
pinpointing
complex
dynamics
mechanisms
their
modulation
in
relation
to
pathophysiology.
We
focus
on
supporting
crucial
role
either
redox
dysregulation,
N-methyl-D-aspartate
receptor
hypofunction,
neuroinflammation
mitochondria
bioenergetics
dysfunction,
initiating
“vicious
circles”
centered
during
neurodevelopment.
These
processes
would
amplify
one
another
positive
feed-forward
loops,
leading
persistent
impairments
maturation
function
local
parvalbumin-GABAergic
neurons
microcircuits
myelinated
fibers
long-range
macrocircuitry.
is
at
basis
neural
circuit
synchronization
cognitive,
emotional,
social
sensory
deficits
characteristic
Potential
therapeutic
approaches
that
aim
breaking
these
different
vicious
circles
represent
promising
strategies
timely
safe
interventions.
In
order
improve
early
detection
increase
signal-to-noise
ratio
adjunctive
trials
antioxidant,
anti-inflammatory
NMDAR
modulator
drugs,
reverse
translation
validated
circuitry
approach
needed.
The
above
presented
allow
identify
mechanism
based
biomarkers
guiding
stratification
homogenous
patients
groups
target
engagement
required
successful
clinical
trials,
paving
way
towards
precision
medicine
psychiatry.
International Journal of Molecular Sciences,
Journal Year:
2021,
Volume and Issue:
22(14), P. 7671 - 7671
Published: July 18, 2021
Schizophrenia
is
a
chronic,
heterogeneous
neurodevelopmental
disorder
that
has
complex
symptoms
and
uncertain
etiology.
Mounting
evidence
indicates
the
involvement
of
genetics
epigenetic
disturbances,
alteration
in
gut
microbiome,
immune
system
abnormalities,
environmental
influence
disease,
but
single
root
cause
mechanism
involved
yet
to
be
conclusively
determined.
Consequently,
identification
diagnostic
markers
development
psychotic
drugs
for
treatment
schizophrenia
faces
high
failure
rate.
This
article
surveys
etiology
with
particular
focus
on
microbiota
regulation
microbial
signaling
correlates
brain
through
vagus
nerve,
enteric
nervous
system,
production
postbiotics.
Gut
microbially
produced
molecules
may
lay
groundwork
further
investigations
into
role
dysbiosis
pathophysiology
schizophrenia.
Current
limited
psychotherapy
antipsychotic
have
significant
side
effects.
Therefore,
alternative
therapeutic
options
merit
exploration.
The
use
psychobiotics
alone
or
combination
antipsychotics
promote
novel
strategies.
In
view
individual
microbiome
structure
personalized
response
drugs,
tailored
targeted
manipulation
diversity
naturally
by
prebiotics
(non-digestible
fiber)
successful
patients.
Current Issues in Molecular Biology,
Journal Year:
2023,
Volume and Issue:
45(5), P. 4080 - 4099
Published: May 6, 2023
The
pathophysiology
of
several
psychiatric
diseases
may
entail
disturbances
in
the
hypothalamic–pituitary–adrenal
(HPA)
axis
and
metabolic
pathways.
Variations
how
these
effects
present
themselves
be
connected
to
individual
variances
clinical
symptoms
treatment
responses,
such
as
observation
that
a
significant
fraction
participants
do
not
respond
current
antipsychotic
drugs.
A
bidirectional
signaling
pathway
between
central
nervous
system
gastrointestinal
tract
is
known
microbiota–gut–brain
axis.
large
small
intestines
contain
more
than
100
trillion
microbial
cells,
contributing
intestinal
ecosystem’s
incredible
complexity.
Interactions
microbiota
epithelium
can
alter
brain
physiology
affect
mood
behavior.
There
has
recently
been
focus
on
relationships
impact
mental
health.
According
evidence,
play
role
neurological
illnesses.
Intestinal
metabolites
origin,
short-chain
fatty
acids,
tryptophan
metabolites,
bacterial
components
might
stimulate
host’s
immune
system,
are
mentioned
this
review.
We
aim
shed
some
growing
gut
inducing/manipulating
disorders,
which
pave
way
for
novel
microbiota-based
therapies.
Journal of Clinical Investigation,
Journal Year:
2018,
Volume and Issue:
129(1), P. 364 - 372
Published: Dec. 9, 2018
Patients
with
schizophrenia
(SCZ)
experience
chronic
cognitive
deficits.
Histone
deacetylases
(HDACs)
are
enzymes
that
regulate
circuitry;
however,
the
role
of
HDACs
in
disorders,
including
SCZ,
remains
unknown
humans.
We
previously
determined
HDAC2
mRNA
levels
were
lower
dorsolateral
prefrontal
cortex
(DLPFC)
tissue
from
donors
SCZ
compared
controls.
Here
we
investigated
relationship
between
vivo
HDAC
expression
and
impairment
patients
matched
healthy
controls
using
[11C]Martinostat
positron
emission
tomography
(PET).In
a
case-control
study,
relative
uptake
was
14
or
schizoaffective
disorder
(SCZ/SAD)
17
hypothesis-driven
region-of-interest
analysis
unbiased
whole
brain
voxel-wise
approaches.
Clinical
measures,
MATRICS
consensus
battery,
administered.Relative
DLPFC
SCZ/SAD
controls,
positively
correlated
performance
scores
across
groups.
also
showed
dorsomedial
orbitofrontal
gyrus,
higher
cerebral
white
matter,
pons,
cerebellum
controls.These
findings
provide
evidence
dysregulation
suggest
altered
may
impact
function
humans.National
Institute
Mental
Health
(NIMH),
Brain
Behavior
Foundation,
Massachusetts
General
Hospital
(MGH),
Athinoula
A.
Martinos
Center
for
Biomedical
Imaging,
National
Imaging
Bioengineering
(NIBIB),
NIH
Shared
Instrumentation
Grant
Program.
Neuroscience & Biobehavioral Reviews,
Journal Year:
2021,
Volume and Issue:
132, P. 1049 - 1066
Published: Nov. 3, 2021
Childhood
trauma
(CT)
can
have
persistent
effects
on
the
brain
and
is
one
of
major
risk
factors
for
neuropsychiatric
diseases
in
adulthood.
Recent
advances
field
epigenetics
suggest
that
epigenetic
such
as
DNA
methylation
histone
modifications,
well
regulatory
processes
involving
non-coding
RNA
are
associated
with
long-term
sequelae
CT.
This
narrative
review
summarizes
current
knowledge
basis
CT
describes
studies
animal
models
human
subjects
examining
how
epigenome
transcriptome
modified
by
brain.
It
discusses
psychological
pharmacological
interventions
counteract
changes
induced
need
to
establish
longitudinal
assessment
after
developing
more
effective
diagnostics
treatment
strategies
based
targets.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(9), P. 1978 - 1978
Published: Sept. 2, 2024
Stress
profoundly
affects
physical
and
mental
health,
particularly
when
experienced
early
in
life.
Early-life
stress
(ELS)
encompasses
adverse
childhood
experiences
such
as
abuse,
neglect,
violence,
or
chronic
poverty.
These
stressors
can
induce
long-lasting
changes
brain
structure
function,
impacting
areas
involved
emotion
regulation,
cognition,
response.
Consequently,
individuals
exposed
to
high
levels
of
ELS
are
at
an
increased
risk
for
health
disorders
like
depression,
anxiety,
post-traumatic
disorders,
well
issues,
including
metabolic
cardiovascular
disease,
cancer.
This
review
explores
the
biological
psychological
consequences
early-life
adversity
paradigms
rodents,
maternal
separation
deprivation
limited
bedding
nesting.
The
study
these
experimental
models
have
revealed
that
organism’s
response
is
complex,
involving
genetic
epigenetic
mechanisms,
associated
with
dysregulation
physiological
systems
nervous,
neuroendocrine,
immune
systems,
a
sex-dependent
fashion.
Understanding
impact
crucial
developing
effective
interventions
preventive
strategies
humans
stressful
traumatic
childhood.
International Journal of Molecular Sciences,
Journal Year:
2017,
Volume and Issue:
18(8), P. 1711 - 1711
Published: Aug. 4, 2017
Brain
development
is
guided
by
the
interactions
between
genetic
blueprint
and
environment.
Epigenetic
mechanisms,
especially
DNA
methylation,
can
mediate
these
may
also
trigger
long-lasting
adaptations
in
developmental
programs
that
increase
risk
of
major
depressive
disorders
(MDD)
schizophrenia
(SCZ).
Early
life
adversity
a
factor
for
MDD/SCZ
persistent
genome-wide
changes
methylation
at
genes
important
to
early,
but
mature,
brain
function,
including
neural
proliferation,
differentiation,
synaptic
plasticity,
among
others.
Moreover,
variations
controlling
dynamic
early
are
thought
influence
later
epigenomic
SCZ.
This
finding
corroborates
high
load
neurodevelopmental
origin
SCZ
shows
epigenetic
responses
environment
are,
least
part,
genetically
controlled.
Interestingly,
variants
influencing
enriched
from
association
studies
(GWAS)
on
supporting
role
neurodevelopment.
Overall,
appear
be
controlled
different
degrees
genetics
MDD/SCZ,
even
though
potential
reversibility
processes
offer
new
hope
timely
therapeutic
interventions
MDD/SCZ.
