Frontiers in Genetics,
Год журнала:
2022,
Номер
13
Опубликована: Янв. 25, 2022
Addiction
is
a
chronically
relapsing
neuropsychiatric
disease
that
occurs
in
some,
but
not
all,
individuals
who
use
substances
of
abuse.
Relatively
little
known
about
the
mechanisms
which
contribute
to
individual
differences
susceptibility
addiction.
Neural
gene
expression
regulation
underlies
pathogenesis
addiction,
mediated
by
epigenetic
mechanisms,
such
as
DNA
modifications.
A
growing
body
work
has
demonstrated
distinct
signatures
brain
reward
regions
may
be
associated
with
addiction
susceptibility.
Furthermore,
factors
influence
are
also
have
basis.
In
present
review,
we
discuss
notion
an
underlying
We
focus
on
major
phenotypes
and
review
evidence
cell
type-specific,
time
dependent,
sex
biased
effects
drug
use.
highlight
role
epigenetics
these
diverse
processes
propose
its
contribution
differences.
Given
prevalence
lack
effective
treatments
for
elucidating
mechanism
vulnerability
represent
expeditious
approach
relieving
burden.
BMJ Open,
Год журнала:
2025,
Номер
15(1), С. e086454 - e086454
Опубликована: Янв. 1, 2025
Introduction
Alcohol
use
disorder
(AUD)
is
a
massive
burden
for
the
individual,
relatives
and
society.
Despite
this,
treatment
gap
wide
compared
with
other
mental
health
disorders.
Treatment
options
are
sparse,
only
three
Food
Drug
Administration
(FDA)-approved
pharmacotherapies.
Glucagon-like
peptide-1
(GLP-1)
receptor
agonists
have
shown
promising
effects
in
reducing
alcohol
consumption
preclinical
experiments,
clinical
trials
high
demand
to
investigate
these
potentially
beneficial
patients
diagnosed
AUD.
Methods
analysis
The
of
once-weekly
GLP-1
agonist
semaglutide
will
be
investigated
26-week,
randomised,
placebo-controlled,
double-blinded
trial.
108
AUD
comorbid
obesity
(body
mass
index
(BMI)≥30
kg/m
2
))
randomised
either
or
placebo
combination
cognitive
behavioural
therapy.
A
subgroup
structural,
functional
neurochemical
brain
imaging
performed
at
baseline
after
26
weeks
treatment.
primary
endpoint
reduction
heavy
drinking
days,
defined
as
days
excess
48/60
g
per
day
(women
men,
respectively).
Secondary
endpoints
include
changes
from
week
consumption,
smoking
status,
quality
life,
fibrosis-4
score,
plasma
concentration
phosphatidylethanol,
gamma-aminobutyric
acid
(GABA)
levels,
cue
reactivity,
connectivity
white
matter
tract
integrity.
Status
Recruitment
started
June
2023.
Ethics
dissemination
study
approved
by
Committee
Capital
Region
Denmark,
Danish
Board
Health
Data
Protection
Agency.
All
sign
written
consent
form
before
being
included
Results
disseminated
through
peer-reviewed
publications
conference
presentations.
After
results
published,
all
de-identified
data
available
Mendeley
database.
Trial
registration
number
NCT05895643
.
American Journal of Psychiatry,
Год журнала:
2023,
Номер
180(6), С. 445 - 453
Опубликована: Март 29, 2023
Objective:
Craving
is
a
central
construct
in
the
study
of
motivation
and
human
behavior
also
clinical
symptom
substance
non-substance-related
addictive
disorders.
Thus,
craving
represents
target
for
transdiagnostic
modeling.
Methods:
The
authors
applied
connectome-based
predictive
modeling
(CPM)
to
functional
connectivity
data
large
(N=274)
sample
individuals
with
without
use–related
conditions,
predict
self-reported
craving.
Functional
connectomes
derived
from
three
guided
imagery
conditions
personalized
appetitive,
stress,
neutral-relaxing
experiences
were
used
rated
before
after
each
condition.
generalizability
“craving
network”
was
tested
an
independent
using
cue-induced
task
collected
fasting
during
fasting.
Results:
CPM
successfully
predicted
craving,
thereby
identifying
network.”
Anatomical
localization
model
contribution
suggested
that
strongest
predictors
regions
salience,
subcortical,
default
mode
networks.
As
external
validation,
sample,
food
task.
Conclusions:
These
provide
perspective
key
phenomenological
feature
disorders—craving—and
identify
common
across
disorders,
suggesting
neural
signature
or
urge
motivated
behaviors.
American Journal of Psychiatry,
Год журнала:
2025,
Номер
182(2), С. 198 - 208
Опубликована: Янв. 15, 2025
The
behavioral
and
diagnostic
heterogeneity
within
the
opioid
use
disorder
(OUD)
diagnosis
is
not
readily
captured
in
current
animal
models,
limiting
translational
relevance
of
mechanistic
research
that
conducted
experimental
animals.
authors
hypothesized
a
nonlinear
clustering
OUD-like
traits
would
capture
population
yield
subpopulations
OUD
vulnerable
rats
with
distinct
neurocircuit
profiles.
Over
900
male
female
heterogeneous
stock
rats,
line
capturing
genetic
present
humans,
were
assessed
for
several
measures
heroin
rewarded
non-rewarded
seeking
behaviors.
A
stochastic
block
model
analysis
was
used
to
assign
vulnerable,
intermediate,
resilient
clusters.
Additional
tests
circuit
analyses
using
c-fos
protein
activation
on
subpopulations.
exhibited
greater
taking
behaviors
relative
those
intermediate
Akin
human
diagnosis,
further
rat
subclustering
revealed
different
combinations
traits,
including
sex
differences.
Lastly,
cue-induced
neuronal
patterns
differed
between
phenotypes.
Behavioral
differences
recapitulated
circuitry
activation,
preferential
engagement
extended
amygdala
stress
males
cortico-striatal
drug
cue-seeking
females.
Using
approach
reflective
diagnosis.
vulnerability
resiliency
associated
patterns,
posing
this
as
tool
assessing
neurobiological
mechanisms
underpinning
OUD.
Biological Psychiatry,
Год журнала:
2020,
Номер
89(10), С. 970 - 979
Опубликована: Дек. 19, 2020
The
balance
between
goal-directed
behavior
and
habits
has
been
hypothesized
to
be
biased
toward
the
latter
in
individuals
with
cocaine
use
disorder
(CUD),
suggesting
possible
neurochemical
changes
putamen,
which
may
contribute
their
compulsive
behavior.
We
assessed
habitual
48
patients
CUD
42
healthy
control
participants
using
a
contingency
degradation
paradigm
Creature
of
Habit
Scale.
In
subgroup
this
sample
(CUD:
n
=
21;
participants:
22),
we
also
measured
glutamate
glutamine
concentrations
left
putamen
ultra-high-field
(7T)
magnetic
resonance
spectroscopy.
that
increased
tendencies
would
associated
abnormal
glutamatergic
metabolites
putamen.
Compared
non-drug-using
peers,
exhibited
greater
during
degradation,
correlated
levels
self-reported
daily
habits.
further
identified
significant
reduction
concentration
turnover
(glutamate-to-glutamine
ratio)
CUD,
was
significantly
related
level
Patients
exhibit
enhanced
behavior,
as
both
by
questionnaire
laboratory
degradation.
This
automatic
tendency
is
reduced
dysregulation
caused
chronic
use.
