Abstract
As
global
population
ages,
maintaining
cognitive
health
in
elderly
is
crucial.
Previous
studies
suggest
a
positive
link
between
healthy
aging
and
cognition,
but
the
neural
mechanisms
remain
unclear.
This
study
used
genome-wide
association
studydata
to
investigate
cognition.
We
employed
2-sample
Mendelian
randomization
evaluate
causal
relationship
(indexed
by
multivariate
genetic
predictor,
mvAge)
6
measurements.
then
2-step
approach
mediation
analysis
identify
brain
imaging-derived
phenotypes
potentially
mediating
this
relationship.
indicated
that
had
with
various
functions
(common
executive
function,
intelligence,
performance,
fluid
intelligence
score).
Two-step
identified
27
having
robust
relationships
Mediation
suggested
volume
of
subcallosal
cortex
might
mediate
effects
on
all
4
functions.
Volume
cerebellum’s
VIIb
could
common
functions,
while
fractional
anisotropy
anterior
thalamic
radiation
performance.
These
findings
specific
regions
may
play
potential
role
maintenance.
Neuropsychopharmacology,
Год журнала:
2021,
Номер
47(1), С. 72 - 89
Опубликована: Авг. 18, 2021
Concepts
of
cognitive
control
(CC)
and
executive
function
(EF)
are
defined
in
terms
their
relationships
with
goal-directed
behavior
versus
habits
controlled
automatic
processing,
related
to
the
functions
prefrontal
cortex
(PFC)
regions
networks.
A
psychometric
approach
shows
unity
diversity
CC
constructs,
3
components
most
commonly
studied
constructs:
general
or
common
specific
mental
set
shifting
working
memory
updating.
These
constructs
considered
against
cellular
systems
neurobiology
PFC
what
is
known
its
functional
neuroanatomical
network
organization
based
on
lesioning,
neurochemical,
neuroimaging
approaches
across
species.
also
context
motivation,
as
"cool"
"hot"
forms.
Its
Common
component
shown
be
distinct
from
intelligence
(g)
closely
response
inhibition.
Impairments
possible
causes
psychiatric
symptoms
consequences
disorders.
The
factor
psychopathology
(p)
dimensional
such
impulsivity
large
scale
developmental
adult
populations
considered,
well
implications
for
genetic
studies
RDoC
classification.
Nature Neuroscience,
Год журнала:
2024,
Номер
27(6), С. 1075 - 1086
Опубликована: Апрель 22, 2024
Abstract
Human
brain
organization
involves
the
coordinated
expression
of
thousands
genes.
For
example,
first
principal
component
(C1)
cortical
transcription
identifies
a
hierarchy
from
sensorimotor
to
association
regions.
In
this
study,
optimized
processing
Allen
Brain
Atlas
revealed
two
new
components
gene
architecture,
C2
and
C3,
which
are
distinctively
enriched
for
neuronal,
metabolic
immune
processes,
specific
cell
types
cytoarchitectonics,
genetic
variants
associated
with
intelligence.
Using
additional
datasets
(PsychENCODE,
Cell
BrainSpan),
we
found
that
C1–C3
represent
generalizable
transcriptional
programs
within
cells
differentially
phased
during
fetal
postnatal
development.
Autism
spectrum
disorder
schizophrenia
were
specifically
C1/C2
respectively,
across
neuroimaging,
differential
genome-wide
studies.
Evidence
converged
especially
in
support
C3
as
normative
program
adolescent
development,
can
lead
atypical
supragranular
connectivity
people
at
high
risk
schizophrenia.
Alzheimer s & Dementia,
Год журнала:
2025,
Номер
21(2)
Опубликована: Фев. 1, 2025
Abstract
INTRODUCTION
The
presence
of
psychosis
in
Alzheimer's
disease
(AD)
is
suggested
to
be
associated
with
distinct
molecular
and
neuropathological
profiles
the
brain.
METHODS
We
assessed
brain
DNA
methylation
AD
donors
(AD+P)
without
(AD−P)
using
EPIC
array.
Weighted
gene
correlation
network
analysis
identified
modules
co‐methylated
genes
a
discovery
cohort
(PITT‐ADRC:
N
=
113
AD+P,
40
AD−P),
validation
an
independent
(BDR:
79
117
Gene
Ontology
cell‐type
enrichment
analysis.
Genetic
data
were
integrated
identify
quantitative
trait
loci
(mQTLs),
which
co‐localized
GWAS
for
related
traits.
RESULTS
replicated
one
AD+P
module,
was
enriched
synaptic
pathways
excitatory
inhibitory
neurons.
mQTLs
this
module
variants
schizophrenia
educational
attainment.
DISCUSSION
This
represents
largest
epigenetic
study
date,
identifying
pleiotropic
relationships
between
Highlights
prefrontal
cortex
subjects
AD−P.
WGCNA
six
cohort.
One
mapping
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 31, 2025
ABSTRACT
Genetic
research
on
nicotine
dependence
has
utilized
multiple
assessments
that
are
in
weak
agreement.
We
conducted
a
genome-wide
association
study
of
defined
using
the
Diagnostic
and
Statistical
Manual
Mental
Disorders
(DSM-NicDep)
61,861
individuals
(47,884
European
ancestry,
10,231
African
3,746
East
Asian
ancestry)
compared
results
to
other
nicotine-related
phenotypes.
replicated
well-known
at
CHRNA5
locus
(lead
SNP:
rs147144681,
p
=1.27E-11
ancestry;
lead
SNP
=
rs2036527,
6.49e-13
cross-ancestry
analysis).
DSM-NicDep
showed
strong
positive
genetic
correlations
with
cannabis
use
disorder,
opioid
problematic
alcohol
use,
lung
cancer,
material
deprivation,
several
psychiatric
disorders,
negative
respiratory
function
educational
attainment.
A
polygenic
score
predicted
DSM-5
tobacco
disorder
6
11
individual
diagnostic
criteria,
but
none
Fagerström
Test
for
Nicotine
Dependence
(FTND)
items,
independent
NESARC-III
sample.
In
genomic
structural
equation
models,
loaded
more
strongly
previously
identified
factor
general
addiction
liability
than
did
“problematic
use”
(a
combination
cigarettes
per
day
by
FTND).
Finally,
was
genetically
correlated
GWAS
as
electronic
health
records,
suggesting
combining
wide
availability
EHR
data
nuanced
criterion-level
analyses
DSM
may
produce
new
insights
into
genetics
this
disorder.
Frontiers in Human Neuroscience,
Год журнала:
2023,
Номер
17
Опубликована: Июль 24, 2023
Executive
functions
(EFs)
are
linked
to
positive
outcomes
across
the
lifespan.
Yet,
methodological
challenges
have
prevented
precise
understanding
of
developmental
trajectory
their
organization.We
introduce
novel
methods
address
for
both
measuring
and
modeling
EFs
using
an
accelerated
longitudinal
design
with
a
large,
diverse
sample
students
in
middle
childhood
(N
=
1,286;
ages
8
14).
We
used
eight
adaptive
assessments
hypothesized
measure
three
EFs,
working
memory,
context
monitoring,
interference
resolution.
deployed
equate
EF
challenge
data-driven,
network
analytic
approach
reveal
evolving
diversity
while
simultaneously
accounting
unity.Using
this
paradigm
shift
brought
new
precision
clarity
development
these
showing
tasks
organized
into
stable
components
by
age
10,
but
refinement
composition
continues
through
at
least
14.
Frontiers in Neuroscience,
Год журнала:
2023,
Номер
17
Опубликована: Авг. 11, 2023
Background
and
purpose
Executive
function
impairment,
a
slight
but
noticeable
cognitive
deficit
in
mild
impairment
(MCI)
patients,
is
influenced
by
gamma-aminobutyric
acid
(GABA)
levels.
Reduced
accompanied
thinning
of
the
cerebral
cortex,
which
has
higher
GABA
levels
than
white
matter.
However,
relationships
among
levels,
cortical
thickness,
executive
MCI
patients
have
not
yet
been
elucidated.
We
investigated
patients.
Methods
In
this
study,
total
36
sex-,
age-,
education-matched
healthy
controls
(HC)
were
recruited.
But
33
35
HC
included
because
head
motion
or
poor
data
quality
for
three
one
HC.
The
plus
relative
to
creatine
(GABA+/Cr)
glutamate-glutamine
(Glx/Cr)
anterior
cingulate
cortex
(ACC)
posterior
(PCC)
measured
using
Meshcher-Garwood
point
resolved
spectroscopy
(MEGA-PRESS)
sequence.
Metabolite
ratios,
their
interrelationships
determined
groups.
Results
Patients
with
showed
lower
GABA+/Cr
ACC
PCC.
Combined
GABA+
Glx
PCC
good
diagnostic
efficacy
(AUC:
0.82).
no
differences
thickness
found
between
two
group,
level
was
correlated
worse
performance
on
digit
span
test
backward,
shape
trail
test-B.
associated
Conclusion
These
results
implied
that
decreased
had
critical
role
early
diagnosis
impaired
MCI.
Therefore,
could
be
potential
marker
decline
