Mainstreaming Diagnostic Genetic Testing and Precision Medicine for Autism Spectrum Disorder
Psychiatric Clinics of North America,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 1, 2025
Language: Английский
Genomic and Developmental Models to Predict Cognitive and Adaptive Outcomes in Autistic Children
JAMA Pediatrics,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 21, 2025
Importance
Although
early
signs
of
autism
are
often
observed
between
18
and
36
months
age,
there
is
considerable
uncertainty
regarding
future
development.
Clinicians
lack
predictive
tools
to
identify
those
who
will
later
be
diagnosed
with
co-occurring
intellectual
disability
(ID).
Objective
To
predict
ID
in
children
autism.
Design,
Setting,
Participants
This
prognostic
study
involved
the
development
validation
models
integrating
genetic
variants
developmental
milestones
ID.
Models
were
trained,
cross-validated,
tested
for
generalizability
across
3
cohorts:
Simons
Foundation
Powering
Autism
Research
(SPARK),
Simplex
Collection,
MSSNG.
Autistic
participants
assessed
older
than
6
years
age
Study
data
analyzed
from
January
2023
July
2024.
Exposures
Ages
at
attaining
milestones,
occurrence
language
regression,
polygenic
scores
cognitive
ability
autism,
rare
copy
number
variants,
de
novo
loss-of-function
missense
impacting
constrained
genes.
Main
Outcomes
Measures
The
out-of-sample
performance
was
using
area
under
receiver
operating
characteristic
curve
(AUROC),
positive
values
(PPVs),
negative
(NPVs).
Results
A
total
5633
autistic
(4574
male
[81.2%])
included
this
analysis.
On
average,
4
(IQR,
3-7)
11
(8-14)
1159
(20.6%)
being
model
all
predictors
yielded
an
AUROC
0.653
(95%
CI,
0.625-0.681),
cross-validated
generalized
cohorts.
modest
reflected
that
only
a
subset
individuals
carried
large-effect
high
scores,
or
presented
delayed
milestones.
However,
combinations
typically
not
considered
clinically
relevant
by
diagnostic
laboratories
achieved
PPVs
55%
correctly
identified
10%
developing
addition
specifically
improved
NPVs
rather
PPVs.
Notably,
stratify
probabilities
up
2-fold
higher
compared
typical
Conclusions
Relevance
suggest
growing
neurodevelopmental
condition–associated
cannot,
most
cases,
used
alone
predicting
combining
different
classes
provide
individual-level
predictions
could
useful
targeting
interventions.
Language: Английский
New technology and emerging theories driving progress in neuropsychiatric disorders
Fundamental Research,
Journal Year:
2024,
Volume and Issue:
4(6), P. 1349 - 1350
Published: Nov. 1, 2024
Language: Английский
Prepartum bumetanide treatment reverses altered neonatal social communication but nonspecifically reduces postpubertal social behavior in a mouse model of fragile X syndrome
Genomic psychiatry :,
Journal Year:
2024,
Volume and Issue:
unknown, P. 1 - 12
Published: Dec. 24, 2024
Fragile
X
syndrome
is
caused
by
monogenic
silencing
of
the
FMR1
gene
and
characterized
high
rates
autism
spectrum
disorder.
A
previous
study
demonstrated
that
prepartum
administration
bumetanide,
a
chloride
transporter
blocker,
normalized
neonatal
vocalization
in
non-congenic
Fmr1
knockout
(KO)
pups.
However,
genuine
contribution
deletion
to
this
phenotype
congenic
KO
mouse
model
long-lasting
effect
bumetanide
on
postpubertal
social
interaction
remains
unclear.
The
current
aimed
determine
impact
at
postnatal
day
7
6
8
weeks
age
which
genetic
backgrounds
were
homogeneous
between
wild-type
(WT)
littermates.
Moreover,
we
applied
computational
analytical
algorithm
determined
predictive
variables
for
interaction.
Our
data
showed
(1)
mice
exhibited
altered
numbers
sequences
distinct
call
types
during
reduced
weeks,
(2)
select
sets
predicted
levels,
(3)
restored
pups
but
nonspecifically
WT
weeks.
These
indicate
selectively
impacts
elements
Additionally,
restores
has
transient
nonspecific
negative
subsequent
Language: Английский