Communications Biology,
Год журнала:
2021,
Номер
4(1)
Опубликована: Сен. 15, 2021
Abstract
Autism
spectrum
disorder
(ASD)
is
commonly
understood
as
an
alteration
of
brain
networks,
yet
case-control
analyses
against
typically-developing
controls
(TD)
have
yielded
inconsistent
results.
Here,
we
devised
a
novel
approach
to
profile
the
inter-individual
variability
in
functional
network
organization
and
tested
whether
such
idiosyncrasy
contributes
connectivity
alterations
ASD.
Studying
multi-centric
dataset
with
157
ASD
172
TD,
obtained
robust
evidence
for
increased
relative
TD
default
mode,
somatomotor
attention
but
also
reduced
lateral
temporal
cortices.
Idiosyncrasy
age
significantly
correlated
symptom
severity
Furthermore,
while
patterns
were
not
ASD-related
cortical
thickness
alterations,
they
co-localized
expression
risk
genes.
Notably,
could
demonstrate
that
atypical
closely
overlapped
are
measurable
conventional
designs
may,
thus,
be
principal
driver
inconsistency
autism
connectomics
literature.
These
findings
support
important
interactions
between
heterogeneity
signatures.
Our
provide
biomarkers
study
development
may
consolidate
prior
research
on
variable
nature
connectome
level
anomalies
autism.
Journal of Anatomy,
Год журнала:
2019,
Номер
235(3), С. 432 - 451
Опубликована: Авг. 2, 2019
The
cerebral
cortex
constitutes
more
than
half
the
volume
of
human
brain
and
is
presumed
to
be
responsible
for
neuronal
computations
underlying
complex
phenomena,
such
as
perception,
thought,
language,
attention,
episodic
memory
voluntary
movement.
Rodent
models
are
extremely
valuable
investigation
development,
but
cannot
provide
insight
into
aspects
that
unique
or
highly
derived
in
humans.
Many
psychiatric
neurological
conditions
have
developmental
origins
studied
adequately
animal
models.
has
some
genetic,
molecular,
cellular
anatomical
features,
which
need
further
explored.
Anatomical
Society
devoted
its
summer
meeting
topic
Human
Brain
Development
June
2018
tackle
these
important
issues.
was
organized
by
Gavin
Clowry
(Newcastle
University)
Zoltán
Molnár
(University
Oxford),
held
at
St
John's
College,
Oxford.
participants
provided
a
broad
overview
structure
context
scaling
relationships
across
brains
mammals,
conserved
principles
recent
changes
lineage.
Speakers
considered
how
progenitors
diversified
generate
an
increasing
variety
cortical
neurons.
formation
earliest
circuits
generated
neurons
subplate
discussed
together
with
their
involvement
neurodevelopmental
pathologies.
Gene
expression
networks
susceptibility
genes
associated
diseases
were
compared
can
identified
organoids
developed
from
induced
pluripotent
stem
cells
recapitulate
vivo
development.
New
views
on
specification
glutamatergic
pyramidal
γ-aminobutyric
acid
(GABA)ergic
interneurons.
With
advancement
various
imaging
methods,
histopathological
observations
now
linked
normal
diseases.
Our
review
gives
general
evaluation
exciting
new
developments
areas.
much
enlarged
association
greater
interconnectivity
areas
each
other
expanded
thalamus.
relative
enlargement
upper
layers,
enhanced
diversity
function
inhibitory
interneurons
transient
layer
during
Here
we
highlight
studies
address
differences
emerge
development
focusing
diverse
facets
our
evolution.
Molecular Psychiatry,
Год журнала:
2020,
Номер
25(12), С. 3178 - 3185
Опубликована: Апрель 30, 2020
Abstract
The
current
diagnostic
practices
are
linked
to
a
20-fold
increase
in
the
reported
prevalence
of
ASD
over
last
30
years.
Fragmenting
autism
phenotype
into
dimensional
“autistic
traits”
results
alleged
recognition
autism-like
symptoms
any
psychiatric
or
neurodevelopemental
condition
and
individuals
decreasingly
distant
from
typical
population,
prematurely
dismisses
relevance
threshold.
Non-specific
socio-communicative
repetitive
DSM
5
criteria,
combined
with
four
quantitative
specifiers
as
well
all
their
possible
combinations,
render
limitless
variety
presentations
consistent
categorical
diagnosis
ASD.
We
propose
several
remedies
this
problem:
maintain
line
research
on
prototypical
autism;
limit
heterogeneity
compatible
situations
phenotypic
overlap
validated
etiological
link
reintroduce
qualitative
properties
specifiers,
language,
intelligence,
comorbidity,
severity
criteria
used
diagnose
replacement
“social”
“repetitive”
criteria;
use
these
features
clinical
intuition
experts
machine-learning
algorithms
differentiate
coherent
subgroups
today’s
spectrum;
study
separately,
then
compare
them;
question
autistic
nature
The
complex
pathophysiology
of
autism
spectrum
disorder
encompasses
interactions
between
genetic
and
environmental
factors.
On
the
one
hand,
hundreds
genes,
converging
at
functional
level
on
selective
biological
domains
such
as
epigenetic
regulation
synaptic
function,
have
been
identified
to
be
either
causative
or
risk
factors
autism.
other
exposure
chemicals
that
are
widespread
in
environment,
endocrine
disruptors,
has
associated
with
adverse
effects
human
health,
including
neurodevelopmental
disorders.
Interestingly,
experimental
results
suggest
an
overlap
regulatory
pathways
perturbed
by
mutations
factors,
depicting
convergences
interplays
susceptibility
toxic
insults.
pervasive
nature
chemical
poses
pivotal
challenges
for
neurotoxicological
studies,
agencies,
policy
makers.
This
highlights
emerging
need
developing
new
integrative
models,
biomonitoring,
epidemiology,
experimental,
computational
tools,
able
capture
real-life
scenarios
encompassing
interaction
chronic
mixture
substances
individuals'
backgrounds.
In
this
review,
we
address
intertwined
roles
lesions
Specifically,
outline
transformative
potential
stem
cell
coupled
omics
analytical
approaches
increasingly
single
resolution,
tools
experimentally
dissect
pathogenic
mechanisms
underlying
disorders,
well
improve
developmental
neurotoxicology
assessment.
The
cellular
complexity
of
the
human
brain
is
established
via
dynamic
changes
in
gene
expression
throughout
development
that
mediated,
part,
by
spatiotemporal
activity
cis-regulatory
elements
(CREs).
We
simultaneously
profiled
and
chromatin
accessibility
45,549
cortical
nuclei
across
six
broad
developmental
time
points
from
fetus
to
adult.
identified
cell
type-specific
domains
which
highly
correlated
with
expression.
Differentiation
pseudotime
trajectory
analysis
indicates
at
CREs
precedes
transcription
structure
play
a
critical
role
neuronal
lineage
commitment.
In
addition,
we
mapped
temporally
specific
genetic
loci
implicated
neuropsychiatric
traits,
including
schizophrenia
bipolar
disorder.
Together,
our
results
describe
complex
regulation
composition
stages
determination
shed
light
on
impact
alterations
disease.
Cell Reports,
Год журнала:
2023,
Номер
42(3), С. 112243 - 112243
Опубликована: Март 1, 2023
Advancing
from
gene
discovery
in
autism
spectrum
disorders
(ASDs)
to
the
identification
of
biologically
relevant
mechanisms
remains
a
central
challenge.
Here,
we
perform
parallel
vivo
functional
analysis
10
ASD
genes
at
behavioral,
structural,
and
circuit
levels
zebrafish
mutants,
revealing
both
unique
overlapping
effects
loss
function.
Whole-brain
mapping
identifies
forebrain
cerebellum
as
most
significant
contributors
brain
size
differences,
while
regions
involved
sensory-motor
control,
particularly
dopaminergic
regions,
are
associated
with
altered
baseline
activity.
Finally,
show
global
increase
microglia
resulting
function
select
implicating
neuroimmune
dysfunction
key
pathway
biology.
Journal of Autism and Developmental Disorders,
Год журнала:
2020,
Номер
51(12), С. 4321 - 4332
Опубликована: Сен. 17, 2020
Abstract
In
the
last
40
years,
there
has
been
a
huge
increase
in
autism
genetics
research
and
rapidly
growing
number
of
discoveries.
We
now
know
is
one
most
highly
heritable
disorders
with
negligible
shared
environmental
contributions.
Recent
discoveries
also
show
that
rare
variants
large
effect
size
as
well
small
common
gene
all
contribute
to
risk.
These
challenge
traditional
diagnostic
boundaries
highlight
heterogeneity
autism.
this
review,
we
consider
some
key
findings
are
shaping
current
understanding
what
these
mean
for
clinicians.
