Molecular Psychiatry,
Journal Year:
2023,
Volume and Issue:
28(5), P. 1843 - 1856
Published: April 11, 2023
Abstract
The
synaptic
hypothesis
of
schizophrenia
has
been
highly
influential.
However,
new
approaches
mean
there
a
step-change
in
the
evidence
available,
and
some
tenets
earlier
versions
are
not
supported
by
recent
findings.
Here,
we
review
normal
development
from
structural
functional
imaging
post-mortem
studies
that
this
is
abnormal
people
at
risk
with
schizophrenia.
We
then
consider
mechanism
could
underlie
changes
update
hypothesis.
Genome-wide
association
have
identified
number
variants
converging
on
pathways
regulating
elimination,
formation
plasticity,
including
complement
factors
microglial-mediated
pruning.
Induced
pluripotent
stem
cell
demonstrated
patient-derived
neurons
show
pre-
post-synaptic
deficits,
signalling
alterations,
elevated,
complement-dependent
elimination
structures
compared
to
control-derived
lines.
Preclinical
data
environmental
linked
schizophrenia,
such
as
stress
immune
activation,
can
lead
synapse
loss.
Longitudinal
MRI
patients,
prodrome,
divergent
trajectories
grey
matter
volume
cortical
thickness
controls,
PET
shows
vivo
for
lower
density
patients
Based
evidence,
propose
version
III
This
multi-hit
model,
whereby
genetic
and/or
render
synapses
vulnerable
excessive
glia-mediated
triggered
during
later
neurodevelopment.
loss
disrupts
pyramidal
neuron
function
cortex
contribute
negative
cognitive
symptoms
disinhibits
projections
mesostriatal
regions
dopamine
overactivity
psychosis.
It
accounts
typical
onset
adolescence/early
adulthood,
its
major
factors,
symptoms,
identifies
potential
synaptic,
microglial
targets
treatment.
Physiological Reviews,
Journal Year:
2019,
Volume and Issue:
99(4), P. 1877 - 2013
Published: Aug. 28, 2019
The
importance
of
the
gut-brain
axis
in
maintaining
homeostasis
has
long
been
appreciated.
However,
past
15
yr
have
seen
emergence
microbiota
(the
trillions
microorganisms
within
and
on
our
bodies)
as
one
key
regulators
function
led
to
appreciation
a
distinct
microbiota-gut-brain
axis.
This
is
gaining
ever
more
traction
fields
investigating
biological
physiological
basis
psychiatric,
neurodevelopmental,
age-related,
neurodegenerative
disorders.
brain
communicate
with
each
other
via
various
routes
including
immune
system,
tryptophan
metabolism,
vagus
nerve
enteric
nervous
involving
microbial
metabolites
such
short-chain
fatty
acids,
branched
chain
amino
peptidoglycans.
Many
factors
can
influence
composition
early
life,
infection,
mode
birth
delivery,
use
antibiotic
medications,
nature
nutritional
provision,
environmental
stressors,
host
genetics.
At
extreme
diversity
diminishes
aging.
Stress,
particular,
significantly
impact
at
all
stages
life.
Much
recent
work
implicated
gut
many
conditions
autism,
anxiety,
obesity,
schizophrenia,
Parkinson’s
disease,
Alzheimer’s
disease.
Animal
models
paramount
linking
regulation
fundamental
neural
processes,
neurogenesis
myelination,
microbiome
activation
microglia.
Moreover,
translational
human
studies
are
ongoing
will
greatly
enhance
field.
Future
focus
understanding
mechanisms
underlying
attempt
elucidate
microbial-based
intervention
therapeutic
strategies
for
neuropsychiatric
JAMA Psychiatry,
Journal Year:
2019,
Volume and Issue:
77(2), P. 201 - 201
Published: Oct. 30, 2019
Importance
Schizophrenia
is
a
common,
severe
mental
illness
that
most
clinicians
will
encounter
regularly
during
their
practice.
This
report
provides
an
overview
of
the
clinical
characteristics,
epidemiology,
genetics,
neuroscience,
and
psychopharmacology
schizophrenia
to
provide
basis
understand
disorder
its
treatment.
educational
review
integrated
with
case
highlight
how
recent
research
findings
can
inform
understanding.
Observations
The
first
theme
considered
role
early-life
environmental
genetic
risk
factors
in
altering
neurodevelopmental
trajectories
predispose
individual
leading
development
prodromal
symptoms.
second
cortical
excitatory-inhibitory
imbalance
cognitive
negative
symptoms
disorder.
third
considers
psychosocial
stressors,
psychological
factors,
subcortical
dopamine
dysfunction
onset
positive
final
mechanisms
underlying
treatment
for
common
adverse
effects
Conclusions
Relevance
has
complex
presentation
multifactorial
cause.
Nevertheless,
advances
neuroscience
have
identified
roles
key
circuits,
particularly
involving
frontal,
temporal,
mesostriatal
brain
regions,
positive,
negative,
Current
pharmacological
treatments
operate
using
same
mechanism,
blockade
D2receptor,
which
contribute
effects.
However,
circuit
discussed
herein
identify
novel
potential
targets
may
be
particular
benefit
symptom
domains
not
well
served
by
existing
medications.
Science,
Journal Year:
2020,
Volume and Issue:
367(6478), P. 688 - 694
Published: Feb. 7, 2020
Microglia
modulate
memories
Synaptic
reorganization
and
circuit
rewiring
leads
to
loss
or
weakening
of
connections
between
neurons
may
result
in
the
erasure
previously
formed
memories.
eliminate
excessive
synapses
developing
brain
regulate
dynamics
synaptic
throughout
life.
However,
it
is
still
unclear
whether
forgetting
related
microglia
activity
how
memory
adult
brain.
Wang
et
al.
discovered
that
eliminated
components
hippocampus
depleting
inhibiting
phagocytosis
prevented
forgetting.
Synapse
elimination
by
thus
lead
degradation
engrams
learned
contextual
fear
memory.
Science
,
this
issue
p.
688
Clinical Microbiology Reviews,
Journal Year:
2022,
Volume and Issue:
35(1)
Published: Jan. 5, 2022
The
human
body
is
full
of
an
extensive
number
commensal
microbes,
consisting
bacteria,
viruses,
and
fungi,
collectively
termed
the
microbiome.
initial
acquisition
microbiota
occurs
from
both
external
maternal
environments,
vast
majority
them
colonize
gastrointestinal
tract
(GIT).
These
microbial
communities
play
a
central
role
in
maturation
development
immune
system,
nervous
GIT
system
are
also
responsible
for
essential
metabolic
pathways.
Various
factors,
including
host
genetic
predisposition,
environmental
lifestyle,
diet,
antibiotic
or
nonantibiotic
drug
use,
etc.,
affect
composition
gut
microbiota.
Recent
publications
have
highlighted
that
imbalance
microflora,
known
as
dysbiosis,
associated
with
onset
progression
neurological
disorders.
Moreover,
characterization
microbiome-host
cross
talk
pathways
provides
insight
into
novel
therapeutic
strategies.
Novel
preclinical
clinical
research
on
interventions
related
to
microbiome
treating
conditions,
autism
spectrum
disorders,
Parkinson's
disease,
schizophrenia,
multiple
sclerosis,
Alzheimer's
epilepsy,
stroke,
hold
significant
promise.
This
review
aims
present
comprehensive
overview
potential
involvement
pathogenesis
particular
emphasis
microbe-based
therapies
and/or
diagnostic
biomarkers.
discusses
health
benefits
administration
probiotics,
prebiotics,
postbiotics,
synbiotics
fecal
transplantation
Nature Communications,
Journal Year:
2020,
Volume and Issue:
11(1)
Published: Jan. 14, 2020
Synaptic
dysfunction
is
hypothesised
to
play
a
key
role
in
schizophrenia
pathogenesis,
but
this
has
not
been
tested
directly
vivo.
Here,
we
investigated
synaptic
vesicle
glycoprotein
2A
(SV2A)
levels
and
their
relationship
symptoms
structural
brain
measures
using
[11C]UCB-J
positron
emission
tomography
18
patients
with
controls.
We
found
significant
group
group-by-region
interaction
effects
on
volume
of
distribution
(VT).
VT
was
significantly
lower
the
frontal
anterior
cingulate
cortices
large
effect
sizes
(Cohen's
d
=
0.8-0.9),
there
no
difference
hippocampus.
also
antipsychotic
drug
administration
SV2A
Sprague-Dawley
rats
western
blotting,
[3H]UCB-J
autoradiography
immunostaining
confocal
microscopy,
finding
any
measure.
These
findings
indicate
that
are
terminal
protein
vivo
exposure
unlikely
account
for
them.
