PLoS Computational Biology,
Journal Year:
2023,
Volume and Issue:
19(4), P. e1010986 - e1010986
Published: April 10, 2023
Reduced
cortical
inhibition
by
somatostatin-expressing
(SST)
interneurons
has
been
strongly
associated
with
treatment-resistant
depression.
However,
due
to
technical
limitations
it
is
impossible
establish
experimentally
in
humans
whether
the
effects
of
reduced
SST
interneuron
on
microcircuit
activity
have
signatures
detectable
clinically-relevant
brain
signals
such
as
electroencephalography
(EEG).
To
overcome
these
limitations,
we
simulated
resting-state
and
EEG
using
detailed
models
human
microcircuits
normal
(healthy)
or
(depression),
found
that
depression
exhibited
increased
theta,
alpha
low
beta
power
(4–16
Hz).
The
changes
involved
a
combination
an
aperiodic
broadband
periodic
theta
components.
We
then
demonstrated
specificity
showing
they
were
distinct
from
those
corresponding
parvalbumin-expressing
(PV)
inhibition.
Our
study
thus
links
level
features
microcircuits,
which
can
serve
better
identify
mechanistic
subtypes
EEG,
non-invasively
monitor
modulation
Science Advances,
Journal Year:
2020,
Volume and Issue:
6(49)
Published: Dec. 3, 2020
Gut
microbiome
disturbances
have
been
implicated
in
major
depressive
disorder
(MDD).
However,
little
is
known
about
how
the
gut
virome,
microbiome,
and
fecal
metabolome
change,
they
interact
MDD.
Here,
using
whole-genome
shotgun
metagenomic
untargeted
metabolomic
methods,
we
identified
3
bacteriophages,
47
bacterial
species,
50
metabolites
showing
notable
differences
abundance
between
MDD
patients
healthy
controls
(HCs).
Patients
with
were
mainly
characterized
by
increased
of
genus
Bacteroides
decreased
genera
Blautia
Eubacterium
These
multilevel
omics
alterations
generated
a
characteristic
coexpression
network.
Disturbed
microbial
genes
consistently
mapped
to
amino
acid
(γ-aminobutyrate,
phenylalanine,
tryptophan)
metabolism.
Furthermore,
combinatorial
marker
panel
that
robustly
discriminated
from
HC
individuals
both
discovery
validation
sets.
Our
findings
provide
deep
insight
into
understanding
roles
disturbed
ecosystem
Parkinson's
disease
(PD)
is
a
progressive
neurodegenerative
brain
due
to
degeneration
of
dopaminergic
neurons
(DNs)
presented
with
motor
and
non-motor
symptoms.
PD
symptoms
are
developed
in
response
the
disturbance
diverse
neurotransmitters
including
γ-aminobutyric
acid
(GABA).
GABA
has
neuroprotective
effect
against
neuropathology
by
protecting
DNs
substantia
nigra
pars
compacta
(SNpc).
It
been
shown
that
GABAergic
linked
progression
neurotransmission
necessary
pathway
for
normal
sleep
patterns,
thus
deregulation
could
be
potential
cause
disorders
PD.
Brain Sciences,
Journal Year:
2025,
Volume and Issue:
15(2), P. 161 - 161
Published: Feb. 6, 2025
Background/Objectives:
Non-response
to
initial
treatment
options
for
major
depressive
disorder
(MDD)
is
a
common
clinical
challenge
with
profound
deleterious
impacts
affected
patients.
Few
treatments
have
received
regulatory
approval
treatment-resistant
depression
(TRD).
Methods:
A
systematic
search
of
United
States
and
European
Union
trials
registries
was
conducted
identify
Phase
II,
III,
or
IV
trials,
last
update
posted
on
after
1
January
2020,
that
were
evaluating
medications
TRD.
For
both
the
US
EU
registries,
condition
term
"treatment
resistant
depression"
associated
lower-level
terms
(per
registry
protocol)
used.
registry,
secondary
using
"depressive
disorders"
modifying
"inadequate"
also
performed
capture
registrations
not
tagged
as
Two
additional
searches
in
"suicide"
"anhedonia"
transdiagnostic
targets
investigational
medications.
Trials
categorized
based
primary
mechanism
action
trial's
medication.
Results:
Fifty
TRD,
20
anhedonia,
25
suicide
identified.
Glutamate
system
modulation
currently
most
compounds
development,
including
antagonists
allosteric
modulators
NMDA
receptors,
AMPA
metabotropic
type
2/3
glutamate
intracellular
effector
molecules
downstream
signaling.
Psychedelics
seen
greatest
surge
among
mechanistic
past
5
years,
however,
psilocybin
particular
garnering
significant
attention.
Other
mechanisms
included
GABA
modulators,
monoamine
anti-inflammatory/immune-modulating
agents,
an
orexin
2
receptor
antagonist.
Conclusions:
These
investigations
offer
substantial
promise
more
efficacious
potentially
personalized
medication
approaches
Challenges
detecting
efficacy
TRD
include
heterogeneity
within
population
stemming
from
presumed
variety
biological
dysfunctions
underlying
disorder,
comorbid
disorders,
chronic
psychosocial
stressors,
enduring
effects
prior
serotonergic
antidepressant
treatments.
npj Aging and Mechanisms of Disease,
Journal Year:
2021,
Volume and Issue:
7(1)
Published: Jan. 4, 2021
Alzheimer's
disease
(AD)
is
the
leading
cause
of
dementia
in
aging
individuals.
Yet,
pathophysiological
processes
involved
AD
onset
and
progression
are
still
poorly
understood.
Among
numerous
strategies,
a
comprehensive
overview
gene
expression
alterations
diseased
brain
could
contribute
for
better
understanding
pathology.
In
this
work,
we
probed
differential
genes
different
regions
healthy
adult
subjects
using
data
from
three
large
transcriptomic
studies:
Mayo
Clinic,
Mount
Sinai
Brain
Bank
(MSBB),
ROSMAP.
Using
combination
isoform
switch
analyses,
provide
detailed
landscape
temporal
frontal
lobes,
harboring
areas
affected
at
early
late
stages
pathology,
respectively.
Next,
took
advantage
an
indirect
approach
to
assign
complex
changes
revealed
bulk
RNAseq
individual
cell
types/subtypes
brain.
This
strategy
allowed
us
identify
previously
overlooked
patients.
these
alterations,
show
switches
causal
amyloid-beta
precursor
protein
(APP)
risk
bridging
integrator
1
(BIN1),
which
have
important
functional
consequences
neuronal
cells.
Altogether,
our
work
proposes
novel
integrative
analyze
other
neurodegenerative
diseases
based
on
both
gene/transcript
regional/cell-type
specificities.
