A new study suggests that
disruptions in energy metabolism contribute to stress-related anxiety.
What links anxiety and mitochondria?
Anxiety disorders
is the umbrella term for several conditions that manifest with symptoms such as
feelings of worry, fear, and panic.
In
the United States, 18.1% of
the population live with an anxiety disorder. These conditions include general
anxiety disorder, panic disorder, social anxiety disorder,
and selective mutism.
Stress, particularly
during childhood, is a risk factor for developing an anxiety disorder. Other
risk factors include being female and having a relative with anxiety or
depressive disorders.
Yet,
while experts can identify these risk factors, it is not really clear what
makes some people more susceptible to the condition than others.
"The underlying reasons for these differences
are not yet fully understood but involve an interaction of complex genetic and
environmental factors that vary among individuals, resulting in stress
susceptibility or resilience," explains Iiris Hovatta, a professor in the
Department of Psychology and Logopedics at the University of Helsinki in
Finland.
Along
with a team of international collaborators, Hovatta has been investigating
which biological pathways underpin stress-related anxiety in mouse models and
humans.
Stress and resilience in mice
The
team has previously shown that
laboratory mice vary in their resilience to stress, just like humans. Interestingly,
the percentage of resilient mice is not the same in different strains.
The
resilience percentage ranges from 5% in the DBA/2NCrl (D2) mouse strain to 69%
in the C57BL/6NCrl (B6) strain.
Presenting
their latest findings in the journal PLOS Genetics, Hovatta and her colleagues made use of
this fact by studying the brains and blood of animals belong to these two
strains after exposing them to what they call chronic social defeat stress
(CSDS).
"It
involves 10 days of brief daily confrontation of two [...] male mice, a
resident-aggressor and an intruder who reacts with defensive, flight, or
submissive behavior," the authors explain in the paper.
"Although
all defeated mice experience stressful stimuli, only some develop
stress-related symptoms, measured as social avoidance, making it an excellent
model to investigate mechanisms associated with susceptibility and
resilience."
After
the CSDS test, the animals displayed significant changes in gene expression and
protein levels in a brain region called the bed nucleus of the stria terminalis
(BNST).
The BNST is
in the forebrain, and researchers are increasingly linking it to
stress-related mental health conditions.
These
changes had a particularly prominent association with mitochondria.
These small structures — that scientists refer to as the cell's powerhouses —
are present in the majority of our cells and responsible for energy production.
Strikingly, in the stress susceptible D2 mouse
strain, several genes related to mitochondrial functions were expressed at
lower levels, while in the stress resilient B6 mouse strain, these were
expressed at higher levels.
The
team saw a similar pattern of gene expression in the blood of the animals.
Trend also in people with panic disorder
For
the second part of their study, Hovatta and her colleagues worked with 21
volunteers — 6 men and 15 women — who attended the anxiety disorder outpatient
unit at the Max Planck Institute of Psychiatry in Munich, Germany.
Each
participant had a diagnosis of panic
disorder, and none took medication for the condition.
The
team exposed each study participant to the trigger that causes them to
experience a panic attack.
During the experiment, the researchers collected blood samples prior to, as
well as 1 hour and 24 hours after exposure.
When
they analyzed gene expression in the cells present in the volunteers' blood,
they also saw changes in genes they associated with mitochondria.
The changes in gene expression most closely
resembled the pattern seen in the D2 mice exposed to CSDS, with several
mitochondrial genes expressed at lower levels.
"Thus,
although we found opposite gene expression patterns in the two mouse strains,
the pattern of the highly stress susceptible mouse strain resembled that of
panic disorder patients," the authors comment in the paper.
Based
on their results, the team thinks this indicates that reduced expression of
several key mitochondrial genes could lead to changes in cellular energy
metabolism in mice and people who experience stress-induced anxiety.
Hovatta
has made the data from the study publicly available and invites other
researchers to develop further working theories on the biological mechanisms
that underpin stress-induced anxiety in humans and animal models.
"Very little is known about how
chronic stress may affect cellular energy metabolism and thereby influence
anxiety symptoms. The underlying mechanisms may offer a key to new targets for
therapeutic interventions of stress-related diseases."
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