|Trust-building Hormone Short-circuits Fear in Humans
A brain chemical recently found to boost trust appears to work by reducing
activity and weakening connections in fear-processing circuitry, a brain imaging
study at the National Institutes of Health’s (NIH) National Institute of Mental
Health (NIMH) has discovered. Scans of the hormone oxytocin’s effect on human
brain function reveal that it quells the brain’s fear hub, the amygdala, and
its brainstem relay stations in response to fearful stimuli. The work at NIMH
and a collaborating site in Germany suggests new approaches to treating diseases
thought to involve amygdala dysfunction and social fear, such as social phobia,
autism, and possibly schizophrenia, report Andreas Meyer-Lindenberg, M.D., Ph.D.,
NIMH Genes Cognition and Psychosis Program, and colleagues, in the December 7,
2005 issue of the Journal of Neuroscience.
“Studies in animals, pioneered by now NIMH director Dr. Thomas Insel, have shown
that oxytocin plays a key role in complex emotional and social behaviors, such
as attachment, social recognition and aggression” noted NIH Director Elias Zerhouni,
M.D.. “Now, for the first time, we can literally see these same mechanisms at
work in the human brain.”
“The observed changes in the amygdala are exciting as they suggest that a long-acting
analogue of oxytocin could have therapeutic value in disorders characterized
by social avoidance,” added Insel.
Inspired by Swiss scientists who last summer reported1 that
oxytocin increased trust in humans, Meyer-Lindenberg and colleagues quickly mounted
a brain imaging study that would explore how this works at the level of brain circuitry.
British researchers had earlier linked increased amygdala activity to decreased
trustworthiness2. Having just discovered decreased
amygdala activity (http://www.nimh.nih.gov/press/williamspathway.cfm)
in response to social stimuli in people with a rare genetic brain disorder that
rendered them overly trusting of others, Meyer-Lindenberg hypothesized that oxytocin
boosts trust by suppressing the amygdala and its fear-processing networks.
To test this idea, he asked 15 healthy men to sniff oxytocin or a placebo prior
to undergoing a functional magnetic resonance imaging (fMRI) scan, which reveals
what parts of the brain that are activated by particular activities. While in
the scanner, the men performed tasks known to activate the amygdala (http://www.nimh.nih.gov/Press/pramygdala.cfm) — matching
angry or fearful faces and threatening scenes.
As expected, the threatening pictures triggered strong activation of the amygdala
during the placebo scan, but markedly less activity following oxytocin. The difference
was especially pronounced in response to threatening faces, suggesting a pivotal
role for oxytocin in regulating social fear. In addition, oxytocin dampened the
amygdala’s communication with sites in the upper brainstem that telegraph the
fear response. The results mirrored findings in rats3,
reported earlier this year by European scientists.
“Because increased amygdala activation has been associated with social fear
in social phobia, genetic risk for anxiety and depression, and possibly with
social fear in autism assessed during faces processing, this dual mode of action
of oxytocin in humans suggests a potentially powerful treatment approach toward
socially relevant fear,” suggest the researchers.
People with autism characteristically avert their gaze from faces. A fMRI study4 reported
earlier this year by NIMH grantee Richard Davidson, Ph.D., University of Wisconsin,
and colleagues, found over-activation of the amygdala in people with autism when
they were looking at faces. Meyer-Lindenberg said future studies may test oxytocin
as a treatment for such social anxiety symptoms in children with autism.
“Future research may also examine how oxytocin affects the amygdala in women,
the mode of action of related hormones such as vasopressin, and how genetic variants
in these hormones and their receptors affect brain function,” he added.
Also participating in the research were: Peter Kirsch, Christin Esslinger, Daniela
Mier, Stefanie Lis, Harald Gruppe, Bernd Gallhofer, Justus-Liebig University,
Giessen, Germany; Qiang Chen, Sarina Siddhanti, Venkata Mattay, NIMH Genes Cognition
and Psychosis Program.
|Functional magnetic resonance imaging
data (red) superimposed on structural MRI scans. Frightful faces triggered
a dramatic reduction in amygdala activity in subjects who had sniffed
oxytocin, suggesting that oxytocin mediates social fear and trust via
the amygdala and related circuitry.
Source: NIMH Genes, Cognition and Psychosis Program
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