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What Role Does Serotonin Play in PTSD?

What Role Does Serotonin Play in PTSD?

The DSM-IV defines a traumatic
event as one that involves a threat
of death or physical integrity to
self or others and results in a subjective
response of fear, helplessness or
horror. Epidemiological research disclosed
that up to 90% of US citizens
are exposed to at least one traumatic
event in the course of their lives (Breslau
and Kessler, 2001), while many more
are exposed to more than one event.

Data gathered from clinical and preclinical
research demonstrate a uniquely
homogeneous response to acute traumatic
exposure in both biology and
phenomenology. Thus, the initial physiological
response to threat should be
considered a normal adaptive survival
mechanism. However, short- and long-term
sequelae of traumatic exposure
greatly vary, ranging from complete recovery
to severe and debilitating PTSD.

The role of neuroimaging

The increasing availability and advancement
of neuroimaging technology provides
a solid backbone for ongoing
studies aimed at deciphering neurological
differences between subjects
diagnosed with psychiatric disorders,
such as PTSD, and healthy controls.
Existing neuroimaging techniques,
including positron emission tomography (PET), single photon computed
tomography (SPECT) and functional
magnetic resonance imaging (fMRI),
offer the ability to assess regional cerebral
blood flow and glucose metabolism
in PTSD subjects in vivo. Previous
studies have included subjects scanned
while in a resting state; during pharmacologic
challenges; while engaged
in cognitive tasks; or experiencing functional
stimuli (such as viewing faces
depicting various emotional states).
Functional imaging allows for pairing the visualization of brain activity with
paradigms and tasks designed to elicit
activation in specific brain areas, thus
parsing out hypothesized differences
between subject groups. PET additionally
provides a modality for examining
neurotransmitter systems. By
studying specific neuronal pathways
throughout the brain that distribute
neurotransmitters such as serotonin (5-HT) and dopamine (DA), we are able
to gain an understanding of how alterations
in brain function may contribute
to anomalous behavioral traits (eg,
PTSD symptomatology).

Imaging studies have already begun
helping researchers distinguish brain
pathways and neuronal circuits that may
be associated with behavior, such as
the involvement of the amygdala in
emotional processing (Figure 1). Techniques
differ in resolution, radioligand availability and analysis methods, providing
an array of imaging options.

The latest generation of PET scanners
is now capable of distinguishing
differences in some smaller brain
regions such as the raphe and amygdala.
Using fMRI, studies in larger
samples may provide definitive answers
regarding cerebral blood flow differences
between PTSD subjects and
controls. MRI studies may also focus
on brain volume comparisons, revealing
possible structural abnormalities (i.e., atrophy) in brain regions associated
with PTSD.

Ultimately, neuronal circuits are not
independently operating mechanisms,
with each translating into one specific
behavioral phenomenon. Rather, they
work in conjunction with multiple pathways
and neurotransmitter systems.
Thus, utilizing various neuroimaging
techniques is useful in identifying
regions of altered activity and may
contribute to understanding the underlying
pathophysiology of PTSD.

Serotonergic mechanisms

Different types of acute stress result in
increased 5-HT turnover in the medial
prefrontal cortex (mPFC), nucleus accumbens,
amygdala and lateral hypothalamus
in experimental animals (Inoue
et al., 1994). However, exposure to repeated stress within a learned-helplessness
model resulted in a decrease of
5-HT release in the frontal cortex (possibly
reflecting 5-HT depletion by continued


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