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 neuroimagingThe 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(Drug information on 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 in PTSDDifferent 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 release).
