By: Sindhur Rao

May, 2016

Post-Traumatic Stress Disorder (PTSD) is a fear-related psychological disorder that has remained to be a therapeutic challenge for years. PTSD can result from witnessing or observing traumatic events that are possibly life-threatening, severely disturbing or that pose threatening bodily injuries.

Common traumatic events that can cause the progression of PTSD include witnessing or experiencing natural disasters, exposure to military combat, or sexual assault. Feelings of fear, horror, and helplessness, that result from these traumatic events, can eventually cause the development of PTSD. It is also characterized by three different types of symptoms among the ones listed. These symptoms are classified as re-experiencing symptoms, avoidance symptoms, and hyper-arousal symptoms (Yahuda et al., 2007). Re- experiencing symptoms are spontaneous recurrences of a traumatic memory usually in the form of nightmares that can cause severe physiological distress. Avoidance symptoms can cause the individual to want to distance themselves from any possible reminders of the traumatic event. This includes emotional and social distancing. Hyper-arousal symptoms involve physiological characteristics such as insomnia, impaired concentration, and irritability (Yahuda et al., 2007). The diagnosis and severity of PTSD depends not only of the various stressors that are presented to an individual at a certain time, but also on specific characteristics of the individual. PTSD has also been described as fear incubation which is a phenomenon defined as “a time-dependent increase in fear responses to trauma-associated cues” (Mumeko et al., 2015). This essentially means that the amount of fear will increase over time as long as the reminders of the specific trauma, the cues, are still actively apparent in the individual’s environment. This fear incubation process takes place in the amygdala (Mumeko et al., 2015). For years researchers have examined the amygdala and its neurological effects on PTSD patients in order to find possible mechanisms for future treatment or ways to prevent the disorder altogether.

The amygdala is a component of the limbic system that modulates emotional responses including fear. Due to its role in emotional processing and on various stress responses, it is clear that the amygdala has important roles on the development, signs, and symptoms of PTSD. The amygdala is also the source of a phenomenon called fear conditioning. Fear conditioning is when a neutral conditioned stimulus causes various fear responses after being associated with an unconditioned stressor. In the case of PTSD patients, individuals will react to a stressful or traumatic event with fear and arousal, but will proceed to express these same symptoms when presented with trauma-related cues months or even years after the traumatic event. Researchers have determined that this phenomenon occurs in the lateral nucleus of the amygdala (Sherin et al., 2011). Therefore, when an individual is exposed to any trauma-related cues, activity in the amygdala relays the information to the hypothalamic region that control behavioral components such as central arousal factors. This can cause the individual to see an event as a possible threat to his or her quality of life. The end result of this process causes the amygdala to also release catecholamines, ACTH, and cortisol into the circulatory system (Sherin et al., 2011. By understanding how the amygdala plays a key role in regulating our emotional processes and our fear responses, researchers can focus on these various mechanisms to find treatment and prevention techniques for PTSD.

In order to assess whether there is more activity in the amygdala of PTSD patients, a study was recently done in 2010 using functional magnetic resonance imaging to test if the amygdala of PTSD individuals would be heightened in response to emotionally neutral pictures as compared with a control group that did not suffer from the disorder. fMRI scans were performed on 10 patients with a mild form of PTSD and 10 control individuals who did not have the disorder (Brunetti, et al., 2010). The results of this study showed that the individuals with PTSD had hyperactive amygdala activity when viewing the neutral pictures compared with the control group who showed normal amygdala activity. Given this information, one can deduce that PTSD individuals have high activity in their amygdala. It is interesting to wonder if damage or alterations to the amygdala can reduce symptoms of fear and arousal in PTSD individuals (Brunetti, et al., 2010).

Furthermore, it was recently found that a neuropeptide called tuberoinfundibulnar peptide of 39 residues (TIP39) can actually regulate the phenomenon of fear incubation. As discussed previously, fear incubation is a major factor as to how symptoms of PTSD can develop and potentially worsen over time. Research has shown that the TIP39 along with the parathyroid hormone 2 receptor can influence various stress responses such as anxiety, nervousness, and other emotional behaviors and feelings associated with psychological disorders such as PTSD (Mumeko, et al., 2015). Both of these components are found in the amygdala, which is where the process of fear incubation occurs.. Therefore, it is possible that at a time of a stressful event inhibition of the PTH2R expressing neurons found in the medial amygdala can delay any fear or trauma recall and can prevent long-term consequences associated with developing PTSD. Additional peptides, such as Neuropeptide Y, have been used to asses psychological disorders as well. Researchers believe that variations in the morphology of neurons in the basolateral amygdala from prolonged stress can enhance Neuropeptide Y functions in the amygdala. This could pose as another mechanisms to provide further clues as to how the amygdala of PTSD patients is different from those who have not been diagnosed with the disorder (Cui, et al., 2008). Although structural changes in the amygdala of PTSD patients are not as well known and understood, focusing on its components, pathways, and on various expressing neurons and peptides such as PTH2R and TIP39, could provide potential insight on how to prevent or treat PTSD in individuals.

References

1. Brunetti, M., G. Sepede, and G. Mingoia. "Elevated response of human amygdala to neutral stimuli in mild post traumatic stress disorder: neural correlates of generalized emotional response." Elsevier Neuroscience. N.p., 14 July 2010. Web.

2. Cui, H., H. Sakamoto, and S. Higashi. "Effects of Single-prolonged Stress on Neurons and Their Afferent Inputs in the Amygdala." Elsevier: Article Locator. N.p., 27 Mar. 2008. Web. 27 May 2016.

3. Sherin, Jonathan E., and Charles B. Nemeroff. "Post-traumatic Stress Disorder: The Neurobiological Impact of Psychological Trauma." Dialogues in Clinical Neuroscience. Les Laboratoires Servier, 27 Sept. 2011. Web. 27 May 2016.

4. Tsuda, Mumeko C., Ho-Man Yeung, and Jonathan Kuo. "Incubation of Fear Is Regulated by TIP39 Peptide Signaling in the Medial Nucleus of the Amygdala." The Journal of Neuroscience. N.p., 2 Sept. 2015. Web.

5. Yahuda, Rachael, and Joseph LeDoux. "Response Variation following Trauma: A Translational Neuroscience Approach to Understanding PTSD." Neuron. N.p., 4 Oct. 2007. Web.