PTSD and Norepinephrine

    Memory storage in the brain is a very complex subject, and in this article, the effects of the Noradrenaline or Norepinephrine release on the strength of memory will be described and related to the development of PTSD. Vanneste et al., in their study, used transcranial direct current stimulation of the greater occipital lobe to upregulate memory performance through the locus coeruleus (Vanneste et al., 2020). The locus coeruleus promotes the release of norepinephrine, and this has been correlated with the increase in connectivity strength between the locus coeruleus, amygdala, and hippocampus (Vanneste et al., 2020). These are critical regions for memory storage. Vanneste et al. found through three behavioral experiments in human models using face-name and word association memory tasks that occipital nerve stimulation (norepinephrine release) increased memory capacity. Tests were also conducted in a rodent model to prove this increase in memory function (Vanneste et al., 2020). Norepinephrine is also an essential hormone released in stressful events and has been shown to increase memory consolidation in the hippocampus in mice and rat studies (Bahtiyar et al., 2020). This strengthening of memories related to stressful events raises the idea that norepinephrine may have a role in post-traumatic stress disorder (PTSD). PTSD often develops when someone is exposed to severe trauma to themselves or another person (Hendrickson et al., 2018).

    Hendrickson et al., in their study, tried to look at the effects of trauma exposure on the reactivity of the brain and the variations in norepinephrine levels in people who do not have trauma and those who have PTSD. The study estimated the presynaptic outflow of norepinephrine in the central nervous system by measuring the amount of norepinephrine in cerebrospinal fluid (Hendrickson et al., 2018). The researchers found an increased response in the body to norepinephrine in participants who faced trauma, especially in those with PTSD (Hendrickson et al., 2018). In addition, there was an increase in postsynaptic receptors of norepinephrine, allowing for the increased effect of the hormone in participants who had faced trauma. They also found that even with high norepinephrine levels, participants without trauma showed no negative behavioral symptoms (Hendrickson et al., 2018). This finding was further clarified by the finding that there was a decreased activation of the medial prefrontal cortex in the participants who faced trauma (Hendrickson et al., 2018). The medial prefrontal cortex is necessary for buffering norepinephrine levels, which explains why participants who did not face trauma did not show negative behavioral symptoms. The study also found reduced neuropeptide Y levels in PTSD patients (Hendrickson et al., 2018). This is important because neuropeptide Y can attenuate the body's response to norepinephrine. With PTSD patients having a lower amount of this in their bodies, it heightens the impact of norepinephrine on the body (Hendrickson et al., 2018). 

    Suppose all the effects of norepinephrine are looked at in combination with the Vanneste et al. and Hendrickson et al. studies. In that case, it can highlight the role of norepinephrine in PTSD development. Vanneste et al. show a correlation between norepinephrine release and increased memory function. The Hendrickson et al. study shows a permanent change in the body's sensitivity to norepinephrine post-trauma. PTSD has a vital memory component, and the hypersensitivity to norepinephrine may heighten the risks of developing this disorder. This may be valuable information in treating patients and screening soldiers before sending them to combat. Drugs such as Prazosin combat this sensitivity to norepinephrine in PTSD patients (Hendrickson et al., 2018). However, additional research is required to examine genetic factors predisposing individuals to norepinephrine sensitivity and whether it can be used as a predictive factor for PTSD. 

Citations: 

Hendrickson RC, Raskind MA, Millard SP, Sikkema C, Terry GE, Pagulayan KF, Li G, Peskind ER. Evidence for altered brain reactivity to norepinephrine in Veterans with a history of traumatic stress. Neurobiol Stress. 2018 Mar 15;8:103-111. doi: 10.1016/j.ynstr.2018.03.001. PMID: 29888305; PMCID: PMC5991318. 

Vanneste S, Mohan A, Yoo HB, Huang Y, Luckey AM, McLeod SL, Tabet MN, Souza RR, McIntyre CK, Chapman S, Robertson IH, To WT. The peripheral effect of direct current stimulation on brain circuits involving memory. Sci Adv. 2020 Nov 4;6(45):eaax9538. doi: 10.1126/sciadv.aax9538. PMID: 33148657; PMCID: PMC7673706. 

Bahtiyar S, Gulmez Karaca K, Henckens MJAG, Roozendaal B. Norepinephrine and glucocorticoid effects on the brain mechanisms underlying memory accuracy and generalization. Mol Cell Neurosci. 2020 Oct;108:103537. doi: 10.1016/j.mcn.2020.103537. Epub 2020 Aug 14. PMID: 32805389.