Psychiatric literature commonly refers to trauma in the context of posttraumatic stress disorder (PTSD) related to adverse childhood events, consequences to Veterans of the Armed Forces, and natural and human-made disasters. Unfortunately, in our contemporary environment, we need to be more expansive in our recognition of trauma to include political violence such as genocide, ethnic war, and displacement; cultural violence, such as school and cyber bullying; and community violence, such as school and mass shootings. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders defines trauma as “exposure to actual or threatened death, serious injury, or sexual violence in one (or more)…ways” (American Psychiatric Association [APA], 2013, p. 271), including directly experiencing or witnessing traumatic events and/or experiencing repeated exposure to aversive details of traumatic events. This definition, however, tends to narrow our focus to a distinctive and discrete diagnosis even as clinical experience demonstrates that individuals with many other diagnoses have an underlying dynamic of trauma in their lives (Isobel & Delgado, 2018). The current article focuses on the neurobiological consequences of trauma, symptomatology, and psychopharmacological treatment beyond the distinct diagnosis of PTSD.
How Common Is PTSD?
The lifetime prevalence of PTSD is between 6% and 9%, with 84% of the population having been exposed to trauma and 8% of those individuals diagnosed with PTSD (Ostrowski & Delahanty, 2014). Women have a two- to three-fold likelihood of a PTSD diagnosis (Ostrowski & Delahanty, 2014), and 25% of American children experience at least one traumatic event by the time they are 16 years old (Connor, Ford, Arnsten, & Greene, 2015). Armed Forces Veterans are likely to experience war trauma; 30% of Veterans of the Vietnam War were diagnosed with PTSD, whereas Veterans of Operation Enduring Freedom/Operation Iraqi Freedom have a lifetime prevalence of PTSD of 12% (Goodson, Lefkowitz, Helstrom, & Gawrysiak, 2013). Steel, Dunlavy, Harding, and Theorell (2017) noted that more than 50 million individuals have been displaced due to political or social conflict and found that 89% of Sub-Saharan African immigrants experienced traumatic events, with 47% diagnosed with PTSD. Indeed, human-made disasters have significantly greater psychological effects than natural disasters (Garcini et al., 2017; Myles et al., 2018).
Neurobiology of Trauma
Stress affects the neuronal circuitry of the prefrontal cortex, amygdala, hippocampus, and hypothalamic-pituitary-adrenal axis (HPA). The amygdala is involved in the recognition and management of extreme emotions of fear, aggression, and sexual encounters (LeDoux, 2015). The thalamus relays sensory input to the amygdala in a quick, direct route to signal the muscles, sympathetic nervous system, and hypothalamus to react immediately to danger. In a slower fashion, the amygdala relates the fear to conditioned memory through the prefrontal cortex to connect the fear stimulus to deliberate learning. It is this pathway that provides anticipatory anxiety about stimuli (e.g., when seeing a coiled object on the ground as the image or memory of a snake). Enduring memories are stored in the neocortex, amygdala, and hippocampus (Higgins, 2018), thereby allowing individuals to appraise potentially harmful events and take deliberate actions. However, in PTSD, positron emission tomography shows increased reactivity in the amygdala but decreased activity in the medial prefrontal cortex, indicating perceiving the object without fully thinking about the appraisal (Higgins, 2018). Individuals who have experienced trauma, therefore, are hyperresponsive to potential alarms without the ability to moderate responsiveness through thoughtful appraisal. Memory is an important element of traumatic responses. A traumatic event is initially encoded in the hippocampus as an emotional memory, and connections of the hippocampal perirhinal cortex to the medial temporal lobe form a conscious memory. If the memory is not consolidated (i.e., processed by the frontal cortex and stored), retrieval is impaired and distorted, resulting in symptoms such as flashbacks, dissociations, and negative cognitions (LeDoux, 2015). In patients with PTSD, especially chronic PTSD, hippocampal volume is decreased; yet with effective treatment, the hippocampus responds to brain-derived neurotrophic factor to return to normal size (LeDoux, 2015).
Clinical studies show that patients with PTSD have persistently activated central nervous systems with elevated norepinephrine levels (Strawn & Geracioti, 2008). The noradrenergic pathway connects the prefrontal cortex, amygdala, hippocampus, hypothalamus, periaqueductal gray, and thalamus. Adrenergic receptors have two major subtypes, alpha and beta. Ordinarily, after a fearful stimulus, noradrenergic activity decreases; however, in PTSD, the negative feedback to restore the system back to normal is disrupted (Strawn & Geracioti, 2008). Because norepinephrine stimulates the hypothalamus and sympathetic nervous system, it also activates the HPA. Again, the HPA normally has a negative feedback mechanism whereby activation of corticotropin-releasing hormone in the hypothalamus signals adrenocortico-tropic hormone for an immediate protective response that is modulated by the parasympathetic system to restore homeostasis (Higgins, 2018). If there is significant downregulation of the HPA with loss of that negative feedback to correct the system, the patient remains in a state of hyperarousal (LeDoux, 2015).
Dopamine, serotonin, gamma-aminobutyric acid (GABA), and glutamate are also neurotransmitters implicated in the stress response. Dopamine alters neuronal activity to signal satisfaction (by way of the nucleus accumbens and striatum) and increases the likelihood of that signal recurring (i.e., reinforces learning that a certain response may or may not bring pleasure). Serotonin is essential in fear memory, and inhibition of the serotonin transporter as well as downregulation of serotonin receptors contribute to memory extinction (Young et al., 2017). That is, once the fear is understood, the stimulus is no longer viewed as fearful, but rather as something that previously evoked fear. GABA, the major inhibitory neurotransmitter, regulates neural firing rate to prevent overstimulation with a net effect of calming neural response (Cortese & Phan, 2005; Higgins, 2018). Excessive GABA contributes to sluggishness, difficulty thinking, and emotional numbing. In contrast to GABA, glutamate is the major excitatory neurotransmitter and is associated with neuronal migration/differentiation and memory consolidation. Glutamate works in collaboration with dopamine in the nucleus accumbens to produce pleasure/satisfaction in response to a stimulus (Nishi et al., 2015). All of these neurotransmitters become important in pharmacological treatment of PTSD.
Treatment of trauma requires a focus on target symptoms more so than diagnosis, especially because there is significant comorbidity of depression, anxiety, and stress. The hallmark symptom clusters of trauma include (APA, 2013):
- hyperarousal (manifested by irritability, hypervigilance, excessive startle, and sleep disturbances),
- intrusive experiences (manifested by sudden memories, dreams, dissociations and flashbacks, and reactions to similar cues to the trauma),
- avoidance (manifested by emotional numbing and withdrawal), and
- negative cognitions and mood (manifested by memory lapses, exaggerated negative beliefs, self-blame and shame, anger, and loss of interest).
The first line of treatment is serotonin reuptake inhibitors (SRIs) and/or serotonin norepinephrine reuptake inhibitors (SNRIs) to address hyperarousal symptoms. Increasing the availability of serotonin, especially in the limbic system and frontal cortex, acts as a counterbalance of norepinephrine. Similarly, SNRIs counter-act the downregulation of serotonin receptors and reinstitute the negative feedback loop in the HPA (Higgins, 2018; LeDoux, 2015). Studies have shown consistent efficacy in treating PTSD with sertraline, citalopram, venlafaxine, duloxetine, and fluoxetine (Bandelow et al., 2012; Connor et al., 2015; Kobayashi, Patel, & Lotito, 2015). SRIs have also shown efficacy in preventing new fear memories in patients undergoing prolonged exposure psychotherapy (Burghardt, Sigurdsson, Gorman, McEwen, & LeDoux, 2013). Key to efficacy is sufficient dosage over a sufficient trial period of 8 to 12 weeks. If SRIs or SNRIs are ineffective, mirtazapine, nefazodone, vilazodone, tricyclic antidepressant agents, and monoamine oxidase inhibitors (MAOIs; specifically phenelzine) should be tried (Cooper, Carty, & Creamer, 2005; Kobayashi et al., 2015). Prescribers need to be especially cautious when using tricyclic antidepressant agents and MAOIs with patients who may have suicidal ideation and behaviors, as these medications can have toxic/fatal effects when taken in overdose.
Serotonin dopamine antagonist agents (e.g., risperidone, olanzapine) and benzodiazepine drugs have been found less effective and the risks outweigh the benefits (Abrams, Lund, Bernardy, & Friedman, 2013; Kobayashi et al., 2015). Benzodiazepine drugs are still heavily used to treat anxiety symptoms; however, the ultimate effect is avoidance and negative cognition symptoms as well as potential for tolerance and dependence.
As an alternative to benzodiazepine drugs, adrenergic blocking agents (e.g., propranolol, prazosin, doxazosin) show greater promise in modulating hyperarousal and intrusive symptoms (Connor et al., 2015; Kobayashi et al., 2015; Ostrowski & Delahanty, 2014). These agents are especially beneficial in treating nightmares, night terrors, and sleep avoidance. Adrenergic blocking agents require titration to full abatement of symptoms and monitoring for hypotension. There is some evidence that administering adrenergic blocking agents when patients initially present for traumatizing events in emergency settings or military deployment may mitigate or prevent the development of PTSD (Ostrowski & Delahanty, 2014). As noted in the neurobiological section, adrenergic blocking agents can stop the sympathetic arousal after the event has occurred, thereby averting downregulation of the negative feedback loop. The individual will still remember events and experience emotional response but without excessive and prolonged or delayed arousal to achieve remission of symptoms.
In addition to pharmacotherapy, psychotherapy is an effective adjunctive treatment for those experiencing traumatizing events or underlying traumatic response in comorbid conditions such as depression and substance use disorders (Black, 2006; Müller et al., 2015). Pharmacotherapy allows patients to tolerate psychotherapy and learn new behaviors to cope and recover from trauma. Cognitive-behavioral therapy, eye movement desensitization and reprocessing therapy, and exposure therapy have been especially effective (Chen, Zhang, Hu, & Liang, 2015; Stein & Rothbaum, 2018; Wheeler, 2014). SRIs may interfere with exposure therapy by preventing fear extinction; therefore, it is essential to coordinate treatment with the psychotherapist and prescriber (if different). In contrast, propranolol, prazosin, and doxazosin permit patients to experience emotional response in exposure therapy without hyperarousal.
Trauma arouses intensive neurobiological mechanisms as a survival strategy, which could lead to severe chronic stress responses and disability. Although PTSD can be considered a distinctive psychiatric disorder, it likely underlies many other psychiatric disorders. Psychiatric–mental health nurses need to carefully assess for trauma symptomatology in all populations. Pharmacotherapy should focus on priority of target symptoms with first-line medications including SRIs, SNRIs, and adrenergic blocking agents. Psychotherapy is an effective adjunct to pharmacotherapy in treating trauma-related conditions.
- Abrams, T.E., Lund, B.C., Bernardy, N.C. & Friedman, M.J. (2013). Aligning clinical practice to PTSD treatment guidelines: Medication prescribing by provider type. Psychiatric Services, 64, 142–148. doi:10.1176/appi.ps.201200217 [CrossRef]
- American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author.
- Bandelow, B., Sher, L., Bunevicius, R., Hollander, E., Kasper, S., Zohar, J. & Möller, H.J. (2012). Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. International Journal of Psychiatry in Clinical Practice, 16, 77–84. doi:10.3109/13651501.2012.667114 [CrossRef]
- Black, D.W. (2006). Efficacy of combined pharmacotherapy and psychotherapy versus monotherapy in the treatment of anxiety disorders. CNS Spectrums, 11, 29–33. doi:10.1017/S1092852900025827 [CrossRef]
- Burghardt, N.S., Sigurdsson, T., Gorman, J.M., McEwen, B.S. & LeDoux, J.E. (2013). Chronic antidepressant treatment impairs the acquisition of fear extinction. Biological Psychiatry, 73, 1078–1086. doi:10.1016/j.biopsych.2012.10.012 [CrossRef]
- Chen, L., Zhang, G., Hu, M. & Liang, X. (2015). Eye movement desensitization and reprocessing versus cognitive-behavioral therapy for adult posttraumatic stress disorder: A systematic review and meta-analysis. Journal of Nervous and Mental Disease, 203, 443–451. doi:10.1097/NMD.0000000000000306 [CrossRef]
- Connor, D.F., Ford, J.D., Arnsten, A.F. & Greene, C.A. (2015). An update on post-traumatic stress disorder in children and adolescents. Clinical Pediatrics, 54, 517–528. doi:10.1177/0009922814540793 [CrossRef]
- Cooper, J., Carty, J. & Creamer, M. (2005). Pharmacotherapy for posttraumatic stress disorder: Empirical review and clinical recommendations. Australian and New Zealand Journal of Psychiatry, 39, 674–682. doi:10.1080/j.1440-1614.2005.01651.x [CrossRef]
- Cortese, B.M. & Phan, K.L. (2005). The role of glutamate in anxiety and related disorders. CNS Spectrums, 10, 820–841. doi:10.1017/S1092852900010427 [CrossRef]
- Garcini, L.M., Peña, J.M., Gutierrez, A.P., Fagundes, C.P., Lemus, H., Lindsay, S. & Klonoff, E.A. (2017). “One scar too many”: The associations between traumatic events and psychological distress among undocumented Mexican immigrants. Journal of Traumatic Stress, 30, 453–462. doi:10.1002/jts.22216 [CrossRef]
- Goodson, J.T., Lefkowitz, C.M., Helstrom, A.W. & Gawrysiak, M.J. (2013). Outcomes of prolonged exposure therapy for veterans with posttraumatic stress disorder. Journal of Traumatic Stress, 26, 419–425. doi:10.1002/jts.21830 [CrossRef]
- Higgins, E. (2018). The neuroscience of clinical psychiatry (3rd ed.). Philadelphia, PA: Wolters Kluwer.
- Isobel, S. & Delgado, C. (2018). Safe and collaborative communication skills: A step towards mental health nurses implementing trauma informed care. Archives of Psychiatric Nursing, 32, 291–296. doi:10.1016/j.apnu.2017.11.017 [CrossRef]
- Kobayashi, T.M., Patel, M. & Lotito, M. (2015). Pharmacotherapy for posttraumatic stress disorder at a Veterans Affairs facility. American Journal of Health-System Pharmacy, 72(Suppl. 1), S11–S15. doi:10.2146/ajhp150095 [CrossRef]
- LeDoux, J. (2015). Anxious: Using the brain to understand and treat fear and anxiety. New York, NY: Penguin Books.
- Müller, M., Rodgers, S., Rössler, W., Castelao, E., Preisig, M., Ajdacic-Gross, V. & Vandeleur, C. (2015). Discrepancies between clinical needs and help seeking behaviors in co-occurring posttraumatic stress and alcohol use disorders. Comprehensive Psychiatry, 62, 209–217. doi:10.1016/j.comppsych.2015.07.013 [CrossRef]
- Myles, P., Swenshon, S., Haase, K., Szeles, T., Jung, C., Jacobi, F. & Rath, B. (2018). A comparative analysis of psychological trauma experienced by children and young adults in two scenarios: Evacuation after a natural disaster vs forced migration to escape armed conflict. Public Health, 158, 163–175. doi:10.1016/j.puhe.2018.03.012 [CrossRef]
- Nishi, D., Hashimoto, K., Noguchi, H., Hamazaki, K., Hamazaki, T. & Matsuoka, Y. (2015). Glutamatergic system abnormalities in posttraumatic stress disorder. Psychopharmacology, 232, 4261–4268. doi:10.1007/s00213-015-4052-5 [CrossRef]
- Ostrowski, S. & Delahanty, D. (2014). Prospects for the pharmacological prevention of post-traumatic stress in vulnerable individuals. CNS Drugs, 28, 195–203. doi:10.1007/s40263-014-0145-7 [CrossRef]
- Steel, J.L., Dunlavy, A.C., Harding, C.E. & Theorell, T. (2017). The psychological consequences of pre-emigration trauma and post-migration stress in refugees and immigrants from Africa. Journal of Immigrant and Minority Health, 19, 523–532. doi:10.1007/s10903-016-0478-z [CrossRef]
- Stein, M.B. & Rothbaum, B.O. (2018). 175 years of progress in PTSD therapeutics: Learning from the past. American Journal of Psychiatry, 175, 508–516. doi:10.1176/appi.ajp.2017.17080955 [CrossRef]
- Strawn, J.R. & Geracioti, T.D. Jr. . (2008). Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder. Depression & Anxiety, 25, 260–271. doi:10.1002/da.20292 [CrossRef]
- Wheeler, K. (2014). Stabilization for trauma and dissociation. In Psychotherapy for the advanced practice psychiatric nurse (2nd ed.). New York, NY: Springer.
- Young, M.B., Norrholm, S.D., Khoury, L.M., Jovanovic, T., Rauch, S.A.M., Reiff, C.M. & Howell, L.L. (2017). Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3, 4-methylenedoxy-methamphetamine (MDMA). Psychopharmacology, 234, 2883–2895. doi:10.1007/s00213-017-4684-8 [CrossRef]