Disease DescriptionPTSD or Post Traumatic Stress Disorder is classified as a psychiatric disorder that occurs in the aftermath of a traumatic experience or simply in the threat of one.

Acute stress disorder is a condition that develops immediately after traumatic experience and if persisted for more than one month, is classified as PTSD. Symptoms include flashback and emotional detachment1.

The condition first gained attention from its prevalence in combat veterans after war, taking on names like ‘shellshock’ in the period of WWI as well as ‘combat fatigue’ in WWII2. These terms are, however, still in use to describe specific PTSDs induced by combat experience. 

From an evolutionary standpoint, the development of PTSD may be associated with survival mechanisms to prevent the occurrence of next traumatic events. The state of hyperarousal for example, demands one to stay on alert and avoid potentially harmful situations3.

Lifetime PTSD prevalence rate in the general population is 6.4% to 7.8% and 20% in war veterans4,5.

Sources:
1.        Bryant, R. A., Moulds, M. L., & Guthrie, R. M. (2000). Acute Stress Disorder Scale: a self-report measure of acute stress disorder. Psychological assessment, 12(1), 61.
2.        Monson, C. M., Friedman, M. J., & La Bash, H. A. (2007). A psychological history of PTSD. Handbook of PTSD: Science and practice, 37-52.
3.        Silove, D. (1998). Is posttraumatic stress disorder an overlearned survival response? An evolutionary-learning hypothesis. Psychiatry, 61(2), 181-190.
4.        Pietrzak, Robert H., Risë B. Goldstein, Steven M. Southwick, and Bridget F. Grant. “Prevalence and Axis I comorbidity of full and partial posttraumatic stress disorder in the United States: results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions.” Journal of anxiety disorders 25, no. 3 (2011): 456-465.
5.        Seal, Karen H., Thomas J. Metzler, Kristian S. Gima, Daniel Bertenthal, Shira Maguen, and Charles R. Marmar. “Trends and risk factors for mental health diagnoses among Iraq and Afghanistan veterans using Department of Veterans Affairs health care, 2002–2008.” American journal of public health 99, no. 9 (2009): 1651-1658.

Causes of the DiseaseThe experience of trauma is closely associated with PTSD.

Besides combat personnels, survivors of violence (physical/sexual. etc) as well as survivors of disasters (man made/natural. etc) are similarly at risk for developing PTSD, with experience of sexual violence being the type of trauma with highest risk1.

Types of trauma includes:
1. Unexpected trauma (eg. witness of sudden death)
2. Intense one-time trauma (eg. being victim of torture)
3. Persisting long-term trauma (eg. harassment or warzone, which may lead to ‘Complex PTSD’, with symptoms more intense)

There are hereditary factors to the development of PTSD as well, as the patients are found to share genetic traits with those who suffer from general anxiety disorders, increasing susceptibility. 

Other factors include neurological, as individuals with smaller hippocampus are found to be more likely to suffer from PTSD2.

Sources:
1.        Kessler, R. C., Aguilar-Gaxiola, S., Alonso, J., Benjet, C., Bromet, E. J., Cardoso, G., … & Koenen, K. C. (2017). Trauma and PTSD in the WHO world mental health surveys. European journal of psychotraumatology, 8(sup5), 1353383.
2.        Quidé, Y., Andersson, F., Dufour‐Rainfray, D., Descriaud, C., Brizard, B., Gissot, V., … & El‐Hage, W. (2018). Smaller hippocampal volume following sexual assault in women is associated with post‐traumatic stress disorder. Acta Psychiatrica Scandinavica, 138(4), 312-324.

Pathophysiology of the DiseaseNote: the pathophysiology of PTSD is not completely understood and varies from patient to patient, but there are important strides that allow us to gain some insight on the mechanisms of disease symptoms

1. Studies have shown reduced volumes of right hippocampus, left amygdala, right ventromedial prefrontal cortex (vmPFC), and anterior cingulate cortex in PTSD patients1,4. vmPFC aberrations are thought to be a mechanism that leads to the progression of PTSD to comorbidities like depression4

2. Abnormal function and functional connectivity (FC) between the hippocampal subregions and regions of emotion and cognitive processing like amygdala, cingulate cortex, and medial prefrontal cortex (mPFC) may contribute to maladaptive cognition and fear responses, and impaired stress regulation3,6.

3. An increase in the central norepinephrine levels of networks connecting to the amygdala and hypothalamus may produce dysfunctional fear conditioning, emotional fear memories, arousal, and vigilance in PTSD patients1,2,6.

4. Serotonin (5HT) system dysfunctions are also observed: Anxiogenic 5HT2 receptors are upregulated and anxiolytic 5HT1A receptors are downregulated in chronic stressed animal models6. SSRIs administered to PTSD patients exert their therapeutic effects by enhancing downregulated serotonin levels to better regulate sleep, mood, appetite and anxiety.

5. Surprisingly, reduced glucocorticoid levels/ hypocortisolism (cortisol aka a stress hormone) has been detected in PTSD patients (with inconsistencies in some studies) probably due to enhanced negative feedback of the HPA axis, to control for heightened stress responses6. Dysregulation of the HPA axis this way may lead to abnormal stress reactivity and fear processing in PTSD patients6.

6. Genetic contributions to PTSD have been observed: Exposure to stress/trauma while harbouring the serotonin transporter promoter variant 5-HTTLPR may predict PTSD5. Large-scale genetics studies suggest the influence of thousands of loci in the genome to contribute to PTSD6.

Sources:
1.        Sareen, Jitender. “Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis.” Retrieved from UpToDate website: https://www. uptodate. com/contents/posttraumatic-stress-disorder-in-adultsepidemiology-pathophysiology-clinical-manifestations-course-assessment-anddiagnosis (2018).
2.        Bailey, Christopher R., Elisabeth Cordell, Sean M. Sobin, and Alexander Neumeister. “Recent progress in understanding the pathophysiology of post-traumatic stress disorder.” CNS drugs 27, no. 3 (2013): 221-232.
3.        Malivoire, Bailee L., Todd A. Girard, Ronak Patel, and Candice M. Monson. “Functional connectivity of hippocampal subregions in PTSD: relations with symptoms.” BMC psychiatry 18, no. 1 (2018): 1-9.
4.        Morey, Rajendra A., Courtney C. Haswell, Stephen R. Hooper, and Michael D. De Bellis. “Amygdala, hippocampus, and ventral medial prefrontal cortex volumes differ in maltreated youth with and without chronic posttraumatic stress disorder.” Neuropsychopharmacology 41, no. 3 (2016): 791-801.
5.        Zhao, Mingzhe, Jiarun Yang, Wenbo Wang, Jingsong Ma, Jian Zhang, Xueyan Zhao, Xiaohui Qiu et al. “Meta-analysis of the interaction between serotonin transporter promoter variant, stress, and posttraumatic stress disorder.” Scientific reports 7, no. 1 (2017): 1-10
6.        Sherin, Jonathan E., and Charles B. Nemeroff. “Post-traumatic stress disorder: the neurobiological impact of psychological trauma.” Dialogues in clinical neuroscience 13, no. 3 (2011): 263.

Risk Factors of DiseaseRisks factors for PTSD make it more likely that an individual who has a traumatic encounter develops symptoms of PTSD:

Pretrauma factors1,2,3:
1. Gender- Women are 2-3 times as likely to develop PTSD than men.
2. Race3,7 – (based in the US) Being indigenous people of the Americas and African Americans have a higher risk for PTSD compared to non-Latina/o Whites. Latina/os have higher conditional risks for PTSD than non-Latina/o whites and Asians have a low risk for PTSD after trauma.

Note: although ethnic/racial differences are found in PTSD, there are inconsistencies among some studies and they are not well understood. 

3. Lower socioeconomic status, social support and education level.
4. History of physical disease, familial and personal history of psychiatric disorders
5. Younger age at trauma
6. Previous traumatic experiencesChildhood abuse and general childhood adversity

Peritrauma factors1,3:
1. Nature of trauma – Trauma severity, initial severity reaction to the trauma, intentional trauma than unintentional trauma, exposure to trauma over an extended period.

Early neuroanatomical risk factors:
1. Hippocampal and Cavum Septum Pellucidum (CSP) volume- Low hippocampal volume has shown to interact with CSP volume, potentially predicting the severity and progression of PTSD symptoms4. Low hippocampal volumes have been indicated as a risk factor for the development of PTSD in females who have been sexually assaulted5.
2. Abnormal structure function and connectivity between the amygdala and dorsal anterior cingulate cortex6.

Sources:
1.        Sareen, Jitender. “Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis.” Retrieved from UpToDate website: https://www. uptodate. com/contents/posttraumatic-stress-disorder-in-adultsepidemiology-pathophysiology-clinical-manifestations-course-assessment-anddiagnosis (2018).
2.        Olff, Miranda. “Sex and gender differences in post-traumatic stress disorder: an update.” European journal of psychotraumatology 8, no. sup4 (2017): 1351204.
3.        Tortella-Feliu, Miquel, Miquel A. Fullana, Ana Pérez-Vigil, Xavier Torres, Jacobo Chamorro, Sergio A. Littarelli, Aleix Solanes et al. “Risk factors for posttraumatic stress disorder: An umbrella review of systematic reviews and meta-analyses.” Neuroscience & Biobehavioral Reviews 107 (2019): 154-165.
4.        Ben-Zion, Ziv, Moran Artzi, Dana Niry, Nimrod Jackob Keynan, Yoav Zeevi, Roee Admon, Haggai Sharon et al. “Neuroanatomical risk factors for posttraumatic stress disorder in recent trauma survivors.” Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 5, no. 3 (2020): 311-319.
5.        Quidé, Y., F. Andersson, D. Dufour‐Rainfray, C. Descriaud, B. Brizard, V. Gissot, H. Cléry et al. “Smaller hippocampal volume following sexual assault in women is associated with post‐traumatic stress disorder.” Acta Psychiatrica Scandinavica 138, no. 4 (2018): 312-324.
6.        Hendler, Talma, and Roee Admon. “Predisposing risk factors for PTSD: Brain biomarkers.” Comprehensive Guide to Post-Traumatic Stress Disorders. Cham: Springer International Publishing (2016): 61-75.
7.        Alegría, Margarita, Lisa R. Fortuna, Julia Y. Lin, L. Frances Norris, Shan Gao, David T. Takeuchi, James S. Jackson, Patrick E. Shrout, and Anne Valentine. “Prevalence, risk, and correlates of posttraumatic stress disorder across ethnic and racial minority groups in the US.” Medical care 51, no. 12 (2013): 1114.

Signs/ Symptoms/ Presentation of Disease.Symptoms of PTSD most often start within 3 months of a traumatic event, but for some people it may not appear until years after the event.

PTSD symptoms generally fall into four categories1,4,5:

A. Intrusion:
1. Flashbacks – where people feel as if they are relieving the traumatic event over and over again.
2. Vivid, frequent nightmares about the event.
3. Hallucinations – intense intrusive imagery.
4. Intense mental and physical distress when reminded of the event such as palpitations, sweating, nausea and trembling.

B. Avoidance3:
1. Avoidance of reminders of the event, such as places, people, thoughts and situations.
2. Detachment and isolation from family and friends.
3. Inability to feel emotions (emotionally numb).
4. Feeling physically numb or detached from your body.
5. Diminished interest in activities that the person once enjoyed.
6. Using alcohol or drugs to avoid memories.

C. Arousal and reactivity:
1. Poor concentration.
2. Getting startled easily.
3. Persistent anxiety- a constant feeling of being on edge.
4. Irritability,outbursts of anger and aggressive behavior.
5. Insomnia.

D. Cognition and mood2:
1. Negative thoughts about yourself,other people or the world.
2. Feelings of guilt, worry or blaming yourself for what happened.
3. Feeling detached from family and friends and difficulty in maintaining close relationships.
4. Difficulty in experiencing positive emotions.

Sources:
1.        Sareen, Jitender. “Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis.” Retrieved from UpToDate website: https://www. uptodate. com/contents/posttraumatic-stress-disorder-in-adultsepidemiology-pathophysiology-clinical-manifestations-course-assessment-anddiagnosis (2018).
2.        Friedman, Matthew J., Terence M. Keane, and Patricia A. Resick, eds. Handbook of PTSD: Science and practice. Guilford Press, 2007:  63.
3.        Lanius, Ruth, Paul A. Frewen, and Bethany Brand. “Dissociative aspects of posttraumatic stress disorder: Epidemiology, clinical manifestations, assessment, and diagnosis.”
4.        Antony, Martin M., and Murray B. Stein, eds. Oxford handbook of anxiety and related disorders. Oxford University Press, 2008: 66-68.
5.        Mann, Sukhmanjeet Kaur, and Raman Marwaha. “Posttraumatic Stress Disorder (PTSD).” (2020).

Complications of the DiseasePTSD is associated with a number of possible mental and physical health complications and it also increases the risk of suicide. 

A. Mental health Complications1,4,5,6
1. Depression
2. Anxiety and Panic Disorders – reminders of the event can frequently trigger anxiety and panic attacks2.
3. Issues with drug and alcohol abuse – with early age of onset of alcohol dependence, increased cravings and legal issues related to alcohol abuse8.
4. Eating disorders – especially bulimia nervosa2
5. Neurological disorders like headache, dementia – due to traumatic injury or alterations in the functioning of the brain6.
6. Suicidal thoughts and actions
7. Conduct disorder

B. Physical Complications2,5
1. Chronic Fatigue Syndrome/Myalgic encephalomyelitis – Muscle, Joint and Nerve pain.
2. Gastroesophageal reflux disease (GORD), Irritable Bowel Syndrome
3. A greater chance of chronic diseases
4. Heart, Liver and Lung Diseases
5. Autoimmune disorders

C. Other Complications5
1. Disrupt the ability to work and function daily
2. Difficulty with work,relationships and enjoyment of everyday activities3.
3. Feeling shame, despair and hopelessness.

Sources:
1.        Sareen, Jitender. “Posttraumatic stress disorder in adults: impact, comorbidity, risk factors, and treatment.” The Canadian Journal of Psychiatry 59, no. 9 (2014): 460-467.
2.        Lanius, Ruth, Paul A. Frewen, and Bethany Brand. “Dissociative aspects of posttraumatic stress disorder: Epidemiology, clinical manifestations, assessment, and diagnosis.”
3.        Sareen, Jitender. “Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis.” Retrieved from UpToDate website: https://www. uptodate. com/contents/posttraumatic-stress-disorder-in-adultsepidemiology-pathophysiology-clinical-manifestations-course-assessment-anddiagnosis (2018).
4.        Antony, Martin M., and Murray B. Stein, eds. Oxford handbook of anxiety and related disorders. Oxford University Press, 2008: 68 .
5.        Javidi, Hojjatollah, and M. Yadollahie. “Post-traumatic stress disorder.” Int J Occup Environ Med (The IJOEM) 3, no. 1 January (2012): 6 .
6.        Mann, Sukhmanjeet Kaur, and Raman Marwaha. “Posttraumatic Stress Disorder (PTSD).” (2020).
7.        Sonne, Susan C., Sudie E. Back, Claudia Diaz Zuniga, Carrie L. Randall, and Kathleen T. Brady. “Gender differences in individuals with comorbid alcohol dependence and post-traumatic stress disorder.” American Journal on Addictions 12, no. 5 (2003): 412-423.
8.        Read, Jennifer P., Jeffrey D. Wardell, and Craig R. Colder. “Reciprocal associations between PTSD symptoms and alcohol involvement in college: a three-year trait-state-error analysis.” Journal of Abnormal Psychology 122, no. 4 (2013): 984.

Treatment modalities and how to assess treatment outcomesPsychotherapy, specifically cognitive behavioral therapy which includes Cognitive processing therapy1, being an academic method appealing to a more cognitive-centric mind, educates patients about the natures and expectation of the PTSD condition, to understand one’s thought as well as emotions, and to correct cognitive errors that are causing harm.

Prolonged exposure therapy2, a method categorized by two main procedures, the imaginal, which is an intense reprocessing session to relive and confront the traumatic memory; and the in vivo, which is gradual exposure to objects and events associated with the memory.

On the other hand, art therapy3 as a means of creative expression would result in the relieving of traumatic experiences, via materializing related thoughts / emotions into an artwork whereby discussions can be made, not to mention that art itself is an excellent de-stressor and means of self-identity.

Eye movement desensitization and reprocessing (EMDR)4 is a technique of therapy aimed to recondition traumatic memories to either reduce its associated distress or to desensitize it; current research has tentatively established its effectiveness against PTSD.

Medication5,6
In recognition of the neurological factors present in the condition of PTSD, pharmacotherapy has been suggested to be an effective method of treatment. Established “first-line” medications for PTSD are – sertraline, fluoxetine, paroxetine, and venlafaxine, united by the fact that they primarily function as antidepressants. SSRI has been found to achieve moderate success as well. Medication tends to be more effective when utilized in concurrence with therapy.

One way the effectiveness of treatment may be diminished is due to the delay of initiating those treatments. The reasons could be cultural stigma, financial constraints, etc, and left untreated it may develop into complicated PTSD7.

Sources:
1.        Galovski, Tara E., Leah M. Blain, Juliette M. Mott, Lisa Elwood, and Timothy Houle. “Manualized therapy for PTSD: Flexing the structure of cognitive processing therapy.” Journal of consulting and clinical psychology 80, no. 6 (2012): 968.
2.        Becker, Carolyn Black, Claudia Zayfert, and Emily Anderson. “A survey of psychologists’ attitudes towards and utilization of exposure therapy for PTSD.” Behaviour research and therapy 42, no. 3 (2004): 277-292.
3.        Schouten, Karin Alice, Gerrit J. de Niet, Jeroen W. Knipscheer, Rolf J. Kleber, and Giel JM Hutschemaekers. “The effectiveness of art therapy in the treatment of traumatized adults: a systematic review on art therapy and trauma.” Trauma, violence, & abuse 16, no. 2 (2015): 220-228..
4.        Shapiro, Francine. “Efficacy of the eye movement desensitization procedure in the treatment of traumatic memories.” Journal of traumatic stress 2, no. 2 (1989): 199-223.
5.        Hoskins, Mathew, Jennifer Pearce, Andrew Bethell, Liliya Dankova, Corrado Barbui, Wietse A. Tol, Mark Van Ommeren et al. “Pharmacotherapy for post-traumatic stress disorder: systematic review and meta-analysis.” The British Journal of Psychiatry 206, no. 2 (2015): 93-100.
6.        Ipser, Jonathan C., and Dan J. Stein. “Evidence-based pharmacotherapy of post-traumatic stress disorder (PTSD).” International Journal of Neuropsychopharmacology 15, no. 6 (2012): 825-840.
7.        Sayer, Nina A., Greta Friedemann-Sanchez, Michele Spoont, Maureen Murdoch, Louise E. Parker, Christine Chiros, and Robert Rosenheck. “A qualitative study of determinants of PTSD treatment initiation in veterans.” Psychiatry: Interpersonal and Biological Processes 72, no. 3 (2009): 238-255.

Prevention of Disease1Risk-targeted / evidence-targeted interventions, in a process known as psychological first aid, administered by first responders and volunteers commonly on the site of disasters, would potentially suppress the development of PTSD through alleviating the immediate impact of traumas until professional clinical counselling can be provided.

Psychological first aid does so via:- 
1. Practicing active listening, reflecting on the recountings of survivors to make them feel heard, and empathized with
2. Guidance of formulating solution, help, as an outsider voice of reason, to evaluate the right course of action to take
3. Provision of resources, establishing support networks for survivors to join, introducing social programs, contacts to specialists, etc.

Sources:
1. Bisson, Jonathan I., and Catrin Lewis. “Systematic review of psychological first aid.” Commissioned by the World Health Organization (available upon request) 2 (2009).

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