Recognizing Posttraumatic Stress Disorder and Its Comorbidities

Resident & Staff Physician®February 2005
Volume 0
Issue 0

Posttraumatic stress disorder is the fourth most common psychiatric condition, affecting about 1 in 10 people at some point during their lifetime. The principal cause is exposure to an extremely traumatic event. The individual's unique biologic or psychosocial character and previous exposure, along with the personal significance of the trauma, shape the intensity of the response. Early recognition of trauma symptoms and signs and prompt intervention are important in the prevention of acute stress disorder and the subsequent development of posttraumatic stress disorder. Obtaining a trauma history during a routine medical examination can lead to the diagnosis and help initiate treatment. In addition to being distressing, symptoms also diminish quality of life, impair psychosocial adjustment, and worsen overall health.

Posttraumatic stress disorder is the fourth most common psychiatric condition, affecting about 1 in 10 people at some point during their lifetime. The principal cause is exposure to an extremely traumatic event. The individual's unique biologic or psychosocial character and previous exposure, along with the personal significance of the trauma, shape the intensity of the response. Early recognition of trauma symptoms and signs and prompt intervention are important in the prevention of acute stress disorder and the subsequent development of posttraumatic stress disorder. Obtaining a trauma history during a routine medical examination can lead to the diagnosis and help initiate treatment. In addition to being distressing, symptoms also diminish quality of life, impair psychosocial adjustment, and worsen overall health.

Ray Pary, MD,Staff Psychiatrist, Mental Health & Behavioral Science, Department of Veterans Affairs, Associate Professor, Department of Psychiatry and Behavioral Sciences, The University of Louisville School of Medicine; Paul R. Matuschka, PharmD, Clinical Coordinator, Pharmacy Service, Department of Veterans Affairs; Susan Lewis, ARNP, PhD, Advanced Practice Nurse, Mental Health & Behavioral Science, Department of Veterans Affairs; Steven Lippman, MD, Professor, Department of Psychiatry and Behavioral Sciences, The University of Louisville School of Medicine, Louisville, Ky

The September 11, 2001, attacks on America took the lives of almost 3000 people and changed the lives of countless others. Research has shown significant mental health effects both in New York and in Washington, DC. Those most intensely affected were the surviving victims, first-hand witnesses, and rescue workers?those in the immediate vicinity of the attacks.

Millions watching television and witnessed the attacks as they happened and saw them replayed on television or discussed in other mass media. Studies conducted immediately after these events showed an increase in reports of depression, insomnia, decreased concentration, fatigue, headaches, digestive problems, nightmares, and intrusive thoughts.1

Research by Dr Roxane Silver and colleagues indicated that early use of coping methods was significantly related to psychological outcomes over time.2 Those who detached themselves from the attacks by using denial, self-distraction, giving up, or refusing to believe what happened fared worse psychologically. Active coping methods, such as religion, emotional support, giving blood, or even going to New York or Washington as a volunteer to help in any way possible, appeared to be protective against continuing distress.2 Study results also showed that 6 months after the events, effects from the attacks remained throughout the population even in persons who were not directly affected.2 Although posttraumatic stress symptoms declined during the 6 months after the attacks, symptoms were still higher than for other types of disasters.

Clinicians can expect to see high levels of trauma-related symptoms even in persons not directly exposed to such a devastating national event. Shock, grief, and fear are considered normal reactions to such an extreme tragedy,1 which was especially devastating because its goal was to incite terror. Many continue to have considerable anxiety about future terrorist attacks. Natural disasters of a large magnitude could have similar consequences.

Diagnostic and Statistical Manual of Mental

Disorders, Third Edition

The symptoms of posttraumatic stress disorder (PTSD) have been recognized for many years. During the American Civil War, they were called "soldier's heart." In 1871, Jacob DaCosta described similar presentations in his paper, "On Irritable Heart." The term "shell shock" was used in World War I, and in World War II soldiers were said to have "combat neurosis" or "combat/operational fatigue."3 In 1980, PTSD was recognized as a clinical psychiatric disorder and was included in the (DSM-III).4 At first, it was thought that the trauma necessary for diagnosis had to be "generally outside the range of usual human experience" and would "evoke significant symptoms of distress in most people."4 This is now believed to be inaccurate, since most people will experience at least 1 highly traumatic event during their lives but only up to one third will develop PTSD.5,6 Trauma exposure is designated as an event involving some encounter with, or the likelihood of, violence.

Studies place PTSD as the fourth most prevalent psychiatric disorder, affecting as many as 10% of men and 18% of women at some point during their lives.5 The higher prevalence in women is explained by their increased vulnerability to rape.7 About one third of persons experiencing extreme trauma will have pathologic sequelae.7


The principal cause of PTSD is exposure to an extremely traumatic event. The trauma itself, however, may not be enough to produce PTSD. The intensity of the response depends on the biologic or psychosocial nature of the individual, previous life experiences, and the personal meaning of the trauma.

When exposed to a major trauma, the mind undergoes change. It is believed that the sympathetic nervous system triggers the amygdala, the area of the brain that coordinates reactions to fear and anger, signaling danger. The person then incorporates memories that prepare him or her for encounters with similar events, should they occur. If the danger signal is never completely switched off, the stress will not be integrated in a normal way and may return in the form of nightmares or other intrusive symptoms.

A number of risk factors for PTSD have been identified (Table 1).3,5 Previous exposure to trauma is a potent risk factor. Individuals who have endured chronic or repeated trauma as children, especially sexual and/or physical abuse, may exhibit a more complicated clinical picture and have marked personality changes.5 Chronic, intense stress during long periods of combat or internment (as in concentration camps) makes an individual highly vulnerable to the development of PTSD. Extreme events involving personal assault, sexual trauma, combat, rape, or violence by an intimate partner are more likely to lead to PTSD than are occurrences such as motor vehicle accidents or natural disasters.8 Persons lacking social support systems or those who have a family history of mental illness are also at increased risk for PTSD, as are those who have a first-degree relative with a history of depression.9

There is support to a genetic predisposition for PTSD. Monozygotic twin studies of Vietnam combat veterans indicate that a smaller hippocampal volume, which represents a preexisting and likely hereditary factor, predisposes trauma victims to PTSD.10 The Vietnam Era Twin Registry study of identical and fraternal twins showed that genetic factors explain about 30% of the variance rate (ie, degree of difference) in PTSD symptoms among individuals, even after considering differences in trauma exposure.8 Personality traits, such as sociopathy in men and neuroticism in women, are thought to predispose to involvement in assaultive events and subsequent PTSD.


Our understanding of the pathophysiology of PTSD is incomplete, although dysregulation of the glutamatergic, noradrenergic, and serotonergic neural pathways are likely part of the explanation (Table 2). Increased levels of stress-responsive neuromodulators, such as adrenocorticotropic hormone (ACTH), vasopressin, epinephrine, or norepinephrine may intensify memories of the traumatic event, followed by an overconsolidation of traumatic memories (ie, memories becoming intrusive).11 Distress associated with reminders of trauma may activate corticotropin-releasing hormone from the hypothalamus. This, in turn, stimulates the pituitary gland to secrete ACTH, which then stimulates the adrenal glands to secrete cortisol.

Although brain neurotransmitter systems and the hypothalamic-pituitary-adrenal (HPA) axis have been regarded as hyperactive in response to stress, several reports indicate that this may be an oversimplification in PTSD. The stress response is not the same in patients with depression and in patients with PTSD. Unlike those with depression, patients with PTSD demonstrate exaggerated cortisol suppression in response to dexamethasone administration. For example, an exaggerated cortisol-suppression response has been noted in individuals with PTSD who were given low doses of dexamethasone (eg, Decadron, Dexameth, Dexone).12 The same response was observed in patients with concurrent major depressive disorder (MDD) and PTSD.12 Persons who develop PTSD may have a different response to stress than those who become depressed. Disinhibition of the HPAaxis has been thought to explain the depression.13 In contrast to patients with PTSD, those with MDD do not demonstrate normal reductions in cortisol production when given dexamethasone.13

Hypersensitivity of the HPA axis is supported by evidence of hypersecretion of corticotropin-releasing factor with paradoxical reduced basal cortisol levels.14 Veterans exposed to intense combat have very low cortisol levels.14 One study showed that patients with PTSD had more lymphocyte glucocorticoid receptors than did controls.15 Enhanced sensitivity of the HPA axis feedback mechanism, resulting in decreased basal cortisol levels, may be a consequence of an increased number of glucocorticoid receptors in the pituitary gland. Great numbers of pituitary glucocorticoid receptors exert a strong negative feedback inhibition on the pituitary gland, thereby attenuating baseline ACTH and cortisol levels. The increased numbers of glucocorticoid receptors on lymphocytes seen in combat veterans suggest that there may be more of these receptors in the pituitary gland.16 The net effect is reduced cortisol in PTSD patients, in the immediate aftermath and chronically.

Neuroimaging Findings

Some individuals with PTSD have changes in brain structure, with diminished hippocampal volume and nonspecific white matter lesions most frequently reported.17 The amygdala is involved in the experience of fearful emotions and is hyperresponsive during the induction of fear.17 It is considered to be the locus for consolidation of traumatic memory experience. High levels of emotional arousal may inhibit hippocampal function and thereby mediate memory loss for events around a specific trauma.

Functional neuronal imaging studies of persons performing specific cognitive tasks designed to produce PTSD symptoms suggest that performance deficits are correlated with specific abnormal patterns of brain activation. In a small, script-driven study, functional magnetic resonance imaging was used to depict subjects' reaction to a traumatic imagery script that was being read to them. Patients with PTSD exhibited less activation of the thalamus, the anterior cingulate gyrus, and the medial frontal gyrus than those without PTSD.18


Early diagnosis and intervention are important in the prevention of acute stress disorder and subsequent symptoms of PTSD. The criteria for acute stress disorder are listed in DSM-III.9 A person responds with intense fear, helplessness, or horror after either experiencing, witnessing, or being confronted by an event of actual or threatened death or serious injury to self or others. Three or more of the following conditions develop within 1 month of exposure to the event: (1) absence of emotional responsiveness, (2) reduction in awareness of surroundings, and (3) derealization, depersonalization, or an inability to recall important aspects of the trauma.

Persistent reexperiencing of the traumatic event takes place with marked avoidance of traumatic stimuli. Increased arousal is expressed as sleep difficulties, irritability, poor concentration, hypervigilance, and exaggerated startle response or restlessness. Impaired social or occupational functioning also begins. The disturbance lasts between 2 days and 4 weeks. The disorder is not a direct physiologic effect of a substance or medical condition.

Taking a trauma history as part of a routine medical examination can facilitate recognition of the condition (Table 3). The following 6 criteria must be present for a valid diagnosis of PTSD.9

1. Exposure to an extreme traumatic stressor involving either direct personal experience of actual or threatened death or serious injury or a threat to one's physical integrity. Witnessing an event that involves death, injury, or threat to another person qualifies as well. Learning about an unexpected or violent death, serious harm, or threat of death or injury experienced by a close family member or other close associate may also represent a traumatic experience sufficient for diagnosis. Examples of stressors include rape, combat, incest, robbery, mugging, kidnapping, a hostage experience, being a prisoner of war or in a concentration camp, environmental disasters, terrorist attacks, and severe accidents. Intense horror, fear, or helplessness are experienced at the time of the trauma, and dissociative symptoms, such as derealization or depersonalization, occur.

2. Reexperiencing the trauma in the form of intrusive thoughts, dreams, dissociative flashback episodes, or reactivity to traumatic reminders. The trauma is vividly remembered; patients cannot get it out of their mind. Intrusive images, thoughts, and perceptions haunt the individual, along with nightmares of the trauma. Physical symptoms include increased heart rate, shortness of breath, and palpitations.

3. Persistent avoidance of stimuli associated with the trauma and emotional numbing. The patient evades situations, persons, places, or things that might evoke memories of the trauma. Emotional numbing refers to detachment or estrangement from others, emotional unresponsiveness, reduced interest in significant activities, and a diminished or constricted sense of the future (eg, does not expect to have a job, get married, or have a normal life span).

4. Increased arousal, evidenced, for example, by irritability and sleep disturbances. The patient may have explosive anger, poor concentration, hypervigilance, and hyperactive responses.

5. The duration of symptoms (eg, reexperiencing, avoidance, increased arousal) must be at least 1 month.

6. Social or occupational functioning is impaired.9

Differential Diagnosis

Comorbid psychiatric conditions are the rule rather than the exception in PTSD and include MDD, anxiety disorders, panic disorder, and chemical abuse or dependency.5 Persons who suffered traumatic events during childhood or those who are exposed to recurrent traumas are at increased risk of developing physical conditions, such as hypertension, asthma, or psychosomatic disorders.5

There is a great deal of symptom overlap between PTSD and depression. Features common to both disorders include sleep disturbances, difficulty concentrating, avoidance of and withdrawal from social interactions, anhedonia, and social isolation.

A distinctive feature of PTSD is an exaggerated startle response to loud noise, which is not observed in either healthy or depressed persons. Other manifestations include reexperiencing trauma, hyperarousal, and trauma-related avoidance behavior.

Panic attacks are common in PTSD and may present as palpitations, chest pain, or fear of having a heart attack. In PTSD, fear is connected to trauma-related memories.

Disease Course

The course of PTSD depends on the individual's ability to adjust to the acute stress response and restore equilibrium at the time of the traumatic event. Patients who already have considerable preexisting psychopathology in the form of character deficits or substance abuse when they are exposed to the trauma are at greater risk for a protracted course. Well-functioning individuals are usually able to either cope with considerable trauma without developing PTSD or have a transient course. An individual is vulnerable to developing PTSD after initial trauma and is more likely to develop it after repeated trauma.6 Secondary depression, substance abuse, downward social drift (move into or failure to rise out of a lower socioeconomic group because of illness), and character changes are particularly common in patients who were traumatized as children.

A study of community-dwelling older survivors of remote trauma found that PTSD prevalence and severity increased over 4 years, supporting the supposition that symptom severity may increase over time.19 Presence of PTSD impairs occupational functioning much like major depression.6 Other consequences include failure to attain educational or career potential and difficulty establishing and maintaining long-term relationships with partners.

A complication of PTSD, especially if combat-related, is secondary traumatization, such as the emotional upset and indirect victimization sometimes reported by spouses of veterans with PTSD.20Women in long-term relationships with veterans who have been involved in extensive warfare may suffer verbal, emotional, or physical abuse.


Exposure therapy has the most empirical support among the psychosocial treatments for PTSD. This approach embraces the concept that exposure to the traumatic event is essential to trauma therapy. Patients are encouraged to confront the feared objects, situations, memories, and images that are connected to a past concern. Usually there is repeated emotional recounting of the traumatic memory, termed "imagined exposure." There may also be repeated confrontation with trauma-related situations and objects. Patients may speak in the first person about their trauma (what they saw, heard, smelled, and felt) and describe their response and its meaning during the first 5 sessions.

Approximately 20 minutes of a trauma-focused session should eventually reduce distress. The session is recorded, and patients are asked to listen to the tape for 1 hour daily between sessions and to record distress levels daily. Five additional sessions focus on trauma-related stimuli that were being avoided or were disabling.

Advantages of exposure therapy are that it requires little effort to master and the instructions are straightforward. Therapists can learn how to deliver the therapy much more easily than cognitive-processing therapy, which requires extensive training and places considerable intellectual demands on patients.21

Psychological debriefing, a technique used both in military and civilian populations immediately following a traumatic incident, has not been successful in people who are experiencing intrusive or avoidant symptoms.22 Cognitive behavioral therapy lasting approximately 3 months has shown efficacy for emergent acute stress disorder and may help prevent PTSD.23

Drug Therapy

Avariety of agents have been used, most of them off-label, to treat PTSD (Table 4). Early studies focused on tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors. Amitriptyline HCl (Elavil), imipramine HCl (Tofranil), and phenelzine sulfate (Nardil) have all demonstrated efficacy in war veterans with long-standing PTSD.24,25 In a comparison study, phenelzine was superior to imipramine in reducing intrusive symptoms.25 An expert consensus report on PTSD, however, considered TCAs to be inappropriate therapy because of their likely side effects (eg, daytime drowsiness, cardiac toxicity in overdose, impaired reaction times).6

Several selective serotonin reuptake inhibitors (SSRIs) have been shown to ameliorate symptom clusters in PTSD. Serotonin is involved in brain mechanisms that affect sleep regulation, aggression, anxiety, and mood?many of which are altered in PTSD. In addition to mitigating symptoms, SSRIs have been shown to reduce disability and improve resilience.26

In a 12-week, double-blind study, sertraline HCl (Zoloft) reduced PTSD symptoms and improved social and occupational functioning compared with placebo.26 Of note, a relative lack of an acute antidepressant effect was evident, suggesting that an antidepressant response is not necessary for sertraline efficacy in PTSD. Avoidance- numbing symptom clusters are reportedly most responsive to sertraline; it is less effective for intrusive reexperiencing and arousal groups of symptomatology.27

Fluoxetine HCl (Prozac) has shown efficacy as early as the second week of therapy in patients with PTSD.28 In open-label studies, paroxetine HCl (Paxil, Pexeva), up to 60 mg/day, and fluvoxamine maleate (Luvox), up to 200 mg/day, improved noncombat chronic PTSD symptoms.29

Although benzodiazepines may have some benefit for acute symptoms of stress, they are ineffective for established PTSD. Extended use of benzodiazepines for acute stress is not recommended.6


Most people will experience an extreme traumatic event during their lives, but less than half will develop a clinical stress disorder. This complicated condition can have a long and protracted course, in which comorbid medical and psychiatric illnesses are common. PTSD affects the psychosocial and physical health of the patient. Exposure therapy and a variety of medications can be effective treatments that may offer relief or resolution.


1. All these statements about PTSD are true, except:

  • It affects almost twice as many women as men
  • Psychological debriefing is not effective treatment

2. Which of the following categories is NOT a risk factor for PTSD?

  • Having a father with MDD
  • Recent heavy alcohol use

3. All these are diagnostic criteria for PTSD, except:

  • Avoiding people who are associated with the traumatic event
  • Symptoms lasting 2 weeks

4. Which of the following symptoms is NOT associated with both depression and PTSD?

  • Poor concentration
  • Social isolation

5. Which of these agents has been approved for PTSD?

  • Fluoxetine
  • Bupropion

(Answers at end of reference list)

Harv Ment

Health Lett

1. Harvard Health Publications. Disaster and trauma. . 2002; 18(1):1-5.


2. Silver RC, Holman EA, McIntosh DN, et al. Nationwide longitudinal study of psychological responses to September 11. . 2002;288:1235-1244.

Kaplan & Sadock's Synopsis of Psychiatry:

Behavioral Sciences/Clinical Psychiatry

3. Sadock BJ, Sadock VA. . 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2003:623-632.

Diagnostic and Statistical Manual

of Mental Disorders, Third Edition

4. American Psychiatric Association. . Washington, DC: American Psychiatric Association; 1980.

Clinician's Manual on Posttraumatic Stress


5. Yehuda R, Davidson J. London, England: Science Press; 2000.

J Clin Psychiatry

6. Ballenger JC, Davidson JR, Lecrubier Y, et al. Consensus statement on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety. . 2000; 61(suppl 5):60-66.

Arch Gen Psychiatry

7. Kessler R, Sonnega A, Bromet E, et al. Posttraumatic stress disorder in the National Comorbidity Survey. . 1995;52:1048-1060.

Am J Psychiatry

8. Stein MB, Jang KL, Taylor S, et al. Genetic and environmental influences on trauma exposure and posttraumatic stress disorder symptoms: a twin study. . 2002;159:1675-1681.

Diagnostic and Statistical Manual

of Mental Disorders, Fourth Edition, Text Revision

9. American Psychiatric Association. . Washington, DC: American Psychiatric Association; 2000.

Nat Neurosci

10. Gilbertson MW, Shenton ME, Ciszewski KK, et al. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. . 2000;5:1242-1247.

Biol Psychiatry

11. Pitman RK. Post-traumatic stress disorder, hormones, and memory. . 1989;26:221-223.

Am J Psychiatry.

12. Yehuda R, Southwick SM, Krystal JH, et al. Enhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder. 1993;150:83-86.

Br J Psychiatry

13. Carroll BJ. The dexamethasone suppression test for melancholia. . 1982;140:292-304.

J Consult Clin Psychol.

14. Boscarino JA. Posttraumatic stress disorder, exposure to combat, and lower plasma cortisol among Vietnam veterans: findings and clinical implications. 1996;64:191-201.

Am J


15. Yehuda R, Lowy MT, Southwick SM, et al. Lymphocyte glucocorticoid receptor number in posttraumatic stress disorder. . 1991;148:499-504.

Arch Gen Psychiatry.

16. Yehuda R, Boisoneau D, Lowy MT, et al. Dose-response changes in plasma cortisol and lymphocyte glucocorticoid receptors following dexamethasone administration in combat veterans with and without posttraumatic stress disorder. 1995;52:583-593.

J Clin Psychiatry.

17. Pitman RK, Shin LM, Rauch SL. Investigating the pathogenesis of posttraumatic stress disorder with neuroimaging. 2001;62(suppl 17):47-54.

Am J Psychiatry.

18. Lanius RA, Williamson PC, Densmore M, et al. Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation. 2001;158:1920-1922.

Am J Psychiatry

19. Port CL, Engdahl B, Frazier P. A longitudinal and retrospective study of PTSD among older prisoners of war. . 2001;158:1474-1479.

J Nerv Ment Dis

20. Prigerson HG, Maciejewski PK, Rosenbeck RA. Combat trauma: trauma with highest risk of delayed onset and unresolved posttraumatic stress disorder symptoms, unemployment, and abuse among men. . 2001;189:99-108.

Arch Gen Psychiatry

21. Marks I, Lovell K, Noshirvani H, et al. Treatment of posttraumatic stress disorder by exposure and/or cognitive restructuring: a controlled study. . 1998;55:317-325.

Br J Psychiatry

22. Deahl MP, Gillham AB, Thomas J, et al. Psychological sequelae following the Gulf War. Factors associated with subsequent morbidity and the effectiveness of psychological debriefing. . 1994;165:60-65.

Am J Psychiatry.

23. Bryant RA, Sackville T, Dang ST, et al. Treating acute stress disorder: an evaluation of cognitive behavior therapy and supportive counseling techniques. 1999;156:1780-1786.

Arch Gen Psychiatry.

24. Davidson J, Kudler H, Smith R, et al. Treatment of posttraumatic stress disorder with amitriptyline and placebo. 1990;47:259-266.

J Nerv

Ment Dis

25. Kosten TR, Frank JB, Dan E, et al. Pharmacotherapy for posttraumatic stress disorder using phenelzine or imipramine. . 1991;179:366-370.

Arch Gen Psychiatry

26. Davidson JR, Rothbaum BO, van der Kolk BA, et al. Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. . 2001;58:485-492.


27. Brady K, Pearlstein T, Asnis GM, et al. Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. . 2000;283:1837-1844.


J Psychiatry

28. Connor KM, Sutherland SM, Tupler LA, et al. Fluoxetine in post-traumatic stress disorder. Randomised, double-blind study. . 1999;175:17-22.

J Clin Psychopharmacol

29. Marshall RD, Schneier FR, Fallon BA, et al. An open trial of paroxetine in patients with noncombat-related, chronic posttraumatic stress disorder. . 1998;18:10-18.


1. C; 2. C; 3. D; 4. A; 5. A

Related Videos
© 2024 MJH Life Sciences

All rights reserved.