In order to understand post-traumatic stress disorder (PTSD) we need to appreciate the concept of "stress." Although the term "stress" is usually used in a negative context to suggest a bad or unpleasant experience, technically stress is defined as "change in homeostasis," meaning that things are no longer going along the way they were. Stress therefore is neither good nor bad, neither beneficial nor harmful by itself. In fact, life events such as getting married, graduating college, having a baby or getting a major promotion are considered to be positive, yet potentially quite stressful.

Traumatic "toxic" stress on the other hand, has the possibility for being harmful. Usually traumatic stress is unexpected, catastrophic and involves either loss of life, violation of person or threat of serious bodily harm. Examples of traumatic stress are child abuse, domestic violence, rape, terrorism, assault, motor vehicle accidents and natural disasters.

Post-traumatic stress disorder represents a severe or extreme reaction to traumatic stress. Post-traumatic stress, in both mild and severe forms will afflict about one person in three that is exposed to a severe traumatic stressor. When we consider that about one in two Americans will experience a severe traumatic stress, we can see that indeed PTSD is a major public health and medical concern. The gender ratio in post-traumatic stress disorder is such that the prevalence of PTSD is twice as high in women as in men. The precise reason for this is not known but may involve both physiological and psychological factors. Studies have shown this increased vulnerability in women to be true even in situations where stress exposures are comparable, such as natural disasters.

The diagnosis of post-traumatic stress disorder was first codified in 1980 in the Diagnostic and Statistical Manual of the American Psychiatric Association, third edition (DSM). In order to have a diagnosis of post-traumatic stress disorder, a person must have been exposed to a traumatic stressor and must have reacted to it with fear, horror or helplessness.

Subsequent to the trauma, symptoms occur in three characteristic clusters: intrusive, avoidance and hyperarousal. The intrusive symptoms of PTSD, also referred to as the core symptoms, consist of intrusive thoughts, nightmares, flashbacks and a physical or psychological reaction to reminders of the trauma. The avoidance symptoms consist of withdrawal, decreased interest in pleasure in normal activities, difficulties feeling or expressing normal human emotions such as love, a sense of a fore-shortened future and avoidance of persons, places, conversations or other reminders of the traumatic stress. Finally, the hyperarousal symptoms of PTSD are manifest in easy startle, hypervigilance, difficulty sleeping, irritability, anger, outburst and trouble relaxing.

In order to have a full diagnosis of post-traumatic stress disorder; a person must have symptoms in all three clusters. However, in less severe or mild cases, only a smaller number of symptoms may be bothersome, such as having nightmares and hyperarousal but not withdrawal.

Although the diagnostic approach to post-traumatic stress disorder might seem superficially straightforward, this is a diagnosis that is often missed even by astute, experienced and sophisticated psychiatrists. Studies have shown that in general psychiatric clinic populations, as many as 40 percent of patients may have post-traumatic stress disorder but that this diagnosis is recognized in less than one out of five cases. There are several reasons for this discrepancy between prevalence and diagnosis including stigma, denial and the fact that obtaining a careful history and symptom profile can be a time-consuming procedure. Additionally, most patients with PTSD solicit medical attention for other or related conditions including depression, anxiety, obsessions or stress. This partly reflects the important clinical fact that post-traumatic stress disorder is a psychiatric diagnosis in which comorbidity is the rule rather than the exception. For example, it is estimated that about 85 percent of persons with PTSD will also suffer a depressive disorder and over half will suffer from a substance-use disorder. In particular, substance-use disorders can represent a serious complication and worsen the prognosis of post-traumatic stress disorder. The self-medication hypothesis is certainly appropriate in the case of PTSD, since many persons with post-traumatic stress disorder find that alcohol is a relatively cheap, readily available and rapidly effective sedative and anti-anxiety drug. Persons may use alcohol in order to relax or to sleep, only to find that tolerance develops; in other words, increasing doses are required to obtain the same effect, eventually leading to an addiction.

Thus, while the diagnosis of post-traumatic stress disorder is operationalized and the criteria are widely accepted and validated, in practical terms the comorbid condition is often what brings the patient to medical attention. Thus, when faced with a patient who is, for example, in alcohol withdrawal or severely depressed, the examining physician may easily miss the underlying diagnosis of post-traumatic stress disorder.

Post-traumatic stress disorder has traditionally been associated with military service. In fact, the problems associated with service in the Vietnam conflict led to the development of operational criteria for PTSD in 1980. However, Post-traumatic stress disorder has been described in the medical literature for almost 200 years. Following the American Civil War, survivors of the Battle of Gettysburg exhibited many of the symptoms we see in veterans with PTSD today, leading Dr. DaCosta, working at the Soldiers Home in Philadelphia, to describe a cardiorespiratory syndrome with prominent features of palpitations and hyperventilation. The term "shell shock" was coined after World War I to describe the condition that afflicted many of the survivors of the trench warfare. The prevailing theory at that time was that an explosion in close proximity to a soldier's head would drive molecules of air through the skull and produce brain damage leading to subsequent symptoms. Physicians noted the common occurrence of "soft" neurological signs in these veterans. A psychological explanation for PTSD did not occur until during World War II when the concept of combat neurosis was developed. It is worth noting that over 25 percent of casualties among American troops in World War II were psychiatric in nature.

Naturally, the question arises, is there anything different or special about PTSD in veterans? Particularly, is there anything about the Vietnam conflict that was peculiar, leading to more severe PTSD? Indeed, persons in military service often encounter situations in which they are both the recipients and perpetrators of traumatic stress, thus receiving a double dose. Furthermore, the average age of infantry in Vietnam was around 19 to 20; thus, many of these troops were relatively immature from a neuropsychological and social perspective, compared to World War II where the average infantryman was in his mid 20s.

Thus, while traumatic stress is well described in veteran populations, it is also common in civilian populations. In fact, veterans with PTSD as a group form a relatively small proportion of the total population with PTSD in the United States. While PTSD has traditionally been associated with combat, its recognition in civilian populations dates back to the 1880s when a "spinal shock syndrome" was described after railway accidents, probably reflecting interest in the emerging chiropractic medical tradition. Survivors of train wrecks were thought to have a misalignment of their spinal column, which led to subsequent symptoms in multiple organ systems. In the 1950s, the rape-trauma syndrome was described, leading to further advances in our appreciation of the universality of symptomotology after trauma.

What are the risk factors for PTSD? This fascinating question continues to be a subject of active research. First, there is a dose effect in developing PTSD. Experience of the Vietnam war showed that soldiers who were in combat longer had a greater tendency to develop PTSD. Similarly, in cases where domestic abuse or violence persists for years, ensuing PTSD is worse than when the trauma was brief. Second, there is a gender effect noted even in situations where the trauma is similar, such as natural disasters; women are twice as likely to develop PTSD, for reasons that are poorly understood. Third, severe child abuse appears to be a significant risk factor for subsequent development of adult PTSD. Finally, a prior experience of developing post-traumatic stress disorder makes a person vulnerable to a reoccurrence of symptoms if there is a subsequent traumatic stressor.

Additionally, there may be risk factors involved that are biological. Post-traumatic stress disorder has a clear environmental precipitant, thus a clear biological basis. Several biological abnormalities have been noted in persons with post-traumatic stress disorder. A low level of cortisol, the stress hormone secreted by the adrenal glands in response to stress, is well documented to occur in persons with PTSD. Previously, it was thought that the low cortisol developed after severe stress reactions, in that the bodies' defense mechanisms were overwhelmed. However, new research has shown that low cortisol may well be an antecedent of PTSD. Studies have shown both in survivors of rape trauma and motor-vehicle accidents that persons who have a low cortisol response at the time of the traumatic stress exposure are more likely to go on to develop PTSD later. Another interesting biological correlate of post-traumatic stress disorder is a small hippocampus. The hippocampus is the part of brain that encodes memory formation and is also involved in emotional response. What we do not know is whether the hippocampal atrophy in persons with PTSD develops because of brain damage to nerve cells as a consequence of severe stress or whether it precedes the stress exposure and is thus a risk factor for PTSD. Additionally, patients with PTSD show very distinct patterns of brain-blood perfusion when they are read a script reminder of the traumatic stress. That is, parts of their brains have abnormal blood flow upon being reminded of the traumatic stress, compared to persons without PTSD. There is no doubt that some of these biological findings eventually will become useful as diagnostic tests.

Having made a diagnosis of post-traumatic stress disorder, what are the physician's options of treatment? First, if substance abuse is an active problem, it must be dealt with before the PTSD can be treated. Simply speaking, it is impossible for a person to improve or benefit from treatment if he is continuing in a state of intoxication or drug abuse. If substance abuse is not a problem or has been addressed with appropriate treatment, then the physician may proceed to treat the PTSD.

Historically, psychotherapy was considered the primary form of treatment for PTSD. It was during the mid 1980s that physicians working within the Veterans Administration noted that many persons continued to suffer severe symptoms of post-traumatic stress disorder even after long and intensive psychotherapy. This led to a renewed interest in pharmacologic treatment for PTSD. The area of pharmacotherapy for post-traumatic stress disorder is relatively in its infancy, with fewer than a dozen published studies available in the literature. In part, this reflects the conventional wisdom that psychotherapy was the treatment of choice for this condition and in part that diagnostic criteria for PTSD have only been available for less than 20 years.

Although the number of clinical trials is small, with most trials at single sites involving relatively small numbers of patients, it is possible to make some generalizations regarding the data. First, the placebo response rate in chronic post-traumatic stress disorder appears to be quite low, in the neighborhood of five percent. Clinically, this means that a patient responds to medication treatment for PTSD, probably not a placebo response. Second, serotonin-acting medications appear to be more effective than those working on the dopamine or noreepinephrine systems since studies involving desipramine and bupropion have yielded negative results.

Treatment should begin with an antidepressant medication. At this time, sertraline (Zoloft) has received approval by the Food and Drug Administration to label its product as being effective for PTSD. Additional antidepressants for which there are some positive data in PTSD are fluoxetine (Prozac) and nefazodone (Serzone). In particular, Serzone may be close to an ideal drug for treatment of PTSD because of its very low incidence of adverse sexual side effects and because of its improving patients' sleep over the course of therapy. Medications for PTSD should be continued for at least a year after a response is noted. The treating physician should be sensitive to the possibility of a seasonal or anniversary worsening of symptoms requiring treatment that is more intensive.

In summary, post-traumatic stress disorder is increasingly recognized as a major public health concern, likely to increase in prevalence and severity during the new millennium. Recent developments in the diagnosis and treatment of PTSD are leading to increased understanding of and more optimistic attitude regarding this condition.

Frederick Petty is Professor of Psychiatry and Wesley Gilliland Professor of Biomedical Research at the University of Texas Southwestern Medical Center in Dallas, Texas. Dr. Petty is also a staff psychiatrist at the Dallas VA Medical Center. If you live in the Dallas area and wish to participate in research on PTSD, please contact Dr. Petty at 214/857-0296 or e-mail at fpettymd@aol.com.