By Larry Culpepper, MD, MPH

In recent years, post-traumatic stress disorder (PTSD) has worked its way into our national vocabulary, reminding us of the deep and lasting human toll exacted by episodes of violence and by natural disasters. This increased awareness has humanized the victims, transforming them from mere statistics into individuals who face enormous struggles as they cope with often unimaginable personal trauma.

It is only now becoming clear how often primary care physicians are regularly confronted with PTSD. Patients with the disorder most frequently present with somatic and psychological symptoms that may not, at first, lead to the diagnosis of PTSD. Because medical, rather than behavioral, settings are the most common point of entry into the health care system for those suffering from PTSD, primary care physicians play a central role in recognizing and managing this illness.

How Common Is PTSD?
Community surveys show that PTSD has a lifetime prevalence of 7% to 12%, (Breslau 1991; Kessler 1995; Resnick 1993) and that in any given month, 6.1% of women and 1.5% of men suffer from PTSD symptoms (Stein 1997). The disorder is more common than many psychiatric illnesses, such as panic disorder, obsessive-compulsive disorder, and schizophrenia, and many medical illnesses, including asthma (prevalence, 5.4%) (Sly 1999) and diabetes (prevalence, 5.9%) (CDC 1998).

According to community surveys, traumatic stress is a public health problem of epidemic proportions. While PTSD was once thought to affect primarily soldiers in combat, we now recognize that civilians become victims of PTSD after experiencing a range of violence that includes rape and other forms of physical and sexual assault, fire, serious accidents, and natural disasters, or as a result of witnessing the injury or death of another. More than 50% of us are exposed to traumatic stress over the course of our lives, and, by one recent estimate, 22% of girls will be victims of physical or sexual assault before age 18 (McCauley 1997). A large community-based national survey conducted by Kessler et al. (1995) estimated the risk of developing PTSD following exposure to a specific trauma (see Fig. 1). The clinical implications are clear: Severe traumatic stress is highly toxic, and if a clinician discovers that a patient has been exposed to trauma, asking a few screening questions to ascertain whether he or she has developed PTSD is advisable.

The importance of maintaining a high index of suspicion is underscored by the numbers. In a busy primary care practice, at least one to three patients with full-fledged PTSD are seen every week. They are often treated for a comorbid depression or anxiety disorder, but diagnosing the underlying PTSD is important for optimizing treatment.

Estimates from epidemiologic studies suggest that approximately 15% to 30% of individuals who are exposed to traumatic events develop full-fledged PTSD (Giaconia 1995; North 1994). Factors that increase the likelihood of developing the disorder include the severity, unexpectedness, and duration of the trauma. None of the high-risk events for males are common, whereas for women, rape and sexual molestation are both high risk and frequent (see Table 1, Fig. 1). The combined effect of increased trauma frequency and toxicity, both of which are more likely for women, results in a much higher likelihood of PTSD in women (20.4%) than in men (8.1%) (Kessler 1995).

In addition to the nature of the stressful event, other individual and social factors contribute to the development of PTSD, including premorbid psychopathology, previous history of trauma, and dysfunctional coping and attributional styles. Neurobiological factors can also contribute to an increased vulnerability to PTSD. Overall, a high degree of adaptive resilience in the face of stress is likely due to a combination of favorable neurobiology and coping skills, together with good social-support systems that function like outriggers on a canoe to reduce the likelihood of emotionally capsizing in the face of the physiological and psychological effects of traumatic stress.

Neurobiology of PTSD
Is there medical evidence that PTSD is anything more than a manifestation of difficulty coping psychologically with the stressful consequences of a traumatic event? Does traumatic stress leave physiological scars, in addition to emotional ones, that alter neurological structure or function? The answer to these questions is an unequivocal "yes." During the past decade we've made enormous progress toward understanding the negative effects of physical and psychological trauma on the structure and function of the brain.

These effects involve dysregulation of the norepinephrine, thyroid, endogenous opioid, and serotonin systems and the hypothalamic-pituitary-adrenocortical axis, as well as disturbances in the patient's appraisal processes, learning, and memory (van der Kolk 1997). Together, these alterations can be viewed as a neurobiological shift from homeostasis to allostasis. In allostasis, systems are in balance but under great stress — akin to a car with the brakes jammed on and the engine racing. Dysregulation of corticotropin-releasing factor alters the production of adrenocorticotropic hormone and glucocorticoids and stimulates the body's adrenergic response.

Upregulated catecholamine levels, typical of fight-or-flight responses, are normally balanced by downregulated adrenergic receptor sites. Following prolonged stress, corticosteroids are reduced, resulting in dampened cortisol modulation of acute physiological stress responses. These alterations also lead to decreased immune responsiveness.

Behaviorally, the neurochemical correlates of chronic physiological arousal result in reduced regulation of autonomic reactions to stimuli and decreased ability to respond normally to emotional arousal or external stressors. Instead of using such cues as normal alerting functions, leading to reasoned responses, the person with PTSD may go directly to fight-or-flight responses, including hyperarousal and hyperstartle. Alterations in serotonin may contribute to an inability to modulate arousal, with resulting hyperirritability, hypersensitivity, excitability, impulsiveness, and hostility. Compensatory mechanisms include shutting down behaviorally, avoiding reminder stimuli, and becoming numb to emotional responses associated with both the originating trauma and day-to-day life. Neurobiological disturbances also lead to memory dysfunction; some individuals are unable to forget, and others unable to recall, all or parts of the traumatic event.

Neuroimaging studies in PTSD consistently find changes in the structure and function of the hippocampus and medial prefrontal cortex (Bremner 1999; Zubieta 1999). MRI data show that PTSD is associated with a reduction in the size of the hippocampus, an area of the brain involved in learning and memory, consistent with the deficits in learning and memory noted earlier.

Thus, the profound neurochemical and structural changes that develop in those exposed to extreme trauma explain many of the emotional and behavioral manifestations of PTSD and provide insight for the development of treatment. The resulting symptoms give rise to the diagnostic criteria for PTSD.

Diagnosis and Clinical Presentation
The DSM-IV diagnostic criteria for PTSD are shown in Table 2. PTSD arises from exposure to extreme trauma, with impairment in social, occupational, or educational functioning. PTSD is characterized by moderate-to-severe symptoms persisting for at least one month in three separate domains: re-experiencing, including intrusive thoughts, nightmares, flashbacks, images, and memories; emotional numbing or avoidance, which includes flattened affect or detachment, loss of interest and motivation, and avoidance of any activity, place, person, or topic associated with the trauma; and hyperarousal, including startle reactions, poor concentration, irritability, jumpiness, insomnia, and hypervigilance.

Because of their unique vantage point in the continuum of their patients' care, primary care physicians may identify patients at high risk for developing PTSD even before the diagnostically required month of symptoms has elapsed. This offers opportunities to intervene early, possibly limiting the development and severity of the disorder.

When to Suspect PTSD
Primary care physicians must be alert to subtle cues that might indicate PTSD or risk of developing the disorder. Patients with PTSD generally present in one of three ways. First, a physician caring for a patient who has suffered a trauma might recognize over time that the patient is developing PTSD. Second, patients might be referred by family members who suspect PTSD or psychological problems originating from a trauma. And third, many with PTSD present for routine visits or for an evaluation of a physical or psychiatric complaint, and their PTSD is easily missed. For this last group of patients, two screening strategies can enhance recognition of PTSD.

The first strategy is to inquire routinely about trauma, as part of any general medical examination. This requires only one screening question: "Have you ever experienced a traumatic event that is still upsetting to you?" In considering the patient's response, remember that most high-risk events are not very common (see Table 1, Fig. 1) and that events that happen more often, but that are less likely to give rise to PTSD, account for a major portion of PTSD. For example, in one study population, the unexpected death of a loved one was reported by 60% of the population and was the originating trauma for 31% of PTSD cases (Breslau 1998). Understanding risk factors is helpful (see Fig. 1). A patient who has a relatively low "toxicity" trauma, such as an auto accident, might be much more likely to develop PTSD if the accident is the second or third major trauma in recent years or if he or she has a history of anxiety or depression.

A second screening strategy is to be alert to clinical complaints that might signal PTSD. Several presentations are associated with the disorder. For example, patients presenting with chronic pelvic pain have an unusually high rate of trauma exposure, as well as PTSD, in the range of 40% (Heim 1998; Walker 1993). In one study of 50 patients with irritable bowel syndrome, 36% suffered from PTSD (Irwin 1996). Patients presenting with depression or an anxiety disorder frequently report a history of trauma, and many have full-fledged concurrent PTSD. Screening questions about trauma exposure and symptoms of PTSD might yield a diagnosis that permits better management of both diagnoses. Table 3 provides a simple patient-rated screening questionnaire for PTSD. This questionnaire has been validated on a community sample of approximately 2,000 and can be completed in one to two minutes. A score of 4 or higher has a positive predictive value of 71% and a negative predictive value of 98% for the diagnosis of PTSD (Breslau 1999). A positive result should be followed by a more detailed evaluation of PTSD symptoms, including their impact on the patient's ability to function.

The Importance of Diagnosis
Chronicity: The importance of recognizing PTSD stems from the enormous disability associated with it, as well as from its chronicity and comorbidity. PTSD has a median time-to-recovery of three to five years. Figure 2 shows the percentage of untreated patients who continue to suffer from PTSD up to ten years after their trauma. The chronicity of the disorder is associated with four main consequences: high psychiatric comorbidity, markedly increased health-related problems, a high likelihood of disability, and impaired function and quality of life.

Comorbidity: Major depression, alcoholism, and substance abuse are the most common psychiatric comorbidities associated with PTSD (see Fig. 3), with a threefold or greater increased risk in patients with PTSD. Whether PTSD is the cause or the consequence of these other psychiatric illnesses is a subject of ongoing debate. Research suggests that a history of a depressive or anxiety disorder is a risk factor for PTSD. However, PTSD frequently occurs first and leads to the development of the other disorders. Anxiety or depressive disorders complicated by comorbid PTSD are more likely to be chronic and treatment-resistant and to benefit from psychotherapy and medications given to treat patients with PTSD (Zlotnick 1997).

Health-Related Problems: The chronic nature of PTSD may underlie patients' increased health problems and utilization of health services and thus might be associated with substantially increased health care costs. PTSD-related trauma occurring in childhood has been associated with a two- to twelvefold increased likelihood of smoking, alcoholism, substance abuse, depression, and suicide attempt as an adult (Felitti 1998). Cigarette, alcohol, and drug use may, in turn, contribute to the increased prevalence of a range of medical illnesses, such as asthma, peptic ulcer disease, and hypertension, noted in those suffering from PTSD.

Disability: In addition to psychiatric and medical problems and utilization of health care services associated with PTSD, this disorder has a profound negative impact on quality of life and function across a range of family, social, and occupational roles, resulting in lower educational attainment, higher rates of unemployment, and lower socioeconomic status. Comorbid depression or anxiety increases the disabling effect of PTSD. Conversely, an individual with a history of depression or anxiety who develops PTSD is much more likely to have increased disability. The negative consequences of the combined disorders are great: Rates of suicide attempt are higher among depressed patients with PTSD than among depressed patients without PTSD. Although it is plausible that early treatment might lead to improved function and cost savings, this needs to be confirmed by further research.

Treatment
PTSD prevention and treatment is just now getting the research attention other anxiety and depressive illnesses have received over the years. One obstacle to treatment, and possibly to treatment research, might be the tendency to view PTSD as simply a severe reaction to stressÑperhaps due to poor coping mechanisms or lack of social supports. Support from family, friends, and counselors in the aftermath of trauma is crucial in mitigating the impact of trauma. (Table 4 provides a guide for early intervention in patients exposed to extreme trauma.) Nonetheless, the growing psychiatric and neurobiological evidence is persuasive that PTSD is not just a "stress reaction" but an illness requiring treatment. As outlined in the previous sections, the psychiatric, medical, and disabling consequences of not treating PTSD make effective treatment a high priority. Both psychotherapy and medications have been widely used, but the evidence for efficacy of various forms of treatment, summarized next, varies widely.

Psychological Therapies
The psychotherapy with the best evidence for efficacy, based on controlled studies, is cognitive-behavioral therapy (Boudewyns 1990; Brom 1989; Foa 1999; Marks 1998). However, the quality of studies is limited by small sample sizes and a lack of adequate controls or well-validated outcome measures (only two well-controlled studies have sample sizes greater than 20 per treatment group). Nonetheless, the consistency of the results across multiple smaller or less well-controlled studies suggests that at least some cognitive-behavioral therapies are likely to be effective in treating PTSD.

Cognitive-behavioral therapy is a large category encompassing a bewildering array of brand-names, including traditional Cognitive Therapy, Stress Inoculation Training, Systematic Desensitization, Biofeedback, Assertiveness Training, Exposure Therapy (e.g., flooding/imaginal/in vivo/prolonged/ directed), Relaxation Training, and combined approaches. Exposure and anxiety-management therapies are the two most widely used and recommended for PTSD. In exposure therapy, the patient confronts memories of the trauma through either repeated re-imagining of the traumatic events or exposure to settings and situations that are anxiety-provoking because of their association with the trauma. Anxiety management includes such techniques as relaxation training, breathing retraining, positive thinking and self-talk, assertiveness training, and thought-stopping.

Eye Movement Desensitization and Reprocessing Therapy (EMDR) has received considerable attention. Briefly, EMDR is a technique intended to connect the right and left brain responses by having the patient focus on an intense memory or image that is strongly associated with the trauma while following the therapist's rapidly moving fingers as they move back and forth across the visual field. Preliminary results have been mixed, and a review by the International Society for Traumatic Stress Studies raises doubt regarding the efficacy of EMDR.

Various forms of group therapy have been used to treat PTSD (Lubin 1998; Zlotnick 1997). One common form is the open-ended supportive group, which provides an interpersonal focus that emphasizes sharing reactions and coping strategies. Group therapy with either a psychodynamic or cognitive-behavioral approach is also employed. Although group approaches might provide cost-effective adjunctive treatment, evidence of efficacy is not available to support their use as a primary treatment for PTSD.

The utility of individual forms of cognitive-behavioral therapy is hindered in some regions of the country by limited access to well-trained practitioners or by inadequate insurance coverage. Moreover, as summarized earlier, the clinical picture of PTSD is frequently complicated by comorbid depression or anxiety disorders. The efficacy of individual or group therapy for PTSD in the presence of such comorbidity is not well studied.

Pharmacological Treatment
Currently, sertraline is the only medication approved by the FDA to treat PTSD. This is perhaps surprising, because 20 years have passed since PTSD was formally recognized as a diagnosis based on DSM-III criteria. A 1992 review in the Journal of the American Medical Association (Solomon) identified only five controlled trials of medications, all of which were limited to males (mostly combat veterans). The tricyclic agent and monoamine oxidase inhibitor antidepressants used in these trials had only modest efficacy for treating PTSD. Since that time, only four placebo-controlled studiesÑtwo using fluoxetine and two using sertraline — have been reported that assess the efficacy of medications for treating PTSD in civilians.

Evidence for the efficacy of fluoxetine in civilians with PTSD comes from two small studies. The first (van der Kolk 1994) was part of a larger negative study of male combat veterans. Although fluoxetine demonstrated efficacy among those in the civilian subgroup, it was not well tolerated, with an overall 30.3% attrition rate, an 81% incidence of diarrhea, and a 65% incidence of increased sweating. Similar problems, possibly autonomically mediated, were reported when 20-mg doses of fluoxetine were used to treat other anxiety disorders such as panic (Gorman 1987).

The second, somewhat larger fluoxetine study (Connor 1999), using a starting dose of 10 mg and a 10 mg/week titration schedule, had better results. Fluoxetine (n = 27), compared with placebo (n = 27), showed greater efficacy in improving the symptoms and functional impairment associated with PTSD. Most patients ended up on a daily dose of 20 to 40 mg of fluoxetine. Adverse events were not reported, so it is difficult to assess whether starting at a lower dose and using a slower titration schedule solved the tolerability problem seen in the previous study.

The efficacy of sertraline in treating PTSD comes from two placebo-controlled studies (Brady 2000; Davidson 1997), each involving approximately 200 civilians who had suffered from moderate-to-severe PTSD for an average of 12 years. In two additional placebo-controlled PTSD trials (FDA on file), the difference in response favored sertraline but did not achieve statistical significance. One of these studies was conducted predominantly in male veterans. The reason for resistance to treatment in this patient group remains unexplained, but it might be related to chronicity, alcoholism, substance abuse, affective illness comorbidity, or psychosocial variables such as service-connected disability status. The two positive civilian placebo-controlled studies formed the basis for the FDA's approval of sertraline as a treatment for PTSD.

Prior to treatment, patients in both positive studies reported substantial disability and impairment in their quality of life due to PTSD. Improvement occurred rapidly and achieved significance, compared with placebo, on the primary outcome measures by the second week of treatment. Significant reduction in symptom severity compared with baseline occurred in all three of the core symptom clusters of PTSD: arousal, avoidance or numbing, and re-experiencing of the trauma through intrusive images, nightmares, or memories. Marked improvement in quality of life and ability to function was evident by the end of 12 weeks of acute treatment. Sertraline was well tolerated; insomnia early in treatment was the most common significant side effect, reported by 16% of patients.

Almost 40-50% of the patients in these two studies suffered from either depression or anxiety, and approximately one third reported a history of alcohol or substance abuse (patients with current substance abuse problems were excluded), which is consistent with the known comorbidity and disability associated with chronic untreated PTSD. Sertraline was as effective in rapidly improving PTSD symptoms in patients with comorbid depression or anxiety disorders as in PTSD patients who did not suffer from these. Thus, its efficacy for PTSD is independent of its efficacy for depression and anxiety disorders.

To avoid activating side effects that would worsen anxiety-related symptoms, treatment with selective serotonin reuptake inhibitors (SSRIs) should be initiated at a dose lower than the starting dose used in treating depression. For sertraline, a starting dose of 25 mg per day for the first week should be increased to 50 mg thereafter, with further titration at one- to two-week intervals up to 200 mg per day as guided by symptom resolution. Pharmacological treatment can help alleviate initial insomnia and anxiety symptoms, allowing patients to progress with anxiety-management psychotherapies.

Practical Management
Patients who have suffered a trauma need a physician who is a sensitive listener. The physician must foster a supportive and empathic rapport with the patient, who should be reassured about the range of distressing symptoms and emotions — from nightmares and anxiety to guilt — that commonly occur following trauma. The patient, family, and friends (as appropriate) should be informed that repeated retelling of the traumatic events is not only common but also may facilitate recovery.

It is useful to tell patients that traumas such as those they have experienced frequently sensitize their systems, triggering a cascade of neurobiological and physiological reactions that usually respond to psychotherapeutic and pharmacological treatment. In some cases, insomnia is a major early problem, and short-term use of the nonbenzodiazepine hypnotics, zolpidem or zaleplon, or trazodone might be useful.

When to Refer
Several groups of patients can be expected to require therapy beyond what most primary care physicians can provide. Veterans with long-standing PTSD respond poorly to most forms of treatment but require ongoing support either through the Veterans Administration or the private sector. Patients with multiple traumas in their past, especially survivors of childhood abuse and those with long-standing psychiatric comorbidities, including substance abuse, depression, and other anxiety disorders, might benefit from intensive psychotherapy treatment available through referral. Patients with PTSD are at high risk for suicide and should be screened for suicidal ideation. Serious suicidal risk obviously should trigger urgent consultation.

In referring patients with PTSD, one of the primary care physician's key roles is to identify a consultant experienced at working with PTSD patients. An additional role might be medication management when the consultant is not a physician. For patients resisting the diagnosis of PTSD or a referral, initiating treatment of symptoms might afford sufficient early symptom relief, thereby encouraging them to engage in the therapeutic work required.

Summary
PTSD is a highly prevalent illness that often goes unrecognized and undiagnosed. This might be due to masking by comorbid anxiety or depressive disorders, as well as to reticence on the part of patients to discuss traumatic events. The importance of proper diagnosis is essential given the chronic nature of this disorder and the disability associated with it. Primary care physicians have a central role in the diagnosis and management of PTSD and can provide early diagnosis and first-line treatment.

Empathic listening, as well as support from family and friends, is essential for healing. Physicians should have a low threshold for referring a patient with PTSD to counseling or to more-targeted cognitive-behavioral treatment if these are available and affordable. Combined treatment using cognitive-behavioral therapy and pharmacotherapy — including an SSRI — is usually indicated.

The development of this article was supported by an unrestricted grant from Pfizer, Inc.

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Fig. 3.

Dr. Culpepper is chairman of Family Medicine at Boston University Medical Center and serves on the editorial board of Hippocrates

SELECTED REFERENCES

Boudewyns PA, Hyer L. Physiological response of combat memories and preliminary treatment outcome in Vietnam veteran PTSD patients treated with direct therapeutic exposure. Behav Ther. 1990;21:63-87.

Brady K et al. Efficacy and safety of sertraline treatment of posttraumatic stress disorder: A randomized controlled trial. JAMA. 2000;283:1837-44.

Bremner JD. Alterations in brain structure and function associated with post-traumatic stress disorder. Semin Clin Neuropsychiatry. 1999;4:249-55.

Breslau N et al. Traumatic events and posttraumatic stress disorder in an urban population of young adults. Arch Gen Psychiatry. 1991;48:216-22.

Breslau N et al. Trauma and posttraumatic stress disorder in the community. Arch Gen Psychiatry. 1998;55:626-32.

Breslau N et al. Short screening scale for DSM-IV posttraumatic stress disorder. Am J Psychiatry. 1999; 156:908-11.

Brom D et al. Brief psychotherapy for posttraumatic stress disorders. J Consult Clin Psychol. 1989; 57:607-12.

Centers for Disease Control and Prevention. National Diabetes Fact Sheet: National estimates and general information on diabetes in the United States. Revised edition. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 1998.

Connor KM et al. Fluoxetine in post-traumatic stress disorder. Randomised, double-blind study. Br J Psychiatry. 1999;175:17-22.

Davidson JR, Farfel GM. Double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Poster presented at: Annual Meeting of the American College of Neuropharmacology; December 1997; Kamuela, HI.

Foa EB et al. A comparison of exposure therapy, stress inoculation training, and their combination for reducing posttraumatic stress disorder in female assault victims. J Consult Clin Psychol. 1999;67:194-200.

Felitti VJ et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. Am J Prev Med. 1998;14:245-58.

Giaconia RM et al. Traumas and posttraumatic stress disorder in a community population of older adolescents. J Am Acad Child Adolesc Psychiatry. 1995; 34:1369-80.

Golding JM. Sexual assault history and physical health in randomly selected Los Angeles women. Health Psychol. 1994;13:130-8.

Gorman JM et al. An open trial of fluoxetine in the treatment of panic attacks. J Clin Psychopharmacol. 1987;7:329-32.

Heim C et al. Abuse-related posttraumatic stress disorder and alterations of the hypothalamic-pituitary-adrenal axis in women with chronic pelvic pain. Psychosom Med. 1998;60:309-18.

Irwin C et al. Comorbidity of posttraumatic stress disorder and irritable bowel syndrome. J Clin Psychiatry. 1996;57:576-8.

Kessler RC et al. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995;52:1048-60.

Lubin H et al. Efficacy of psychoeducational group therapy in reducing symptoms of posttraumatic stress disorder among multiply traumatized women. Am J Psychiatry. 1998;155:1172-7.

Marks I et al. Treatment of posttraumatic stress disorder by exposure and/or cognitive restructuring: A controlled study. Arch Gen Psychiatry. 1998;55:317-25.

McCauley J et al. Clinical characteristics of women with a history of childhood abuse: Unhealed wounds. JAMA. 1997;277:1362-68.

North CS et al. Posttraumatic stress disorder in survivors of a mass shooting. Am J Psychiatry. 1994;151:82-8.

Resnick HS et al. Prevalence of civilian trauma and posttraumatic stress disorder in a representative national sample of women. J Consult Clin Psychol. 1993;61:984-91.

Sly MR. Changing prevalence of allergic rhinitis and asthma. Ann Allergy Asthma Immunol 1999;82:233-48.

Solomon SD et al. Efficacy of treatments for posttraumatic stress disorder. An empirical review. JAMA. 1992;268:633-8.

Stein MB et al. Full and partial posttraumatic stress disorder: Findings from a community survey. Am J Psychiatry. 1997;154:1114-9.

van der Kolk BA. The psychobiology of posttraumatic stress disorder. J Clin Psychiatry. 1997;58:16-24. van der Kolk BA et al. Fluoxetine in posttraumatic stress disorder. J Clin Psychiatry. 1994;55:517-22.

Walker EA, Stenchever MA. Sexual victimization and chronic pelvic pain. Obstet Gynecol Clin North Am. 1993;20:795-807.

Zlotnick C et al. An affect-management group for women with posttraumatic stress disorder and histories of childhood sexual abuse. J Trauma Stress. 1997;10:425-36.

Zlotnick C et al. Chronicity in posttraumatic stress disorder (PTSD) and predictors of course of comorbid PTSD in patients with anxiety disorders. J Trauma Stress 1999;12:89-100.

Zubieta JK et al. Medial frontal cortex involvement in PTSD symptoms: A SPECT study. J Psychiatr Res. 1999;33:259-64.

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