ESTABLISHING POSTTRAUMATIC STRESS DISORDER AS A PSYCHIATRIC DISORDER
As with many other disorders introduced decades ago, posttraumatic stress disorder (PTSD) was first added to psychiatry’s diagnostic manual without what is considered by today’s standards to be rigorous evidence from systematic research. Its introduction was based on clinicians’ informal experience with groups of Vietnam veterans and Holocaust victims rather than on formal studies (Brewin 2003; Shepherd 2001). Nevertheless, many of the symptoms originally listed in the first diagnostic criteria for PTSD introduced in the third edition (1980) of the American Psychiatric Association (APA) Diagnostic and Statistical Manual of Mental Disorders, DSM-III, have remained largely unchanged in the current (fourth) edition of the manual, DSM-IV.
Today, health professionals in the United States diagnose psychiatric disorders according to criteria listed in DSM-IV (APA 2000). DSM is the most authoritative source used by clinicians, mental health professionals, government agencies, and health insurers. Its diagnoses have myriad applications in health statistics, reimbursement, disability claims, and recordkeeping. The decision to revise diagnostic criteria or to add a new disorder to DSM is made by a consensus of experts organized under the auspices of the APA. The process relies on evaluation of the best available evidence from clinical practice and research.
A decade before the DSM-III, a landmark paper proposed five criteria to establish the validity of a psychiatric diagnosis on the basis of methods used in other fields of medicine for validation of medical diagnoses (Robins and Guze 1970). The criteria, which Robins and Guze’s influential paper called phases, were on the leading edge of the effort to classify psychiatric illness on the basis of systematic studies. The concept constituted a departure from the traditional dependence of psychiatric diagnosis on psychoanalytic theory. Robins and Guze wanted
the field of psychiatry to split with its nonscientific past and, through more systematic data-based studies, achieve an equal footing with the rest of medicine (Luhrmann 2000). “We believe that a valid classification is an essential step in science…One of the reasons that diagnostic classification has fallen into disrepute among some psychiatrists is that diagnostic schemes have been largely based on a priori principles rather than upon systematic studies” (Robins and Guze 1970). The a priori principles alluded to were psychoanalytic theories about causation of psychiatric illness. The work of Robins and Guze was elaborated on by Kendler (1980), Kendell (1989), and Kendell and Jablensky (2003), who distinguished between antecedent validators (precipitating factors), concurrent validators (psychologic tests), and predictive validators (diagnostic consistency over time).
Applying the five phases of Robins and Guze, this section examines the evidence that PTSD is a valid disorder (as defined below). It is not an exhaustive review but illustrates the complex nature of diagnostic validation, a process that often takes years or decades. The process is always receptive to new empirical evidence in shaping the outcome, the diagnostic criteria themselves. The five phases set a high bar for any diagnosis in medicine, and few existing diagnoses, whether in psychiatry or in other fields, would meet all of them. Therefore, fulfilling all the phases should not be seen as an absolute requirement for inclusion of a disorder in a classification scheme, such as DSM.
At the outset, it is important to emphasize that validating PTSD as a disorder is not the same as making a PTSD diagnosis. Making a diagnosis is guided by knowledge of diagnostic criteria, to be sure, but it also requires clinical judgment in application of criteria: “the specific diagnostic criteria included in DSM-IV are meant to serve as guidelines to be informed by clinical judgment and are not meant to be used in a cookbook fashion” (APA 2000).
The five phases for establishing the validity of a disorder (Robins and Guze 1970) are as follows:
Describe the core clinical features of the disorder.
Differentiate the disorder from other disorders.
Conduct laboratory studies.
Determine the temporal stability of the disorder.
Determine whether the disorder aggregates in families.
This appendix is organized according to each of the five phases. Wherever possible, we draw on studies of veterans or other groups with comparable traumatic exposures.
CORE CLINICAL FEATURES
Defining a disorder begins by describing individual cases and then proceeds to the gathering of more data. In the 1970s, clinicians treating Vietnam veterans described two core symptom clusters: reexperiencing a trauma through flashbacks and other symptoms, and reacting to the reminders of the trauma with avoidance (avoiding thoughts, feelings, or conversations about the traumatic event or situations that remind one of it) and emotional numbness (diminished responsiveness to the external world, feeling of detachment from other people, or having a marked inability to feel emotions, such as intimacy and tenderness). A third core symptom cluster, hyperarousal, was added in 1987 with publication of a revision of DSM-III, DSM-III-R, because high levels of arousal had been associated with PTSD in studies during the intervening years (Brewin 2003).
Several additional lines of evidence help to characterize PTSD’s core clinical features in the first phase of validating the disorder. The first draws from statistical studies that use factor analysis to explore whether PTSD symptom clusters cohere. The questions for research are, Do the symptom clusters (re-experiencing, numbing and avoidance, and hyperarousal) cohere (occur together)? Do they correspond to underlying biologic or psychologic processes? Asmundson et al. (2004) examined the results of numerous factor analysis studies and concluded that many of them support PTSD as having four core symptom clusters instead of three: re-experiencing and hyperarousal were indeed separate symptom clusters, but avoidance and numbing actually represented two separate ones instead of a single cluster, as defined in DSM-IV.
The second line of evidence draws from epidemiologic research suggesting that PTSD’s core clinical features have been found to be consistent among the diverse populations in which it has been studied.
After the Gulf War, veterans from three developed countries, the United States (Iowa), Australia, and Canada, displayed a similar prevalence of PTSD (Black et al. 2004; Goss Gilroy Inc. 1998; Ikin et al. 2004; McKenzie et al. 2004). The consistency of PTSD in diverse populations is also supported by studies that compared PTSD prevalence in developed and undeveloped countries. People in undeveloped countries and non-Western cultures might be expected, a priori, to have different ways of manifesting distress from trauma exposure (Department of Health and Human Services 2001), but PTSD has been documented worldwide in postconflict settings, including Algeria and Palestinian territories (de Jong et al. 2003), whether after war or after mass violence. In one study, cross-national similarities were found among civilians in the United States and Kenya after the same type of traumatic event, a terrorist bombing (North et al. 2005). That study evaluated people who several months earlier had been directly exposed to a terrorist bombing and also measured PTSD with uniformity of assessment (a fully structured psychiatric interview, the Diagnostic Interview Schedule, with adjustments for cultural differences in expression). The study found similar bombing-related PTSD prevalence among survivors in the two countries and similar prevalence in the two sexes: some 30% of men and 50% of the women from both the United States and Kenya had PTSD related to the terrorist bombing. Those studies of veterans from different countries and numerous other populations and traumatic events support the concept of PTSD as a distinct disorder.
DIFFERENTIATING POSTTRAUMATIC STRESS DISORDER FROM OTHER DISORDERS
A valid disorder is one that is distinct from others with similar symptoms, rather than merely another manifestation of them. The differentiation phase is difficult to apply to PTSD because it shares many symptoms with other psychiatric disorders, notably other types of anxiety disorders and major depressive disorder. Another difficulty is that a patient who has PTSD is likely also to have at least one other psychiatric disorder (a phenomenon known as comorbidity). Comorbidity, by itself,
does not preclude the validation of PTSD as a distinct disorder, but it makes the process of demonstrating its distinctiveness more difficult.
A study (Keane et al. 1997) sought to determine systematically whether PTSD is distinguishable from major depressive disorder (MDD) and generalized anxiety disorder (GAD). Psychologists and psychiatrists highly experienced in diagnosing PTSD were asked to distinguish among the three disorders by carefully rating their distinguishing clinical features. The investigators gave more than 300 Department of Veterans Affairs clinicians a list of 80 descriptors for all three disorders (using symptoms from DSM-III-R and associated features), and 10 distracters (features not directly related to any of the three). Sixteen of the 80 descriptors overlapped with two disorders and in some cases overlapped with all three. The clinicians were asked to rate the extent to which each item on the list characterized each of the three disorders. The study found that experienced clinicians could readily identify features distinguishing PTSD from the other two disorders, although this was not tested in patients.
In particular, these distinguishing characteristics of PTSD were identified: symptoms linked to a specific trauma, symptoms of avoiding anything reminiscent of the trauma, and fears of acting out anger and frustration in response to lingering effects of the trauma. Features that the clinicians identified as distinguishing PTSD from MDD in particular were involvement with current activities not reminiscent of the trauma. MDD was related to inactivity. GAD was accompanied by widespread physiologic reactivity, whereas physiologic reactivity in PTSD was more closely associated with memories of traumas. The study also identified the 34 descriptors most strongly identified with each of the three disorders. Finally, using factor analysis, the study uncovered the minimal number of hypothetical factors that the clinicians used to identify the three disorders. The study did not demonstrate that health professionals can distinguish PTSD, GAD, and MDD from each other in patients, but it did show that features of PTSD are conceptually distinct from the other disorders.
DSM-IV spells out the particular diagnoses that must be considered when a patient is being evaluated for PTSD. Differential diagnoses include panic disorder, GAD, phobias, MDD, bipolar II disorder, somatization disorder, substance-use disorders, adjustment
disorders, psychotic disorders, obsessive-compulsive disorder, and malingering.
CONDUCTING LABORATORY STUDIES OF POSTTRAUMATIC STRESS DISORDER
The broad term laboratory studies refers to a variety of physiologic tests, imaging techniques, pathology studies, and other means of medical examination that can support the investigation of PTSD as a valid disorder. Laboratory studies are of two general types: reproducible psychologic tests and studies of biologic markers (Robins and Guze 1970). A psychologic test, in this context, measures objectively observed behaviors (patterns of responses to test questions) associated with a disorder. The Minnesota Multiphasic Personality Inventory, for example, can help to distinguish between expression of genuine illness and symptom exaggeration.
A biologic marker (biomarker) is a measurable biologic change that occurs before, during, or as a consequence of a disease process. Many biomarkers are under study, and they support a biologic basis of PTSD (see Chapter). The last 2 decades have witnessed progress in developing laboratory tests to validate PTSD as a disorder but none has been shown to be specific enough to distinguish people who have PTSD from those who do not. In other words, no laboratory test is currently useful for diagnosing PTSD.
DEMONSTRATING TEMPORAL STABILITY OF POSTTRAUMATIC STRESS DISORDER
Temporal stability is related to whether a disorder retains its distinct profile or evolves into another, established disorder. During the first days and weeks after a traumatic event, an immediate stress response might occur in a large proportion of those exposed. The immediate phase can last for several days or weeks. Thereafter, effects start to decline in most people, depending on the traumatic event and its
intensity. For that reason, DSM-IV does not permit the diagnosis of PTSD before the passage of at least a month after the traumatic event.
To establish temporal stability, the same disorder must be present in the same person at a second time in a longitudinal assessment. For example, all the people in the index sample with a diagnosis might no longer report symptoms of that diagnosis at followup, but they might be replaced by an equal number of new cases in people who did not have the disorder at the index time. That is, the overall percentages with PTSD at index and followup could be the same, but the stability of the cases would be zero. Therefore, individual cases, rather than overall rates, should be examined because of individual fluctuations.
Temporal stability also requires that the condition not evolve into a different psychiatric disorder. It is important to evaluate a person for all the other disorders that are part of a differential diagnosis of PTSD, such as GAD and MDD, both at the index time and at followup. Meeting those two criteria requires that studies be longitudinal and use a broad-based assessment method that evaluates participants for PTSD and for other psychiatric disorders. However, the committee was unable to locate such studies for PTSD.
DETERMINING WHETHER POSTTRAUMATIC STRESS DISORDER AGGREGATES IN FAMILIES
The fifth phase in validating a disorder is to determine whether it aggregates in families (Robins and Guze 1970). A key question is how a family history contributes to PTSD. Is it through genetic vulnerability, shared family environment, or both? Research in the 1980s suggested that PTSD occurred in families with other anxiety disorders and depression. It found that family members of veterans with PTSD had higher rates of GAD, alcoholism, and (to a lesser extent) MDD and other types of depressive illness (Davidson et al. 1989; Davidson et al. 1985). A family history of psychiatric illness might increase vulnerability to developing PTSD, but according to the conclusions of two recent meta-analyses, it plays a relatively small role (Brewin et al. 2000; Ozer et al. 2003).
Twin studies help to sort out the relative contributions of shared genes versus shared environment. In one study of more than 4,000 twins during the Vietnam era (True et al. 1993), the investigators analyzed data from members of male twin pairs both of whom served in Southeast Asia versus twin pairs neither of whom served there. Monozygotic twins had a higher concordance than dizygotic twins for combat exposure. That indicates that exposure was not random and complicates the analysis of the role of genes versus shared environment in predisposition to PTSD. The investigators first had to make a statistical adjustment to remove the effect of monozygotic twins’ having higher concordance for combat exposure. Even after the adjustment, they found that genetic factors accounted for around one-third of PTSD symptoms. They interpreted their findings as indicating that genes played a dual role: as risk factors for onset of PTSD and as risk factors for exposure to combat (which, in turn, enhances the risk of PTSD). That finding is supported by several other studies (Breslau et al. 1991; Lyons et al. 1993). The shared environment in which twins grew up played a very small role, predicting only one symptom: painful memories. A separate analysis of the same twins dataset found that the severity of combat exposure itself was far more important than genetics in the long-term persistence of PTSD symptoms (Goldberg et al. 1990; Roy-Byrne et al. 2004).
A separate avenue of research implicating genes involves the study of the hippocampus, a brain structure associated with attention and memory. Reduced hippocampal volume has been found to be associated with PTSD (Bremner et al. 1995).
Also, in light of the evidence suggesting genetic involvement in PTSD, recent studies have begun to identify specific genes. The two potential genes noted here are related to neurotransmission in the brain. One potential candidate is the serotonin transporter promoter gene (Lee et al. 2005). It was chosen for study because alterations in serotonin concentrations are associated with symptoms commonly seen in PTSD, including hypervigilance, exaggerated startle, irritability, impulsivity, aggression, and intrusive memories (Southwick et al. 1999). Another potential candidate is the D2 dopamine receptor gene, which might be linked to a favorable treatment response to the drug paroxetine. Investigators considered that the gene might be useful in predicting
which PTSD patients would improve in social functioning if treated with paroxetine (Lawford et al. 2003).
This appendix has examined the evidence for establishing PTSD as a valid disorder by using the five criteria proposed by Robins and Guze (1970): describing the core clinical features; differentiating from other disorders, conducting laboratory studies, determining temporal stability, and determining aggregation in families. The evidence is robust for the core clinical features of PTSD, which appear to be consistent among diverse populations. Progress has been made in fulfilling the remaining criteria.
American Psychiatric Association. 2000. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association.
Asmundson GJ, Stapleton JA, Taylor S. 2004. Are avoidance and numbing distinct PTSD symptom clusters? Journal of Traumatic Stress 17(6):467–475.
Black DW, Carney CP, Peloso PM, Woolson RF, Schwartz DA, Voelker MD, Barrett DH, Doebbeling BN. 2004. Gulf War veterans with anxiety: Prevalence, comorbidity, and risk factors. Epidemiology 15(2):135–142.
Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, Delaney RC, McCarthy G, Charney DS, Innis RB. 1995. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. American Journal of Psychiatry 152(7):973–981.
Breslau N, Davis GC, Andreski P, Peterson E. 1991. Traumatic events and posttraumatic stress disorder in an urban population of young adults. Archives of General Psychiatry 48(3):216–222.
Brewin CR. 2003. Posttraumatic Stress Disorder: Malady or Myth? New Haven, CT: Yale University Press.
Brewin CR, Andrews B, Valentine JD. 2000. Meta-analysis of risk factors for posttraumatic stress disorder in trauma-exposed adults. Journal of Consulting and Clinical Psychology 68(5):748–766.
Davidson J, Swartz M, Storck M, Krishnan RR, Hammett E. 1985. A diagnostic and family study of posttraumatic stress disorder. American Journal of Psychiatry 142(1):90–93.
Davidson J, Smith R, Kudler H. 1989. Familial psychiatric illness in chronic posttraumatic stress disorder. Comprehensive Psychiatry 30(4):339–345.
de Jong JT, Komproe IH, Van Ommeren M. 2003. Common mental disorders in postconflict settings. Lancet 361(9375):2128–2130.
Department of Health and Human Services. 2001. Mental Health: Culture, Race, and Ethnicity. A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Center for Mental Health Services, National Institutes of Health, National Institute of Mental Health.
Goldberg J, True WR, Eisen SA, Henderson WG. 1990. A twin study of the effects of the Vietnam War on posttraumatic stress disorder. Journal of the American Medical Association 263(9):1227–1232.
Goss Gilroy Inc. 1998. Health Study of Canadian Forces Personnel Involved in the 1991 Conflict in the Persian Gulf. Ottawa, Canada: Goss Gilroy Inc. Department of National Defence.
Ikin JF, Sim MR, Creamer MC, Forbes AB, McKenzie DP, Kelsall HL, Glass DC, McFarlane AC, Abramson MJ, Ittak P, Dwyer T, Blizzard L, Delaney KR, Horsley KWA, Harrex WK, Schwarz H. 2004. War-related psychological stressors and risk of psychological disorders in Australian veterans of the 1991 Gulf War. British Journal of Psychiatry 185(Aug.):116–126.
Keane TM, Taylor KL, Penk WE. 1997. Differentiating post-traumatic stress disorder (PTSD) from major depression (MDD) and generalized anxiety disorder (GAD). Journal of Anxiety Disorders 11(3):317–328.
Kendell R, Jablensky A. 2003. Distinguishing between the validity and utility of psychiatric diagnoses. American Journal of Psychiatry 160(1):4–12.
Kendell RE. 1989. Clinical validity. Psychological Medicine 19(1):45– 55.
Kendler KS. 1980. The nosologic validity of paranoia (simple delusional disorder): A review. Archives of General Psychiatry 37(6):699–706.
Lawford BR, Young RM, Noble EP, Kann B, Arnold L, Rowell J, Ritchie TL. 2003. D2 dopamine receptor gene polymorphism: Paroxetine and social functioning in posttraumatic stress disorder. European Neuropsychopharmacology 13(5):313–320.
Lee HA, Gabriel R, Bale AJ. 2005. Clinical outcomes of Gulf veterans’ medical assessment programme referrals to specialized centers for Gulf veterans with post-traumatic stress disorder. Military Medicine 170(5):400–405.
Luhrmann TM. 2000. Of Two Minds: The Growing Disorder in American Psychiatry. New York: Knopf.
Lyons MJ, Goldberg J, Eisen SA, True W, Tsuang MT, Meyer JM, Henderson WG. 1993. Do genes influence exposure to trauma? A twin study of combat. American Journal of Medical Genetics 48(1):22–27.
McKenzie DP, Ikin JF, McFarlane AC, Creamer M, Forbes AB, Kelsall HL, Glass DC, Ittak P, Sim MR. 2004. Psychological health of Australian veterans of the 1991 Gulf War: An assessment using the SF-12, GHQ-12 and PCL-S. Psychological Medicine 34(8):1419– 1430.
North CS, Pfefferbaum B, Narayanan P, Thielman S, McCoy G, Dumont C, Kawasaki A, Ryosho N, Kim YS, Spitznagel EL. 2005. Comparison of post-disaster psychiatric disorders after terrorist bombings in Nairobi and Oklahoma City. British Journal of Psychiatry 186(June):487–493.
Ozer EJ, Best SR, Lipsey TL, Weiss DS. 2003. Predictors of posttraumatic stress disorder and symptoms in adults: A meta-analysis. Psychological Bulletin 129(1):52–73.
Robins E, Guze SB. 1970. Establishment of diagnostic validity in psychiatric illness: Its application to schizophrenia. American Journal of Psychiatry 126(7):983–987.
Roy-Byrne P, Arguelles L, Vitek ME, Goldberg J, Keane TM, True WR, Pitman RK. 2004. Persistence and change of PTSD symptomatology—a longitudinal co-twin control analysis of the Vietnam Era Twin Registry. Social Psychiatry and Psychiatric Epidemiology 39(9):681–685.
Shepherd B. 2001. A War of Nerves: Soldiers and Psychiatrists in the Twentieth Century. Cambridge, MA: Harvard University Press.
Southwick SM, Paige S, Morgan CA 3rd, Bremner JD, Krystal JH, Charney DS. 1999. Neurotransmitter alterations in PTSD: Catecholamines and serotonin. Seminars in Clinical Neuropsychiatry 4(4):242–248.
True WR, Rice J, Eisen SA, Heath AC, Goldberg J, Lyons MJ, Nowak J. 1993. A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms. Archives of General Psychiatry 50(4):257–264.