Psychiatr Clin N Am 25 (2002) xi xv Preface Recent advances in the study of biological alterations in post-traumatic stress disorder (PTSD) Rachel Yehuda, PhD Guest Editor This issue of The Psychiatric Clinics of North America consists of 12 articles that review advances in the biology of post-traumatic stress disorder (PTSD) and its potential relevance to pathophysiology. The biologic component of PTSD has become increasingly important as findings delineate that this psychological condition is associated with distinct, often circumscribed alterations in the same hormonal, immune, neurochemical, and physiological systems involved in other medical and psychiatric illnesses. In tandem with observations of the phenomenology and psychology of PTSD, neurobiological examinations of trauma survivors have supported the possibility that the development of PTSD is facilitated by a failure to contain the normal stress response at the time of the trauma, resulting in a cascade of biological alterations that lead to intrusive, avoidance, and hyperarousal symptoms. This failure may represent an alternative trajectory to the normal process of adaptation and recovery observed in most people who undergo traumatic experiences. The issue begins with an article by McFarlane and colleagues who discuss the role of neural networks in modeling the biological aspects of PTSD. The authors articulate the need to think about biologic aspects of PTSD in a more complex manner than is usually achieved, in a way that tolerates seemingly disparate observations, and allows for variation in findings due to 0193-953X/02/$ - see front matter Ó 2002, Elsevier Science (USA). All rights reserved. PII: S 0 1 9 3-9 5 3 X ( 0 2 ) 0 0 0 2 7-8
xii R.Y. Yehuda / Psychiatr Clin N Am 25 (2002) xi xv individual differences. The emphasis on longitudinal course, developmental trajectories, and dynamic processes that continually modify each other provides a sophisticated method for conceptualizing the onset of PTSD as well as changes in this disorder with the passage of time. The authors specifically focus on how the neural networks approach helps model noradrenergic alterations in PTSD and its relationship with disordered information processing, but in so doing, offer a more global approach that should be considered in evaluating the biologic literature in the aggregate. Next, Orr and colleagues provide a comprehensive and thoughtful summary of the psychophysiology and electrophysiology of PTSD. The psychophysiologic findings were the first biological alterations observed in symptomatic trauma survivors, even before the diagnosis of PTSD came into existence. It is not particularly surprising to document changes in heart rate, blood pressure and measures in response to traumatic cues in trauma survivors in view of the fact that physiologic responses to distressing cues constitutes one of the 17 symptoms of PTSD. Interestingly, however, this response does not occur uniformly in PTSD, raising the important possibility that these measures may reflect symptom severity. Following the discussion of the psychophysiological responses to trauma, Dr. Golier and I summarize the literature on neuropsychological processes in PTSD. Many of the symptoms of PTSD are directly or indirectly related to memory processing. The presence of traumatic memories is in fact a hallmark of the disorder. However, in recent decades, investigators have struggled to understand whether cognitive alterations in PTSD result from trauma, or rather, are present prior to trauma exposure serving to increase the likelihood of developing PTSD. Furthermore, although persons with PTSD certainly demonstrate altered responses to traumatic stimuli either in over-remembering or failing to remember traumatic words it is not clear whether and to what extent such memory alterations are a continuation of more fundamental cognitive impairments or rather, lead to a more generalized disturbance. These issues are discussed in detail. Dr. Grossman and colleagues address the structural, biochemical, and functional neuroanatomy of PTSD, and illustrate how these findings inform the neuropsychological observations described in Golier and Yehuda. Since the initial report in 1995 of smaller hippocampal volumes in PTSD, and the general fascination with applying neuroimaging techniques to psychiatric disorder, there has been interest in examining neuroanatomical correlates of memory impairments and other stress-related disorders. Grossman and colleagues first describe the brain regions that one would hypothesize would be relevant in PTSD based on animal studies of stress and clinical studies of memory impairment. They then review the neuroimaging techniques that have been used to study areas of interest, the findings generated in such studies and their implications for the pathophysiology of PTSD. In the next article, I summarize hypothalamic-pituitary-adrenal alterations in PTSD. Certainly there is a conceptual link between studies of memory, neu-
R.Y. Yehuda / Psychiatr Clin N Am 25 (2002) xi xv xiii roanatomy, and stress hormones. However, to date, neuroendocrine studies of PTSD have yielded discrepant findings. The review looks very carefully at the discrepant findings and attempts to determine how they may or may not be consistent with various models that have been proposed. The potential importance of the neuroendocrine studies in PTSD is in identifying a series of biologic alterations that are rather specific to PTSD. Neuroendocrine studies have also offered an understanding that the biology of PTSD is not simply a reflection of the biological response to stress or trauma. Following this discussion, Dr. Wong presents a review of immune findings. Although the examination of immune parameters is certainly of interest in PTSD given the relationship between PTSD and somatic illness, it has been difficult to obtain a cohesive picture of this area that has been plagued by inconsistent findings and methodologic challenges. Yet, Dr. Wong s overview provides an explanation at least for the theoretical importance of this area of study in PTSD. Examining biological parameters in trauma survivors with chronic PTSD provides important information about the systems that may be altered in this disorder, but does not illuminate how such disorders may have developed following trauma exposure. In the last few years, the field of traumatology has been greatly informed by prospective, longitudinal studies of this disorder. Dr. Marshall and Mr. Garakani review the psychobiology of the acute stress response and its relationship with the psychobiology of PTSD. Given that there have been only few studies in this area, the authors opted to provide extensive reviews of each of the studies. In the aggregate, the emerging literature suggests that there are a number of biologic factors that seem to be associated with the development of PTSD, whereas other alterations develop over time. Factors associated with risk appear to reflect biological correlates of earlier traumatic exposures. Data relating to the development of PTSD as it occurs in children versus adults have also accrued in the last several years. Dr. Teicher and his colleagues discuss the developmental neurobiology of childhood stress and trauma, and point to ubiquitous changes in neurogenesis, synaptic overproduction and pruning, and myelination that can affect the neuroanatomy and neurochemistry of the brain, and likely cognitive functioning and behavior in a way that lays the groundwork for sensitization in response to exposure to trauma in adulthood. Dr. Teicher s data can best be understood in the context of a neural network model, similar to the one presented by McFarlane and colleagues. As such, the information presented by Teicher and colleagues form the basis for integrating the biologic findings in PTSD in a developmental context, while accounting for individual differences in both exposure variables and psychiatric and biologic outcomes. The next two additions to this issue provide an integration of the biologic findings to pharmacotherapy and psychotherapy for PTSD, respectively. Dr. Matthew Friedman discusses the implications of biologic findings in terms of how they can inform rational pharmacotherapy of PTSD. It is critical to consider whether and to what extent one should develop
xiv R.Y. Yehuda / Psychiatr Clin N Am 25 (2002) xi xv pharmacotherapeutic strategies based on biologic alterations in PTSD, particularly if these alterations constitute risk factors rather than manifestations of stress and/or pathophysiologic expressions of the disease. Dr. Friedman tackles some difficult issues regarding the optimal timing for treatment following traumatic stress, in consideration of reslience factors. Indeed, in the aftermath of September 11th the question of how soon to intervene following traumatic stress has been a salient one. Finally, Dr. Friedman discusses issues relating to psychopharmacologic strategies for prevention of PTSD. Drs. Rabois and colleagues struggle with the equally difficult challenge of articulating the implications of biologic studies for psychological treatments. The approach taken in this review is to consider different implications on the basis of different types of findings that have been demonstrated. The authors wisely highlight the limitations of current biologic studies, and emphasize the importance of empirically-validated treatment approaches. Indeed, it may be that rather than having biological studies inform psychological treatment of PTSD, the study of biologic changes before and after a successful psychological intervention may lead to clarification of the biological basis of PTSD, and specifically the determination of which variables may be related to risk versus symptom severity. As more information is obtained about the biology of PTSD, it has become apparent that many alterations observed in PTSD are fairly specific to this disorder, whereas some biologic disturbances in PTSD are similar to those observed in other anxiety and mood disorders. In the case of the neuroendocrine findings, for example, many changes observed in PTSD are opposite of those that have been described in major depressive disorder. Drs. Sullivan and Gorman consider the issue of whether and to what extent the biologic findings in PTSD resemble those observed in other anxiety disorders, mood, stress or memory disorders. They consider the fact that most diagnostic conceptions are multidetermined by social, political, and legal considerations as well as medical or scientific ones. Indeed, the biologic findings in PTSD have certainly helped establish the legitimacy of this disorder as well as its distinctness from other conditions. Drs. Sullivan and Gorman ultimately address the question of the nature of biologic findings in PTSD versus other conditions by examining the relationship of these findings to data from animal studies of fear and anxiety. The concluding article picks up on the theme of the relationship between biologic findings in PTSD to those in preclinical stress studies to make several important observations both about how basic science models inform the study of PTSD, and also how the study of PTSD has informed basic science models of stress. Dr. McEwen s articulation of the concept of allostatic load is particularly helpful in grappling with the issues related to individual differences in responses to stress as well as disparate biologic observations in the field of PTSD. Allostatic load refers to the impact of the amplification of activities involved in the regulation and counter-regulation of physiologic systems as a function of stress. Dr. McEwen points out that the biologic
R.Y. Yehuda / Psychiatr Clin N Am 25 (2002) xi xv xv changes that are associated with stress can be both protective and damaging depending on where in the time course of stress adaptation these changes occur. So too, the issue of brain plasticity in response to the environment can be a double-edged sword in allowing for both detrimental as well as positive change. Dr. McEwen s observations are grounded in the basic sciences, but provide a sophisticated model for how to think about the role of trauma in PTSD as well as how to consider PTSD in the context of a developmental progression that modifies and is modified by other processes. I hope you find this issue of The Psychiatric Clinics of North America informative. I thank the authors very much for their outstanding contributions. Rachel Yehuda, PhD Guest Editor Bronx VA Medical Center Psychiatry OOMH 130 West Kingsbridge Road Bronx, NY 10468, USA E-mail address: Rachel.yehuda@med.va.gov