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Posttraumatic Stress Disorder: Neurobiology, Psychology, and Public Health

(PSYCHIATRIC TIMES) - In recent years, we have learned a great deal about posttraumatic stress disorder (PTSD) and its public health implications. From 9/11 to Katrina and the present Iraq war, PTSD has been in the forefront of health concerns and public policy. Recent advances as well as emerging needs are leading us to new and exciting opportunities to provide better care and gain a better understanding of the complex nature of human responses to traumatic events. As we look to the future, we can be both reassured and concerned that it will, on one hand, be similar to the present and, on the other, provide new opportunities and challenges for care of those exposed to traumatic events—natural and human-made, large- and small-scale.

PTSD is a disorder of forgetting perhaps even more than of remembering. It is the inability to forget the trauma that leads to the pathology and suffering in PTSD. Forgetting is a critical component of recovery. Of course, if we could not forget, our brains would rapidly be cluttered with information and observations and perhaps more limited in cognitive control functions for other activities.1

PTSD is not uncommon following many traumatic events from terrorism to motor vehicle accidents, or industrial explosions (Figure 1).2,3 In its acute form, PTSD may be like the common cold, experienced at some time in one's life by nearly all. Some colds progress to pneumonia and may create substantial illness and impairment of function. Similarly, PTSD, when it becomes chronic, may cause major distress and requires psycho-therapeutic and/or pharmacological intervention.

To understand the breadth of the emerging treatments, interventions, and comprehension of PTSD and other trauma-related responses, we must think across neurobiology, psychology, and community and from individuals to populations. In all areas, breakthroughs and opportunities as well as challenges are evident.

The power of translating across human tissues, animal models, and biomarker studies is remarkable and offers opportunities to identify treatment targets not previously recognized.4 In the past year we have seen the first studies of postmortem PTSD human brain tissue. Exciting and groundbreaking studies have shown the possibility of identifying critical gene activity in PTSD related to various brain regions.5,6 In the prefrontal cortex and the amygdala, for instance, studies have suggested that there are unique genes in patients with PTSD, some of which (eg, the p11 gene) have also been found in animal models of PTSD and initial biomarker studies. Recent studies of hurricane victims have shown that PTSD is 20 times more likely to develop in those with the short/short genotype of the serotonin transporter gene (5-HTTLPR) and poorer social supports.7 The science of PTSD now requires a well-developed brain bank8 like those that exist for other psychiatric and neurological disorders (eg, schizophrenia, depression/mania, amyotrophic lateral sclerosis, Alzheimer disease).

The development of animal models is also critical for the study of therapeutic and prophylactic treatments of stress-associated psychiatric disorders, such as PTSD. Our increased ability to identify endophenotypes—specific genetically linked behavioral characteristics/phenotypes9—that relate to PTSD will greatly enhance our neurobiological understanding.

Historically, adequate animal models have been central to developing effective therapeutic treatments. Our present animal models of PTSD include models of predator stress, social defeat, shock, restraint and shock, and serial prolonged stress. None is complete, but each provides a model of different symptoms of the trauma response. Knock-out and knock-in strains offer additional sources of study. Animal models have rarely addressed the observation that even in animal species (as in humans) PTSD-like symptoms being studied in the particular model do not develop in all individual animals; this is an important area for additional future study to identify resilience and genetic targets for risk.
Psychology: PTSD as impaired forgetting

As noted above, PTSD is a disorder of forgetting. It is the inability to forget that leads to the pathology and suffering in PTSD. In clinical practice, forgetting is often overlooked as an important part of recovery, not only pathology. Forgetting is critical to our ability to maintain attention and conserve cognitive resources. Extinction of fear is one paradigm for examining forgetting.10-12 Extinction—which may also be conceived of as new learning—is a potentially important mechanism for PTSD formation and also for its treatment.13 Guthrie and Bryant14 have shown that PTSD is more likely to develop following a traumatic event in firefighters who had shown impaired extinction before exposure. Similarly, those with PTSD show impaired ability to extinguish conditioned responses.15-17 The ventral medial prefrontal cortex appears to be central to extinction of conditioned fear. Understanding of the story of extinction, forgetting, and the prefrontal cortex holds opportunities for treatments yet to come.
Public health

Events from the war in Iraq to bombings in London to Hurricane Katrina have reminded us of the important public health issues raised by PTSD. The public health response to large-scale emergencies and catastrophes requires consideration of the disorders (eg, PTSD, depression), distress (eg, sleep disturbance, fear, changes in economic behaviors such as purchasing houses), and health-risk behaviors (eg, increased smoking, evacuation behaviors) of those who have been exposed (Figure 2).18,19 Because the National Comorbidity Replication study had surveyed the mental health of those in the Katrina disaster region before the hurricane struck, we know that the rates of mental disorder had doubled 6 months after Katrina, from about 15% to 30%.20,21 The mental health costs of this, the largest natural disaster to hit the United States, continue to be seen today. Such disasters, as well as those caused by terrorism and war, remind us that recovery of populations is a long and arduous process.

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