Post Traumatic Stress Disorder: Epidemiology, Etiology and Pathophysiology

Post Traumatic Stress Disorder

Definition

PTSD is defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) by six different cri-teria (American Psychiatric Association, 1994,). First, the disorder arises in a person who has been exposed to a traumatic event in which he or she experienced, witnessed, or was confronted with actual or threatened death or serious injury or a threat to the physical integrity of self or others. Furthermore, the response must have involved intense fear, helplessness, or horror. In children, it is allowed that the response may take the form of disorganized or agitated behavior.

Secondly, there must have been at least one of five possible intrusive symptoms occurring as a result of exposure to the trauma, as exhibited in either dream activity or waking life. These include recollections, images, thoughts, or perceptions of the event, recur-rent distressing dreams, acting as if the trauma were recurring, and intense psychological or physical distress on exposure to internal or external cues resembling the trauma. Allowance is made for a different set of reactions in children, in whom intrusive symptoms may take the form of repetitive play, frightening dreams without recognizable content, or reenactment of the trauma.

Thirdly, persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness must occur as ex-hibited by at least three of seven symptoms. Although grouped to-gether as one criterion, it is likely that phobic avoidance, numbing and withdrawal do not reflect the same underlying phenomenon.

Fourthly, there must be at least two symptoms indicating the presence of increased arousal (i.e., difficulty sleeping, irrita-bility or anger, difficulty concentrating, hypervigilance, or exag-gerated startle response). Symptoms of PTSD should last at least 1 month, and it is necessary that the disturbances cause clini-cally significant distress or impairment in social, occupational, or other areas of functioning.

PTSD is considered to be “acute” if the duration of symp-toms is between 1 and 3 months or “chronic” if it is 3 months or greater. If symptoms do not occur until at least 6 months have passed since the stressor, the delayed-onset subtype is given.

Epidemiology

Community-based studies conducted in the USA have documented a lifetime prevalence rate for PTSD of approximately 8% of the adult population (Kessler et al., 1995). In the National Comorbidity Survey replication this figure was 6.8% (Kessler et al., 2005). The highest rates of PTSD occurrence for particular traumatic expo-sures (occurring in one-third to three-fourths of those exposed) are among survivors of rape, military combat and captivity, graves registration (i.e., registering dead bodies through the morgue), and ethnically or politically motivated internment and genocide.

Epidemiological studies show that PTSD often remains chronic, with a significant number of people remaining symp-tomatic several years after the initial event. In support of this view are epidemiological data that show that recovery frequently does not occur. For example, the National Vietnam Veterans Readjustment study (Kulka et al., 1990) found lifetime and cur-rent prevalence rates of PTSD to be, respectively, 30.9% and 15.2% in men and 26.9% and 8.5% in women. In a population of rape victims, Kilpatrick and colleagues (1987) found a lifetime prevalence rate of 75.8% and a current prevalence rate of 39.4%. In children, studies by Pynoos and associates (1993) revealed prevalence rates of 58.4% in children exposed to sniper attacks in the USA and 70.2% in those exposed to an earthquake in Arme-nia. Kessler and colleagues (1995) documented that one-third of those diagnosed with PTSD fail to recover even after many years. Therefore, chronicity of PTSD is not limited to the more severe treatment-seeking samples.

Etiology and Pathophysiology

The Event

PTSD is defined in terms of etiology as much as phenomenology. The disorder cannot exist unless the individual has been exposed to a traumatic event with a particular set of properties. Commu-nity-based epidemiological studies suggest that 70% of individu-als will experience at least one traumatic event meeting criterion A(1) over the course of their lifetime. The relative severity of the traumatic event, predisposing factors and peritraumatic envi-ronmental factors must all be considered in understanding the etiology of PTSD. In most instances, occurrence of the disorder represents the outcome of an interaction among these three groups of factors. The likelihood of developing PTSD with regard to the nature of the event has shown consistent relationship occurred between magnitude of stress exposure and risk of developing PTSD. This association held up in many different trauma popula-tions in adults and children.

Cognitive and affective responses to the stressor are also important in determining the likelihood that PTSD will develop. A traumatic event is defined as an event that involves experiencing or witnessing actual or threatened death or serious injury or learning about an unexpected or violent death and hav-ing a response that involves intense fear, helplessness, or horror.

Biological Factors

Patients with chronic PTSD have increased circulating levels of norepinephrine and increased reactivity of the alpha-2-adren-ergic receptors. These changes have been hypothesized possi-bly to account for some of the somatic symptoms that occur in individuals with PTSD. Neuroanatomical studies have implicated alterations in the amygdala and hippocampus in patients with PTSD. Functional magnetic resonance imaging and positron-emission tomography have demonstrated increased reactivity of the amygdala and anterior paralimbic region to trauma-related stimuli. Furthermore, in response to trauma-related stimuli, there is decreased reactivity of the anterior cingulate and orbitofrontal areas. These biological alterations suggest that there may be a neuroanatomical substrate for symptoms (intrusive recollections and other cognitive problems) that characterize PTSD. However, it is unknown whether these changes are preexisting, a result of traumatic exposure, or a result of having PTSD.

Sympathetic Nervous System Alterations

There is a positive association between the diagnosis of PTSD and basal cardiovascular activity. Particularly, individuals with a current PTSD diagnosis have a higher resting heart rate relative to both trauma-exposed individuals without a PTSD diagnosis and nontrauma-exposed controls and this appears to be greatest in studies with the most chronic PTSD samples. Along with increased 24-hour urinary catecholamines, results suggest an increase in sympathetic tone. There has been repeated demonstration that there is heightened sympathetic arousal in PTSD patients when reexposed to the original trauma in controlled settings.

Although a conditioning model provides a viable expla-nation of the process through which trauma-related cues may generate the heightened physiological responses characteristic of PTSD, it does not explain why some individuals develop PTSD when exposed to traumatic events, while others do not. It has been hypothesized that differential susceptibility to developing PTSD might be attributable in part to individual differences in condi-tionability, such that some individuals more readily acquire and maintain a conditioned response compared with others, and thus may be more likely to develop PTSD after a traumatic event.

There is evidence of brain dysfunction in individuals with PTSD as evidenced by abnormalities in evoked potentials. These ERP findings suggest that PTSD patients have increased corti-cal inhibition to high-intensity stimuli, impairments in memory and concentration, auditory gating deficits and heightened selec-tive attention to trauma-related stimuli. However, whether these processing abnormalities are a precursor or a result of PTSD awaits further study.

Psychophysiological response to acute trauma exposure may predict the development of PTSD. Shalev and colleagues (1990) demonstrated that on arrival to the emergency depart-ment, regardless of whether PTSD ultimately developed, survi-vors of traumatic events showed elevated heart rates upon arrival to the emergency department, which at later assessment occa-sions were normal. However, those who subsequently developed PTSD showed higher emergency department and 1-week heart rates than those who did not.

Neuroendocrine Factors

The hypothalamic–pituitary–adrenal (HPA) axis has been the most extensively studied neuroendocrine system in PTSD. The principal findings are as follows: reduced 24-hour urinary cor-tisol excretion, supersuppression of cortisol after low-dose dex-amethasone administration, blunting of corticotropin in response to corticotropin-releasing hormone and increased numbers of glucocorticoid receptors. This suggests that chronic PTSD is accompanied by supersuppression of the emergency HPA re-sponse to acute stress. This may result from the organism’s at-tempt to protect itself from the potentially toxic effect of high levels of corticosteroids that might occur with repeated exposure to stress or from reminders of the trauma. In further support of the importance of HPA axis alteration in PTSD is the finding that glucocorticoid receptor changes also correlate with the severity of PTSD symptoms, but not with the less specific anxiety and depressive symptoms measured on other rating scales. More re-cently, in a large sample of Vietnam veterans, combat-exposed veterans with current PTSD had lower cortisol compared with noncombat-exposed veterans without PTSD or combat-exposed veterans with lifetime PTSD but without current PTSD (Bosca-rino, 1996).

Further evidence for abnormalities in neurotransmitter reg-ulation comes from provocation studies conducted with Vietnam veterans. Administration of yohimbine, an alpha-₂-adrenergic antagonist, provoked symptoms of PTSD in combat veterans who had PTSD as did the serotoninergic challenge with m-chlo-rophenylpiperazine. Of considerable interest is that there was nooverlap between these two groups, suggesting some selectivity in the way in which neurotransmitter systems can be affected be-tween individuals (Southwick et al., 1993; Krystal et al., 1989). Finally, evidence to support alteration of noradrenergic and sero-toninergic pathways in PTSD comes from the clinical effects of medications that are selective for these neurotransmitter systems, as discussed later. The opioid system has also been investigated, but less extensively and without any consensus being obtained.

Sleep Studies

Studies support that there are two distinct, but possibly interre-lated types of sleep complaints in individuals with PTSD: night-mares that replicate traumatic events and impairment in initiating and maintaining sleep. Data further suggest that sleep problems in PTSD can also include excessive motor activity and awaken-ings with somatic anxiety symptoms. There is support for these complaints using polysomnography (PSG) studies, particularly in reduced sleep time or efficiency, and increased awakenings in the PTSD patients. There has also been documentation of PTSD subgroups that evidence breathing-related sleep disorders. PTSD is associated with a more fragmented rapid eye movement sleep as well.