PTSD development

The intensity of the trauma may contribute to the development of PTSD (Shalev and Freedman, 2005). Posttraumatic Stress Syndrome rates after terrorist attacks in Israel were higher than rates after motor vehicle accidents. The authors suggest that the highly traumatic nature of a terrorist attack (exposure to death, body parts) may impact the higher rate of PTSD development. Additionally, the authors hypothesized that the longitudinal course of PTSD would be affected by the frequent versus sporadic terrorist attacks however, this was not the case. The authors suggest that there may be some sort of resiliency that develops during an era of continuous terror. Others... 

Clinicians have more recently become more aware of elevated rates of posttraumatic stress disorder (PTSD) in both men and women with opioid dependence (Hien et al. 2000). A lifetime prevalence of PTSD of 20% in women and 11% in men was found in one sample of methadone maintenance patients (Villagomez et al. 1995). Patients often deny a PTSD history during initial assessment. They should be reassessed after they have had the opportunity to develop trust in their treating clinicians. 

Post-traumatic stress disorder (PTSD) is a severe condition with a lifetime prevalence of about 12.5% in women and 6.2% in men (Pigott, 1999). About one in four individuals exposed to trauma develop the syndrome. Drug treatments are still being developed, mostly using antidepressants. Few systematic data are available on the pharmacoeconomics of the condition. 

The development of mild forms of anxiety and neuroveg-etative and/or cognitive responses to stress may represent an adaptive evolutionary step against environmentally (external) or self-triggered (internal) threats, but maladaptive reactions have also emerged in human evolution. Thus, anxiety disorders are maladaptive conditions in which disproportionate responses to stress, or even self-evoked responses, are displayed. Anxiety disorders are one of the most frequent psychiatric illnesses, and have a lifetime prevalence of 15- 20% [1, 89]. The most common presentations are generalized anxiety disorder, with a lifetime prevalence rate of close to 5% [1, 89] social anxiety disorder, with very variable lifetime prevalence rates ranging from 2 to 14% [90] panic disorder, with rates from 2 to 4% [1,89] and post-traumatic stress disorder (PTSD), with a prevalence rate close to 8%. Specific phobias, acute stress and obsessive-compulsive behavior are other clinical presentations of anxiety disorders. 

HT model. GAD symptoms may reflect excessive 5-HT transmission or overactivity of the stimulatory 5-HT pathways. Patients with SAD have greater prolactin response to buspirone challenge, indicating an enhanced central serotonergic response. The role of 5-HT in panic disorder is unclear, but it may have a role in development of anticipatory anxiety. Preliminary data suggest that the 5-HT and 5-HT2 antagonist meta-chlorophenylpiperazine causes increased anxiety in PTSD patients. 

Patients with PTSD have a hypersecretion of corticotropin-releasing factor but demonstrate subnormal levels of cortisol at the time of trauma and chronically. Dysregulation of the hypothalamic-pituitary-adrenal axis may be a risk factor for eventual development of PTSD. 

Individual characteristics can determine how a person reacts to a trauma and thereby contribute to the risk for developing PTSD. These include neurosis, limited social support, a family history of an anxiety disorder, and a personal history of previous significant stressors, particularly childhood sexual or physical abuse. 

Gender is another important risk factor for PTSD. Although men are more likely to experience a traumatic event, PTSD is at least twice as common among women. This apparent gender discrepancy, however, provides an opportunity to examine the manner in which varied risk factors might interact. The gender difference might be explained, at least in part, by the nature of the traumatic stressors that are more likely to be experienced by women. In particular, women are disproportionately victimized by sexual traumas, such as rape or childhood sexual abuse. Sexual traumas, in both men and women, are more likely to lead to the development of PTSD than other traumas such as natural disasters. 

The course of PTSD is variable. Typical estimates are that 50% of those who develop acute PTSD will ultimately suffer a persistent form of the illness that... 

PTSD pharmacotherapy has been an area of intense research interest over the past decade. This has been complemented by a plethora of studies regarding the neurobiology of the disorder that may ultimately serve to inform the development and refinement of novel therapies. Pharmacotherapy is used to target one or more of the main PTSD symptom clusters, that is, reexperiencing symptoms, avoidance/numbing symptoms, and hyperarousal symptoms. 

Benzodiazepines. These agents, particularly alprazolam and clonazepam, have been widely used in the treatment of PTSD, despite little evidence to demonstrate their effectiveness. The few studies exploring the effectiveness of benzodiazepines for PTSD suggest that they provide modest relief for anxiety in general but offer no benefit for the core symptoms of PTSD, namely, intrusive recollections and emotional numbing. Furthermore, a small controlled study investigating prophylactic treatment with a benzodiazepine in the immediate aftermath of trauma exposure failed to protect patients from the subsequent development of PTSD symptoms. Consequently, we do not recommend benzodiazepines for the routine management of PTSD. 

Many patients with anxiety disorders experience an increased susceptibihty to psychosocial stress. Behavioral sensitization may account for these cHnical phenomena, hi the laboratory model of sensitization, single or repeated exposure to physical stimuU or pharmacological agents sensitizes an animal to subsequent stressors (reviewed in Charney et al. 1993). For example, in animals with a history of prior stress, there is a potentiated release of NE in the hippocampus with subsequent exposure to stressors (Nisenbaum et al. 1991). Similar findings were observed in medial prefrontal cortex (Finlay and Abercrombie 1991). The hypothesis that sensitization is underlying neural mechanism contributing to the course of anxiety disorders is supported by clinical studies demonstrating that repeated exposure to traumatic stress is an important risk factor for the development of anxiety disorders, particularly PTSD (Table 1). 

In a study examining the cortisol response in the acute aftermath of rape, low cortisol levels were associated with prior rape or assault, themselves risk factors for PTSD (Resnick et al. 1995), but not with the development of PTSD per se. A post hoc analysis of the data reported in (Yehuda et al. 1998) confirmed the observation that low cortisol levels were also associated with prior trauma exposure in this group as well (A.C. McFarlane et al., personal communication). 

One of most compelling lines of evidence supporting the hypothesis that lower cortisol levels may be an important pathway to the development of PTSD symptoms involves results of studies by Schelling et al. (2001) who administered stress doses of hydrocortisone during septic shock and evaluated the... 

Numerous studies found that childhood sexual, physical, and emotional abuse also predisposes victims of such abuse to the development of depression in adulthood (e.g., McCauley et ah, 1997). The risk for depression increases with early onset and severity of the abuse as well as with the experience of multiple types of abuse. In addition, child abuse is related to an array of anxiety disorders, including generalized anxiety disorder and PTSD (e.g., Kendler et ah, 2000). Other disorders related to childhood abuse include substance abuse, eating disorders, dissociation, and so-... 

Interestingly, while peripheral neuroendocrine function appears normal in patients with panic disorder, decreased basal cortisol concentrations have been reported in most studies in PTSD patients. This relative hypocortisolism occurs in the context of increased feedback inhibition of the HPA axis (see Yehuda, 2000). However, a dissociation between central and adrenocortical (re)activity has been found in animal models of severe early-life stress as well as in abused children and women, suggesting that adrenal dysfunction may, at least in part, contribute to hypocortisolism in PTSD. In the face of hypocortisolism, it seems surprising that hippocampal atrophy is one of the most prominent findings in patients with PTSD, including adult survivors of childhood abuse with PTSD (see Newport and Nemeroff, 2000). While increased glucocorticoid sensitivity of hippocampal cells may play a role in the development of hippocampal atrophy, another potential mechanism may involve toxic effects of markedly increased cortisol responses to everyday stress in patients with PTSD. 

Childhood abuse has been associated with a predisposition for the development of anxiety disorders in adulthood, including generalized anxiety disorder and panic disorder (Kaufman and Charney, 1999 Stein et al., 2000), and may increase the risk of developing PTSD in response to extreme stressors such as combat experience in adulthood (Zaidi and Foy, 1994 Bremner, 2001). Parental loss in childhood and negative parenting have also been associated with the development of mood and anxiety disorders, including PTSD (Ken-dler, 1993). 

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