Genetics of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a prevalent anxiety disorder marked by behavioral, physiologic, and hormonal alterations. PTSD is disabling and commonly follows a chronic course. The etiology of PTSD is unknown, although exposure to a traumatic event constitutes a necessary, but not sufficient, factor. A twin study of Vietnam veterans has shown significant genetic contribution to PTSD. The fact that PTSD's underlying genotypic vulnerability is only expressed following trauma exposure limits the usefulness of family-based linkage approaches. In contrast to the other major psychiatric disorders, large studies for the search of underlying genes have not been described in PTSD to date. Complementary approaches for locating involved genes include association-based studies employing case-control or parental genotypes for transmission dysequilibrium analysis and quantitative trait loci studies in animal models. Identification of susceptibility genes will increase our understanding of traumatic stress disorders and help to elucidate their molecular basis. The current review provides an up-to-date outline of progress in the field of PTSD.     

Gender differences in posttraumatic stress disorder

One of the most consistent findings in the epidemiology of posttraumatic stress disorder (PTSD) is the higher risk of this disorder in women. Explanations reviewed within a psychobiological model of PTSD suggest that women's higher PTSD risk may be due to the type of trauma they experience, their younger age at the time of trauma exposure, their stronger perceptions of threat and loss of control, higher levels of peri-traumatic dissociation, insufficient social support resources, and greater use of alcohol to manage trauma-related symptoms like intrusive memories and dissociation, as well as gender-specific acute psychobiological reactions to trauma. This review demonstrates the need for additional research of the gender differences in posttraumatic stress. Recommendations are made for clinical practice.     

Emotional processing in posttraumatic stress disorder

The emotional deficits associated with posttraumatic stress disorder (PTSD) are the least understood and the most understudied aspect of the syndrome. In this study, the connection was evaluated between trauma-context reactivity and subsequent emotional deficits in PTSD. Combat veterans with PTSD and well-adjusted veteran control participants were exposed to reminders of combat, after which their emotional behavior was assessed in response to a series of emotionally evocative images. Under the neutral condition, both groups exhibited emotional behavior modulated by stimulus valence. Partially consistent with the conceptual model described by B. Litz (1992), the PTSD group exhibited suppressed expressive-motor responses to positively valenced images, in comparison with the control group, only after being exposed to a trauma-related prime. Contrary to expectations, the PTSD group showed no augmentation of emotional response to negatively valenced cues after being exposed to trauma reminders. However, the PTSD group responded to all images, in both prime conditions, with higher heart rate reactivity, suggesting an automatic preparation for demand or threat in any uncertain emotional context. Possible causes and consequences of these results are discussed.     

Psychotic symptoms in posttraumatic stress disorder

Recent data suggest that the presence of psychotic symptoms in patients suffering from posttraumatic stress disorder (PTSD) may represent an underrecognized and unique subtype of PTSD. Among combat veterans with PTSD, 30% to 40% report auditory or visual hallucinations and/or delusions. The presence of psychotic symptoms in PTSD is associated with a more severe level of psychopathology, similar to that of chronic schizophrenia. In this review, the differential diagnosis of psychotic symptoms in PTSD is discussed, including possible comorbid schizophrenia, psychotic depression, substance-induced psychosis, and personality disorder. A recent biologic study supporting the existence of a unique subtype of PTSD with psychotic features is also addressed, as are the similarities between PTSD with psychotic features and psychotic depression disorder. Finally, data on the treatment implications of psychotic symptoms in PTSD are presented. The intriguing recent findings on psychotic symptoms in PTSD need further investigation in noncombat-related PTSD populations before findings can be generalized to all individuals with PTSD.     

Brain-imaging studies of posttraumatic stress disorder

Brain-imaging studies of posttraumatic stress disorder (PTSD) have rapidly increased in recent years. Structural studies have identified potential smaller volumes of the hippocampus of traumatized and/or PTSD subjects. Functional activation studies have implicated hyperactive or altered functioning of brain regions, such as the amygdala and the insula, and a failure to engage emotional regulatory structures, such as the medial prefrontal and anterior cingulate cortex. Recent neurochemical investigations have suggested that neuromodulatory systems (eg, gamma-aminobutyric acid, micro-opioid) may underlie these aberrant brain activation patterns. This article reviews the literature on structural, functional, and neurochemical brain-imaging studies of PTSD.     

A cognitive model of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a common reaction to traumatic events. Many people recover in the ensuing months, but in a significant subgroup the symptoms persist, often for years. A cognitive model of persistence of PTSD is proposed. It is suggested that PTSD becomes persistent when individuals process the trauma in a way that leads to a sense of serious, current threat. The sense of threat arises as a consequence of: (1) excessively negative appraisals of the trauma and/or its sequelae and (2) a disturbance of autobiographical memory characterised by poor elaboration and contextualization, strong associative memory and strong perceptual priming. Change in the negative appraisals and the trauma memory are prevented by a series of problematic behavioural and cognitive strategies. The model is consistent with the main clinical features of PTSD, helps explain several apparently puzzling phenomena and provides a framework for treatment by identifying three key targets for change. Recent studies have provided preliminary support for several aspects of the model.     

Sustained attention in combat-related posttraumatic stress disorder

There is substantial evidence that PTSD patients have information processing abnormalities for stimuli that are highly relevant to the traumas they have endured. The goal of the present study was to examine whether this extends to neutral stimuli as well. Twenty-four male Vietnam combat veterans with PTSD were compared to fifteen normal male comparison subjects on their performance on a sensitive measure of sustained attention, the Continuous Performance Test-Identical Pairs version (CPT-IP). PTSD subjects did not differ from controls in their ability to discriminate target stimuli from background noise on the CPT. Additionally they performed as well as controls, even in the presence of external distraction. Thus, this study did not find a generalized deficit in attention associated with PTSD on the CPT-IP. Nevertheless, further clarification of the nature of the information processing disturbance in PTSD is warranted.     

World assumptions and combat-related posttraumatic stress disorder

The authors examined the association between (a) personal world assumptions and (b) combat stress reactions (CSRs), posttraumatic stress disorder (PTSD), and PTSD's course among three groups of Israeli veterans: 109 veterans who suffered from CSR on the battlefield, 98 decorated veterans, and 189 control participants. Participants completed standardized questionnaires that measured PTSD and world assumption. Both CSR and chronic PTSD were associated with lower levels of self-worth and beliefs about the benevolence of people. In addition, the authors found a linear association between self-worth perceptions and levels of mental status. The authors examined the results of the study considering the extraordinary characteristics and meaning of war.     

Qualitative block design analysis in posttraumatic stress disorder

Qualitative and quantitative Block Design performance was examined in Vietnam combat veterans with PTSD diagnoses (n = 23) and Vietnam combat veterans without PTSD or other mental disorders diagnoses (n = 19). Results indicated that PTSD-diagnosed veterans committed more single block rotations than the comparison sample, and that their errors occurred more frequently in right hemispace than errors made by the comparison sample. The two groups did not differ in the number of configural errors made, errors committed in left hemispace, or in quantitative performance measures. Findings are suggestive of relative left hemisphere hypoactivation and are congruent with prior research documenting cerebral asymmetries in emotional disorders.     

Treatment-resistant posttraumatic stress disorder: strategies for intervention

The mainstay of treatment for chronic posttraumatic stress disorder (PTSD) is a combination of psychotherapy and medication treatments. The first-line medications for PTSD are antidepressants, with two selective serotonin reuptake inhibitors (sertraline and paroxetine) currently Food and Drug Administration-indicated for PTSD. However, many patients do not have an adequate response to antidepressants, therefore, combinations with other antidepressants or with other classes of psychotropic medication are often utilized to enhance the therapeutic response. Other agents that have been used include mood stabilizers, anti-adrenergics, anxiolytics, and atypical antipsychotics. The heterogeneity of symptom clusters in PTSD as well as the complex psychiatric comorbidities (eg, with depression or substance abuse) further support the notion that combinations of medications may be needed. To date, there is a paucity of data to support specific strategies for augmenting antidepressants in PTSD. This review will address representative existing studies and discuss several potential pharmacologic strategies for patients suffering from treatment-refractory PTSD.     

Gender differences in susceptibility to posttraumatic stress disorder

We examined data from a community survey of trauma exposure and DSM-IV PTSD in Winnipeg, Canada to explore factors associated with the higher rate of PTSD in women than men. Women were found to be at significantly increased risk for PTSD following exposure to serious trauma (odds ratio approximately 5), even when sexual trauma--which predominates in women--was excluded (odds ratio approximately 3). Adjusting for gender differences in the number of lifetime traumata, or in the likelihood of the trauma being associated with particular reactions to or consequences of the event (i.e. thinking that one would be killed or seriously injured; sustaining a serious physical injury; seeing someone else seriously injured or killed) did not result in a lessening of the PTSD risk in women. Women were found to be at increased risk for PTSD following nonsexual assaultive violence (e.g. mugging or other physical attack) but not following non-assaultive trauma (e.g. fire, witnessing injury to others). Understanding the basis of (and parameters for) this increased susceptibility to PTSD in women compared to men following trauma exposure should be a priority for future traumatic stress research.     

Traumatic memories and pseudomemories in posttraumatic stress disorder

Intrusive imagery was investigated in survivors of motor vehicle accidents with (a) posttraumatic stress disorder (PTSD) and accurate recall of the trauma, (b) PTSD and amnesia of the trauma, (c) no PTSD, or (d) control participants who simulated PTSD. Imagery was precipitated by presentation of an audiotape of a motor vehicle accident. Whereas the traumatic imagery of participants who had accurate recall of their trauma was consistent with third party accounts of the trauma, the imagery of amnesic participants was inconsistent with these accounts. Participants were then interviewed about cognitive and emotional aspects of their responses. All participants with PTSD and simulators reported similar levels of imagery detail, involuntariness, re-experiencing, and emotional response, and reported higher levels than participants with no PTSD. Findings are discussed in terms of cognitive and contextual factors that can mediate accurate and inaccurate traumatic imagery. © 1998 John Wiley & Sons, Ltd.     

Intrusive memories in depression and posttraumatic stress disorder

This study compared the stressors and consequent intrusive memories reported by matched samples of patients with posttraumatic stress disorder (PTSD) and major depression. Although intrusive memories were slightly more common among PTSD patients, both quantitative and qualitative measures revealed few differences between the groups. PTSD patients were more likely to have experienced personal illness or assault, and depressed patients family deaths and illness, and interpersonal events. Factor analysis of the associated emotions and memory characteristics suggested the existence of specific links between fear and reliving, and helplessness and out-of-body experiences. Possible inhibitory relationships between fear and sadness, and between guilt and anger, were also noted.     

Cognitive behavioral therapy of violence-related posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) represents the most common psychiatric condition following exposure to violence. Although an increasing number of cognitive behavioral therapy (CBT) studies point to efficacy of this approach in ameliorating PTSD following violence, the methodological rigor of many studies has not been optimal. Further, a significant proportion of traumatized individuals does not benefit from CBT. This article reviews CBT outcome studies, discusses the methodological limitations of CBT studies for PTSD, and offers suggestions for future research. This review highlights the need for more systematic studies of components of CBT with a range of trauma populations to delineate the parameters of effective CBT for individuals with PTSD.     

The relationship between acute stress disorder and posttraumatic stress disorder in severely injured trauma survivors

This prospective longitudinal study was designed to investigate the relationship between acute stress disorder (ASD) and the subsequent development of posttraumatic stress disorder (PTSD) in a population of severely injured hospitalised trauma survivors. Symptoms of ASD were assessed just prior to discharge in 307 consecutive admissions to a Level 1 Trauma Centre, with PTSD assessments completed at 3 and 12 months post-injury. A well-established structured clinical interview was adopted for both assessments. Only 1% of the sample met criteria for an ASD diagnosis (at a mean of 8 days post-injury), while the incidence of PTSD was 9% at 3 months and 10% at 12 months. Although all ASD symptom clusters contributed to the prediction of subsequent PTSD severity, logistic regression indicated that only re-experiencing and arousal predicted a categorical PTSD diagnosis. The dissociative symptoms that form the core of ASD were rarely endorsed and showed high specificity but low sensitivity, resulting in a high proportion of false negative diagnoses. Reducing the number of dissociative symptoms required for a diagnosis ameliorated, but did not resolve, the problem. In this particular population, the low sensitivity of the ASD diagnosis renders it a poor screening test for use in identifying high risk individuals for early intervention and prevention strategies.     

A prospective study of psychophysiological arousal, acute stress disorder, and posttraumatic stress disorder

This study investigated the role of acute arousal in the development of posttraumatic stress disorder (PTSD). Hospitalized motor-vehicle-accident survivors (n = 146) were assessed for acute stress disorder (ASD) within 1 month of the trauma and were reassessed (n = 113) for PTSD 6 months posttrauma. Heart rate (HR) and blood pressure (BP) were assessed on the day of hospital discharge. Participants with subclinical ASD had higher HR than those with ASD and no ASD. Participants who developed PTSD had higher HR in the acute posttrauma phase than those without PTSD. Diagnosis of ASD and resting HR accounted for 36% of the variance of the number of PTSD symptoms. A formula composed of a diagnosis of ASD or a resting HR of > 90 beats per minute possessed strong sensitivity (88%) and specificity (85%) in predicting PTSD. These findings are discussed in terms of acute arousal and longer term adaptation to trauma.     

Specificity of autonomic arousal to DSM-IV panic disorder and posttraumatic stress disorder

Although research on the hierarchical model of anxiety and depression has confirmed that autonomic arousability (AA) is more germane to panic disorder with or without agoraphobia (PD/A) than other DSM-IV anxiety and mood disorders, studies have not evaluated the differential relevance of AA to posttraumatic stress disorder (PTSD). This issue was addressed in multivariate analytic models using 295 outpatients with anxiety and mood disorders. Consistent with prediction, the presence of current DSM-IV PTSD and PD/A was significantly predictive of AA, even when other forms of anxiety disorder comorbidity were held constant. Moreover, latent structural analyses indicated that PTSD and PD/A were the only DSM-IV anxiety disorder constructs to have significant direct effects on AA (in accord with previous findings, the DSM-IV constructs of generalized anxiety disorder, social phobia, and obsessive-compulsive disorder did not have significant structural relationships with AA). The current findings, which attest to the specificity of AA to PTSD and PD/A, are discussed in context of other clinically salient shared features of these disorders and their relevance to treatment and diagnostic classification.