Is acute stress reaction a risk factor for early mortality?

OBJECTIVE: This study aimed to examine the role of combat stress reaction (CSR) in predicting all-cause mortality over a 33-year period following the end of the war. METHOD: Two groups of male veterans from the 1982 Lebanon War participated in this study in 1983 (T1) and 2016 (T2): the CSR group (n = 375) and a matched comparison group (n = 305) consisting of combatants who had participated in combat in the same units as the CSR group but were not identified as having CSR. Participants were assessed for posttraumatic stress disorder symptoms and depressive symptoms in T1 and mortality in T2. RESULTS: The distribution of mortality rates was significantly different between the 2 groups and higher among the CSR group (n = 32, 8.5%) as compared to the comparison group (n = 12, 3.9%; χ2 = 5.89, p = .01). Both posttraumatic stress disorder symptoms and depressive symptoms were controlled for because they have been shown to be risk factors for all-cause mortality. The mortality curve of the CSR group increased steeply around the age of 40 years, whereas in the comparison group, the increase was less substantial. CONCLUSIONS: CSR was found to be a significant predictor of all-cause mortality. The risk for mortality was higher and earlier among the CSR group compared with the comparison group. The findings of this study call attention to the importance of immediately identifying CSR to better care for the individual and minimize long-term negative effects. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Sexual Satisfaction in Spouses of Ex-POWs: The Role of PTSD Symptoms and Self-Differentiation.

Spouses of former prisoners-of-war (ex-POWs) are at risk for posttraumatic stress symptoms (PTSS) and marital distress. This study assessed the implications of PTSS and self-differentiation for sexual satisfaction among 90 ex-POWs' spouses and 75 matched combatants' spouses from the 1973 Yom Kippur War. Standardized questionnaires were used. Ex-POWs' spouses had elevated PTSS and imbalanced self-differentiation. PTSS were associated with poorer self-differentiation and lower sexual satisfaction. Imbalanced self-differentiation mediated the association between PTSS and sexual satisfaction. The findings imply that PTSS and imbalanced self-differentiation contribute to low sexual satisfaction among spouses of primary trauma survivors.

Long-Term Trajectories of Posttraumatic Stress Disorder: Categorical versus Continuous Assessment.

Objective: Long-term trajectories of posttraumatic stress disorder (PTSD) may fluctuate over time and typically conform to four heterogeneous patterns: resilience, recovery, delayed-onset, and chronic symptomatology. However, such fluctuations are typically short ranged and have rarely been investigated over the course of decades after the trauma. Moreover, existing studies have used a variety of measurements, either employing a categorical Diagnostic and Statistical Manual of Mental Disorders (DSM)-oriented approach or a continuous measure of symptom severity. The aim of this study was to evaluate the two methods of analyzing trajectories of PTSD by examining the level of concordance between them, their sensitivity, and their validity. Method: A total of 349 Israeli veterans from the 1973 Yom Kippur War were examined at four time points over more than four decades since the war. A latent class growth analysis (LCGA) was conducted to identify different PTSD trajectories, using both categorical and continuous PTSD assessments. Results: Descriptive results revealed that the four commonly observed patterns of PTSD are insufficient for capturing the range of individual PTSD trajectories. Using a categorical measure in the explorative LCGA yielded three trajectories (resilient, chronic, and delayed onset). The continuous measure yielded five trajectories (resilient, chronic, recovered, and two delayed-onset trajectories), which provided a slightly more nuanced distinction of participants' distress-induced psychosocial dysfunction as compared to the three-trajectory solution. Conclusion: These findings suggest that using a continuous PTSD trajectory measure provides a somewhat more sensitive estimation of PTSD trajectories. More specifically, taking into consideration symptom intensity and fluctuation over time may provide a more comprehensive picture of the survivors' distress.

The Impact of Captivity and Posttraumatic Stress Disorder on Cognitive Performance Among Former Prisoners of War: A Longitudinal Study.

OBJECTIVE: War captivity is a potent pathogen for various aspects of mental health, including cognitive impairments. However, little is known about the long-term impact of war captivity and posttraumatic stress disorder (PTSD) on cognitive functioning among former prisoners of war (ex-POWs). This study assesses the effect of captivity, PTSD trajectories, and the accumulating differential effect in the prediction of cognitive performance. METHODS: This longitudinal research includes 4 assessments (1991 [T1], 2003 [T2], 2008 [T3], 2015 [T4]) of Israeli ex-POWs and comparable combatants from the 1973 Yom Kippur War. Accordingly, 95 ex-POWs and 26 comparable combatants were included in this study. PTSD was assessed according to the DSM-IV, and cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA). RESULTS: Ex-POWs reported higher levels of PTSD symptoms compared to controls (P = 0.007). No difference was found between the groups regarding MoCA total score. Ex-POWs with chronic PTSD were found to have more difficulty in overall cognitive functioning, compared to ex-POWs with delayed, recovery, and resilient trajectories (P = 0.03). Finally, physical and psychological suffering in captivity and intrusion symptoms predicted cognitive performance (P < .001, R² = 37.9%). These findings support the potent pathogenic effects of war captivity on cognitive abilities, more than 4 decades after the end of the traumatic event. CONCLUSIONS: Our results showed captivity to be a unique and powerful traumatic experience, leading to PTSD and long-lasting and enduring neuropsychological implications. These findings highlight the importance of viewing ex-POWs, in particular those suffering from chronic PTSD, especially as they age, as a high-risk population for cognitive disorders. This requires the appropriate diagnosis and cognitive therapy as a way to preserve cognitive abilities among this population.

Auditory hallucinations and PTSD in ex-POWS.

Literature has suggested that auditory hallucinations might be prevalent in the general population and could be linked to the experience of trauma. This prospective study examines the prevalence of auditory hallucinations in trauma survivors and its association with posttraumatic stress disorder (PTSD) symptoms, over time. Former prisoners of war (ex-POWs) from the 1973 Yom Kippur War (n = 99) with and without PTSD and comparable veterans (n = 103) were assessed twice, in 1991 (T1) and 2003 (T2) in regard to auditory hallucinations and PTSD symptoms. Findings indicated that ex-POWs who suffered from PTSD reported higher levels of auditory hallucinations at T2 as well as increased hallucinations over time, compared to ex-POWs without PTSD and combatants who did not endure captivity. The relation between PTSD and auditory hallucinations was unidirectional, so that the PTSD overall score at T1 predicted an increase in auditory hallucinations between T1 and T2, but not vice versa. Assessing the role of PTSD clusters in predicting hallucinations revealed that intrusion symptoms had a unique contribution, compared to avoidance and hyperarousal symptoms. The findings suggest that auditory hallucinations might be a consequence of the posttraumatic reaction among veterans.

Attachment in detachment: The positive role of caregivers in POWs' dissociative hallucinations.

Humans are social creatures and therefore exhibit a pervasive need for others. Hence, when benevolent human contact is scarce, this dearth may be compensated imaginatively. War captivity is an extreme example of such deprivation and one wherein dissociative hallucinations have been exhibited. Although hallucinations may serve to virtually summon benevolent others and thus provide the prisoner of war (POW) with a platform for compensation, the contents of such hallucinations have yet to be investigated. The current qualitative study is the first to examine whether the content of such hallucinations may harbor positive effects. Guided by the notion that people search for compensation in lack of companionship, we scrutinized testimonies of former POWs for accounts of hallucinatory experiences. A narrative analysis was utilized in an attempt to understand the meaning of the hallucinations for the POW. Findings reveal that benevolent figures and concomitant acts of care are exhibited in war captivity hallucinatory experiences. Thus, it is argued that the content of such hallucinations may be protective. These findings are discussed in light of the literature concerning peritraumatic dissociative experiences. In addition, attachment theory is suggested as a plausible framework for understanding these findings. Finally, limitations of the study are discussed, and future researched is suggested.

Deimmunization of monoclonal antibodies.

Immunogenicity is a major limitation to therapy with certain monoclonal antibodies and proteins. A major driver for immunogenicity is the presence of human T-cell epitopes within the protein sequence which can activate helper T-cells resulting in the sustained production of antibodies and neutralization of the therapeutic effect. Deimmunization is a new technology for location and removal of T-cell epitopes through the combined use of immunological and molecular biology techniques. In the case of deimmunization of antibodies, mutations to remove T-cell epitopes can generally be introduced without significantly reducing the binding affinity of the antibody. Typically, "deimmunized" antibodies are created with human constant regions and by expression of genes encoding these antibodies in mammalian cells. This chapter details a method for creation of a deimmunized antibody for production in mammalian cells.

CD4+ T cells specific for glycoprotein B from cytomegalovirus exhibit extreme conservation of T-cell receptor usage between different individuals.

Antigen-specific CD8(+) cytotoxic T cells often demonstrate extreme conservation of T-cell receptor (TCR) usage between different individuals, but similar characteristics have not been documented for CD4(+) T cells. CD4(+) T cells predominantly have a helper immune role, but a cytotoxic CD4(+) T-cell subset has been characterized, and we have studied the cytotoxic CD4(+) T-cell response to a peptide from human cytomegalovirus glycoprotein B presented through HLA-DRB*0701. We show that this peptide elicits a cytotoxic CD4(+) T-cell response that averages 3.6% of the total CD4(+) T-cell repertoire of cytomegalovirus-seropositive donors. Moreover, CD4(+) cytotoxic T-cell clones isolated from different individuals exhibit extensive conservation of TCR usage, which indicates strong T-cell clonal selection for peptide recognition. Remarkably, this TCR sequence was recently reported in more than 50% of cases of CD4(+) T-cell large granular lymphocytosis. Immunodominance of cytotoxic CD4(+) T cells thus parallels that of CD8(+) subsets and suggests that cytotoxic effector function is critical to the development of T-cell clonal selection, possibly from immune competition secondary to lysis of antigen-presenting cells. In addition, these TCR sequences are highly homologous to those observed in HLA-DR7(+) patients with CD4(+) T-cell large granular lymphocytosis and implicate cytomegalovirus as a likely antigenic stimulus for this disorder.

The CD4+ T-cell response to adenovirus is focused against conserved residues within the hexon protein.

Adenovirus is a significant pathogen in immunocompromised patients and is widely utilized as a gene delivery vector, so a detailed understanding of the human immune response to adenovirus infection is critical. This study characterized the adenovirus-specific CD4(+) T-cell response of healthy donors by incubation with whole virus or with individual hexon and fiber proteins. Adenovirus-specific CD4(+) T cells averaged 0.26 % of the CD4(+) T-cell pool and were detectable in all donors. T cells recognizing the highly conserved hexon protein accounted for 0.09 %, whereas no response was observed against the fiber protein. A panel of hexon-specific CD4(+) T-cell clones was generated and shown to lyse targets infected with adenovirus from different serotypes and species. Three CD4 T-cell epitopes are described, which map to highly conserved regions of the hexon protein.