A Study on the Factors Affecting Anger in Patients With Post-traumatic Stress Disorder.

OBJECTIVE: To identify the factors affecting anger in post-traumatic stress disorder (PTSD) patients who underwent Clinician-Administered PTSD Scale (CAPS) and Minnesota Multiphasic Personality Inventory-2 (MMPI-2). METHODS: We retrospectively reviewed patients who underwent CAPS and MMPI-2 at Veteran Health Service Medical Center, Seoul, Korea. Based on the CAPS score, the patients were divided into the PTSD group (n=46) and the trauma exposed without PTSD group (n=29). After checking the correlation between anger, CAPS, and MMPI-2 scales, logistic regression analysis was performed to identify the risk factors for clinically relevant symptoms. RESULTS: The PTSD group showed significant differences in schizophrenia-related symptoms, ideas of persecution, aggressiveness, psychoticism, and anger scales compared to the trauma-exposed without PTSD group. There was a significant correlation between anger, CAPS, and MMPI-2 except masculinity/femininity, disconstraint, and MacAndrew Alcoholism-Revised. In particular, anger has been shown to have a substantial connection with paranoia, schizophrenia-related symptoms, ideas of persecution, aberrant experiences, and psychoticism. Multiple regression analysis identified that the only significant risk factor for anger was the negative emotionality/neuroticism scale (odds ratio=1.152, p<0.001). CONCLUSION: The PTSD group had increased anger compared to the trauma-exposed without PTSD group, and that negative emotions may be a risk factor for PTSD.

Possible Association of Polymorphisms in Ubiquitin Specific Peptidase 46 Gene With Post-traumatic Stress Disorder.

Introduction: Dynamic proteolysis, through the ubiquitin-proteasome system, has an important role in DNA transcription and cell cycle, and is considered to modulate cell stress response and synaptic plasticity. We investigated whether genetic variants in the ubiquitin carboxyl-terminal hydrolase 46 (USP46) would be associated with post-traumatic stress disorder (PTSD) in people with exposure to combat trauma using a case-control candidate gene association design. Methods: Korean male veterans exposed to the Vietnam War were grouped into those with (n = 128) and without (n = 128) PTSD. Seven tagging SNPs of USP46 were selected, and single-marker and haplotype-based association analyses were performed. All analyses were adjusted for sociodemographic factors and levels of combat exposure severity and alcohol problem. Results: One single-marker (rs2244291) showed nominal evidence of association with PTSD status and with the "re-experiencing" cluster, although the association was not significant after Bonferroni correction. No significant association with the other SNPs or the haplotypes was detected. Conclusion: The present finding suggests preliminarily that genetic vulnerability regarding the ubiquitin-proteasome system may be related to fear memory processes and the development of PTSD symptoms after trauma exposure. Further studies with a larger sample size will be needed to examine the role of the ubiquitin-proteasome system including USP46 in PTSD.

REM Sleep Behavior Disorder among Veterans with and without Post-Traumatic Stress Disorder.

OBJECTIVE: Among veterans, the prevalence of rapid eye movement sleep behavior disorder (RBD) is higher than among the general population, and some evidence suggests that this is related to post-traumatic stress disorder (PTSD). The purpose of this study was to determine whether the frequency of RBD differs depending on the presence of PTSD or trauma. METHODS: Patients who underwent nocturnal polysomnography (PSG) and sleep-related questionnaire surveys at the Veteran Health Service Medical Center were reviewed retrospectively. Based on patients with PTSD (n=20; 100% male; 67.9±8.5 years of age), we matched patients exposed to trauma without PTSD (n23; 100% male; age 64.0±13.4) and patients without trauma (n=21; 100% male; age 59.86±10.9). RESULTS: PTSD patients reported dream enactment behavior more than the trauma-exposed group without PTSD or the control group (p=0.006). After adjusting for age, there were more RBD patients in the PTSD group than in the trauma exposed group (p=0.049). CONCLUSION: The results showed that RBD occurred significantly more in veterans with PTSD than those exposed to trauma, which suggests that there may be a pathophysiological association between PTSD and RBD.

Allele-specific DNA methylation level of FKBP5 is associated with post-traumatic stress disorder.

BACKGROUND: FK506-binding protein 5 (FKBP5) binds to glucocorticoid receptors and modulates glucocorticoid sensitivity. The FKBP5 gene has been implicated in the dysregulation of human stress responses, contributing to the risk and treatment response of stress-related disorders. The present study examined whether epigenetic changes in FKBP5 are associated with chronic post-traumatic stress disorder (PTSD) status in the context of FKBP5 genetic variation (rs1360780 polymorphism) among male veterans exposed to combat trauma. METHODS: Korean male veterans who served on active duty during the Vietnam War were categorized into 2 groups: with PTSD (n = 123) and without PTSD (n = 116). The genotype of FKBP5 rs1360780 and DNA methylation levels of two CpG sites at the FKBP5 intron 7 region were assessed in peripheral blood. Analysis of covariance was performed to examine main and interaction effects of PTSD status and FKBP5 genotype on FKBP5 DNA methylation level, with age, trauma levels, and alcohol use as covariates. RESULTS: A significant main effect of FKBP5 rs1360780 and PTSD and an interaction effect between genotype and PTSD status were found on mean FKBP5 DNA methylation level. The T allele of rs1360780 was associated with lower FKBP5 methylation level. In addition, the PTSD group showed significantly higher methylation than did the non-PTSD group among veterans carrying the risk T allele (n = 96), while no group difference was observed on methylation levels among veterans with the CC genotype (n = 143). Among veterans carrying the T allele, FKBP5 methylation levels were positively correlated with the severity of PTSD symptoms. CONCLUSIONS: The present study demonstrated different FKBP5 methylation levels in PTSD depending on FKBP5 genetic variation among veterans exposed to combat trauma. The present finding suggests that the genetic and epigenetic modulation of FKBP5 is involved in the pathophysiology of PTSD. Further longitudinal research involving people exposed to trauma is required to understand causal relationships of FKBP5 in the development and recovery of PTSD.

Clinical utility of heart rate variability during Head-up tilt test in subjects with chronic posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is characterized by psychophysiological abnormalities, such as an altered baseline heart rate and hyperarousal, implying dysfunctional arousal regulation. Heart rate variabilities (HRVs) is known to reflect autonomic nervous system activity. We examined the changes of HRVs in PTSD patients with head-up tilt position to closely investigate disease-specific changes in autonomic function in PTSD patients. Sixty-seven patients with PTSD and 72 patients without PTSD were assessed using the PTSD Checklist for DSM-5 (PCL-5) and psychiatric interview. Heart rate data including standard deviation of the NN intervals, the square root of the mean squared differences of successive NN intervals, log low-frequency and log high-frequency were collected for 10 min before and after tilting. Considering interactions between groups and head-up tilting, the head-up tilting induced reduction of the high-frequency component of HRVs was significantly greater in the PTSD group [F (1, 272) = 4.718, p = 0.031]. The change of HRVs in PTSD patients suggested the presence of autonomic dysfunction in despite of the posture.

Reduced NK cell IFN-γ secretion and psychological stress are independently associated with herpes zoster.

The pathogenesis of herpes zoster is closely linked to reduced varicella-zoster virus-specific cell-mediated immunity. However, little is known about the interplay between natural killer cells and psychological stress in the pathogenesis of herpes zoster. This study aimed to investigate possible associations among natural killer cells, T cells and psychological stress in herpes zoster. Interferon-gamma secretion from natural killer cell, psychological stress events, stress cognition scale scores and cytomegalovirus-specific cell-mediated immunity were compared between 44 patients with herpes zoster and 44 age- and gender-matched control subjects. A significantly lower median level of interferon-gamma secreted by natural killer cells was observed in patients with a recent diagnosis of herpes zoster than in control subjects (582.7 pg/ml vs. 1783 pg/ml; P = 0.004), whereas cytomegalovirus-specific cell-mediated immunity was not associated with herpes zoster. Psychological stress events and high stress cognition scale scores were significantly associated in patients with herpes zoster (P<0.001 and P = 0.037, respectively). However, reduced interferon-gamma secretion from natural killer cell and psychological stress were not associated. In conclusion, patients with a recent diagnosis of herpes zoster display reduced interferon-gamma secretion from natural killer cells and frequent previous psychological stress events compared with controls. However, reduced natural killer cell activity is not an immunological mediator between psychological stress and herpes zoster.

Heart rate variability of chronic posttraumatic stress disorder in the Korean veterans.

Patients with post-traumatic stress disorder (PTSD) have lower heart rate variability (HRV) than the general population, but findings in this area have been inconsistent. This study was conducted to investigate the characteristics of HRV in patients with PTSD and to evaluate associations between PTSD symptoms and HRV indices. Sixty-eight patients with PTSD and 73 controls without PTSD were evaluated. HRV was measured in all subjects after they completed self-reported questionnaires. Patients with PTSD had significantly more depressed moods, anxiety, and poorer sleep quality than individuals in the non-PTSD group. Standard deviations of NN intervals (SDNN), the square root of the mean squared differences of successive NN intervals (RMSSD), and log high-frequency (LNHF) were significantly lower in the PTSD group than in the non-PTSD group. Comparisons of HRV indices among four sub-groups according to presence/absence of PTSD and experiences of combat-related or other trauma indicated that individuals in the PTSD group who had experienced combat-related trauma had the lowest HRV indices. These indices included SDNN, RMSSD, and LNHF. Further, SDNN, RMSSD, and HF power were significantly associated with symptoms of hyperarousal. HRV measures might be useful physiological parameters in assessing and monitoring sympathovagal function in patients with PTSD.

Application of Short Screening Tools for Post-Traumatic Stress Disorder in the Korean Elderly Population.

OBJECTIVE: Post-traumatic stress disorder (PTSD) is often missed or incorrectly diagnosed in primary care settings. Although brief screening instruments may be useful in detecting PTSD, an adequate validation study has not been conducted with older adults. This study aimed to evaluate the reliability and validity of the Korean version of the primary care PTSD screen (PC-PTSD) and single-item PTSD screener (SIPS) in elderly veterans. METHODS: The PC-PTSD and SIPS assessments were translated into Korean, with a back-translation to the original language to verify accuracy. Vietnamese war veterans [separated into a PTSD group (n=41) and a non-PTSD group (n=99)] participated in several psychometric assessments, including the Korean versions of the PC-PTSD (PC-PTSD-K), SIPS (SIPS-K), a structured clinical interview from the Diagnostic and Statistical Manual of Mental Disorders-IV(SCID), and PTSD checklist(PCL). RESULTS: The PC-PTSD-K showed high internal consistency (Cronbach α=0.76), and the test-retest reliability of the PC-PTSD-K and SIPS-K were also high (r=0.97 and r=0.91, respectively). A total score of 3 from the PC-PTSD-K yielded the highest diagnostic efficiency, with sensitivity and specificity values of 0.90 and 0.86, respectively. The 'bothered a lot' response level from the SIPS-K showed the highest diagnostic efficiency, with sensitivity and specificity values of 0.85 and 0.89, respectively. CONCLUSION: Our findings suggest that both PC-PTSD-K and SIPS-K have good psychometric properties with high validity and reliability for detecting PTSD symptoms in elderly Korean veterans. However, further research will be necessary to increase our understanding of PTSD characteristics in diverse groups with different types of trauma.

Bone density in chronic schizophrenia with long-term antipsychotic treatment: preliminary study.

OBJECTIVE: Decreased bone mineral density has been found in the chronic schizophrenic patients who have been given a long-term administration of antipsychotics. Hyperprolactinemia from the antipsychotics and the negative symptom of schizophrenia were considered as the causes for this finding. In this study, the effect of hyperprolactinemia and the negative symptom of schizophrenia on bone mineral density was investigated on male schizophrenic patients. METHODS: The cross-sectional study was carried out with the subjects of 45 male schizophrenic patients who have undertaken the monotherapy with risperidone, olanzapine and clozapine for at least one year. The demographic factors, clinical symtoms, bone mineral density and hematological test were examined for all the subjects. RESULTS: No significant relationship was found between hyperprolactinemia and the decreased bone mineral density in the subjects. The negative schizophrenia symptom of the subjects showed a significant effect on the decreased bone mineral density. CONCLUSION: The decreased bone mineral density finding in the male schizophrenic patients may be caused by the negative schizophrenia symptom rather than the hyperprolactinemia due to the antipsychotics. Additional studies are further required regarding other factors that may affect the decreased bone mineral density such as activity, calcium intake and exposure to sunlight.