"It's Not Deterministic and It Will Never Be Deterministic": A Qualitative Study on Stakeholder Perspectives of Polygenic Risk Score Testing for Post-Traumatic Stress Disorder.

Objectives To examine whether attachment style moderates the relationship between polygenic risk scores (PRS) for posttraumatic stress disorder (PTSD) re-experiencing (PTSDREX) symptoms and the severity of and positive screen for traumatic loss-related PTSD. Methods Data were analysed from 631 US veterans who endorsed ‘unexpected death of a loved one’ as their ‘worst’ traumatic event. Multivariable models evaluated the association between PRS for PTSDREX, attachment style, and their interaction in predicting severity and positive screen for PTSD. A gene enrichment analysis was conducted to identify possible molecular mechanisms underlying the association between PTSDREX PRS and PTSD. Results PTSDREX PRS (β = 0.17; odds ratio [OR] = 1.85), attachment style (β= −0.33; OR = 0.14), and PTSDREX PRS × attachment style interaction (β= −0.12; OR = 0.53) were significant predictors of the severity and positive screen for PTSD. The most significant gene set detected was the gene ontology (GO) cellular component podosome set (GO:0002102, p < 3.95 × 10−5). Conclusions Having a secure attachment style may help mitigate polygenic risk for developing traumatic loss-related PTSD in US veterans. Podosomes, which are implicated in inflammatory and neuroplasticity processes, may contribute to the genetic liability to developing loss-related PTSD. Psychological treatments targeting attachment security may help mitigate increased polygenic risk for loss-related PTSD in this population.

Disturbed sleep is a hallmark feature of posttraumatic stress disorder (PTSD). However, few studies have examined sleep objectively in individuals with PTSD compared to trauma-exposed controls. This study used wrist actigraphy to measure and compare sleep patterns in trauma-exposed Australian Vietnam veterans (VV) with and without PTSD. Trauma-exposed Australian VV with and without PTSD were recruited from the PTSD Initiative. VV wore wrist accelerometers over 14 days and completed daily sleep diaries. Sleep parameters were compared between groups including sleep latency (SL), time in bed (TIB), total sleep time (TST), wake after sleep onset (WASO), and movement index (MI). Night-to-night and overall within-individual variability were assessed by root mean squared successive differences and comparison of individual standard deviations. Correlations between sleep diary (self-reported) and wrist actigraphy (objective) variables were also assessed. A total of 40 male VV (20 with PTSD) participated in the study. We found no difference in sleep patterns determined by wrist actigraphy between groups with the exception of reduced SL in VV with PTSD (3.9 ± 0.9 versus 4.9 ± 1.4 minutes, P < .05). Overall within-individual variability was significantly greater in VV with PTSD for TIB, TST, WASO, and MI. Self-reported and objective TST and WASO were more strongly correlated in VV without PTSD than those with PTSD. Although there were no significant differences in sleep parameters, VV with PTSD had increased within-individual overall sleep variability and reduced correlation between self-reported and objective sleep parameters compared to trauma-exposed controls. Further evaluation of extended sleep patterns by actigraphy in VV with PTSD is warranted.

PTSD and Combat-Related Injuries: Functional Neuroanatomy

Though still in infancy, the field of psychiatric genetics holds great potential to contribute to the development of new diagnostic and therapeutic options to treat these disorders. Among a large number of existing neurotransmitter systems, the serotonin system dysfunction has been implicated in many psychiatric disorders and therapeutic efficacy of many drugs is also thought to be based on modulation of serotonin. Serotonin transporter gene polymorphism is one of the most extensively studied polymorphisms in psychiatric behavioral genetics. In this article, we review the status of evidence for association between the serotonin gene polymorphism and some common mental disorders like affective disorders, post-traumatic stress disorder, obsessive-compulsive disorder, suicide, autism, and other anxiety and personality disorders. Going beyond traditional association studies, gene-environment interaction, currently gaining momentum, is also discussed in the review. While the existing information of psychiatric genetics is inadequate for putting into practice genetic testing in the diagnostic work-up of the psychiatric patient, if consistent in future research attempts, such results can be of great help to improve the clinical care of a vast majority of patients suffering from such disorders.

Changes in Relative Glucose Metabolic Rate Following Cortisol Administration in Aging Veterans with Posttraumatic Stress Disorder: An FDG-PET Neuroimaging Study

The authors aim to delineate cognitive dysfunction associated with posttraumatic stress disorder (PTSD) by evaluating a well-defined cohort of former World War II prisoners of war (POWs) with documented trauma and minimal comorbidities. The authors studied a cross-sectional assessment of neuropsychological performance in former POWs with PTSD, PTSD with other psychiatric comorbidities, and those with no PTSD or psychiatric diagnoses. Participants who developed PTSD had average IQ, while those who did not develop PTSD after similar traumatic experiences had higher IQs than average (approximately 116). Those with PTSD performed significantly less well in tests of selective frontal lobe functions and psychomotor speed. In addition, PTSD patients with co-occurring psychiatric conditions experienced impairment in recognition memory for faces. Higher IQ appears to protect individuals who undergo a traumatic experience from developing long-term PTSD, while cognitive dysfunctions appear to develop with or subsequent to PTSD. These distinctions were supported by the negative and positive correlations of these cognitive dysfunctions with quantitative markers of trauma, respectively. There is a suggestion that some cognitive decrements occur in PTSD patients only when they have comorbid psychiatric diagnoses.

Context:In this study, we assessed the relation of possible risk factors with post-traumatic stress disorder (PTSD) in the survivors of December 2004 tsunami in Kanyakumari district.Materials and Methods:We identified cases (n=158) and controls (n=141) by screening a random sample of 485 tsunami survivors from June 2005 to October 2005 using a validated tool, “Impact of events scale-revised (IES-R),” for symptoms suggestive of PTSD. Subjects whose score was equal to or above the 70th percentile (total score 48) were cases and those who had score below or equal to 30th percentile (total score 33) were controls. Analysis was done using statistical package for the social sciences to find the risk factors of PTSD among various pre-disaster, within-disaster and post-disaster factors.Results:Multivariate analysis showed that PTSD was related to female gender [odds ratio (OR) 6.35, 95% confidence interval (CI) 3.26-12.39], age 40 years and above (OR 2.38, 95% CI 1.23-4.63), injury to self (OR 2.97, 95% CI 1.55-5.67), injury to family members (OR 2.09, 95% CI 1.05-4.15), residence in urban area (area of maximum destruction) (OR 3.37, 95% CI 1.35-8.41) and death of close relatives (OR 3.83, 95% CI 1.91-7.68). Absence of fear of recurrence of tsunami (OR 0.32, 95% CI 0.17-0.60), satisfaction of services received (OR 0.57, 95% CI 0.36-0.92) and counseling services received more than three times (OR 0.45, 95% CI 0.26-0.78) had protective effect against PTSD.Conclusions:There is an association of pre-disaster, within-disaster and post-disaster factors with PTSD, which demands specific interventions at all phases of disaster, with a special focus on vulnerable groups.

IntroductionChildbirth, traditionally viewed as a natural and positive process, can become a traumatic experience when obstetric violence or disrespectful treatment occurs. This type of experience can cause symptoms consistent with Post-Traumatic Stress Disorder negatively affecting maternal mental health, bonding with the newborn, and the development of the newborn.ObjectivesTo analyze the relationship between perceptions of inadequate treatment during childbirth and the risk of postpartum Post-Traumatic Stress Disorder at 6 months in a sample of women assessed 3 months after birth.MethodsAn observational study with six-month follow-up was conducted in 341 women in Spain, initially recruited 3 months postpartum. Validated questionnaires were used: Childbirth Abuse and Respect Evaluation-Maternal Questionnaire (perceived abuse or disrespect), Perinatal Post Traumatic Stress Disorder, Family Apgar, and MOS social support survey Bivariate and multivariate analyses were performed using logistic regression.ResultsThree hundred forty-one women participated, with a mean age of 33.38 years (SD = 4.23). 10.9% of the participants were at risk of Post-Traumatic Stress Disorder. Childbirth Abuse and Respect Evaluation-Maternal Questionnaire dimensions correlated positively with the Perinatal Post Traumatic Stress Disorder, with “inappropriate treatment by professionals” being the most significant (r = 0.60; 95% CI: 0.53–0.67). A greater perception of obstetric violence (Abuse and Respect Evaluation-Maternal Questionnaire ≥ P95) significantly increased the likelihood of developing Perinatal Post Traumatic Stress Disorder (aOR: 48.38; 95%CI: 10.07–232.44). Associations with risk of developing Post-Traumatic Stress Disorder were also observed for instrumental birth (aOR: 5.29; 95% CI: 1.53–18.28) and previous cesarean section (aOR: 7.54; 95% CI: 1.10–51.79). More social support was associated with a lower risk of Post-Traumatic Stress Disorder (aOR: 0.96; 95%CI: 0.94–0.99).Discussion and conclusionA higher perception of obstetric violence is associated with an increased risk of developing postpartum Post-Traumatic Stress Disorder. Furthermore, invasive interventions such as instrumental births or previous cesarean sections increase psychological vulnerability. In contrast, social support acts as a protective factor. It is recommended to implement screening tools such as Abuse and Respect Evaluation-Maternal Questionnaire, reinforce training in respectful treatment, and promote humane care models to ensure the physical and emotional safety of women.

Objectives: This study aimed to determine the risk of depression and post-traumatic stress disorder among Filipino adults with respiratory allergies in an allergy unit during the COVID-19 pandemic. Also, we sought to identify if certain demographic variables are associated with these mental health conditions. Methodology: Respondents from an allergy unit completed the online survey from January to May 2022. Data obtained included sociodemographic factors and the presence of respiratory allergies. Patient Health Questionnaire - 9 (PHQ-9) and Impact of Event Scale-Revised (IES-R) ratings were used to measure depression and risk of post-traumatic stress disorder (PTSD), respectively. The relative risk or risk ratio (RR) of depression and post-traumatic stress disorder (PTSD) among subjects and the influence of demographic characteristics, type, and severity on the risk of depression and post-traumatic stress disorder (PTSD) among the subjects were estimated using log-binomial regression. Results: A total of 173 respondents were included in the study: 92 with respiratory allergies and 80 without respiratory allergies. Compared to those without allergies, those with allergies had a much higher proportion of post-graduate degree and higher monthly income. Of the individuals, 40.12% suffered from allergic rhinitis, 3.49% from asthma, and 9.88% from both allergies. The mean PHQ-9 score for all respondents was 7.80 (SD = 6.23), with a mean score of 7.89 (SD = 6.34) and 7.72 (SD = 6.29) for those without and with respiratory allergies, respectively. Among those without respiratory allergies, 41.25% had mild depression, 12.50% had moderate depression, 11.25% had moderately severe depression, and 6.25% had severe depression. Among those with allergies, 33.70% had mild depression, and 19.57% had moderate depression. The mean score for the intrusion, avoidance, and hyperarousal subscales of the IES-R were 10.32 (SD = 6.34), 11.17 (SD = 7.21), and 6.99 (SD = 5.38), respectively, and the overall mean IES-R score for the respondents was 10.32 (SD = 7.34). Among those without respiratory allergies, 31.50% had high scores for PTSD, 2.50% had probable PTSD, 20% had PTSD as a clinical concern, and 46.25% did not have PTSD. For those with allergic rhinitis, the prevalence of high scores for PTSD was 40.58%, while it was 50.00% for those with asthma. Depression was highly correlated with age and marital status. For PTSD, those who were married (OR = 0.31, p = 0.012) were 3.23 times less likely to develop the condition than their single counterparts. The type of respiratory allergies, the severity of allergic rhinitis, and the level of asthma control were not significantly associated with the severity of depression and PTSD of any degree. Conclusion: Patients with respiratory allergies did not have an increased risk of depression and post-traumatic stress disorder in this particular population. The PHQ-9 AND IES-R scores among those with respiratory allergies and those without were shown to have no significant difference. Demographic factors found to be associated with depression were age and marital status, while for PTSD, it was only marital status. The type of respiratory allergy, control, and severity were not associated with depression and PTSD of any degree.

Background Post Traumatic Stress Disorder (PTSD) is a psychiatric debilitating condition that can occur in individuals who experience extremely stressful or traumatic life events. Sexual assault is considered as one of the most traumatic stressor in life. Although few studies investigated the association between history of sexual assault and PTSD, no studies have examined the impact of age at sexual assault on PTSD.Method A cross-sectional telephone survey was conducted among adult female residents of Virginia from November 2002 to February 2003. A total of 1,769 women aged 18 and older were interviewed using a random digit dialing method. Detailed screening questionnaire was utilized to ascertain the occurrence of sexual assault, age at sexual assault and PTSD. The DSM-IV diagnostic criteria were used to define PTSD.Result The prevalence of PTSD among women with no history of sexual assault, those victimized before the age of 18 and 18 and above was 8.1%, 35.3%, and 30.2% respectively. Multivariate logistic regression model showed an increase risk of PTSD among women assaulted at a younger age. Compared to women with no history of sexual assault, women who were victimized before their 18th birthday were 2.8 times more likely to suffer from PTSD [OR=2.78 (95% C1=1.87- 4.23)]. The risk of PTSD among women victimized as adults was 2.6 times higher compared to women with no history of sexual assault [OR=2.59 (95%CI =1.43-4.70)].Conclusion This study provided important information on the association between PTSD and age at sexual assault. The risk of PTSD is relatively higher among those assaulted before the age of 18. The adverse effect of sexual assault as a risk for PTSD in addition to other negative health problems is a major public health concern. Primary prevention strategies should be in place to detect sexual assault victims and prevent the occurrence of PTSD.

The volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function. Genetic variants, associated with subcortical volumes in two large normative discovery samples, were used to compute polygenic scores (PGS) for the volume of seven subcortical structures. These were applied to a target sample enriched for childhood trauma and PTSD. Subcortical volume PGS from the discovery sample were strongly associated in our trauma/PTSD enriched sample (n = 7580) with respective subcortical volumes of the hippocampus (p = 1.10 × 10−20), thalamus (p = 7.46 × 10−10), caudate (p = 1.97 × 10−18), putamen (p = 1.7 × 10−12), and nucleus accumbens (p = 1.99 × 10−7). We found a significant association between the hippocampal volume PGS and hippocampal volume in control subjects from our sample, but was absent in individuals with PTSD (GxE; (beta = −0.10, p = 0.027)). This significant GxE (PGS × PTSD) relationship persisted (p < 1 × 10−19) in four out of five threshold peaks (0.024, 0.133, 0.487, 0.730, and 0.889) used to calculate hippocampal volume PGSs. We detected similar GxE (G × ChildTrauma) relationships in the amygdala for exposure to childhood trauma (rs4702973; p = 2.16 × 10−7) or PTSD (rs10861272; p = 1.78 × 10−6) in the CHST11 gene. The hippocampus and amygdala are pivotal brain structures in mediating PTSD symptomatology. Trauma exposure and PTSD modulate the effect of polygenic markers on hippocampal volume (GxE) and the amygdala volume PGS is associated with PTSD risk, which supports the role of amygdala volume as a risk factor for PTSD.

Many patients with mild traumatic brain injury (mTBI) are at risk for mental health problems such as posttraumatic stress disorder (PTSD). The objective of this study was to determine whether the polygenic risk for PTSD (or for related mental health disorders or traits including major depressive disorder [MDD] and neuroticism [NEU]) was associated with an increased likelihood of PTSD in the aftermath of mTBI. We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma center patients. One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5 score ≥33) at 6 months post-injury. We used summary statistics from recent GWAS studies of PTSD, MDD, and NEU to generate polygenic risk scores (PRS) for individuals in our sample. A multivariable model that included age, sex, pre-injury history of mental disorder, and cause of injury explained 7% of the variance in the PTSD outcome; the addition of the PTSD-PRS (and five ancestral principal components) significantly increased the variance explained to 11%. The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly four times higher (aOR = 3.71, 95% CI 1.80–7.65) than in the lowest PTSD-PRS quintile. There was no evidence of a statistically significant interaction between PTSD-PRS and prior history of mental disorder, indicating that PTSD-PRS had similar predictive utility among those with and without pre-injury psychiatric illness. When added to the model, neither MDD-PRS nor NEU-PRS were significantly associated with the PTSD outcome. These findings show that the risk for PTSD in the context of mTBI is, in part, genetically influenced. They also raise the possibility that an individual’s PRS could be clinically actionable if used—possibly with other non-genetic predictors—to signal the need for enhanced follow-up and early intervention; this precision medicine approach needs to be prospectively studied.

Toward the Predeployment Detection of Risk for PTSD

Recent genome-wide association studies (GWAS) have identified genetic markers of post-traumatic stress disorder (PTSD) in civilian and military populations. However, studies have yet to examine the genetics of PTSD while factoring in risk for alcohol dependence, which commonly co-occur. We examined genome-wide associations for DSM-IV PTSD among 4,978 trauma-exposed participants (31% with alcohol dependence, 50% female, 30% African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA). We also examined associations of polygenic risk scores (PRS) derived from the Psychiatric Genomics Consortium (PGC)-PTSD Freeze 2 (N = 3533) and Million Veterans Program GWAS of PTSD (N = 5200) with PTSD and substance dependence in COGA, and moderating effects of sex and alcohol dependence. 7.3% of COGA participants met criteria for PTSD, with higher rates in females (10.1%) and those with alcohol dependence (12.3%). No independent loci met genome-wide significance in the PTSD meta-analysis of European (EA) and African ancestry (AA) participants. The PGC-PTSD PRS was associated with increased risk for PTSD (B = 0.126, p < 0.001), alcohol dependence (B = 0.231, p < 0.001), and cocaine dependence (B = 0.086, p < 0.01) in EA individuals. A significant interaction was observed, such that EA individuals with alcohol dependence and higher polygenic risk for PTSD were more likely to have PTSD (B = 0.090, p < 0.01) than those without alcohol dependence. These results further support the importance of examining substance dependence, specifically alcohol dependence, and PTSD together when investigating genetic influence on these disorders.

The gene expression approach has provided promising insights into the pathophysiology of posttraumatic stress disorder (PTSD). However, few studies used hypothesis-free transcriptome-wide approach to comprehensively understand gene expression underpinning PTSD. A transcriptome-wide expression study using RNA sequencing of whole blood was conducted in 324 World Trade Center responders (201 with never, 81 current, 42 past PTSD). Samples from current and never PTSD reponders were randomly split to form discovery (N = 195) and replication (N = 87) cohorts. Differentially expressed genes were used in pathway analysis and to create a polygenic expression score. There were 448 differentially expressed genes in the discovery cohort, of which 99 remained significant in the replication cohort, including FKBP5, which was found to be up-regulated in current PTSD regardless of the genotypes. Several enriched biological pathways were found, including glucocorticoid receptor signaling and immunity-related pathways, but these pathways did not survive FDR correction. The polygenic expression score computed by aggregating 30 differentially expressed genes using the elastic net algorithm achieved sensitivity/specificity of 0.917/0.508, respectively for identifying current PTSD in the replication cohort. Polygenic scores were similar in current and past PTSD, with both groups scoring higher than trauma-exposed controls without any history of PTSD. Together with the pathway analysis results, these findings point to HPA-axis and immune dysregulation as key biological processes underpinning PTSD. A novel polygenic expression aggregate that differentiates PTSD patients from trauma-exposed controls might be a useful screening tool for research and clinical practice, if replicated in other populations.