S M Southwick’s research while affiliated with U.S. Department of Veterans Affairs and other places

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 analyzed from 631 U.S. 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 x 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 < 3.95x10⁻⁵). Conclusions Having a secure attachment style may help mitigate polygenic risk for developing traumatic loss-related PTSD in U.S. 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.

Objective: Exposure to traumatic life events is associated with increased risk of posttraumatic stress disorder (PTSD) and other mental health problems such as suicidal ideation (SI), alcohol use disorder (AUD), and decreased quality of life (QOL). Mindfulness, which involves attending to the present moment, may help individuals cope with traumatic events by increasing acceptance of trauma-related experiences and decreasing trauma-related negative affect and avoidance of trauma reminders. The current study evaluated whether mindful attention to the present moment mediated the association between number of lifetime traumas and mental health. Method: The sample consisted of 1,268 trauma-exposed U.S. veterans who participated in the National Health and Resilience in Veterans Study, a nationally representative study of U.S. veterans. On average, the sample was 60.6 years of age (SD = 15.2, range = 20-94), predominantly male (89.8%), Caucasian (75.0%), and noncombat veterans (59.2%). Results: Path analyses revealed that mindfulness partially mediated the relation between number of lifetime traumas and PTSD symptoms (β = -.55), AUD (β = -.17), and QOL (β = .38), and fully mediated the relation between number of lifetime traumas and SI (β = -.36). Conclusions: The relationship between lifetime trauma burden and various mental health issues of relevance to U.S. veterans may be mediated by mindfulness, or the ability to pay attention to the present moment. Interventions that bolster mindfulness may help mitigate the negative impact of cumulative traumas in this population. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Aims The main objective of the study was to compare the differences in craving following trauma and stress scripts in individuals with alcohol dependence (AD) who have experienced trauma but did not meet criteria for post-traumatic stress disorder (PTSD). Methods Twenty-eight men and women who participated in a treatment trial were included in this study before starting treatment. All had to meet criteria for AD and had experienced trauma at some point of their lives but were never diagnosed with PTSD. All participants had one laboratory session and were exposed to stress, trauma and neutral scripts randomly assigned. Main measures of craving, anxiety and mood were administered before, during and after each script. Results Stress and trauma scripts induced significantly more craving and anxiety than the neutral scripts. Interestingly, stress scripts produced stronger craving and anxiety than the trauma scripts but only with some measures. Stress and trauma scripts produced significantly more fear, anger and sadness and significantly lower ratings of joy and relaxation than the neutral script. Again, there were no differences between stress and trauma scripts for any of the emotional subscales. Conclusions Trauma scripts did not result in stronger craving than stress scripts. These findings suggest that trauma in the absence of PTSD diagnosis does not lead to stronger craving for alcohol.

Background: Although several studies have identified risk factors for suicidal behaviors in general samples of Veterans, fewer studies have examined protective factors, particularly in high-risk samples. To address this gap, we examined protective correlates of suicidal ideation (SI) and suicide attempts (SA) in a sample of Veterans with histories of posttraumatic stress disorder (PTSD) and/or major depressive disorder (MDD). Method: Data were analyzed from a nationally representative sample of 3157 U.S. Veterans who completed the first wave of a web-based survey as part of the National Health and Resilience in Veterans Study (NHRVS). Of this sample, 577 Veterans met criteria for history of PTSD, MDD or both. Results: Multivariable logistic regression analyses were used to examine relationships between protective factors (curiosity, resilience, purpose in life, dispositional gratitude, optimism, and community integration) and suicidal behaviors (SI and SA). The prevalence of any SI during the previous two weeks was 29.4% and the prevalence of lifetime SA was 28.0%. After adjusting for relevant sociodemographic and military characteristics, greater purpose in life, curiosity, and optimism were negatively associated with SI. None of the protective correlates were associated with SA. Limitations: Given the cross-sectional nature of this study, conclusions about causality cannot be made. The assessment of suicidality also was limited to three self-report items. Conclusion: Results provide a characterization of protective factors for suicidality, and may help inform prevention and treatment approaches designed to mitigate suicide risk among high-risk military Veterans.

The Met allele of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with reduced levels of BDNF release, heightened hypothalamic-pituitary-adrenal axis reactivity, and impaired fear extinction. As a result, Met allele carriers may be at risk for greater severity of posttraumatic stress disorder (PTSD) symptoms. In this study, we examined the relationship between the BDNF Val66Met polymorphism and PTSD symptoms in two nationally representative samples of European American U.S. military veterans (main sample, n = 1386; replication sample, n = 509). Results revealed that, relative to Val/Val homozygotes, Met allele carriers reported greater severity of lifetime and current PTSD symptoms, specifically re-experiencing symptoms. Met allele carriers with high trauma burden also reported greater severity of lifetime and past-month PTSD symptoms. Greater engagement in physical exercise moderated this gene-by-environment interaction. Specifically, among veterans with high lifetime trauma burden, Met allele carriers who exercised had significantly lower severity of PTSD symptoms compared to those who did not exercise. These findings suggest that interventions designed to bolster engagement in physical exercise may help mitigate PTSD symptoms in veterans who are Met allele carriers and highly exposed to trauma.

Objective Posttraumatic stress disorder (PTSD) is often difficult to treat, and many patients do not achieve full remission. Complementary and integrative health approaches, such as mindfulness meditation, are intended to be integrated with evidence‐based treatment. This study examined the efficacy of mindfulness‐based stress reduction (MBSR) in the treatment of PTSD in U.S. military veterans. Methods Veterans with a diagnosis of PTSD (N=214) were randomly assigned to either 90‐minute group MBSR or present‐centered group therapy (PCGT) for eight weeks. Follow‐up assessments were obtained at baseline and weeks 3, 6, 9 (primary endpoint), and 16. Results Both the MBSR and PCGT groups achieved significant improvement in PTSD as measured by the Clinician‐Administered PTSD Scale for DSM‐IV (CAPS‐IV), with no statistically significant differences between groups. However, compared with PCGT, the MBSR group showed a statistically significant improvement in PTSD on the self‐reported PTSD Checklist for DSM‐IV over the nine weeks. This difference was not maintained posttreatment, at week 16. Strengths of the study include its large sample size, multisite design, active control group, single‐blind outcome ratings, fidelity monitoring, large minority representation, and randomized approach. The study was limited by its high attrition rate and low representation of women. Conclusions Both MBSR and PCGT appear to have beneficial effects in treating PTSD in veterans, with greater improvement observed in self‐reported PTSD symptoms in the MBSR group. No differences between groups were observed on the CAPS‐IV scale.

The purpose of the present study was to investigate associations between the 7-factor hybrid model of DSM-5 posttraumatic stress disorder (PTSD) symptoms, which includes intrusions, avoidance, negative affect, anhedonia, externalizing behaviors, anxious arousal, and dysphoric arousal symptoms, and alcohol consumption and consequences. A nationally representative sample of 916 trauma-exposed U.S. military veterans were administered the Trauma History Screen, PTSD Checklist-5, and Alcohol Use Disorders Identification Test. Confirmatory factor analyses were conducted to determine associations between the 7-factor hybrid model of PTSD symptoms, and alcohol consumption and consequences. Results revealed that lifetime dysphoric arousal (r = 0.31), negative affect (r = 0.30), and anhedonia (r = 0.29) symptom clusters were most strongly associated with past-year alcohol consequences. No significant associations were observed for alcohol consumption. While the cross-sectional study design does not allow one to ascertain causative associations between PTSD factors and alcohol consumption and consequences, results generally align with the self-medication hypothesis, as PTSD factors reflecting internalizing were most strongly related to alcohol-related consequences. These results underscore the importance of assessing for alcohol use problems in veterans who score highly on PTSD symptoms reflecting internalizing symptomatology.

Background: Combat exposure is associated with increased risk of mental disorders and suicidality. Moral injury, or persistent effects of perpetrating or witnessing acts that violate one's moral code, may contribute to mental health problems following military service. The pervasiveness of potentially morally injurious events (PMIEs) among U.S. combat veterans, and what factors are associated with PMIEs in this population remains unknown. Methods: Data were analyzed from the National Health and Resilience in Veterans Study (NHRVS), a contemporary and nationally representative survey of a population-based sample of U.S. veterans, including 564 combat veterans, collected September-October 2013. Types of PMIEs (transgressions by self, transgressions by others, and betrayal) were assessed using the Moral Injury Events Scale. Psychiatric and functional outcomes were assessed using established measures. Results: A total of 10.8% of combat veterans acknowledged transgressions by self, 25.5% endorsed transgressions by others, and 25.5% endorsed betrayal. PMIEs were moderately positively associated with combat severity (? = .23, P < .001) and negatively associated with white race, college education, and higher income (?s = .11-.16, Ps < .05). Transgressions by self were associated with current mental disorders (OR = 1.65, P < .001) and suicidal ideation (OR = 1.67, P < .001); betrayal was associated with postdeployment suicide attempts (OR = 1.99, P < .05), even after conservative adjustment for covariates, including combat severity. Conclusions: A significant minority of U.S combat veterans report PMIEs related to their military service. PMIEs are associated with risk for mental disorders and suicidality, even after adjustment for sociodemographic variables, trauma and combat exposure histories, and past psychiatric disorders.

The anterior hippocampus (aHPC) has a central role in the regulation of anxiety-related behavior, stress response, emotional memory and fear. However, little is known about the presence and extent of aHPC abnormalities in posttraumatic stress disorder (PTSD). In this study, we used a multimodal approach, along with graph-based measures of global brain connectivity (GBC) termed functional GBC with global signal regression (f-GBCr) and diffusion GBC (d-GBC), in combat-exposed US Veterans with and without PTSD. Seed-based aHPC anatomical connectivity analyses were also performed. A whole-brain voxel-wise data-driven investigation revealed a significant association between elevated PTSD symptoms and reduced medial temporal f-GBCr, particularly in the aHPC. Similarly, aHPC d-GBC negatively correlated with PTSD severity. Both functional and anatomical aHPC dysconnectivity measures remained significant after controlling for hippocampal volume, age, gender, intelligence, education, combat severity, depression, anxiety, medication status, traumatic brain injury and alcohol/substance comorbidities. Depression-like PTSD dimensions were associated with reduced connectivity in the ventromedial and dorsolateral prefrontal cortex. In contrast, hyperarousal symptoms were positively correlated with ventromedial and dorsolateral prefrontal connectivity. We believe the findings provide first evidence of functional and anatomical dysconnectivity in the aHPC of veterans with high PTSD symptomatology. The data support the putative utility of aHPC connectivity as a measure of overall PTSD severity. Moreover, prefrontal global connectivity may be of clinical value as a brain biomarker to potentially distinguish between PTSD subgroups.