Hospitalization for physical injury may contribute to recovery of invisible war wounds: Response to Peterson's (2021) commentary on Soumoff et al. (2021).

Peterson's (2021) commentary on our recently published manuscript (Soumoff et al., 2021) suggests that our findings are an example of visible, physical injuries of war facilitating communication with others, which, in turn, fosters recovery from invisible war wounds. We agree that in the proper context, the retelling of one's traumatic story can be important for recovery from and, perhaps, even the prevention of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Participants in our study cohort differed from most others who experienced combat trauma in that while they were hospitalized, they experienced nearly daily visits from a behavioral health provider to address traumatic stress-related symptoms. It is likely that individuals who sustained more severe physical injury (i.e., higher Injury Severity Score [ISS] ratings) had longer hospital stays, received more support, and had more opportunities to retell their stories than those with less severe injuries, leading to decreases in PTSD and MDD symptoms. To note support of this supposition, in Table 5 of Soumoff et al. (2021), although not significant, the adjusted odds ratios (aORs) for PTSD and MDD were below 1 for service members with high (i.e., above 16) ISS ratings. The physical injury-related hospitalizations participants in our sample experienced fostered activities described by Peterson (2021) that likely contributed to the prevention and resolution of PTSD and MDD symptoms, benefits not received by most individuals who suffer only invisible wounds of war.

Somatic Symptom Severity, Not Injury Severity, Predicts Probable Posttraumatic Stress Disorder and Major Depressive Disorder in Wounded Service Members.

Although previous studies have reported an association between patient-reported somatic symptom severity and the development of posttraumatic stress disorder (PTSD) or major depressive disorder (MDD) in injured military service members (SMs), conclusions from other studies regarding the association between clinician-determined injury severity and PTSD or MDD remain unclear. The present study investigated whether somatic symptoms or injury severity predict the development of probable PTSD or MDD in wounded SMs medically evacuated from combat areas. Data including SM demographic characteristics, clinician-determined injury severity (i.e., Injury Severity Score [ISS] and Abbreviated Injury Scale [AIS] values), and self-report assessments of PTSD (PTSD Checklist-Civilian Version), MDD (Patient Health Questionnaire [PHQ]-9), and somatic symptoms (PHQ-15) were analyzed. A total of 2,217 SMs completed at least one self-assessment between 2003 and 2014, with 425 having completed assessments at each assessment period (AP), conducted 1-75 (AP1), 76-165 (AP2), and 166-255 (AP3) days postinjury. Between AP1 and AP3, the rates of probable PTSD and MDD increased from 3.0% to 11.7% and from 2.8% to 9.2%, respectively. Somatic symptom severity at AP1 predicted probable PTSD and MDD at all three APs, odds ratios (ORs) = 3.5-11.5; however, ISS values did not predict probable PTSD or MDD at any AP, ORs = 0.6-0.9. This suggests that the initial severity of self-reported somatic symptoms rather than clinician-determined injury severity predicts the development of probable PTSD and MDD in wounded SMs.

Mental Disorders, Gun Ownership, and Gun Carrying Among Soldiers After Leaving the Army, 2016-2019.

Objectives. To examine associations of current mental and substance use disorders with self-reported gun ownership and carrying among recently separated US Army soldiers. Veterans have high rates of both gun ownership and mental disorders, the conjunction of which might contribute to the high suicide rate in this group. Methods. Cross-sectional survey data were collected in 2018-2019 from 5682 recently separated personnel who took part in the Army Study to Assess Risk and Resilience in Servicemembers. Validated measures assessed recent mood, anxiety, substance use, and externalizing disorders. Logistic regression models examined associations of sociodemographic characteristics, service characteristics, and mental disorders with gun ownership and carrying. Results. Of the participants, 50% reported gun ownership. About half of owners reported carrying some or most of the time. Mental disorders were not associated significantly with gun ownership. However, among gun owners, major depressive disorder, panic disorder, posttraumatic stress disorder, and intermittent explosive disorder were associated with significantly elevated odds of carrying at least some of the time. Conclusions. Mental disorders are not associated with gun ownership among recently separated Army personnel, but some mental disorders are associated with carrying among gun owners. (Am J Public Health. 2021;111(10):1855-1864. https://doi.org/10.2105/AJPH.2021.306420).

Severity and Symptom Trajectory in Combat-Related PTSD: a Review of the Literature.

PURPOSE OF REVIEW: Combat-related posttraumatic stress disorder is increasingly recognized as having a variable course in returning veterans. Relatively few studies have identified predictors of illness duration or severity in this population. This review sought to synthesize the existing literature. RECENT FINDINGS: The existing literature remains limited and heterogeneous. However, several studies identified hyperarousal and pre-deployment dissociation as predictive of disease severity, and re-experiencing as predictive of suicidality in veterans with combat-related PTSD. No other pre-, peri-, or posttraumatic psychosocial predictors of individual symptoms or overall disease severity have been identified in replicated studies. Important clinical factors to explore in the assessment of PTSD in combat veterans may now include hyperarousal and a history of dissociation as these may predict disease severity, and re-experiencing as this has been identified as a significant predictor of suicidality. Further study into this topic may reveal biological or more sensitive psychosocial markers predicting illness severity and prognosis.

Implementation and clinical characteristics of a posttraumatic stress disorder brain collection.

A postmortem human brain collection to study posttraumatic stress disorder (PTSD) is critical for uncovering the molecular mechanisms that contribute to this psychiatric disorder. We describe here the PTSD brain collection at the Lieber Institute for Brain Development in Baltimore, Maryland, consisting of postmortem brain donations acquired between 2012 and 2017. Thus far, 87 brains from individuals meeting DSM-5 criteria for PTSD were collected after consent was obtained from legal next-of-kin, and subsequently clinically characterized for molecular studies. PTSD brain donors had high rates of comorbid diagnoses, including depression (62.1%), substance abuse (74.7%), drug-related death (69.0%), and suicide completion (17.2%). PTSD cases were subdivided into two categories: combat-related PTSD (n = 24) and noncombat/domestic PTSD (n = 63). The major differences between the combat-related and domestic PTSD cohorts were sex, drug-related death, and the prevalence of bipolar disorder (BPD) comorbidity. The combat-related group was entirely male, with only one BPD subject (4.2%), and had significantly fewer drug-related deaths (45.8%) in contrast to the domestic group (31.8% male, 36.5% bipolar, and 77.8% drug-related deaths). Medical examiners' offices, particularly in areas with higher military populations, are an excellent source for PTSD brain donations of both combat-related and domestic PTSD.

Predeployment predictors of psychiatric disorder-symptoms and interpersonal violence during combat deployment.

BACKGROUND: Preventing suicides, mental disorders, and noncombat-related interpersonal violence during deployment are priorities of the US Army. We used predeployment survey and administrative data to develop actuarial models to identify soldiers at high risk of these outcomes during combat deployment. METHODS: The models were developed in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) Pre-Post Deployment Study, a panel study of soldiers deployed to Afghanistan in 2012-2013. Soldiers completed self-administered questionnaires before deployment and one (T1), three (T2), and nine months (T3) after deployment, and consented to administrative data linkage. Seven during-deployment outcomes were operationalized using the postdeployment surveys. Two overlapping samples were used because some outcomes were assessed at T1 (n = 7,048) and others at T2-T3 (n = 7,081). Ensemble machine learning was used to develop a model for each outcome from 273 predeployment predictors, which were compared to simple logistic regression models. RESULTS: The relative improvement in area under the receiver operating characteristic curve (AUC) obtained by machine learning compared to the logistic models ranged from 1.11 (major depression) to 1.83 (suicidality).The best-performing machine learning models were for major depression (AUC = 0.88), suicidality (0.86), and generalized anxiety disorder (0.85). Roughly 40% of these outcomes occurred among the 5% of soldiers with highest predicted risk. CONCLUSIONS: Actuarial models could be used to identify high risk soldiers either for exclusion from deployment or preventive interventions. However, the ultimate value of this approach depends on the associated costs, competing risks (e.g. stigma), and the effectiveness to-be-determined interventions.

VA's National PTSD Brain Bank: a National Resource for Research.

The National PTSD Brain Bank (NPBB) is a brain tissue biorepository established to support research on the causes, progression, and treatment of PTSD. It is a six-part consortium led by VA's National Center for PTSD with participating sites at VA medical centers in Boston, MA; Durham, NC; Miami, FL; West Haven, CT; and White River Junction, VT along with the Uniformed Services University of Health Sciences. It is also well integrated with VA's Boston-based brain banks that focus on Alzheimer's disease, ALS, chronic traumatic encephalopathy, and other neurological disorders. This article describes the organization and operations of NPBB with specific attention to: tissue acquisition, tissue processing, diagnostic assessment, maintenance of a confidential data biorepository, adherence to ethical standards, governance, accomplishments to date, and future challenges. Established in 2014, NPBB has already acquired and distributed brain tissue to support research on how PTSD affects brain structure and function.

Domestic Civil Support Missions Can Aggravate Negative Mental Health Outcomes Among National Guardsmen: The Moderating Role of Economic Difficulties.

Little research has addressed potentially negative health outcomes associated with domestic civil-oriented operations, but has focused instead on traditional military operations (e.g., combat). This study, conducted following a United States Defense Support to Civilian Authorities mission undertaken by National Guard forces (N = 330), showed that responding to such missions was linked to more negative mental health outcomes, including posttraumatic stress disorder (ß = 0.23) and depression (ß = 0.23), but only among those who reported difficulty meeting their basic socioeconomic needs and not among those who did not have difficulty meeting their basic needs. The study offers suggestions for identifying individuals who may be especially vulnerable to stressors.

Large-Scale Simulation for Teaching Combat and Operational Stress Control: Operation Bushmaster.

Large-scale high-fidelity casualty simulation and exposure to realistic environmental stressors in Operation Bushmaster represents a unique teaching environment that challenges military medical students to apply skills in assessment and acute management of stress responses. While this training event is specific to military medical students, the skills demonstrated could be readily applied in natural disaster or other mass civilian casualties. Schools seeking to teach mass casualty response could implement many of the elements of the curriculum outlined in this article on a smaller scale. Doing so exposes students to decision making in a disaster where the number of patients exceeds available resources and damage to infrastructure may limit their capabilities. Our experience with large-scale simulation suggests that this is an effective teaching tool.

Randomized effectiveness trial of a brief course of acupuncture for posttraumatic stress disorder.

BACKGROUND: Initial posttraumatic stress disorder (PTSD) care is often delayed and many with PTSD go untreated. Acupuncture appears to be a safe, potentially nonstigmatizing treatment that reduces symptoms of anxiety, depression, and chronic pain, but little is known about its effect on PTSD. METHODS: Fifty-five service members meeting research diagnostic criteria for PTSD were randomized to usual PTSD care (UPC) plus eight 60-minute sessions of acupuncture conducted twice weekly or to UPC alone. Outcomes were assessed at baseline and 4, 8, and 12 weeks postrandomization. The primary study outcomes were difference in PTSD symptom improvement on the PTSD Checklist (PCL) and the Clinician-administered PTSD Scale (CAPS) from baseline to 12-week follow-up between the 2 treatment groups. Secondary outcomes were depression, pain severity, and mental and physical health functioning. Mixed model regression and t test analyses were applied to the data. RESULTS: Mean improvement in PTSD severity was significantly greater among those receiving acupuncture than in those receiving UPC (PCLΔ=19.8±13.3 vs. 9.7±12.9, P<0.001; CAPSΔ=35.0±20.26 vs. 10.9±20.8, P<0.0001). Acupuncture was also associated with significantly greater improvements in depression, pain, and physical and mental health functioning. Pre-post effect-sizes for these outcomes were large and robust. CONCLUSIONS: Acupuncture was effective for reducing PTSD symptoms. Limitations included small sample size and inability to parse specific treatment mechanisms. Larger multisite trials with longer follow-up, comparisons to standard PTSD treatments, and assessments of treatment acceptability are needed. Acupuncture is a novel therapeutic option that may help to improve population reach of PTSD treatment.

Association of Traumatic Brain Injury Severity and Self-Reported Neuropsychiatric Symptoms in Wounded Military Service Members.

The impact of traumatic brain injury (TBI) severity and loss of consciousness (LOC) on the development of neuropsychiatric symptoms was studied in injured service members (SMs; n = 1278) evacuated from combat settings between 2003 and 2012. TBI diagnoses of mild TBI (mTBI) or moderate-to-severe TBI (MS-TBI) along with LOC status were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes and the Defense and Veterans Brain Injury Center Standard Surveillance Case Definition for TBI. Self-reported psychiatric symptoms were evaluated for post-traumatic stress disorder (PTSD) with the PTSD Checklist, Civilian Version for PTSD, the Patient Health Questionnaire-9 for major depressive disorder (MDD), and the Patient Health Questionnaire-15 for somatic symptom disorder (SSD) in two time periods post-injury: Assessment Period 1 (AP1, 0.0-2.5 months) and Assessment Period 2 (AP2, 3-12 months). mTBI, but not MS-TBI, was associated with increased neuropsychiatric symptoms: PTSD in AP1 and AP2; MDD in AP1; and SSD in AP2. A subgroup analysis of mTBI with and without LOC revealed that mTBI with LOC, but not mTBI without LOC, was associated with increased symptoms as compared to non-TBI: PTSD in AP1 and AP2; MDD in AP1; and SSD in AP1 and AP2. Moreover, mTBI with LOC was associated with increased MDD symptoms in AP2, and SSD symptoms in AP1 and AP2, compared to mTBI without LOC. These findings reinforce the need for the accurate characterization of TBI severity and a multi-disciplinary approach to address the devastating impacts of TBI in injured SMs.

Recent Stressful Experiences and Suicide Risk: Implications for Suicide Prevention and Intervention in U.S. Army Soldiers.

Objectives: To identify the extent to which the presence of recent stressful events are risk factors for suicide among active-duty soldiers as reported by informants. Methods: Next-of-kin (NOK) and supervisors (SUP) of active duty soldiers (n = 135) who died by suicide and two groups of living controls: propensity-matched (n = 128) and soldiers who reported suicidal ideation in the past year, but did not die (SI) (n = 108) provided data via structured interviews from the Study to Assess Risk and Resilience in Servicemembers (Army STARRS). Multivariate logistic regression analyses were used to create a risk score for suicide. Results: The odds of suicide increased significantly for soldiers experiencing relationship problems, military punishment, and perceived failure or humiliation in the month prior to death. Suicide risk models with these risk factors predicted suicide death among those who reported SI in the past year (OR = 5.9, [95% CI = 1.5, 24.0] χ 2 = 6.24, p = 0.0125, AUC, 0.73 (0.7, 0.8) NOK) and (OR = 8.6, [95% CI = 1.4, 51.5] χ 2 = 5.49, p = 0.0191, AUC, 0.78 (0.7, 0.8); SUP) suggesting the combination of these recent stressors may contribute to the transition from ideation to action. Conclusions: Our findings suggest for the first time recent stressors distinguished suicide ideating controls from suicide decedents in the month prior to death as reported by informants. Implications for preventive intervention efforts for clinicians, supervisors and family members in identifying the transition from ideation to action are discussed.

Effects of propranolol on the modification of trauma memory reconsolidation in PTSD patients: A systematic review and meta-analysis.

Post-traumatic stress disorder (PTSD) develops after an exposure to a life-threatening event and is characterized by intrusive memories. According to memory reconsolidation theory retrieval of memory under certain conditions leads to its labilization and subsequent re-storage which could be disrupted by drugs. Propranolol has been the most commonly investigated drug for memory reconsolidation therapy in clinical trials. Intervention with propranolol have shown mixed results in PTSD patients with some studies showing improvement in symptoms while other failing to replicate these findings. We conducted a systematic review and meta-analysis to determine the efficacy of trauma memory disruption by propranolol on PTSD symptoms and physiological responses in PTSD patients. 3224 publications were assessed for eligibility. Seven studies on effects of propranolol on PTSD symptoms and 3 studies on effects of propranolol on physiological responses were incorporated in the meta-analyses. Overall, results indicate that propranolol did not show a beneficial effect on PTSD symptoms (standardized mean difference: 1.29; 95% CI = -2.16 - 0.17). Similarly, propranolol did not influence skin conductance (standardized mean difference: 0.77; 95% CI = -1.85 - 0.31) or EMG response (standardized mean difference: 0.16; 95% CI = -0.65 - 0.33). However, propranolol significantly reduced heart rate after trauma memory recall compared to placebo (standardized mean difference: 0.67; 95% CI = -1.27 to -0.07). This study finds a lack of evidence for the efficacy of propranolol on traumatic memory disruption, in PTSD patients, to recommend its routine clinical use. However, a high level of heterogeneity, variation in propranolol dosage and inadequate sample sizes mean that these findings require cautious interpretation.

Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation.

Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for treatment of PTSD. These drugs have limited efficacy as they only reduce symptoms related to depression and anxiety without producing permanent remission. PTSD remains a significant public health problem with high morbidity and mortality requiring major advances in therapeutics. Early evidence has emerged for the beneficial effects of psychedelics particularly in combination with psychotherapy for management of PTSD, including psilocybin, MDMA, LSD, cannabinoids, ayahuasca and ketamine. MDMA and psilocybin reduce barrier to therapy by increasing trust between therapist and patient, thus allowing for modification of trauma related memories. Furthermore, research into the memory reconsolidation mechanisms has allowed for identification of various pharmacological targets to disrupt abnormally persistent memories. A number of pre-clinical and clinical studies have investigated novel and re-purposed pharmacological agents to disrupt fear memory in PTSD. Novel therapeutic approaches like neuropeptide Y, oxytocin, cannabinoids and neuroactive steroids have also shown potential for PTSD treatment. Here, we focus on the role of fear memory in the pathophysiology of PTSD and propose that many of these new therapeutic strategies produce benefits through the effect on fear memory. Evaluation of recent research findings suggests that while a number of drugs have shown promising results in preclinical studies and pilot clinical trials, the evidence from large scale clinical trials would be needed for these drugs to be incorporated in clinical practice.