White matter microstructure of the uncinate fasciculus is associated with subthreshold posttraumatic stress disorder symptoms and fear potentiated startle during early extinction in recently deployed Service Members.

Early intervention following combat deployment has the potential to prevent posttraumatic stress disorder (PTSD), but there is a need for greater understanding of the factors that contribute to PTSD symptom progression. This study investigated: (1) fear-potentiated startle during a fear extinction, (2) white matter microstructure, and (3) PTSD symptom severity, in 48 recently deployed service members (SMs) who did not have sufficient PTSD symptoms to meet criteria for a clinical diagnosis. Electromyography startle during a conditional discrimination paradigm, diffusion tensor imaging, and the Clinician Administered PTSD Scale were assessed in a cohort of SMs within 2 months after their return from Iraq or Afghanistan. Significant correlations were found between left uncinate fasciculus (UF) white matter tract integrity and total PTSD symptoms, r=-0.343, p=0.018; the left UF and hyperarousal symptoms, r=-0.29, p=0.047; right UF integrity and total PTSD symptoms r=-0.3371, p=0.01; right UF integrity and hyperarousal symptoms r=-0.332, p=0.023; left UF and startle during early extinction, r=.31, p=0.033. Our results indicate that compromise of UF tract frontal-limbic connections are associated with greater PTSD symptom severity and lower startle response during extinction. In a subthreshold population, such a relationship between brain structure, physiological reactivity, and behavioral expression may reveal vulnerabilities that could have significant implications for PTSD symptom development.

Predictors of Neurocognitive Syndromes in Combat Veterans.

Traumatic brain injury, depression and posttraumatic stress disorder (PTSD) are neurocognitive syndromes often associated with impairment of physical and mental health, as well as functional status. These syndromes are also frequent in military service members (SMs) after combat, although their presentation is often delayed until months after their return. The objective of this prospective cohort study was the identification of independent predictors of neurocognitive syndromes upon return from deployment could facilitate early intervention to prevent disability. We completed a comprehensive baseline assessment, followed by serial evaluations at three, six, and 12 months, to assess for new-onset PTSD, depression, or postconcussive syndrome (PCS) in order to identify baseline factors most strongly associated with subsequent neurocognitive syndromes. On serial follow-up, seven participants developed at least one neurocognitive syndrome: five with PTSD, one with depression and PTSD, and one with PCS. On univariate analysis, 60 items were associated with syndrome development at p < 0.15. Decision trees and ensemble tree multivariate models yielded four common independent predictors of PTSD: right superior longitudinal fasciculus tract volume on MRI; resting state connectivity between the right amygdala and left superior temporal gyrus (BA41/42) on functional MRI; and single nucleotide polymorphisms in the genes coding for myelin basic protein as well as brain-derived neurotrophic factor. Our findings require follow-up studies with greater sample size and suggest that neuroimaging and molecular biomarkers may help distinguish those at high risk for post-deployment neurocognitive syndromes.

Psychophysiological response to virtual reality and subthreshold posttraumatic stress disorder symptoms in recently deployed military.

OBJECTIVE: Subthreshold posttraumatic stress disorder (PTSD) has garnered recent attention because of the significant distress and functional impairment associated with the symptoms as well as the increased risk of progression to full PTSD. However, the clinical presentation of subthreshold PTSD can vary widely and therefore is not clearly defined, nor is there an evidence-based treatment approach. Thus, we aim to further the understanding of subthreshold PTSD symptoms by reporting the use of a virtual combat environment in eliciting distinctive psychophysiological responses associated with PTSD symptoms in a sample of subthreshold recently deployed US service members. METHODS: Heart rate, skin conductance, electromyography (startle), respiratory rate, and blood pressure were monitored during three unique combat-related virtual reality scenarios as a novel procedure to assess subthreshold symptoms in a sample of 78 service members. The Clinician-Administered PTSD Scale was administered, and linear regression analyses were used to investigate the relationship between symptom clusters and physiological variables. RESULTS: Among the range of psychophysiological measures that were studied, regression analysis revealed heart rate as most strongly associated with Clinician-Administered PTSD Scale-based measures hyperarousal (R = 0.11, p = .035,) reexperiencing (R = 0.24, p = .001), and global PTSD symptoms (R = 0.17, p = .003). CONCLUSIONS: Our findings support the use of a virtual reality environment in eliciting physiological responses associated with subthreshold PTSD symptoms.

Connecting combat-related mild traumatic brain injury with posttraumatic stress disorder symptoms through brain imaging.

Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) may share common symptom and neuropsychological profiles in military service members (SMs) following deployment; while a connection between the two conditions is plausible, the relationship between them has been difficult to discern. The intent of this report is to enhance our understanding of the relationship between findings on structural and functional brain imaging and symptoms of PTSD. Within a cohort of SMs who did not meet criteria for PTSD but were willing to complete a comprehensive assessment within 2 months of their return from combat deployment, we conducted a nested case-control analysis comparing those with combat-related mTBI to age/gender-matched controls with diffusion tensor imaging, resting state functional magnetic resonance imaging and a range of psychological measures. We report degraded white matter integrity in those with a history of combat mTBI, and a positive correlation between the white matter microstructure and default mode network (DMN) connectivity. Higher clinician-administered and self-reported subthreshold PTSD symptoms were reported in those with combat mTBI. Our findings offer a potential mechanism through which mTBI may alter brain function, and in turn, contribute to PTSD symptoms.

Heart rate response to fear conditioning and virtual reality in subthreshold PTSD.

Posttraumatic stress disorder (PTSD) is a significant health concern for U.S. military service members (SMs) returning from Afghanistan and Iraq. Early intervention to prevent chronic disability requires greater understanding of subthreshold PTSD symptoms, which are associated with impaired physical health, mental health, and risk for delayed onset PTSD. We report a comparison of physiologic responses for recently deployed SMs with high and low subthreshold PTSD symptoms, respectively, to a fear conditioning task and novel virtual reality paradigm (Virtual Iraq). The high symptom group demonstrated elevated heart rate (HR) response during fear conditioning. Virtual reality sequences evoked significant HR responses which predicted variance of the PTSD Checklist-Military Version self-report. Our results support the value of physiologic assessment during fear conditioning and combat-related virtual reality exposure as complementary tools in detecting subthreshold PTSD symptoms in Veterans.

Psychophysiologic identification of subthreshold PTSD in combat veterans.

Posttraumatic stress disorder (PTSD) is linked with adverse health outcomes, and many military service members (SMs) are afflicted with it after they return from combat. Since many SMs have an initial honeymoon period characterized by limited symptoms before the onset of full-blown PTSD, the identification of independent predictors of PTSD upon return from deployment could facilitate early intervention. We measured psychophysiologic responses to stimuli including explosions in a Virtual Iraq/Afghanistan environment, as well as a fear potentiated startle paradigm, in a prospective cohort of SMs who did not meet criteria for PTSD and were within 2 months after return from deployment. We report marked psychophysiologic differences between those with (n = 29) and without (n = 30) subthreshold PTSD symptoms (PTSD Checklist score ≥ 28 vs. < 28). We believe this is evidence that psychophysiologic measures can help to identify individuals at high risk for PTSD.

Randomized trial of a decision aid for BRCA1/BRCA2 mutation carriers: impact on measures of decision making and satisfaction.

OBJECTIVE: Genetic testing is increasingly part of routine clinical care for women with a family history of breast cancer. Given their substantially elevated risk for breast cancer, BRCA1/BRCA2 mutation carriers must make the difficult decision whether or not to opt for risk reducing mastectomy. To help BRCA1/2 carriers make this decision, the authors developed a computer-based interactive decision aid that was tested against usual care in a randomized controlled trial. DESIGN: After the completion of genetic counseling, 214 female (aged 21-75) BRCA1/BRCA2 mutation carriers were randomized to Usual Care (UC; N = 114) or Usual Care plus Decision Aid (DA; N = 100) arms. UC participants received no additional intervention. DA participants were sent the CD-ROM DA to view at home. MAIN OUTCOME MEASURES: The authors measured final management decision, decisional conflict, decisional satisfaction, and receipt of risk reducing mastectomy at 1-, 6-, and 12-months postrandomization. RESULTS: Longitudinal analyses revealed that the DA was effective among carriers who were initially undecided about how to manage their breast cancer risk. Within this group, the DA led to an increased likelihood of reaching a management decision (OR = 3.09, 95% CI = 1.62, 5.90; p < .001), decreased decisional conflict (B = -.46, z = -3.1, p <002), and increased satisfaction (B = .27, z = 3.1, p = .002) compared to UC. Among carriers who had already made a management decision by the time of randomization, the DA had no benefit relative to UC. CONCLUSION: These results demonstrate that BRCA1/BRCA2 mutation carriers who are having difficulty making a breast cancer risk management decision can benefit from adjunct decision support.