The Middle-Out Approach to reconceptualizing, assessing, and analyzing traumatic stress reactions.

Alternative models of traumatic stress and broader psychopathology have been proposed to address issues of heterogeneity, comorbidity, clinical utility, and equitable representation. However, systematic and practical methods and guidelines to organize and apply these models remain scarce. The Middle-Out Approach is a novel, integrative, contextually informed framework for organizing and applying existing empirical methods to evaluate current and alternative traumatic stress reactions. Rather than beginning to identify traumatic stress reactions from the top-down (i.e., disorder-first approach) or bottom-up (i.e., symptom-first approach), constructs are evaluated from the middle out (i.e., presentation-first approach), unconstrained by higher-order disorders or lower-order diagnostic symptoms. This approach provides innovation over previous methods at multiple levels, including the conceptualization of traumatic stress reactions as well as the type of assessments and data sources used and how they are used in statistical analyses. Conceptualizations prioritize the identification of middle-order phenotypes, representing person-centered clinical presentations, which are informed by the integration of multidimensional, transdiagnostic, and multimodal (e.g., psychosocial, physiological) assessments and/or data sources. Integrated data are then analyzed concurrently using person-centered statistical models to identify precise, discrete, and representative health outcomes within broader heterogeneous samples. Subsequent variable-centered analyses are then used to identify culturally sensitive and contextually informed correlates of phenotypes, their clinical utility, and the differential composition within and between broader traumatic stress reactions. Examples from the moral injury literature are used to illustrate practical applications that may increase clinical utility and the accurate representation of health outcomes for diverse individuals and communities.

Impact of hormonal contraceptives on sex differences in fear conditioning and fear extinction in PTSD.

Sex differences in the neurobiological mechanisms involved in fear conditioning and extinction have been suggested to contribute to differential vulnerability for the development of posttraumatic stress disorder (PTSD) in women compared with men. Reproductive hormones, such as estradiol, have been shown to facilitate fear conditioning and extinction learning and may explain some of these differences. However, the effect of commonly used hormonal contraceptives on the neurobiological mechanisms of fear conditioning and extinction is poorly understood. A laboratory study was conducted in trauma-exposed men and women with and without full or partial PTSD to examine effects of sex and use of hormonal birth control on fear conditioning, fear extinction learning, and extinction retention. Participants underwent fear conditioning with stimuli that were paired (CS+) or unpaired (CS-) with shock. Extinction learning occurred 72 h later, and extinction retention was tested 1 wk after extinction. Women on hormonal contraceptives (HCs) demonstrated enhanced acquisition of fear conditioning and enhanced extinction of fear as compared with women off hormonal birth control and men. While clinical implications have yet to be determined, these results suggest that hormonal contraceptives may facilitate learning during both fear acquisition and extinction. Understanding the impact of sex and hormones on fear conditioning and extinction processes may lead to new insights into the pathophysiology of PTSD and result in advancements in treatment that may vary by sex.

Comparing Heart Rate Analytical Methods to Examine Engagement During Imaginal Prolonged Exposure Therapy: Multicase Study.

OBJECTIVE: As mobile health technologies proliferate, their use during exposure-based therapies has the potential to illuminate treatment mechanisms. The primary purpose of this study was to examine three approaches to using continuously collected physiological data of patients with posttraumatic stress disorder during prolonged exposure (PE) therapy, in an effort to examine physiological markers of treatment response. METHODS: Photoplethysmogram-measured heart rates from three non-Hispanic White male veterans, during clinic-based PE therapy sessions, were analyzed to assess three potential therapeutic mechanisms: emotional engagement (examined via correlation analysis between self-reported peak distress ratings and objectively measured peak heart rate in the minute prior to distress ratings), initial emotion activation (examined through time to peak heart rate and peak self-reported distress), and extinction processes within and between therapy sessions (examined via multilevel modeling of within- and between-person changes in heart rate over time and across imaginal PE therapy sessions). RESULTS: Results for each analytical approach with each patient are presented, and benefits and limitations of each approach are discussed. Treatment outcomes were as follows: one participant with overengagement did not benefit from PE, one participant with initial underengagement demonstrated clinical improvement, and one participant with optimal engagement had associated clinical improvements. CONCLUSIONS: Mobile health technologies may provide a new avenue toward unveiling treatment mechanisms in psychotherapy. Use of standardized analytical approaches will enable cross-study comparison and greater understanding of treatment mechanisms, ultimately leading to increased treatment response.

Work by day and sleep by night, do not sleep too little or too much: Effects of sleep duration, time of day and circadian synchrony on flanker-task performance in internet brain-game users from teens to advanced age.

Research elucidating the effects of sleep and circadian rhythm on cognitive performance is advancing, yet many important questions remain. Using flanker-task performance scores from a large internet sample (N = 48,881) with repeated measures of cognitive performance and linked prior-night self-reported sleep duration, we analysed the relationship between sleep duration, time of day of task performance, and chronotype synchrony with performance in participants aged 15-80 years. Results indicate a performance peak at 7 hr habitual sleep duration, and point to a variable effect of deviation from habitual sleep duration depending on users' habitual sleep duration and age. Time-of-day effects were notable for a steady decline in performance up until 01:00 hours-02:00 hours for the group as a whole, which was accounted for by nighttime deterioration on trials requiring inhibitory executive functioning, particularly in older subjects. Analyses did not demonstrate an advantage for playing in synchrony with self-identified chronotype. Results strengthen findings indicating an inverted U-shaped relationship between sleep duration and cognitive performance across a broad spectrum of age groups. These findings underscore the importance of daytime task performance for tasks requiring inhibitory function, especially in elderly people. Findings highlight the utility of large-scale internet data in contributing to sleep and circadian science.

Gender Differences in Threat Biases: Trauma Type Matters in Posttraumatic Stress Disorder.

Women are diagnosed with posttraumatic stress disorder (PTSD) at twice the rate of men. This gender difference may be related to differences in PTSD experiences (e.g., more hypervigilance in women) or types of trauma experienced (e.g., interpersonal trauma). We examined whether attentional threat biases were associated with gender, PTSD diagnosis, and/or trauma type. Participants were 70 civilians and veterans (38 women, 32 men; 41 with PTSD, 29 without PTSD) assessed with the Clinician Administered PTSD Scale for DSM-IV who completed a facial dot-probe attention bias task and self-report measures of psychiatric symptoms and trauma history. Factorial ANOVA and regression models examined associations between gender, PTSD diagnosis, index trauma type, lifetime traumatic experiences, and attentional threat biases. Results revealed that compared to women without PTSD and men both with and without PTSD, women with PTSD demonstrated attentional biases toward threatening facial expressions, d = 1.19, particularly fearful expressions, d = 0.74. Psychiatric symptoms or early/lifetime trauma did not account for these attentional biases. Biases were related to interpersonal assault index traumas, ηp 2 = .13, especially sexual assault, d = 1.19. Trauma type may be an important factor in the development of attentional threat biases, which theoretically interfere with trauma recovery. Women may be more likely to demonstrate attentional threat biases due to higher likelihood of interpersonal trauma victimization rather than due to gender-specific psychobiological pathways. Future research is necessary to clarify if sexual assault alone or in combination with gender puts individuals at higher risk of developing PTSD.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Diferencias de género en los sesgos de amenaza: el tipo de trauma es importante en TEPT INFLUENCIA DE GÉNERO Y TIPO DE TRAUMA EN SESGOS DE AMENAZA Las mujeres diagnosticadas con trastorno de estrés postraumático (TEPT) duplican la tasa de los hombres. Esta la diferencia de género puede estar relacionada con diferencias en las experiencias de TEPT (por ejemplo, más hipervigilancia en mujeres) o tipos de trauma experimentados (por ejemplo, trauma interpersonal). Examinamos si los sesgos atencionales de la amenaza se asociaron con el género, el diagnóstico de TEPT y/o el tipo de trauma. Los participantes fueron 70 civiles y veteranos (38 mujeres, 32 hombres; 41 con TEPT, 29 sin TEPT) evaluados con la Escala de TEPT Administrada por el Médico para DSM-IV que se completó con una tarea de sesgo atencional con puntos faciales y medidas autoinformadas de síntomas psiquiátricos e historia de trauma. Por medio de una ANOVA factorial y modelos de regresión se examinaron las asociaciones entre género, diagnóstico de TEPT, tipo de trauma índice, experiencias traumáticas a lo largo de la vida y sesgos atencionales de la amenaza. Los resultados revelaron que, en comparación con las mujeres sin TEPT y los hombres con y sin TEPT, las mujeres con TEPT mostraron sesgos atencionales hacia expresiones faciales amenazantes, d = 1.19, especialmente expresiones de miedo, d = 0.74. Los síntomas psiquiátricos o experiencias tempranas de trauma en la vida no explicaron estos sesgos atencionales. Los sesgos se relacionaron con el índice de traumas por asalto interpersonal, ηp 2 = .13, especialmente agresión sexual, d = 1.19. El tipo de trauma puede ser un factor importante en el desarrollo de sesgos atencionales de la amenaza, que teóricamente interfieren con la recuperación del trauma. Las mujeres pueden ser más propensas a demostrar sesgos atencionales de las amenazas debido a una mayor probabilidad de victimización por trauma interpersonal más que debido a vías psicobiológicas específicas del género. La investigación futura es necesaria para aclarar si la agresión sexual sola o en combinación con el género pone a las personas en mayor riesgo de desarrollar TEPT.

Subjective Sleep Related to Post Traumatic Stress Disorder Symptoms among Trauma-Exposed Men and Women.

Objective/Background: Sleep difficulty is both a common symptom of posttraumatic stress disorder (PTSD) and a risk factor for the development and maintenance of PTSD symptomatology. Gender differences in sleep following trauma exposure have been posited to contribute to the increased risk for the development of PTSD among women, but the persistence and long-term contributions of these potential differences to the maintenance and severity of PTSD symptoms is unclear. Participants: Men and women reporting a history of trauma exposure (n = 112, 63% female) participated in this study. Methods: Subjective sleep complaints and PTSD symptom severity were assessed using well-validated measures (Pittsburgh Sleep Quality Index, PTSD Symptom Checklist). Multivariable regression models (full sample and gender-stratified) were used to predict PTSD symptom severity from global, subscale, and individual item sleep parameters, adjusted for gender, age, race/ethnicity, education, and body mass index. Results: In the full sample, traditional measures of sleep quality and sleep disturbance were associated with PTSD symptom severity. Difficulty falling asleep, poor sleep quality, and sleep disturbance from a variety of sources were related to higher PTSD symptom severity in men, while self-reported sleep disturbance related to nightmares and emotional regulation were associated with PTSD symptom severity among women. Conclusions: These findings add to the limited literature on gender-specific risk factors related to sleep and PTSD, and may inform intervention development and implementation related to PTSD severity among vulnerable adults.

Association among anterior cingulate cortex volume, psychophysiological response, and PTSD diagnosis in a Veteran sample.

Posttraumatic stress disorder (PTSD) is associated with fear response system dysregulation. Research has shown that the anterior cingulate cortex (ACC) may modulate the fear response and that individuals with PTSD have abnormalities in ACC structure and functioning. Our objective was to assess whether ACC volume moderates the relationship between PTSD and fear-potentiated psychophysiological response in a sample of Gulf War Veterans. 142 Veteran participants who were associated with a larger study associated with Gulf War Illness were exposed to no threat, ambiguous threat, and high threat conditions in a fear conditioned startle response paradigm and also provided MRI imaging data. PTSD was assessed using the Clinician Administered PTSD Scale (CAPS). Decreased caudal ACC volume predicted greater psychophysiological responses with a slower habituation of psychophysiological magnitudes across trials (p < 0.001). PTSD diagnosis interacted significantly with both caudal and rostral ACC volumes on psychophysiological response magnitudes, where participants with PTSD and smaller rostral and caudal ACC volumes had greater psychophysiological magnitudes across trials (p < 0.05 and p < 0.001, respectively) and threat conditions (p < 0.05 and p < 0.005). Our results suggest that ACC volume may moderate both threat sensitivity and threat response via impaired habituation in individuals who have been exposed to traumatic events. More research is needed to assess whether ACC size and these associated response patterns are due to neurological processes resulting from trauma exposure or if they are indicative of a premorbid risk for PTSD subsequent to trauma exposure.

Gender Differences in Cardiovascular Risk Related to Diabetes and Posttraumatic Stress Disorder.

OBJECTIVES: To examine relationships between posttraumatic stress disorder (PTSD), diabetes, and cardiovascular disease (CVD) among older men and women. METHODS: In a national retrospective cohort study of Veterans aged ≥55 (n=2,789,264, 6% female), associations between PTSD and diabetes (2008-2011) and incident CVD (2012-2015) were assessed with gender-stratified Fine-Gray proportional hazard models, adjusted for demographics and medical comorbidities. RESULTS: Incident CVD was observed in 22% of men and 12% of women, and related to PTSD (men HR=1.05, 95% CI=1.04-1.06, Wald χ2=80.46, df=1, p<.001; women HR=1.47, 95% CI=1.38-1.57, Wald χ2=148.60, df=1, p<.001), diabetes (men HR=1.34, 95% CI=1.34-1.35, Wald χ2=9177.64, df=1, p<.001; women HR=1.49, 95% CI=1.44-1.55, Wald χ2=419.02, df=1, p<.001), and comorbid PTSD-diabetes (men HR=1.50, 95% CI=1.48-1.52, Wald χ2=4180.92, df=1, p<.001; women HR=1.96, 95% CI=1.80-2.12, Wald χ2=257.28, df=1, p<.001). CONCLUSIONS: CVD risk was increased with PTSD and diabetes, and strongly increased with comorbid PTSD-diabetes. Among women, PTSD and diabetes conferred equivalent CVD risk.

Effects of Threat Context, Trauma History, and Posttraumatic Stress Disorder Status on Physiological Startle Reactivity in Gulf War Veterans.

In the current study, we explored exaggerated physiological startle responses in posttraumatic stress disorder (PTSD) and examined startle reactivity as a biomarker of PTSD in a large veteran sample. We assessed heart rate (HR), skin conductance (SC), and electromyographic (EMG) startle responses to acoustic stimuli under low-, ambiguous-, and high-threat conditions in Gulf War veterans with current (n = 48), past (n = 42), and no history of PTSD (control group; n = 152). We evaluated PTSD status using the Clinician-Administered PTSD Scale and trauma exposure using the Trauma History Questionnaire. Participants with current PTSD had higher HR, ds = 0.28-0.53; SC, d = 0.37; and startle responses than those with past or no history of PTSD. The HR startle response under ambiguous threat best differentiated current PTSD; however, sensitivity and specificity analyses revealed it to be an imprecise indicator of PTSD status, ROC AUC = .66. Participants with high levels of trauma exposure only showed elevated HR and SC startle reactivity if they had current PTSD. Results indicate that startle is particularly elevated in PTSD when safety signals are available but a possibility of danger remains and when trauma exposure is high. However, startle reactivity alone is unlikely to be a sufficient biomarker of PTSD.

Metabolic risk factors and posttraumatic stress disorder: the role of sleep in young, healthy adults.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with indicators of poor physical health and sleep disturbance. This study investigated the relationship between PTSD and metabolic risk factors and examined the role of sleep duration in medically healthy and medication-free adults. METHODS: Participants with PTSD (n = 44, mean age = 30.6 years) and control participants free of lifetime psychiatric history (n = 50, mean age = 30.3 years) recorded sleep using sleep diary for 10 nights and actigraphy for 7 nights. We assessed metabolic risk factors including fasting triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol, as well as abdominal fat using dual-energy x-ray absorptiometry. RESULTS: PTSD was associated with shorter sleep duration (based on self-report, not actigraphy) and higher metabolic risks (controlling for body fat percentage), including increased triglycerides (p = .03), total cholesterol (p < .001), LDL cholesterol (p = .006), very low density lipoprotein cholesterol (p = .002), and cholesterol/high-density lipoprotein ratio (p = .024). In addition, sleep duration was associated with metabolic risks in PTSD (significant correlations ranged from r = -0.20 to r = -0.40) but did not fully account for the association between PTSD and metabolic measures. CONCLUSIONS: Metabolic risk factors are associated with PTSD even in early adulthood, which highlights the need for early intervention. Future longitudinal research should assess whether sleep disturbance in PTSD is a mechanism that contributes to heightened metabolic risk to elucidate the pathway from PTSD to higher rates of medical disorders such as obesity, diabetes, and heart disease.

An exploratory study on lipidomic profiles in a cohort of individuals with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) can develop after trauma exposure. Some studies report that women develop PTSD at twice the rate of men, despite greater trauma exposure in men. Lipids and their metabolites (lipidome) regulate a myriad of key biological processes and pathways such as membrane integrity, oxidative stress, and neuroinflammation in the brain by maintaining neuronal connectivity and homeostasis. In this study, we analyzed the lipidome of 40 adults with PTSD and 40 trauma-exposed non-PTSD individuals (n = 20/sex/condition; 19-39 years old). Plasma samples were analyzed for lipidomics using Quadrupole Time-of-Flight (QToF) mass spectrometry. Additionally, ~ 90 measures were collected, on sleep, and mental and physical health indices. Poorer sleep quality was associated with greater PTSD severity in both sexes. The lipidomics analysis identified a total of 348 quantifiable known lipid metabolites and 1951 lipid metabolites that are yet unknown; known metabolites were part of 13 lipid subclasses. After adjusting for BMI and sleep quality, in women with PTSD, only one lipid subclass, phosphatidylethanolamine (PE) was altered, whereas, in men with PTSD, 9 out of 13 subclasses were altered compared to non-PTSD women and men, respectively. Severe PTSD was associated with 22% and 5% of altered lipid metabolites in men and women, respectively. Of the changed metabolites, only 0.5% measures (2 PEs and cholesterol) were common between women and men with PTSD. Several sphingomyelins, PEs, ceramides, and triglycerides were increased in men with severe PTSD. The correlations between triglycerides and ceramide metabolites with cholesterol metabolites and systolic blood pressure were dependent upon sex and PTSD status. Alterations in triglycerides and ceramides are linked with cardiac health and metabolic function in humans. Thus, disturbed sleep and higher body mass may have contributed to changes in the lipidome found in PTSD.

The lipidome of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) can develop after trauma exposure. Some studies report that women develop PTSD at twice the rate of men, despite greater trauma exposure in men. Lipids and their metabolites (lipidome) regulate a myriad of key biological processes and pathways such as membrane integrity, oxidative stress, and neuroinflammation in the brain by maintaining neuronal connectivity and homeostasis. In this study, we analyzed the lipidome of 40 individuals with PTSD and 40 trauma-exposed non-PTSD individuals. Plasma samples were analyzed for lipidomics using Quadrupole Time-of-Flight (QToF) mass spectrometry. Additionally, ~ 90 measures were collected, on sleep, mental and physical health indices. Sleep quality worsened as PTSD severity increased in both sexes. The lipidomics analysis identified a total of 348 quantifiable known lipid metabolites and 1951 lipid metabolites that are yet unknown; known metabolites were part of 13 classes of lipids. After adjusting for sleep quality, in women with PTSD, only one lipid subclass, phosphatidylethanolamine (PE) was altered, whereas, in men with PTSD, 9 out of 13 subclasses were altered compared to non-PTSD women and men, respectively. Severe PTSD was associated with 22% and 5% of altered lipid metabolites in men and women, respectively. Of the changed metabolites, only 0.5% measures (2 PEs and cholesterol) were common between women and men with PTSD. Several sphingomyelins, PEs, ceramides, and triglycerides were increased in men with severe PTSD. The triglycerides and ceramide metabolites that were most highly increased were correlated with cholesterol metabolites and systolic blood pressure in men but not always in women with PTSD. Alterations in triglycerides and ceramides are linked with cardiac health and metabolic function in humans. Thus, disturbed sleep and higher weight may have contributed to changes in the lipidome found in PTSD.

Tumor Suppressor MicroRNAs in Clinical and Preclinical Trials for Neurological Disorders.

Cancers and neurological disorders are two major types of diseases in humans. We developed the concept called the "Aberrant Cell Cycle Disease (ACCD)" due to the accumulating evidence that shows that two different diseases share the common mechanism of aberrant cell cycle re-entry. The aberrant cell cycle re-entry is manifested as kinase/oncoprotein activation and tumor suppressor (TS) inactivation, which are associated with both tumor growth in cancers and neuronal death in neurological disorders. Therefore, some cancer therapies (e.g., kinase/oncogene inhibition and TS elevation) can be leveraged for neurological treatments. MicroRNA (miR/miRNA) provides a new style of drug-target binding. For example, a single tumor suppressor miRNA (TS-miR/miRNA) can bind to and decrease tens of target kinases/oncogenes, producing much more robust efficacy to block cell cycle re-entry than inhibiting a single kinase/oncogene. In this review, we summarize the miRNAs that are altered in both cancers and neurological disorders, with an emphasis on miRNA drugs that have entered into clinical trials for neurological treatment.

Sex differences in objective measures of sleep in post-traumatic stress disorder and healthy control subjects.

A growing literature shows prominent sex effects for risk for post-traumatic stress disorder and associated medical comorbid burden. Previous research indicates that post-traumatic stress disorder is associated with reduced slow wave sleep, which may have implications for overall health, and abnormalities in rapid eye movement sleep, which have been implicated in specific post-traumatic stress disorder symptoms, but most research has been conducted in male subjects. We therefore sought to compare objective measures of sleep in male and female post-traumatic stress disorder subjects with age- and sex-matched control subjects. We used a cross-sectional, 2 × 2 design (post-traumatic stress disorder/control × female/male) involving83 medically healthy, non-medicated adults aged 19-39 years in the inpatient sleep laboratory. Visual electroencephalographic analysis demonstrated that post-traumatic stress disorder was associated with lower slow wave sleep duration (F(3,82)  = 7.63, P = 0.007) and slow wave sleep percentage (F(3,82)  = 6.11, P = 0.016). There was also a group × sex interaction effect for rapid eye movement sleep duration (F(3,82)  = 4.08, P = 0.047) and rapid eye movement sleep percentage (F(3,82)  = 4.30, P = 0.041), explained by greater rapid eye movement sleep in post-traumatic stress disorder females compared to control females, a difference not seen in male subjects. Quantitative electroencephalography analysis demonstrated that post-traumatic stress disorder was associated with lower energy in the delta spectrum (F(3,82)  = 6.79, P = 0.011) in non-rapid eye movement sleep. Slow wave sleep and delta findings were more pronounced in males. Removal of post-traumatic stress disorder subjects with comorbid major depressive disorder, who had greater post-traumatic stress disorder severity, strengthened delta effects but reduced rapid eye movement effects to non-significance. These findings support previous evidence that post-traumatic stress disorder is associated with impairment in the homeostatic function of sleep, especially in men with the disorder. These findings suggest that group × sex interaction effects on rapid eye movement may occur with more severe post-traumatic stress disorder or with post-traumatic stress disorder comorbid with major depressive disorder.

Lifetime history of interpersonal partner violence is associated with insomnia among midlife women veterans.

OBJECTIVE: Over a third of women in the United States report a lifetime history of intimate partner violence. Although a recent review found that intimate partner violence is related to poor subjective sleep, the majority of studies involved reproductive-aged women and used suboptimal measures of interpersonal violence and/or insomnia. We examined the relationship between lifetime intimate partner violence and current clinical insomnia in a cross-sectional sample of midlife women veterans. METHODS: Cross-sectional data were drawn from the Midlife Women Veterans Health Survey. Women Veterans (N = 232) aged 45 to 64 years enrolled in Department of Veterans Affairs health care in Northern California completed an adapted version of the Extended-Hurt, Insult, Threaten, Scream to assess lifetime history of intimate partner violence (screening threshold score and any physical, sexual, and psychological intimate partner violence) and the Insomnia Severity Index to assess current insomnia. RESULTS: In multivariable analyses, lifetime history of intimate partner violence was associated with twofold to fourfold odds of current clinical insomnia, including overall intimate partner violence (odds ratio, 3.24; 95% confidence interval, 1.57-6.69), physical intimate partner violence (odds ratio, 2.01; 95% confidence interval, 1.09-3.70), psychological intimate partner violence (odds ratio, 3.98; 95% confidence interval, 2.06-7.71), and sexual intimate partner violence (odds ratio, 2.09; 95% confidence interval, 1.08-4.07). CONCLUSIONS: Lifetime history of intimate partner violence is common and may be associated with clinical insomnia during midlife. Findings highlight the importance of screening midlife women for intimate partner violence and recognizing the potential role of this traumatic exposure on women's health.

Veterans Health Administration Screening for Military Sexual Trauma May Not Capture Over Half of Cases Among Midlife Women Veterans.

BACKGROUND: Approximately 1 in 3 women veterans endorse military sexual trauma (MST) during Veterans Health Administration (VHA) screening. Higher rates have been reported in anonymous surveys. OBJECTIVE: We compared MST identified by VHA screening to survey-reported MST within the same sample and identified participant characteristics associated with discordant responses. METHODS: Cross-sectional data were drawn from an observational study of women veterans aged 45-64 enrolled in VHA care in Northern California, with data from mail- and web-based surveys linked to VHA electronic health records (EHRs). Between March 2019 and May 2020, participants reported sociodemographic characteristics, current depressive (Patient Health Questionnaire-9) and posttraumatic stress (PTSD checklist for DSM-5) symptoms, and MST (using standard VHA screening questions) in a survey; depression and posttraumatic stress disorder diagnoses (ICD-10 codes) and documented MST were identified from EHRs. Associations between sociodemographic characteristics, mental health symptoms and diagnoses, and discordant MST reports (EHR-documented MST vs. MST reported on survey, not in EHR) were examined with multivariable logistic regression. RESULTS: In this sample of midlife women veterans (n = 202; mean age 56, SD = 5), 40% had EHR-documented MST, and 74% reported MST on the survey. Sociodemographic characteristics, mental health symptoms, and diagnosed depression were not associated with discordant MST responses. Women with an EHR-documented PTSD diagnosis had fivefold higher odds of having EHR-documented MST (vs. survey only; odds ratio 5.2; 95% confidence interval 2.3-11.9). CONCLUSIONS: VHA screening may not capture more than half of women who reported MST on the survey. VHA screening may underestimate true rates of MST, which could lead to a gap in recognition and care for women veterans.

The relationship of fear-potentiated startle and polysomnography-measured sleep in trauma-exposed men and women with and without PTSD: testing REM sleep effects and exploring the roles of an integrative measure of sleep, PTSD symptoms, and biological sex.

STUDY OBJECTIVES: Published research indicates that sleep is involved in emotional information processing. Using a fear-potentiated startle (FPS) and nap sleep protocol, we examined the relationship of emotional learning with REM sleep (REMS) in trauma-exposed participants. We also explored the roles of posttraumatic stress disorder (PTSD) symptoms, biological sex, and an integrative measure of polysomnography-measured (PSG) sleep in the learning-sleep relationship. METHODS: After an adaptation nap, participants (N = 46) completed two more visits (counterbalanced): a stress-condition visit, which included FPS conditioning procedures prior to a nap and assessment of learning retention and fear extinction training after the nap, and a control visit, which included a nap opportunity without stressful procedures. FPS conditioning included a "fear" visual stimulus paired with an air blast to the neck and a "safety" visual stimulus never paired with an air blast. Retention and extinction involved presentation of the visual stimuli without the air blast. Primary analyses examined the relationship between FPS responses pre- and post-sleep with stress-condition REMS duration, controlling for control-nap REMS duration. RESULTS: Higher safety learning predicted increased REMS and increased REMS predicted more rapid extinction learning. Similar relationships were observed with an integrative PSG sleep measure. They also showed unexpected effects of PTSD symptoms on learning and showed biological sex effects on learning-sleep relationships. CONCLUSIONS: Findings support evidence of a relationship between adaptive emotional learning and REMS. They underscore the importance of examining sex effects in sleep-learning relationships. They introduce an integrative PSG sleep measure with potential relevance to studies of sleep and subjective and biological outcomes.

Randomized controlled experimental study of hydrocortisone and D-cycloserine effects on fear extinction in PTSD.

Fear extinction underlies prolonged exposure, one of the most well-studied treatments for posttraumatic stress disorder (PTSD). There has been increased interest in exploring pharmacological agents to enhance fear extinction learning in humans and their potential as adjuncts to PE. The objective of such adjuncts is to augment the clinical impact of PE on the durability and magnitude of symptom reduction. In this study, we examined whether hydrocortisone (HC), a corticosteroid, and D-Cycloserine (DCS), an N-methyl-D-aspartate receptor partial agonist, enhance fear extinction learning and consolidation in individuals with PTSD. In a double-blind placebo-controlled 3-group experimental design, 90 individuals with full or subsyndromal PTSD underwent fear conditioning with stimuli that were paired (CS+) or unpaired (CS-) with shock. Extinction learning occurred 72 h later and extinction retention was tested one week after extinction. HC 25 mg, DCS 50 mg or placebo was administered one hour prior to extinction learning. During extinction learning, the DCS and HC groups showed a reduced differential CS+/CS- skin conductance response (SCR) compared to placebo (b = -0.19, CI = -0.01 to -37, p = 0.042 and b = -0.25, CI = -08 to -0.43, p = 0.005, respectively). A nonsignificant trend for a lower differential CS+/CS- SCR in the DCS group, compared to placebo, (b = -0.25, CI = 0.04 to -0.55, p = 0.089) was observed at retention testing, one week later. A single dose of HC and DCS facilitated fear extinction learning in participants with PTSD symptoms. While clinical implications have yet to be determined, our findings suggest that glucocorticoids and NMDA agonists hold promise for facilitating extinction learning in PTSD.

Protective factors for posttraumatic stress disorder symptoms in a prospective study of police officers.

Although police officers are frequently exposed to potentially traumatic incidents, only a minority will develop chronic posttraumatic stress disorder (PTSD). Identifying and understanding protective factors could inform the development of preventive interventions; however, few studies have examined this. In the present prospective study, 233 police officers were assessed during academy training and again following 2 years of police service. Caucasian race, less previous trauma exposure, and less critical incident exposure during police service as well as greater sense of self-worth, beliefs of greater benevolence of the world, greater social support and better social adjustment, all assessed during academy training, were associated with lower PTSD symptoms after 2 years of service. Positive personality attributes assessed during training with the NEO Five-Factor Personality Inventory were not associated with lower PTSD symptoms. In a hierarchical linear regression model, only Caucasian race, lower critical incident exposure during police service, greater assumptions of benevolence of the world and better social adjustment during training remained predictive of lower PTSD symptoms after 2 years of police service. These results suggest that positive world assumptions and better social functioning during training may protect police officers from critical incident related PTSD.

Ventromedial and insular cortical volume moderates the relationship between BDNF Val66Met and threat sensitivity.

While the BDNF Val66Met polymorphism has been linked to various trauma and anxiety - related psychiatric disorders, limited focus has been on the neural structures that might modulate its relationship with objective measures of threat sensitivity. Therefore, we assessed whether there was an interaction of Val66Met polymorphism with brain area volumes previously associated with anxiety and PTSD, such as the ventromedial prefrontal cortex (vmPFC), insular cortex (IC), and dorsal and ventral anterior cingulate cortices (dACC and vACC), in predicting fear-potentiated psychophysiological response in a clinical sample of Veterans. 110 participants engaged in a fear-potentiated acoustic startle paradigm and provided genetic and imaging data. Fear conditions included no, ambiguous, and high threat conditions (shock). Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate (HR). PTSD status, trauma history, and demographics were also assessed. There was an interaction of Met allele carrier status with vmPFC, IC, dACC, and vACC volumes for predicting SCR (p < 0.001 for all regions). However, only vmPFC and IC significantly moderated the relationship between Val66Met and psychophysiological response (SCR). The Val66met polymorphism may increase susceptibility to PTSD and anxiety disorders via an interaction with reduced vmPFC and IC volume. Future research should examine whether these relationships might be associated with a differential course of illness longitudinally or response to treatments.