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.

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.

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.

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.

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.

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.

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.

Impulsivity as a multifactorial construct and its relationship to PTSD severity and threat sensitivity.

Changes to the DSM-5's conceptualization of posttraumatic stress disorder (PTSD) highlight the importance of impulsivity within the context of PTSD-related arousal dysregulation. While the relationship between PTSD and threat sensitivity is well defined, how they relate to impulsivity remains understudied. We examined the relationship between PTSD symptom severity, threat sensitivity, and impulsivity. 124 participants completed the PTSD Checklist (PCL-C) and the Barratt Impulsiveness Scale 11th ed (BIS-11). BIS-11 items were separated to define cognitive and behavioral impulsivity subdomains. A trauma-exposed subsample of 39 participants were also exposed to no, ambiguous, and high threat conditions in a threat-enhanced acoustic startle paradigm with psychophysiological response as the outcome variable. PTSD severity was significantly associated with greater overall impulsivity and behavioral impulsivity. Greater overall impulsivity and both cognitive and behavioral impulsivity subdomains were significantly associated with psychophysiological magnitudes across threat conditions in the traumatized subsample. Our results suggest PTSD severity may linked to behavioral impulsivity and both cognitive and behavioral impulsivity are associated with threat sensitivity and hyperarousal. Assessing impulsivity within the context of PTSD, particularly in terms of its cognitive and behavioral subdomains, may provide important, clinically relevant information.

Acute cognitive effects of the hypocretin receptor antagonist almorexant relative to zolpidem and placebo: a randomized clinical trial.

STUDY OBJECTIVES: Hypnotic medications can adversely affect behavior during unanticipated awakenings during the night. Animals treated with the hypocretin (Hcrt) receptor antagonist almorexant (ALM) have less acute cognitive impairment compared to the GABAA receptor modulator zolpidem (ZOL). This study aimed to determine whether ALM produces less acute cognitive impairment than ZOL in human subjects. METHODS: Healthy, young adult, unmedicated male and female subjects participated in a controlled trial of a single dose of ALM 100 mg (N = 48), ALM 200 mg (N = 53), ZOL 10 mg (N = 49), and placebo (PBO, N = 52). RESULTS: ZOL and both doses of ALM produced similar levels of subjective sleepiness and impaired the ability of subjects to remain awake in a dark, low-stimulus setting relative to PBO. For most cognitive measures, performance under ZOL was significantly worse than ALM or PBO. For tasks involving verbal memory or visual-motor coordination, ZOL impaired performance, whereas the two doses of ALM were no different than PBO. For tasks involving higher-order executive function, ZOL produced impairment in processing speed and inhibitory control, whereas the two doses of ALM were no different than PBO. Performance decrements for ALM were less than ZOL but greater than PBO for some reaction time measures. CONCLUSIONS: The data provide support for the hypothesis that Hcrt receptor antagonists produce less functional impairment than a benzodiazepine receptor agonist (BzRA). These observations are particularly relevant to patients treated with sedative-hypnotics who are at elevated risk for falls and other untoward events during the intended hours for sleep.

Validation of sleep measurement in a multisensor consumer grade wearable device in healthy young adults.

STUDY OBJECTIVES: Our objective was to examine the ability of a consumer-grade wearable device (Basis B1) with accelerometer and heart rate technology to assess sleep patterns compared with polysomnography (PSG) and research-grade actigraphy in healthy adults. METHODS: Eighteen adults underwent consecutive nights of sleep monitoring using Basis B1, actigraphy, and PSG; 40 nights were used in analyses. Discrepancies in gross sleep parameters and epoch-by-epoch agreements in sleep/wake classification were assessed. RESULTS: Basis B1 accuracy was 54.20 ± 8.20%, sensitivity was 98.90 ± 2.70%, and specificity was 8.10 ± 15.00%. Accuracy, sensitivity, and specificity for distinguishing between the different sleep stages were 60-72%, 48-62%, and 57-86%, respectively. Pearson correlations demonstrated strong associations between Basis B1 and PSG estimates of sleep onset latency and total sleep time; moderate associations for sleep efficiency, duration of light sleep, and duration of rapid eye movement sleep; and a weak association for duration of deep sleep. Basis B1 significantly overestimates total sleep time, sleep efficiency, and duration of light sleep and significantly underestimates wake after sleep onset and duration of deep sleep. CONCLUSIONS: Basis B1 demonstrated utility for estimates of gross sleep parameters and performed similarly to actigraphy for estimates of total sleep time. Basis B1 specificity was poor, and Basis B1 is not useful for the assessment of wake. Basis B1 accuracy for sleep stages was better than chance but is not a suitable replacement for PSG assessment. Despite low cost, ease of use, and attractiveness for patients, consumer devices are not yet accurate or reliable enough to guide treatment decision making in clinical settings.

Psychophysiological treatment outcomes: Corticotropin-releasing factor type 1 receptor antagonist increases inhibition of fear-potentiated startle in PTSD patients.

After exposure to a traumatic event, a subset of people develop post-traumatic stress disorder (PTSD). One of the key deficits in PTSD is regulation of fear, and impaired inhibition of fear-potentiated startle (FPS) has been identified as a potential physiological biomarker specific to PTSD. As part of a larger clinical trial, this study investigated the effects of a CRF receptor 1 antagonist, GSK561679, on inhibition of fear-potentiated startle during a conditional discrimination fear-conditioning paradigm, termed AX+/BX-. Prior research using this paradigm has demonstrated deficits in inhibition of conditioned fear in several PTSD populations. The randomized, double-blind, placebo-controlled clinical trial compared fear inhibition between female PTSD participants taking 350 mg/day GSK561679 (n = 47 pre- and 29 post-treatment) and patients taking a placebo pill (n = 52 pre- and 30 post-treatment) daily for 6 weeks. There was no significant difference between the two groups in their acquisition of fear or discrimination between threat and safety cues, and no pre-post-treatment effect on these measures. However, there was a significant effect of treatment on inhibition of FPS during the AB trials in the AX+/BX- transfer test (p < 0.05). While all PTSD participants showed typical impairments in fear inhibition prior to treatment, GSK561679 enhanced fear inhibition post-treatment, independent of clinical effects. The current study suggests that CRF receptor 1 antagonism may have specific effects within neural circuitry mediating fear inhibition responses, but not overall symptom presentation, in PTSD.

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.

Child abuse interacts with hippocampal and corpus callosum volume on psychophysiological response to startling auditory stimuli in a sample of veterans.

Child abuse (CA), which is linked to posttraumatic stress disorder (PTSD), has been associated with a reduction in both hippocampal and corpus callosum (CC) volume. However, few studies have explored these relationships on psychophysiological variables related to trauma exposure. Therefore, we assessed whether the interaction between CA and hippocampal and CC volume were associated with enhanced fear potentiated psychophysiological response patterns in a sample of Veterans. 147 Veteran participants who were part of a larger study of Gulf War Illness were exposed to startling sounds in no, ambiguous, and high threat conditions and also provided MRI data. The Clinician Administered PTSD Scale and Trauma History Questionnaire were used to measure PTSD and CA respectively. Psychophysiological response was measured by EMG, SCR, and heart rate. Repeated-measures mixed linear models were used to assess the significance of CA by neural structure interactions. CA interacted with both hippocampal and CC volume on psychophysiological response magnitudes, where participants with CA and smaller hippocampal volume had greater EMG (p < 0.01) and SCR (p < 0.05) magnitudes across trials and over threat conditions. Participants with CA and smaller CC volume had greater SCR magnitudes across trials and over threat conditions (p < 0.01). Hippocampal and genu volume mediated CA and psychophysiological response magnitude. CA may impact psychophysiological response via a reduction in hippocampal and CC volume. Volumetric reduction in these structures may indicate a neurofunctional, CA-related increase in threat sensitivity, which could portend increased PTSD susceptibility and adverse interpersonal and social consequences across the lifespan.

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.