Sleep Spindles Favor Emotion Regulation Over Memory Consolidation of Stressors in Posttraumatic Stress Disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a trauma-induced condition, characterized by intrusive memories and trauma-associated anxiety. Non-rapid eye movement (NREM) sleep spindles might play a crucial role in learning and consolidating declarative stressor information. However, sleep and possibly sleep spindles are also known to regulate anxiety, suggestive of a dual role for sleep spindles in the processing of stressors. Specifically, in individuals with high PTSD symptom burden, spindles might fail to regulate anxiety levels after exposure and instead might maladaptively consolidate stressor information. METHODS: To disentangle the role of spindles in declarative memory versus anxiety regulation after stressor exposure and to examine the role of PTSD in these processes, we measured nap sleep after a cohort of 45 trauma-exposed participants were exposed to laboratory stress. Participants (high vs. low PTSD symptoms) completed 2 visits: a stress visit involving exposure to negatively valent images before nap and a control visit. In both visits, sleep was monitored via electroencephalography. A stressor recall session occurred after the nap in the stress visit. RESULTS: Stage 2 NREM (NREM2) spindle rates were higher in stress versus control sleep, indicative of stress-induced changes in spindles. In participants with high PTSD symptoms, NREM2 spindle rates in stress sleep predicted poorer recall accuracy of stressor images relative to participants with low PTSD symptoms, while correlating with greater reduction in stressor-induced anxiety levels after sleep. CONCLUSIONS: Contrary to our expectations, although spindles are known to play a role in declarative memory processes, our findings highlight an important role for spindles in sleep-dependent anxiety regulation in PTSD.

The sleep physiology of nightmares in veterans with psychological trauma: Evaluation of a dominant model using participant-applied electroencephalography in the home environment.

Nightmares are a core feature of posttraumatic stress disorder, are poorly understood, and are associated with serious negative outcomes. Their biology has been difficult to study, and the feasibility of capturing them in the naturalistic home environment has been poor. This said, the published research and dominant scientific model has focused on nightmares as a manifestation of noradrenergic hyperarousal during rapid eye movement sleep. The current study used at-home, participant-applied devices to measure nightmare physiology in posttraumatic stress disorder treatment-seeking veterans, by examining heartrate measures as indicators of noradrenergic tone, and sleep-stage characteristics and stability in the sleep preceding time-stamped nightmare awakenings. Our data indicate the high feasibility of participant-administered, at-home measurement, and showed an unexpected stability of -rapid eye movement sleep along with no evidence of heartrate elevations in sleep preceding nightmare awakenings. Altogether, these data highlight new opportunities for the study of nightmares while questioning the sufficiency of dominant models, which to date are largely theoretically based.

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.

Brief behavioral treatment for insomnia decreases trauma-related nightmare frequency in veterans.

STUDY OBJECTIVES: Trauma-related nightmares are highly prevalent among veterans and are associated with higher-severity insomnia and posttraumatic stress disorder. Cognitive behavioral therapy for insomnia (typically 6-8 sessions) has been shown to reduce trauma-related nightmares. Brief behavioral treatment for insomnia (BBTI, 4 sessions) has been found to be comparable to CBT-I in decreasing insomnia severity; however, the effects of BBTI on nightmares have not been investigated. The current study tested the effects of BBTI on both trauma-related nightmares and nontrauma-related bad dreams using an active control group treated using progressive muscle relaxation therapy. In addition, we tested whether baseline trauma-related nightmare frequency and baseline nontrauma-related bad dream frequency moderated changes in insomnia severity. METHODS: Participants were 91 military veterans with insomnia disorder randomized to BBTI or progressive muscle relaxation therapy. Participants reported insomnia severity on the Insomnia Severity Index and reported trauma-related nightmare frequency and nontrauma-related bad dream frequency on the Pittsburgh Sleep Quality Index-PTSD Addendum. RESULTS: We found that BBTI significantly reduced trauma-related nightmares from baseline to posttreatment, whereas progressive muscle relaxation therapy did not. However, reductions in trauma-related nightmares were not maintained at the 6-month follow up. Neither BBTI nor progressive muscle relaxation therapy reduced nontrauma-related bad dreams from baseline to posttreatment. We also found that neither baseline trauma-related nightmare frequency nor baseline nontrauma-related bad dream frequency moderated changes in insomnia symptom severity. CONCLUSIONS: Findings from the current study suggest that BBTI may help reduce trauma-related nightmares. Further research is needed to better understand the potential mechanisms underlying how improved sleep may reduce trauma-related nightmares. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Brief Behavioral Insomnia Treatment Study (BBTI); URL: https://clinicaltrials.gov/ct2/show/NCT02571452; Identifier: NCT02571452. CITATION: Ranney RM, Gloria R, Metzler TJ, Huggins J, Neylan TC, Maguen S. Brief behavioral treatment for insomnia decreases trauma-related nightmare frequency in veterans. J Clin Sleep Med. 2022:18(7):1831-1839.

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.

Cognitive behavioral therapy for insomnia in veterans with gulf war illness: Results from a randomized controlled trial.

AIMS: To examine whether cognitive behavioral therapy for insomnia (CBT-I), delivered by telephone, improves sleep and non-sleep symptoms of Gulf War Illness (GWI). MAIN METHODS: Eighty-five Gulf War veterans (21 women, mean age: 54 years, range 46-72 years) who met the Kansas GWI case definition, the Centers for Disease Control and Prevention (CDC) case definition for Chronic Multisymptom Illness (CMI), and research diagnostic criteria for insomnia disorder were randomly assigned to CBT-I or monitor-only wait list control. Eight weekly sessions of individual CBT-I were administered via telephone by Ph.D. level psychologists to study participants. Outcome measures included pre-, mid-, and post-treatment assessments of GWI and insomnia symptoms, subjective sleep quality, and continuous sleep monitoring with diary. Outcomes were re-assessed 6-months post-treatment in participants randomized to CBT-I. KEY FINDINGS: Compared to wait list, CBT-I produced significant improvements in overall GWI symptom severity, individual measures of fatigue, cognitive dysfunction, depression and anxiety, insomnia severity, subjective sleep quality, and sleep diary outcome measures. The beneficial effects of CBT-I on overall GWI symptom severity and most individual GWI symptom measures were maintained 6-months after treatment. SIGNIFICANCE: GWI symptoms have historically been difficult to treat. Because CBT-I, which is associated with low stigma and is increasingly readily available to veterans, improved both sleep and non-sleep symptoms of GWI, these results suggest that a comprehensive approach to the treatment of GWI should include behavioral sleep interventions.

Classification and Prediction of Post-Trauma Outcomes Related to PTSD Using Circadian Rhythm Changes Measured via Wrist-Worn Research Watch in a Large Longitudinal Cohort.

Post-Traumatic Stress Disorder (PTSD) is a psychiatric condition resulting from threatening or horrifying events. We hypothesized that circadian rhythm changes, measured by a wrist-worn research watch are predictive of post-trauma outcomes. APPROACH: 1618 post-trauma patients were enrolled after admission to emergency departments (ED). Three standardized questionnaires were administered at week eight to measure post-trauma outcomes related to PTSD, sleep disturbance, and pain interference with daily life. Pulse activity and movement data were captured from a research watch for eight weeks. Standard and novel movement and cardiovascular metrics that reflect circadian rhythms were derived using this data. These features were used to train different classifiers to predict the three outcomes derived from week-eight surveys. Clinical surveys administered at ED were also used as features in the baseline models. RESULTS: The highest cross-validated performance of research watch-based features was achieved for classifying participants with pain interference by a logistic regression model, with an area under the receiver operating characteristic curve (AUC) of 0.70. The ED survey-based model achieved an AUC of 0.77, and the fusion of research watch and ED survey metrics improved the AUC to 0.79. SIGNIFICANCE: This work represents the first attempt to predict and classify post-trauma symptoms from passive wearable data using machine learning approaches that leverage the circadian desynchrony in a potential PTSD population.

Brief behavioral treatment for insomnia improves psychosocial functioning in veterans: results from a randomized controlled trial.

STUDY OBJECTIVES: Our goal was to compare brief behavioral treatment for insomnia (BBTI) to a progressive muscle relaxation training (PMRT) control condition among veterans with insomnia, examining psychosocial functioning as a primary outcome and sleep-related outcomes, mood, cognition, and pain as secondary outcomes. METHODS: Veterans were randomly assigned to either BBTI or PMRT (N = 91; 24-74 years; M = 49 years). BBTI consisted of two in-person (60-min and 30-min sessions) and two telephone sessions (20-min each), and the PMRT control condition was matched to BBTI for session duration and type. Veterans were assessed through clinical interview at baseline and self-report measures at pre-, mid-, and posttreatment, as well as 6-month follow-up for the BBTI condition to assess sustained response. Measures also included continuous sleep monitoring with sleep diary. RESULTS: Intent-to-treat analyses demonstrated that individuals who completed BBTI versus PMRT reported greater improvements in work, home, social and cognitive functioning, insomnia symptom severity, mood, and energy. Improvements in psychosocial functioning, insomnia symptoms, and mood were maintained 6-months following BBTI treatment completion. CONCLUSIONS: Veterans who received BBTI improved and maintained gains in psychosocial functioning, insomnia, and mood. BBTI is a treatment that can be implemented in primary care, mental health, or integrated care settings and provide symptom relief and improved functioning among those with insomnia, one of the most commonly reported mental health problems among veterans. CLINICAL TRIAL REGISTRATION: NCT02571452.

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.

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.

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.

Looking into the One-way Mirror: A Pilot Study on the Impact of Reflecting Teams on Family Members.

Reflecting Teams (RTs) are an internationally recognized clinical consultation methodology, first developed by Tom Andersen in 1985. Over the last three decades, family therapists around the world have used RTs to enhance treatment. However, this innovation to family therapy practice is not well-standardized nor evaluated. The pilot study described in this article is an attempt to expand on the previous studies on RTs, and quantitatively examines RTs conducted with family therapy participants at a university medical center psychiatric institute. Preliminary analyses indicate that after participating in a single RT, family members may feel more hopeful, believe they can better support each other in times of stress, have more confidence in working together, and resolve conflicts. Additionally, the analyses suggest that family members may feel better understood and have more ideas about how to have a conversation with their family members, even though, after the RT, they may not view their family differently. These preliminary results suggest that further studies should explore the influence of RTs on family functioning.

Los "equipos reflexivos" (Reflecting Teams, RTs) son una metodología de consulta clínica reconocida a nivel internacional que fue desarrollada por primera vez por Tom Andersen en 1985 (Andersen, 1992). Durante las últimas tres décadas, los terapeutas familiares de todo el mundo han usado los equipos reflexivos para optimizar el tratamiento (p. ej.: Brownlee, Vis, & McKenna, 2009; Höger, Temme, Reiter, & Steiner, 1994). Sin embargo, esta innovación en la práctica de terapia familiar no está bien estandarizada ni evaluada. El estudio piloto descrito en este artículo es un intento de ampliar estudios previos sobre los equipos reflexivos y de analizar cuantitativamente los equipos reflexivos implementados con los participantes de una terapia familiar en un instituto psiquiátrico y un centro médico universitario. Los análisis preliminares indican que después de participar en un solo equipo reflexivo, los familiares pueden sentirse más optimistas, creer que pueden apoyarse mejor mutuamente en momentos de estrés, tener más confianza en trabajar juntos y resolver conflictos. Los integrantes de la familia también pueden sentirse mejor comprendidos y tener más ideas acerca de cómo conversar con sus familiares. Sin embargo, después del equipo reflexivo, es posible que no vean a su familia de forma diferente. Estos resultados preliminares sugieren que otros estudios deberían analizar la influencia de los equipos reflexivos en el funcionamiento familiar.

Inflammation as a predictor of disease course in posttraumatic stress disorder and depression: A prospective analysis from the Mind Your Heart Study.

BACKGROUND: Prior research has focused largely on the pro-inflammatory states of PTSD and depression, with few studies evaluating the direction of inflammation's association with these disorders. To clarify whether inflammation plays a role in the development of PTSD or depression, we assessed the predictive value of inflammatory biomarkers on the courses of these conditions in a cohort of Veterans. METHODS: This research was part of the Mind Your Heart Study, a prospective cohort study designed to examine PTSD-related health outcomes. Between 2008 and 2010, 746 San Francisco area Veterans Administration patients were enrolled. At baseline, inflammatory biomarkers were measured from fasting morning venous blood draws, and cortisol and catecholamine levels were measured from 24-hour urine samples. PTSD was diagnosed using the PTSD Checklist at baseline and annual follow-up. Depression was evaluated using the 9-item Patient Health Questionnaire at baseline and follow-up. Ordinal logistic regression models were used to assess the predictive value of baseline biomarker levels on clinically relevant courses of PTSD and depression categorized and ordered as none, resolved, developed, and chronic. RESULTS: After adjustment for age and sex, elevated levels of white blood cell count (OR = 1.27(1.10-1.47), p = 0.001), C-reactive protein (OR = 1.20(1.04-1.39), p = 0.02), fibrinogen (OR = 1.19(1.03-1.38), p = 0.02), and ESR (OR = 1.17(1.00-1.36, p = 0.05), and decreased levels of urine cortisol (OR = 0.84(0.71-0.99), p = 0.04) were significant predictors of poorer courses of PTSD. Elevated levels of WBC count (OR = 1.31(1.14-1.50), p < 0.001), CRP (OR = 1.24(1.07-1.43), p = 0.003), fibrinogen (OR = 1.26(1.09-1.46), p = 0.002), and catecholamines (OR = 1.17(1.01-1.36), p = 0.04) were significant predictors of poorer courses of depression. After additionally controlling for physical activity, elevated WBC count (p = 0.002) and decreased levels of urine cortisol (p = 0.05) remained significant predictors of PTSD course, and elevated WBC count (p = 0.001), CRP (p = 0.03), and fibrinogen (p = 0.02) remained significant predictors of depression course. After adjusting for all significant variables, elevated WBC count (p = 0.02) was a significant predictor of a poorer course of PTSD, and elevated WBC count (p = 0.04) and platelet count (p = 0.03) were significant predictors of a poorer course of depression. CONCLUSIONS: Increased levels of several inflammatory biomarkers were associated with significantly increased odds of clinically worse courses of PTSD and depression. Inflammation may be a target for prevention and treatment of these mental health disorders.

Altered overnight levels of pro-inflammatory cytokines in men and women with posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with disturbed sleep and elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Studies in animals and healthy humans have also shown that disrupted sleep elevates pro-inflammatory cytokines, including IL-6 and TNF-α. A better understanding of overnight cytokine levels and sleep might shed light on possible mechanisms for elevated inflammation in PTSD. Thus, we investigated overnight levels of IL-6 and TNF-α in individuals with and without PTSD while recording sleep polysomnography (PSG). METHOD: Serum samples were collected from otherwise healthy, medication-free participants with chronic PTSD (n = 44; 50% female; M age = 30.34 ± 8.11) and matched controls (n = 49; 53% female; M age = 30.53 ± 6.57) during laboratory PSG. Levels of IL-6 and TNF-α were measured at hours 0, 2, 4, 6, and 8 after typical sleep onset time using serial serum samples. Plasma IL-6 and TNF-α levels were quantified using enzyme-linked immunosorbent assays. RESULTS: Growth model analysis indicated a significantgroup by time interaction for IL-6 (t[247] = -2.92, p = .005) and a significant group by sex by time interaction for TNF-α (t[275] = 2.02, p = .04). PTSD positive men and women initially had higher IL-6 and TNF-α at sleep onset, but not at the end of their sleep cycle. Men with PTSD showed a peak of TNF-α at the end of the sleep cycle, whereas male control subjects demonstrated an inverted U-shaped profile. There were no significant differences in TNF-α levels overnight between women with and without PTSD. CONCLUSION: To our knowledge, this is the largest study to examine IL-6 overnight in a PTSD sample and the first study to examine overnight TNF-α in PTSD. Overnight IL-6 and TNF-α levels may be altered in individuals with PTSD compared to those without PTSD, and TNF-α trajectories also differed by sex. The current findings highlight the need to consider sex, sleep, time of day, and circadian variation when examining inflammation in PTSD. Additional research in broader study samples will be necessary to clarify associations between disrupted sleep, cytokines, and increased risk for disease in PTSD.

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.

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.

Cognitive Behavioral Therapy for Insomnia Reduces Fear of Sleep in Individuals With Posttraumatic Stress Disorder.

STUDY OBJECTIVES: Our study aims were to examine (1) the association between fear of sleep and posttraumatic stress disorder (PTSD) symptoms, (2) the association between fear of sleep and subjective and objective insomnia symptoms and disruptive behaviors during sleep, and (3) whether fear of sleep decreases following cognitive behavioral therapy for insomnia (CBT-I). METHODS: Forty-five adults with PTSD and insomnia participated in the study. Fear of sleep was assessed using the Fear of Sleep Inventory; PTSD symptoms were assessed using the Clinician Administered PTSD Scale; and sleep disturbance symptoms were assessed using the Insomnia Severity Index, polysomnography, sleep diaries, and the Pittsburgh Sleep Quality Index Addendum for PTSD. Participants were randomly assigned to 8 weeks of CBT-I (n = 29) or a waitlist control condition (n = 16). RESULTS: Greater fear of sleep was associated with greater PTSD symptom severity, greater nightmare frequency, and greater hypervigilance intensity. Greater fear of sleep was associated with decreased wake after sleep onset (WASO), reduced total sleep time, and greater disruptive nocturnal behaviors. Following CBT-I, there was a significant reduction in fear of sleep compared to the waitlist condition. These improvements persisted 6 months later. CONCLUSIONS: Fear of sleep was related to sleep disturbances specific to trauma rather than "classic" insomnia symptoms. Unexpectedly, greater fear of sleep was associated with reduced WASO. These results may be related to having a truncated sleep period and thus more consolidated sleep. Fear of sleep deceased following CBT-I despite not being a permissible target for this research protocol and not being related to insomnia symptoms. CLINICAL TRIAL REGISTRATION: Registry: CinicalTrials.gov; Name: Treating People with Post-traumatic Stress Disorder with Cognitive Behavioral Therapy for Insomnia; Identifier: NCT00881647; URL: https://clinicaltrials.gov/ct2/show/NCT00881647.

Posttraumatic stress disorder, depression, and suicidal ideation in veterans: Results from the mind your heart study.

Veterans with PTSD or depression are at increased risk for suicidal ideation. However, few studies have examined that risk in those with comorbid PTSD and depression, instead focusing on these disorders individually. This study investigates the association of suicidal ideation with comorbid PTSD and depression and examines the role of military and psychosocial covariates. We evaluated 746 veterans using the CAPS to assess PTSD and the PHQ-9 to measure depression and suicidal ideation. Covariates were assessed via validated self-report measures. 49% of veterans with comorbid PTSD and depression endorsed suicidal ideation, making them more likely to do so than those with depression alone (34%), PTSD alone (11%), or neither (2%). In multivariate logistic regression models, this association remained significant after controlling for demographics and symptom severity. Anger, hostility, anxiety, alcohol use, optimism and social support did not explain the elevated risk of suicidal ideation in the comorbid group in fully adjusted models. As suicidal ideation is a known risk factor for suicide attempts and completions, veterans with comorbid PTSD and depression represent a vulnerable group who may need more intensive monitoring and treatment to reduce risk of suicide.

The effects of early trauma and the FKBP5 gene on PTSD and the HPA axis in a clinical sample of Gulf War veterans.

Previous research indicates that interactions between FKBP5 single nucleotide polymorphisms (SNPs) and child abuse are associated with posttraumatic stress disorder (PTSD) in adulthood. We examined the relationship between the T-allele of the rs1360780 FKBP5 SNP and child abuse on PTSD and the HPA axis in a clinical sample of Gulf War veterans. Genotyping was completed on 266 veterans and 174 veterans additionally participated in a low dose dexamethasone suppression test (DST). The CAPS was used to determine PTSD status and the THQ was used to determine child abuse operationalized as either childhood physical or sexual abuse. Hierarchical regression models were used to assess FKBP5 × child abuse interactions on PTSD, basal cortisol levels, and post DST cortisol levels. The FKBP5 risk allele and child abuse were separately associated with PTSD diagnosis. The risk allele was also associated with significantly lower cortisol levels at baseline. However, no significant FKBP5 × child abuse interaction on PTSD diagnosis, basal cortisol levels, or greater cortisol suppression was observed. Our results suggest that FKBP5 may be a viable biomarker for PTSD. Nonetheless, further work will be required to reconcile our findings with previous reports of an FKBP5 × child abuse interaction on posttraumatic stress response.