The Relative Impact of Different Types of Military Sexual Trauma on Long-Term PTSD, Depression, and Suicidality.

Sexual assault and harassment in the U.S. military are very common. Military sexual trauma (MST) is defined as sexual assault or harassment experienced during military service; yet, the relative impact of sexual assault, harassment, and their combination is not well understood. Given the extent and potential severity of the long-term outcomes of MST, it is critical to evaluate the relative impacts of these types of MST on long-term mental health outcomes. Veterans (n = 2499; 54% female) completed self-report measures of experiences of sexual assault and harassment perpetrated by coworkers during military service, posttraumatic stress disorder (PTSD), depression, and suicidality. Controlling for combat exposure, all types of MST experiences (Harassment Only, Assault Only, or Both) compared to No MST predicted greater severity of PTSD, depression, and suicidality after military service. Compared to Veterans with No MST, those who experienced Both Assault and Harassment reported significantly more severe PTSD, depression, and suicidality followed by Harassment Only, and then Assault Only. Data suggest that different types of MST experiences have an impact on long-term mental health outcomes, and the combination of Both sexual Assault and Harassment is particularly deleterious.

Change in posttraumatic stress disorder-related thoughts during treatment: Do thoughts drive change when pills are involved?

Posttraumatic negative thoughts about one's self and the world are related to posttraumatic stress disorder (PTSD) symptom severity and change in cognitive behavioral treatment (CBT), but little is known about this association when CBT is delivered with medication. The current study presents a planned comparison of changes in negative posttraumatic thoughts during (a) prolonged exposure (PE) plus pill placebo (PE+PLB), (b) sertraline plus enhanced medication management (SERT+EMM), and (c) PE plus sertraline (PE+SERT) as part of a randomized clinical trial in a sample of 176 veterans. Lagged regression modeling revealed that change in posttraumatic negative thoughts was associated with PTSD symptom change in the conditions in which participants received sertraline, ds = 0.14-0.25, ps = 0.04-.001). However, contrary to previous research, the models that started with symptom change were also statistically significant, d = 0.23, p < .001, for the lagged effect of symptoms on negative thoughts about self in the SERT+EMM condition, indicating a bidirectional association between such thoughts and PTSD symptoms. In the PE+PLB condition, no significant association between posttraumatic thoughts and PTSD symptoms emerged in either direction. These results suggest that the previously demonstrated role of change in posttraumatic thoughts leading to PTSD symptom reduction in PE may be altered when combined with pill administration, either active or placebo.

An intensive outpatient program with prolonged exposure for veterans with posttraumatic stress disorder: Retention, predictors, and patterns of change.

High rates of drop-out from treatment of PTSD have challenged implementation. Care models that integrate PTSD focused psychotherapy and complementary interventions may provide benefit in retention and outcome. The first 80 veterans with chronic PTSD enrolled in a 2-week intensive outpatient program combining Prolonged Exposure (PE) and complementary interventions completed symptom and biological measures at baseline and posttreatment. We examined trajectories of symptom change, mediating and moderating effects of a range of patient characteristics. Of the 80 veterans, 77 completed (96.3%) treatment and pre- and posttreatment measures. Self-reported PTSD (p < .001), depression (p < .001) and neurological symptoms (p < .001) showed large reductions with treatment. For PTSD, 77% (n = 59) showed clinically significant reductions. Satisfaction with social function (p < .001) significantly increased. Black veterans and those with a primary military sexual trauma (MST) reported higher baseline severity than white or primary combat trauma veterans respectively but did not differ in their trajectories of treatment change. Greater cortisol response to the trauma potentiated startle paradigm at baseline predicted smaller reductions in PTSD over treatment while greater reductions in this response from baseline to post were associated with better outcomes. Intensive outpatient prolonged exposure combined with complementary interventions shows excellent retention and large, clinically significant reduction in PTSD and related symptoms in two weeks. This model of care is robust to complex presentations of patients with varying demographics and symptom presentations at baseline. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Mycobacterial para-Hydroxybenzoic Acid-Derivatives (pHBADs) and Related Structures Induce Macrophage Innate Memory.

Macrophages are key immune cells for combatting Mycobacterium tuberculosis. However, M. tuberculosis possesses means to evade macrophage bactericidal responses by, for instance, secretion of the immunomodulatory para-hydroxybenzoic acid derivatives (pHBADs). While these molecules have been implicated in inhibiting macrophage responses in an acute context, little is known about their ability to reprogram macrophages via induction of long-term innate memory. Since innate memory has been highlighted as a promising strategy to augment bactericidal immune responses against M. tuberculosis, investigating corresponding immune evasion mechanisms is highly relevant. Our results reveal for the first time that pHBAD I and related molecules (unmethylated pHBAD I and the hexose l-rhamnose) reduce macrophage bactericidal mechanisms in both the short- and the long-term. Moreover, we demonstrate how methyl-p-anisate hinders bactericidal responses soon after exposure yet results in enhanced pro-inflammatory responses in the long-term. This work highlights new roles for these compounds in M. tuberculosis pathogenesis.

Patients need to remain in treatment for PTSD to receive the full benefit.

Despite strong evidence to support trauma-focused treatment as the gold standard in treating PTSD, many studies report elevated drop-out rates. The study by Holmes et al. (2019) examines temporal patterns of treatment non-completion and reported individuals who improved at a greater rate attended all sessions. This commentary discusses some of the factors that contribute to premature termination, including treatment modality (e.g., exposure-based), barriers to care, treatment format, motivation, treatment resistance, and lack of multimodal assessments. Future investigations comparing individual differences in response to treatment would allow for the examination of characteristics that facilitate or impede treatment response.

Chemoselective Synthesis of N-Terminal Cysteinyl Thioesters via ß,γ-C,S Thiol-Michael Addition.

Dehydroalanine (ΔAla) is a highly electrophilic residue that can react efficiently with sulfur nucleophiles to furnish cysteinyl analogues. Herein, we report an efficient synthesis of N-terminal cysteinyl thioesters, suitable for S, N-acyl transfer, based on ß,γ-C,S thiol-Michael addition. Both ionic and radical-based methodologies were found to be efficient for this process.

Neuroscience Informed Prolonged Exposure Practice: Increasing Efficiency and Efficacy Through Mechanisms.

Prolonged exposure (PE) is an empirically supported efficacious treatment for posttraumatic stress disorder (PTSD). In this focused review, we briefly review the neurobiological networks in PTSD relevant to PE, discuss the theoretical basis of PE, review the neurobiological mechanisms underlying the effectiveness of PE and identify the enhancements that can be applied to increase treatment response and retention. Based on the reviewed studies, it is clear that PTSD results in disrupted network of interconnected regions, and PE has been shown to increase the connectivity within and between these regions. Successful extinction recall in PE is related to increased functional coherence between the ventromedial prefrontal cortex (vmPFC), amygdala and the hippocampus. Increased connectivity within the dorsolateral PFC (dlPFC) following PE is associated with more effective downregulation of emotional responses in stressful situations. Pre-existing neural connectivity also in some cases predicts response to exposure treatment. We consider various enhancements that have been used with PE, including serotonin reuptake inhibitors (SSRIs), D-cycloserine (DCS), allopregnanolone (ALLO) and propranolol, repetitive transcranial magnetic stimulation (rTMS), oxytocin and MDMA. Given that neural connectivity appears to be crucial in mechanisms of action of PE, rTMS is a logical target for further research as an enhancement of PE. Additionally, exploring the effectiveness and mechanisms of action of oxytocin and MDMA in conjunction with PE may lead to improvement in treatment engagement and retention.

Postconcussive symptoms (PCS) following combat-related traumatic brain injury (TBI) in Veterans with posttraumatic stress disorder (PTSD): Influence of TBI, PTSD, and depression on symptoms measured by the Neurobehavioral Symptom Inventory (NSI).

Mild traumatic brain injury (mTBI) is commonly reported in recent combat Veterans. While the majority resolve, some Veterans develop postconcussive symptoms (PCS). Previous research suggests these symptoms are not specific to head injury and are often associated with psychiatric symptoms. The current study examines the relative contributions of posttraumatic stress, depressive symptoms, and TBI on postconcussive symptoms, and explores whether the relationship remains after controlling for symptom overlap. Two hundred eighteen combat Veterans from Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF), and Operation New Dawn (OND) provided the data for this study as part of a baseline evaluation for inclusion into larger treatment study for posttraumatic stress disorder (PTSD). Participants completed the Brief Traumatic Brain Injury Screen (BTBIS), Neurobehavioral Symptom Inventory (NSI), PTSD Checklist-Stressor Version (PCL-S), Beck Depression Inventory-II (BDI-II). Significant differences in NSI total score between individuals with and without history of TBI were not found. A series of regression analyses demonstrated that Depression and PTSD were significant predictors of NSI score even after removal of NSI symptoms that overlap with PTSD or depression. TBI status was also a significant predictor of PCS in most models, but its relative contribution was much smaller than that of depression and PTSD. Within PTSD symptoms, hyperarousal cluster was a significant predictor of NSI scores. Findings demonstrate that depression and PTSD are related to PCS beyond similarities in construct. Further, within a primarily PTSD treatment-seeking population, these psychiatric symptoms appear to be a stronger contributor than TBI.

Predictors of Help-Seeking Intentions in Operation Enduring Freedom and Operation Iraqi Freedom Veterans and Service Members.

OBJECTIVES: Despite significant numbers of Afghanistan and Iraqi veterans and service members who report symptoms of posttraumatic stress disorder, depression, anxiety, and substance abuse, the majority do not seek help for these problems. A better understanding of the help-seeking process might aid providers and administrators in outreach and provision of services for those who need them. Past research has shown several variables that influence an individual's help-seeking behavior: demographic variables, the nature and severity of a mental health problem, and psychological variables. The three goals of the study were to determine which variables predicted help-seeking intentions from various sources for a psychological problem, identify barriers to help seeking, and identify sources of help sought in the past year. MATERIALS AND METHODS: All Operation Enduring Freedom and Operation Iraqi Freedom veterans and service members registered with a Midwestern VA Healthcare System between 2001 and 2007 received a letter requesting participation in an Internet-based survey. Participants completed nine questionnaires regarding their current physical and psychological health, social support, self-efficacy, public and self-stigma, and barriers to seeking help for a psychological problem. In addition, patterns of help seeking from informal (i.e., partner/spouse, family, friends) and formal (i.e., physician, psychiatrist, or psychologist, either from Veterans Affairs [VA] or the private sector) sources of help were examined. RESULTS: Results from the linear regression model including all formal and informal sources of help indicated a significant model fit with attitudes toward psychotherapy, social support, and current mental health status as significant coefficients. Of note, attitudes toward psychotherapy were a significant coefficient in all help-seeking models; stigma was a significant coefficient with formal and VA sources, and social support was found to be a significant predictor with informal sources. Documentation of a mental health problem on one's record was found to be a significant barrier to help seeking and participants indicated they would most likely seek help in the next year from their partner/spouse, family, or friends versus formal VA or non-VA sources. CONCLUSIONS: This is one of the first studies to examine attitudes toward psychotherapy as contributing to help-seeking intentions of veterans and service members and results provide strong support for inclusion of this variable in future studies in addition to social support and stigma. Limitations of the study are discussed as well as suggestions for future research. It is our hope that findings from this study may inform administrators and providers regarding assessment, outreach, and program development for our country's veterans and service members.

Contrasting Gender and Combat Versus Military Sexual Traumas: Psychiatric Symptom Severity and Morbidities in Treatment-Seeking Veterans.

BACKGROUND: Military sexual trauma (MST) and military combat trauma (MCT) are significant risk factors for posttraumatic stress disorder (PTSD). However, no studies have directly contrasted the clinical profiles of Veterans between military-related traumas. Moreover, a notable gender difference in the likelihood of trauma exposure limits our ability to disentangle gender and trauma type. MATERIALS AND METHODS: To address these gaps, we aimed at (1) contrasting psychiatric complaints in Veterans with MST versus MCT exposure and (2) investigating gender differences in Veterans with MST histories. Treatment-seeking Veterans (N = 563) completed semi-structured diagnostic interviews and self-report assessments of PTSD, depressive, and dissociative symptoms. RESULTS: Psychiatric complaints and morbidity were notable after all military-associated traumas, although those seeking care for MST-related events demonstrated more severe PTSD, depressive, and dissociative symptoms and were more likely to meet criteria for non-PTSD anxiety and psychotic disorders. In contrast, few gender-related differences were noted between male and female Veterans with histories of MST. CONCLUSIONS: The experience of MST may reduce typically observed gender-related buffering effects for certain conditions.

Temporal Sequencing of Change in Posttraumatic Cognitions and PTSD Symptom Reduction During Prolonged Exposure Therapy.

Prolonged exposure (PE) effectively reduces negative cognitions about self, world, and self-blame associated with posttraumatic stress disorder (PTSD), with changes in posttraumatic cognitions being associated with reductions in PTSD symptoms (Foa & Rauch, 2004). Further, recent research has demonstrated that cognitive change is a likely mechanism for PTSD symptom reduction in PE (Zalta et al., 2014). The present study examines temporal sequencing of change in three domains of posttraumatic cognitions (i.e., negative cognitions about the self, negative cognitions about the world, and self-blame) and PTSD symptoms during the course of PE. Adult outpatients meeting diagnostic criteria for PTSD were recruited at 4 sites. Participants (N=46) received 8 sessions of PE over 4 to 6weeks. PTSD symptoms and posttraumatic cognitions were assessed at pretreatment and Sessions 2, 4, 6, and 8. PTSD symptom severity and negative cognitions about the self and the world each decreased significantly from pre- to posttreatment, while self-blame cognitions were unchanged. Examination of temporal sequencing of changes during the course of PE via time-lagged mixed effects regression modeling revealed that preceding levels of negative cognitions about the world drove successive severity levels of PTSD symptoms, whereas preceding PTSD symptom severity did not drive subsequent negative cognitions about the world. Reductions in negative cognitions about the self led to subsequent improvement in PTSD. Improvement in PTSD symptoms in prior sessions was related to later reduction in negative cognitions about the self, though the impact of negative cognitions in influencing subsequent symptom change demonstrated a stronger effect. Results support that reductions in negative cognitions about the self and world are mechanisms of change in PE, which may have valuable implications for maximizing treatment effectiveness.

Exploratory Factor Analysis of Diagnostic and Statistical Manual, 5th Edition, Criteria for Posttraumatic Stress Disorder.

One change to the posttraumatic stress disorder (PTSD) nomenclature highlighted in the Diagnostic and Statistical Manual, 5th Edition (DSM-5; American Psychiatric Association, 2013) is the conceptualization of PTSD as a diagnostic category with four distinct symptom clusters. This article presents exploratory factor analysis to test the structural validity of the DSM-5 conceptualization of PTSD via an online survey that included the PTSD Checklist-5. The study utilized a sample of 113 college students from a large Midwestern university and 177 Amazon Mechanical Turk users. Participants were primarily female, Caucasian, single, and heterosexual with an average age of 32 years. Approximately 30% to 35% of participants met diagnostic criteria for PTSD based on two different scoring criteria. Results of the exploratory factor analysis revealed five distinct symptom clusters. The implications for the classification of PTSD are discussed.

Intramolecular thiol-yne cyclisation as a novel strategy for thioglycal synthesis.

A novel intramolecular thiol-yne cyclisation strategy has been developed for the synthesis of thioglycals. Both ionic and radical mediated cyclisation pathways have been investigated for D- and L-sugars. The ionic cyclisation provides exclusive access to 5-exo products directly from the thioesters whereas the radical cyclisation provides access to both 5-exo and 6-endo products upon photochemical irradiation of the free thiols. These are the first examples of intramolecular thiol-yne cyclisation reactions applied to thiosugar synthesis.

Sleep problems among persons with a lifetime history of posttraumatic stress disorder alone and in combination with a lifetime history of other psychiatric disorders: a replication and extension.

OBJECTIVE: Sleep problems are a clinical and/or diagnostic feature for a broad array of mood, substance use, and anxiety disorders, including posttraumatic stress disorder (PTSD). Previous research by Leskin et al (Leskin GA, Woodward SH, Young HE, Sheikh J. Effects of comorbid diagnoses on sleep disturbance in PTSD. J Psychiat Res 2002;36:449-452) using the baseline National Comorbidity Survey (NCS) data found that persons with PTSD and panic disorder had a greater proportion of sleep problems than persons with other comorbid disorders. The current study extends Leskin et al's findings using the replication of the NCS. It compared persons with a lifetime history of PTSD (either alone or in combination) with 6 comparison disorders (adult separation anxiety, alcohol dependence, generalized anxiety, dysthymia, major depression, and panic) on severity of sleep disorder symptoms. METHOD: The NCS Replication was a national probability survey of 9282 individuals that examined the prevalence and correlates of mental disorders. Subjects were chosen through a multistage probability sample of US households and interviewed using a computer-aided version of the Composite International Diagnostic Interview. RESULTS: The PTSD (alone) group did not differ from the comparison disorders on difficulties of falling/staying asleep but did report more weeks per year when they had sleep difficulties than persons with adult separation anxiety, alcohol dependence, and major depression. CONCLUSION: Unlike Leskin et al, the additive effects of a second disorder on sleep difficulties are not unique to panic disorder. However, when sleep difficulties were indexed by the number of weeks per year, differences between diagnostic groups emerged. If the goal of a diagnostic system is to carve nature at its joints, a sleep disturbance symptom reflecting frequency of difficulties in this way is clearly superior to less precise alternatives.

Development of a borderline personality disorder-relevant picture stimulus set.

Individuals with borderline personality disorder (BPD) report erratic and poorly regulated emotional behavior. However, these abnormalities have not been confirmed in laboratory studies. This may be because the emotional stimuli employed have not been sufficiently relevant or evocative of psychological themes germane to BPD (e.g., threats to attachment). The aim of this study was to develop a picture stimulus set relevant to BPD that could be employed in research to examine emotion dysregulation thought to be central to BPD. Ninety pictures were initially selected from the International Affective Picture System that had putative interpersonal and social content across a range of pleasantness and intensity. The set was then rated by 19 clinical BPD research experts on two dimensions: How self-referential the picture would be to someone with BPD and the extent to which the picture represented an ideal-other to a prototypic BPD case. Two sets of pictures were generated for future research with BPD participants.

Depressive symptoms and baseline prefrontal EEG alpha activity: a study utilizing Ecological Momentary Assessment.

Prefrontal cortex (PFC) electroencephalography (EEG) alpha asymmetry has been found in individuals with major depression. However, EEG activity has never been examined in regard to specific depressive symptoms. We examine the relationship between resting baseline PFC alpha activity and both rumination and self-esteem in a depressed outpatient group (N=6) and a healthy control group (N=7) using high-density EEG sampling and multiple longitudinal self report measures, i.e. Ecological Momentary Assessment (EMA). Symptom measures were collected five times daily for 7 days, i.e. 35 assessments. Using a mixed-level analysis, significant Group x Hemisphere interactions for PFC sites and both rumination and self-esteem were found. Within the depressed group, lower bilateral PFC activity predicted higher levels of rumination, and lower right PFC activity predicted higher levels of self-esteem. There were no significant effects for the control group. Results indicate that specific symptoms of depression are uniquely associated with patterns of PFC EEG alpha activity.

The subsyndromal phenomenology of borderline personality disorder: a 10-year follow-up study.

OBJECTIVE: The purpose of this study was to characterize the course of 24 symptoms of borderline personality disorder in terms of time to remission. METHOD: The borderline psychopathology of 362 patients with personality disorders, all recruited during inpatient stays, was assessed using two semistructured interviews of proven reliability. Of these, 290 patients met DSM-III-R criteria as well as Revised Diagnostic Interview for Borderlines criteria for borderline personality disorder, and 72 met DSM-III-R criteria for another axis II disorder. Over 85% of the patients were reinterviewed at five distinct 2-year follow-up waves by interviewers blind to all previously collected information. RESULTS: Among borderline patients, 12 of the 24 symptoms studied showed patterns of sharp decline over time and were reported at 10-year follow-up by less than 15% of the patients who reported them at baseline. The other 12 symptoms showed patterns of substantial but less dramatic decline over the follow-up period. Symptoms reflecting core areas of impulsivity (e.g., self-mutilation and suicide efforts) and active attempts to manage interpersonal difficulties (e.g., problems with demandingness/entitlement and serious treatment regressions) seemed to resolve the most quickly. In contrast, affective symptoms reflecting areas of chronic dysphoria (e.g., anger and loneliness/emptiness) and interpersonal symptoms reflecting abandonment and dependency issues (e.g., intolerance of aloneness and counterdependency problems) seemed to be the most stable. CONCLUSIONS: The results suggest that borderline personality disorder may consist of both symptoms that are manifestations of acute illness and symptoms that represent more enduring aspects of the disorder.