Sexual vs. Non-sexual trauma, sexual satisfaction and function, and mental health in female veterans.

Trauma in general, and sexual assault in particular, is associated with serious mental health and functional problems. The quality of sexual satisfaction/function may be particularly impacted by sexual assault, and such sexual problems may account for some of the broader mental health and functioning impairments in sexual assault survivors. Accordingly, we examined self-reports of sexual health and mental health in a sample of 255 female veterans in committed, monogamous relationships who provided data regarding sexual assault (n = 153) or nonsexual trauma (n = 102). Trauma type was not associated with differences in sexual function, but sexual trauma was associated with significantly lower sexual satisfaction, greater posttraumatic stress disorder (PTSD) and depressive symptoms, and higher suicidal ideation. Furthermore, the indirect effect of trauma type on all mental health outcomes was significant via sexual satisfaction but not via sexual function. Finally, trauma type moderated the association of sexual function with suicidality, such that the association was significantly positive in those with a history of sexual assault but nonsignificant in those with nonsexual trauma. These results suggest that (1) female veterans' experience of sexual assault is related to sexual satisfaction, which in turn is related to mental health outcomes, and (2) a history of sexual assault may increase the importance of sexual functioning with regard to suicidality.

Creation of a S1P Lyase bacterial surrogate for structure-based drug design.

S1P Lyase (SPL) has been described as a drug target in the treatment of autoimmune diseases. It plays an important role in maintaining intracellular levels of S1P thereby affecting T cell egress from lymphoid tissues. Several groups have already published approaches to inhibit S1P Lyase with small molecules, which in turn increase endogenous S1P concentrations resulting in immunosuppression. The use of structural biology has previously aided SPL inhibitor design. Novel construct design is at times necessary to provide a reagent for protein crystallography. Here we present a chimeric bacterial protein scaffold used for protein X-ray structures in the presence of early small molecule inhibitors. Mutations were introduced to the bacterial SPL from Symbiobacterium thermophilum which mimic the human enzyme. As a result, two mutant StSPL crystal structures resolved to 2.8Å and 2.2Å resolutions were solved and provide initial structural hypotheses for an isoxazole chemical series, whose optimization is discussed in the accompanying paper.

Anxiety and Shame as Risk Factors for Depression, Suicidality, and Functional Impairment in Body Dysmorphic Disorder and Obsessive Compulsive Disorder.

Body dysmorphic disorder (BDD) and obsessive compulsive disorder (OCD) are associated with elevated depression, suicidality, functional impairment, and days housebound, yet little research has identified risk factors for these outcomes. Using path analysis, the present study examined anxiety and shame as risk factors for these outcomes across Internet-recruited self-report groups (BDD [n = 114], OCD [n = 114], and healthy control [HC; n = 133]). Paths from anxiety and shame to outcomes were similar and mostly significant across BDD and OCD, compared to non-significant paths for HCs, with one exception: the path from shame to depression was significant in the BDD group (b = 0.32) but non-significant in the OCD group (b = 0.07). Findings underscore similarities in BDD and OCD, supporting their reclassification into the same Obsessive Compulsive Related Disorders category. Results emphasize the importance of targeting shame, in addition to anxiety, in treatments for BDD and OCD.

Perceived Support From Multiple Sources: Associations With PTSD Symptoms.

Perceived social support is negatively associated with severity of posttraumatic stress disorder (PTSD), but the literature lacks data about specific sources of support. Using 2 service member (SM) samples (n = 207 and 465), this study examined perceived support from family/friends and the broader public. SMs perceived high support from both sources. In multivariate regressions, perceived support from the broader public was not significantly associated with severity of PTSD symptoms, but it demonstrated a nearly identical effect size (ß = -.21) as support from family/friends (ß = -.23) in a sample of active duty and National Guard/Reserve SMs. We found that, SMs perceived high levels of support from the broader public, with modest evidence that such perceptions may relate to severity of PTSD.

Wise Additions Bridge the Gap between Social Psychology and Clinical Practice: Cognitive-Behavioral Therapy as an Exemplar.

Progress in clinical science, theory, and practice requires the integration of advances from multiple fields of psychology, but much integration remains to be done. The current article seeks to address the specific gap that exists between basic social psychological theories and the implementation of related therapeutic techniques. We propose several "wise additions," based upon the principles outlined by Walton (2014), intended to bridge current social psychological research with clinical psychological therapeutic practice using cognitive behavioral therapy as an example. We consider how recent advances in social psychological theories can inform the development and implementation of wise additions in clinical case conceptualization and interventions. We specifically focus on self and identity, self-affirmation, transference, social identity, and embodied cognition, five dominant areas of interest in the field that have clear clinical applications.

Characteristics of hoarding in older adults.

OBJECTIVE: This study determined the clinical characteristics of late-life hoarding disorder (HD). METHODS: Older adults (age 60 and older) with HD (n = 55) and without psychiatric diagnoses (n = 39) were compared on psychiatric, functional, cognitive, and health-related measures. Associations between age and clinical characteristics in a large sample of mixed age (n = 210; age range: 20-78) participants with HD were also determined. RESULTS: Individuals with late-life HD were characterized by substantial impairments in psychiatric, functional, cognitive, and medical status. Health risks (e.g., risks of falls and fire) were also common. However, older age was generally not associated with increased severity of hoarding or other clinical correlates (with the exception of one global clinician-rated measure of severity). CONCLUSIONS: Late-life HD is characterized by considerable morbidity and health risks, and these characteristics may be consistent across the lifespan in cross-sectional mixed-age samples of individuals with HD.

Trauma-Related Disclosure in Sexual Assault Survivors' Intimate Relationships: Associations With PTSD, Shame, and Partners' Responses.

Relative to survivors of other traumatic events, survivors of sexual assault have an increased likelihood of meeting criteria for posttraumatic stress disorder (PTSD). They are also comparatively more likely to exhibit higher levels of PTSD symptom severity. Recent research has highlighted the importance of trauma-related disclosure within the context of intimate relationships for posttrauma functioning and recovery, but this phenomenon has yet to be examined specifically in sexual assault survivor samples. Accordingly, this study examines the association of PTSD symptom severity with disclosure about one's experience of sexual assault to one's intimate partner, as well as the association of such disclosure with trauma-related shame and perception of partners' negative and positive responses to trauma-related disclosure. A sample of 104 female participants who had disclosed their experience of sexual assault to their current romantic partner provided survey data. On average, these participants reported a moderate amount of trauma-related disclosure. Counter to hypotheses, level of engagement in trauma-related disclosure was not significantly correlated with PTSD symptom severity, shame, or perceived negative responses to disclosure. Only perceived positive responses to disclosure demonstrated a significant, bivariate association with overall level of engagement in trauma-related disclosure. Similarly, when trauma-related shame, negative responses, and positive responses were accounted for simultaneously, only positive responses were related to level of disclosure. Overall, results suggest that intimate relationships may serve as a unique context for disclosure about one's history of sexual assault, with perceived positive responses demonstrating particularly strong associations with level of engagement in trauma-related disclosure.

2,4-Diaminopyrimidine MK2 inhibitors. Part I: Observation of an unexpected inhibitor binding mode.

MK2 is a Ser/Thr kinase of significant interest as an anti-inflammatory drug discovery target. Here we describe the development of in vitro tools for the identification and characterization of MK2 inhibitors, including validation of inhibitor interactions with the crystallography construct and determination of the unique binding mode of 2,4-diaminopyrimidine inhibitors in the MK2 active site. Use of these tools in the optimization of a potent and selective inhibitor lead series is described in the accompanying Letter.

Rational mutagenesis to support structure-based drug design: MAPKAP kinase 2 as a case study.

BACKGROUND: Structure-based drug design (SBDD) can provide valuable guidance to drug discovery programs. Robust construct design and expression, protein purification and characterization, protein crystallization, and high-resolution diffraction are all needed for rapid, iterative inhibitor design. We describe here robust methods to support SBDD on an oral anti-cytokine drug target, human MAPKAP kinase 2 (MK2). Our goal was to obtain useful diffraction data with a large number of chemically diverse lead compounds. Although MK2 structures and structural methods have been reported previously, reproducibility was low and improved methods were needed. RESULTS: Our construct design strategy had four tactics: N- and C-terminal variations; entropy-reducing surface mutations; activation loop deletions; and pseudoactivation mutations. Generic, high-throughput methods for cloning and expression were coupled with automated liquid dispensing for the rapid testing of crystallization conditions with minimal sample requirements. Initial results led to development of a novel, customized robotic crystallization screen that yielded MK2/inhibitor complex crystals under many conditions in seven crystal forms. In all, 44 MK2 constructs were generated, ~500 crystals were tested for diffraction, and ~30 structures were determined, delivering high-impact structural data to support our MK2 drug design effort. CONCLUSION: Key lessons included setting reasonable criteria for construct performance and prioritization, a willingness to design and use customized crystallization screens, and, crucially, initiation of high-throughput construct exploration very early in the drug discovery process.

PTSD and relationship satisfaction in female survivors of sexual assault.

OBJECTIVE: Intimate relationships are critical to posttrauma functioning and recovery. The vast majority of research focusing on PTSD and relationship functioning has focused exclusively on male combat veterans, from whom female sexual assault survivors may differ in critical ways. This study investigates the strength of the association between PTSD symptoms and relationship satisfaction, as well as the role of three interpersonal processes (sexuality, communication, and hostility) in female sexual assault survivors. METHOD: Data was collected from female survivors of sexual assault in romantic relationships via online survey. RESULTS: PTSD symptom severity and relationship satisfaction were not significantly correlated. The direct effect of PTSD symptom severity on relationship satisfaction was positive, whereas indirect effects through negative communication, positive communication, and sexual satisfaction were all significantly negative, as expected. Finally, the correlation of PTSD symptom severity with relationship satisfaction differed depending on whether or not participants were in treatment. Results suggest that for those not in treatment, greater PTSD symptoms are associated with poorer relationship satisfaction. CONCLUSIONS: Preliminary evidence suggests that communication and sexual satisfaction may be particularly salient issues for sexual assault survivors' posttrauma psychopathological and relationship functioning, but participation in treatment may be associated with reduced impact of PTSD symptoms on interpersonal functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Longitudinal associations of friend-based social support and PTSD symptomatology during a cannabis cessation attempt.

Research supports bidirectional associations between social support and posttraumatic stress disorder (PTSD), whereby social support may buffer against PTSD, and individuals with PTSD may experience decreasing support over time. Research examining contexts that may affect these relations is needed. This study examined the longitudinal associations between PTSD and social support from friends over a 6-month period in 116 veterans with cannabis dependence who had recently initiated an attempt to quit cannabis use. A cross-lagged autoregressive model revealed a significant, negative relation between earlier PTSD symptoms and later support. An exploratory multigroup analysis comparing those with and without a relapse in the first month after their quit attempt revealed that the significant negative association between PTSD and future support was present only in those who relapsed. Although this analysis was limited by a small sample size, results suggest that substance use may be an influential contextual variable that impacts the longitudinal associations between PTSD and support.

A historical review of trauma-related diagnoses to reconsider the heterogeneity of PTSD.

Based on the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders, there are 636,120 ways for an individual to qualify for a diagnosis of posttraumatic stress disorder (PTSD) (Galatzer-Levy & Bryant, 2013). To unravel this heterogeneity, we examine the historical trajectory of trauma-related diagnoses. Our review addresses four traumas (i.e., combat, natural disaster, life-threatening accident and sexual assault) that have contributed the most to conceptual models of PTSD. Although these trauma types are all subsumed under the same diagnostic label, our literature review indicates that the psychological consequences of different traumatic experiences are traditionally studied in isolation. Indeed, most research addresses hypotheses regarding specific trauma types using samples of individuals selected for their experience with that specific event. We consider the possibility that PTSD is not a single, unified construct and what this means for future research and clinical applications.

Do People with Hoarding Disorder Under-Report Their Symptoms?

Previous research indicates that people with hoarding sometimes under- or over-report the severity of their symptoms. This article examines the results of two separate studies that evaluate severity ratings made by participants with hoarding disorder (HD) in comparison to ratings by family members or independent evaluators. In Study 1, HD participants' ratings of the severity of the clutter in their home and their hoarding behaviors were less severe than those made by their friends or family members. This result may be accounted for by family members' rejecting attitudes towards the participant. In Study 2, HD participants appeared to under-report specific hoarding symptoms while over-reporting their overall global impression of hoarding severity. A three-pronged assessment approach is recommended in which ratings of hoarding severity are made by the HD participant, their family member, and an independent observer or clinician. Such an approach would better inform future research, and also clinical treatment.

Long-term effectiveness of CBT for anxiety disorders in an adult outpatient clinic sample: a follow-up study.

The short-term efficacy and effectiveness of Cognitive-Behavioral Therapy (CBT) for treating anxiety disorders in adults has been well established by a multitude of clinical studies and well-controlled randomized trials. However, though the long-term efficacy of CBT as a treatment modality is fairly well established, the degree of its long-term effectiveness has yet to be fully evaluated. Thus, the present study sought to assess both the immediate and long-term effectiveness of individually-administered CBT for the treatment of anxiety disorders in an outpatient psychological clinic. Individuals with a primary diagnosis of Panic Disorder, Social Phobia, Posttraumatic Stress Disorder, Generalized Anxiety Disorder, or Obsessive-Compulsive Disorder who had received 3 or more sessions of CBT were assessed for symptom severity and improvement prior to initiating treatment, at posttreatment, and at one-year follow-up. Symptom severity and improvement ratings were used to categorize patients as "responders" or "remitters" at posttreatment, and "maintained responders" or "maintained remitters" at follow-up. Findings demonstrated that posttreatment success as responder and remitter was significantly maintained at one-year follow-up. Additionally, pre- and posttreatment severity and posttreatment improvement scores were also predictive of maintenance. Furthermore, effect sizes were used to compare the effectiveness of CBT in the present clinical sample to research treatment outcomes demonstrated by previous efficacy studies.