Mucosal integrin α4ß7 blockade fails to reduce the seeding and size of viral reservoirs in SIV-infected rhesus macaques.

Cellular viral reservoirs are rapidly established in tissues upon HIV-1/SIV infection, which persist throughout viral infection, even under long-term antiretroviral therapy (ART). Specific integrins are involved in the homing of cells to gut-associated lymphoid tissues (GALT) and inflamed tissues, which may promote the seeding and dissemination of HIV-1/SIV to these tissue sites. In this study, we investigated the efficacy of prophylactic integrin blockade (α4ß7 antibody or α4ß7/α4ß1 dual antagonist TR-14035) on viral infection, as well as dissemination and seeding of viral reservoirs in systemic and lymphoid compartments post-SIV inoculation. The results showed that blockade of α4ß7/α4ß1 did not decrease viral infection, replication, or reduce viral reservoir size in tissues of rhesus macaques after SIV infection, as indicated by equivalent levels of plasma viremia and cell-associated SIV RNA/DNA to controls. Surprisingly, TR-14035 administration in acute SIV infection resulted in consistently higher viremia and more rapid disease progression. These findings suggest that integrin blockade alone fails to effectively control viral infection, replication, dissemination, and reservoir establishment in HIV-1/SIV infection. The use of integrin blockade for prevention or/and therapeutic strategies requires further investigation.

Intranasal oxytocin modulates higher order social cognition in body dysmorphic disorder.

BACKGROUND: Body dysmorphic disorder (BDD) is a psychiatric disorder with specific impairments in social cognition related to excessive concerns about one's appearance. Individuals with BDD have difficulty identifying emotional expressions and attribute internal factors for others' emotional expressions in self-referent (but not other-referent) scenarios. Given the role of oxytocin in regulating social approach behavior and social salience, we hypothesized that oxytocin would improve biases in emotion recognition, attributions, and threat interpretations in individuals with BDD, compared to healthy controls (HCs). This is the first study to examine the effects of oxytocin in people with BDD. METHODS: Eighteen participants with BDD and 16 HCs received a single dose of 24 international units of intranasal oxytocin (Syntocinon®) or matching placebo in a randomized, placebo-controlled, within-subject crossover design. Participants completed the Emotion Recognition Task and Interpretation Questionnaire 45 min after administration. RESULTS: Oxytocin, relative to placebo, did not improve emotion recognition accuracy in either self-referent or other-referent contexts for individuals with BDD. However, oxytocin led to greater internal attributions in other-referent contexts for those with BDD compared to HCs. Rather than reducing self-blame, oxytocin led to other-directed blame. Oxytocin did not impact threat interpretations in BDD. CONCLUSIONS: Oxytocin may only impact specific aspects of higher order social cognition in BDD and may have unwanted effects on emotion attributions. Our results caution its clinical use in BDD.

Clinical features, cognitive biases, and treatment of body dysmorphic disorder.

In the past two decades, research advances have enhanced our understanding of the clinical features, cognitive biases, and treatment of body dysmorphic disorder (BDD). In this review, we critically examine the current state of the evidence on the proposed cognitive and emotional processing mechanisms of BDD. We describe how major findings in these areas made unique contributions to the development of an empirically informed cognitive-behavioral model of BDD, which in turn facilitated the translation of research to treatment strategies. Finally, we outline important areas of future research.

Clinical characteristics among sexual minority and heterosexual women with body dysmorphic disorder.

Body dysmorphic disorder (BDD) is a common disorder associated with substantial comorbidity, impairment, and poor quality of life. Research on subcultural variations of BDD is limited but may impact assessment and treatment of the disorder. The current study examined clinical features in a sample of sexual minority (SM; n = 43) and heterosexual (n = 155) women with diagnosed BDD. Participants completed self-report and clinician-administered measures of demographic and clinical characteristics. Results indicated largely similar clinical features across groups with some exceptions: compared to non-SM women, SM women were younger (M = 25.50 vs 31.96 years, p < .001), had better BDD-related insight (M = 14.51 vs 16.26, p = .01), endorsed a greater number of disliked body parts, and were more likely to express preoccupation with body build (OR = 4.6, 95% CI [2.0, 10.9]), chin/jaw (OR = 4.7, 95% CI [2.1, 10.3]), and shoulders (OR = 10.1, 95% CI [2.7, 37.9]), possibly reflecting nuanced beauty ideals within the SM community. There were no significant group differences in other body parts of concern, BDD severity, or depression. Future studies are needed in larger, more inclusive samples to explore the relationship between diverse identities on BDD and its associated features.

Self-focused brain predictors of cognitive behavioral therapy response in a transdiagnostic sample.

BACKGROUND: Effective biomarkers of cognitive behavioral therapy (CBT) response provide information beyond available behavioral or self-report measures and may optimize treatment selection for patients based on likelihood of benefit. No single biomarker reliably predicts CBT response. In this study, we evaluated patterns of brain connectivity associated with self-focused attention (SFA) as biomarkers of CBT response for anxiety and obsessive-compulsive disorders. We hypothesized that pre-treatment as well as pre-to post-treatment changes in functional connectivity would be associated with improvement during CBT in a transdiagnostic sample. METHODS: Twenty-seven patients with primary social anxiety disorder (n = 14) and primary body dysmorphic disorder (n = 13) were scanned before and after 12 sessions of CBT targeting their primary disorder. Eligibility was based on elevated trait SFA scores on the Public Self-Consciousness Scale. Seed-based resting state functional connectivity associated with symptom improvement was computed using a seed in the posterior cingulate cortex of the default mode network. RESULTS: At pre-treatment, stronger positive connectivity of the seed with the cerebellum, and stronger negative connectivity with the putamen, were associated with greater clinical improvement. Between pre-to post-treatment, greater anticorrelation between the seed and postcentral gyrus, extending into the inferior parietal lobule and precuneus/superior parietal lobule was associated with clinical improvement, although this did not survive thresholding. CONCLUSIONS: Pre-treatment functional connectivity with the default mode network was associated with CBT response. Behavioral and self-report measures of SFA did not contribute to predictions, thus highlighting the value of neuroimaging-based measures of SFA. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT02808702 https://clinicaltrials.gov/ct2/show/NCT02808702.

A broad-spectrum antiviral targeting entry of enveloped viruses.

We describe an antiviral small molecule, LJ001, effective against numerous enveloped viruses including Influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, and HIV-1. In sharp contrast, the compound had no effect on the infection of nonenveloped viruses. In vitro and in vivo assays showed no overt toxicity. LJ001 specifically intercalated into viral membranes, irreversibly inactivated virions while leaving functionally intact envelope proteins, and inhibited viral entry at a step after virus binding but before virus-cell fusion. LJ001 pretreatment also prevented virus-induced mortality from Ebola and Rift Valley fever viruses. Structure-activity relationship analyses of LJ001, a rhodanine derivative, implicated both the polar and nonpolar ends of LJ001 in its antiviral activity. LJ001 specifically inhibited virus-cell but not cell-cell fusion, and further studies with lipid biosynthesis inhibitors indicated that LJ001 exploits the therapeutic window that exists between static viral membranes and biogenic cellular membranes with reparative capacity. In sum, our data reveal a class of broad-spectrum antivirals effective against enveloped viruses that target the viral lipid membrane and compromises its ability to mediate virus-cell fusion.

Social Mishap Exposures for Social Anxiety Disorder: An Important Treatment Ingredient.

Conventional cognitive-behavioral therapy for social anxiety disorder, which is closely based on the treatment for depression, has been shown to be effective in numerous randomized placebo-controlled trials. Although this intervention is more effective than waitlist control group and placebo conditions, a considerable number of clients do not respond to this approach. Newer approaches include techniques specifically tailored to this particular population. One of these techniques, social mishap exposure practice, is associated with significant improvement in treatment gains. We will describe here the theoretical framework for social mishap exposures that addresses the client's exaggerated estimation of social cost. We will then present clinical observations and outcome data of a client who underwent treatment that included such social mishap exposures. Findings are discussed in the context of treatment implications and directions for future research.

Mechanisms of cognitive behavioral therapy vs. supportive psychotherapy in body dysmorphic disorder: An exploratory mediation analysis.

Body dysmorphic disorder (BDD) is common, severe, and often chronic. Cognitive behavioral therapy (CBT) is the first-line psychosocial treatment for BDD, with well-established efficacy. However, some patients do not improve with CBT, and little is known about how CBT confers its effects. Neurocognitive processes have been implicated in the etiology and maintenance of BDD and are targeted by CBT-BDD treatment components. Yet, the malleability of these factors in BDD, and their potential role in mediating symptom improvement, are not well understood. Understanding how treatment works could help optimize treatment outcomes. In this secondary data analysis of a randomized clinical trial of CBT vs. supportive psychotherapy (SPT) in BDD (n = 120), we examined whether treatment-related changes in detail processing (Rey-Osterrieth Complex Figure test), maladaptive appearance beliefs (Appearance Schemas Inventory-Revised), and emotion recognition (Emotion Recognition Task) mediated treatment outcome. All constructs improved over time and were associated with symptom improvement. CBT was associated with greater improvements in maladaptive beliefs than SPT. None of the variables examined mediated symptom improvement. Findings suggest that with successful treatment, individuals with BDD demonstrate reduced neurocognitive deficits (detail processing, emotion recognition, maladaptive beliefs) and that CBT is more likely than SPT to improve maladaptive appearance beliefs. More work is needed to understand mechanisms of change and thus maximize treatment outcomes.

Self-Focused Brain Predictors of Cognitive Behavioral Therapy Response in a Transdiagnostic Sample.

Background: Effective biomarkers of cognitive behavioral therapy (CBT) response provide information beyond available behavioral or self-report measures and may optimize treatment selection for patients based on likelihood of benefit. No single biomarker reliably predicts CBT response. In this study, we evaluated patterns of brain connectivity associated with self-focused attention (SFA) as biomarkers of CBT response for anxiety and obsessive-compulsive disorders. We hypothesized that pre-treatment as well as pre- to post-treatment changes in functional connectivity would be associated with improvement during CBT in a transdiagnostic sample. Methods: Twenty-seven patients with primary social anxiety disorder (n=14) and primary body dysmorphic disorder (n=13) were scanned before and after 12 sessions of CBT targeting their primary disorder. Eligibility was based on elevated trait SFA scores on the Public Self-Consciousness Scale. Seed-based resting state functional connectivity associated with symptom improvement was computed using a seed in the posterior cingulate cortex/precuneus that delineated a self-other functional network. Results: At pre-treatment, stronger positive connectivity of the seed with the cerebellum, insula, middle occipital gyrus, postcentral gyrus, and precuneus/superior parietal lobule, and stronger negative connectivity with the putamen, were associated with greater clinical improvement. Between pre- to post-treatment, greater anticorrelation between the seed and precuneus/superior parietal lobule was associated with clinical improvement, although this did not survive thresholding. Conclusions: Pre-treatment functional connectivity between regions involved in attentional salience, self-generated thoughts, and external attention predicted greater CBT response. Behavioral and self-report measures of SFA did not contribute to predictions, thus highlighting the value of neuroimaging-based measures of SFA. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT02808702 https://clinicaltrials.gov/ct2/show/NCT02808702.

Emotion dysregulation model of mood and anxiety disorders.

In this review, we present a transdiagnostic emotion dysregulation model of mood and anxiety disorders. This model posits that a triggering event, in conjunction with an existing diathesis, leads to negative or positive affect, depending on the person's affective style. Mood and anxiety disorders are the result of emotion dysregulation of negative affect, coupled with deficiencies in positive affect. The theoretical background of the model is discussed and a range of clinical applications of the model is described.

State and Trait Risk and Resilience Factors Associated with COVID-19 Impact and Obsessive-Compulsive Symptom Trajectories.

The COVID-19 pandemic may exacerbate common symptoms of obsessive-compulsive disorder, such as fears of contamination or causing harm to others. To investigate the potential impact of COVID-19 on obsessive-compulsive (OC) symptoms, we utilized a frequent sampling prospective design to assess changes in OC symptoms between April 2020 and January 2021. We examined in a broad clinical and non-clinical sample whether baseline risk (e.g., emotion dysregulation, anxiety sensitivity, intolerance of uncertainty) and protective (e.g., resilience) factors would predict OC symptom changes, and whether coping strategies would mediate week-to-week changes in COVID-19 impact and OC symptoms. Emotion dysregulation was associated with greater likelihood of OC symptom worsening, whereas resilience was associated with lower likelihood. Longitudinal mediation analyses revealed that coping strategies were not significant mediators; however, changes in adaptive coping were associated with subsequent-week OC symptom reductions. Regardless of perceived COVID-19 impact, implementing adaptive coping strategies may prospectively reduce OC symptoms. Supplementary Information: The online version contains supplementary material available at 10.1007/s41811-021-00128-4.

COVID-19 and obsessive-compulsive symptoms in a large multi-site college sample.

The COVID-19 pandemic poses unique risks to college students' mental health, and specifically to symptoms of obsessive-compulsive disorder (OCD). To better understand the relationship between COVID-19 impact and OC symptoms in this population, six colleges from across the US administered a battery of questionnaires and an emotion differentiation paradigm to eligible students (N = 841). We examined whether degree of pandemic-related disruption was associated with OC severity, and if so, whether this relationship was explained by trait (poor emotion regulation and differentiation) and state risk factors (poor sleep quality, less exercise frequency, less social support, thwarted sense of belongingness, and greater loneliness). Results indicated that the positive relationship between COVID-19 impact and OC severity was mediated by trait emotion-related processes (e.g., emotion regulation and differentiation), but no state risk factors emerged as significant mediators. Our findings contribute to the literature demonstrating a significant relationship between COVID-19 impact and OC severity, and highlight that emotion regulation difficulties may help explain this association. Our findings can inform evidence-based interventions on college campuses; however, the cross-sectional design precludes causal inferences. Future research should evaluate these relationships longitudinally and incorporate other psychosocial factors that may operate as mechanisms.

Maladaptive self-focused attention and default mode network connectivity: a transdiagnostic investigation across social anxiety and body dysmorphic disorders.

Maladaptive self-focused attention (SFA) is a bias toward internal thoughts, feelings and physical states. Despite its role as a core maintaining factor of symptoms in cognitive theories of social anxiety and body dysmorphic disorders (BDDs), studies have not examined its neural basis. In this study, we hypothesized that maladaptive SFA would be associated with hyperconnectivity in the default mode network (DMN) in self-focused patients with these disorders. Thirty patients with primary social anxiety disorder or primary BDD and 28 healthy individuals were eligible and scanned. Eligibility was determined by scoring greater than 1SD or below 1SD of the Public Self-Consciousness Scale normative mean, respectively, for each group. Seed-to-voxel functional connectivity was computed using a DMN posterior cingulate cortex (PCC) seed. There was no evidence of increased DMN functional connectivity in patients compared to controls. Patients (regardless of diagnosis) showed reduced functional connectivity of the PCC with several brain regions, including the bilateral superior parietal lobule (SPL), compared to controls, which was inversely correlated with maladaptive SFA but not associated with social anxiety, body dysmorphic, depression severity or rumination. Abnormal PCC-SPL connectivity may represent a transdiagnostic neural marker of SFA that reflects difficulty shifting between internal versus external attention.

Comparative prevalence, correlates of impairment, and service utilization for eating disorders across US ethnic groups: Implications for reducing ethnic disparities in health care access for eating disorders.

OBJECTIVE: The study compared the prevalence, correlates of functional impairment, and service utilization for eating disorders across Latinos, Asians, and African Americans living in the United States to non-Latino Whites. METHOD: Pooled data from the NIMH Collaborative Psychiatric Epidemiological Studies (CPES;NIMH, 2007) were used. RESULTS: The prevalence of anorexia nervosa (AN) and binge-eating disorder (BED) were similar across all groups examined, but bulimia nervosa (BN) was more prevalent among Latinos and African Americans than non-Latino Whites. Despite similar prevalence of BED among ethnic groups examined, lifetime prevalence of any binge eating (ABE) was greater among each of the ethnic minority groups in comparison to non-Latino Whites. Lifetime prevalence of mental health service utilization was lower among ethnic minority groups studied than for non-Latino Whites for respondents with a lifetime history of any eating disorder. DISCUSSION: These findings suggest the need for clinician training and health policy interventions to achieve optimal and equitable care for eating disorders across all ethnic groups in the United States.

Conformity to masculine norms and symptom severity among men diagnosed with muscle dysmorphia vs. body dysmorphic disorder.

Body dysmorphic disorder (BDD) is associated with severe comorbidity and impairment. Muscle dysmorphia (MD) is a subtype of BDD which has rarely been assessed outside of undergraduate student samples. Further, there are limited data comparing MD to other psychiatric disorders, including BDD. Thus, the aim of the current study is to explore differences in symptom severity and conformity to masculine norms in men diagnosed with BDD or MD. Men from the greater Boston, Massachusetts area completed a one-time assessment, which included clinician-based structured interviews and self-report questionnaires assessing MD symptom severity, BDD symptom severity, and conformity to traditional masculine norms. The sample was N = 30 men (MD: n = 15; BDD: n = 15). Statistically significant medium to large effects emerged with the MD group experiencing greater MD and BDD symptom severity, and positive attitudes towards the use of violence to solve problems. Although not reaching statistical significance, additional medium-to-large effects also emerged with the MD group reporting greater emotional restriction/suppression, heterosexual self-presentation, and desired sexual promiscuity compared to the BDD group. Findings suggest that men diagnosed with MD may experience greater MD/BDD symptom severity and endorsement of some components of 'traditional' masculine norms, compared to men diagnosed with BDD. Results may suggest that addressing some forms of rigid masculine norms (e.g., use of violence) in therapy could be useful in treating MD; however, additional research comparing clinical samples of men with MD and BDD are needed to guide the nosology, assessment, and treatment of MD.

Mechanisms of Change in Cognitive Behavioral Therapy for Body Dysmorphic Disorder.

Although cognitive-behavioral therapy (CBT) is highly efficacious for body dysmorphic disorder (BDD), not all patients benefit, and mechanisms underlying response remain unknown. In this first report of the mechanisms underlying improvement with CBT for BDD, we examined whether cognitive (maladaptive beliefs, perfectionism, schemas) and behavioral (checking, grooming, avoidance behaviors) changes mediate the effect of CBT on BDD symptom reduction. Forty-five participants with BDD who enrolled in a CBT for BDD treatment development study were included in two sets of analyses: (1) between-subject mediation of the effect of 12 weeks of CBT versus waitlist, and (2) within-subject mediation of longitudinal change in BDD symptom severity during 24 weeks of CBT. No significant mediators emerged in the between-subject analysis. Checking, grooming, avoidance behaviors, and maladaptive beliefs mediated within-subject improvements over time. Findings suggest that BDD symptom reduction occurs through the very mechanisms that have been hypothesized to maintain BDD in CBT models. Targeting certain cognitive (beliefs about appearance) and behavioral (checking, grooming, and avoidance behaviors) mechanisms in future treatment trials may enhance symptom improvement during CBT. National Clinical Trials Registration Identifier # NCT00106223.

Serum oxytocin levels are elevated in body dysmorphic disorder and related to severity of psychopathology.

The neurobiological mechanisms underlying the pathophysiology of body dysmorphic disorder (BDD) are not well-understood. Oxytocin is a central nervous system peptide which regulates socioemotional functioning and may mediate physiologic processes in a range of psychiatric disorders, particularly those characterized by interpersonal dysfunction. Examining the role of oxytocin in the development and maintenance of BDD may elucidate new targets for intervention. The present study examined endogenous serum oxytocin levels in BDD. Given the prominent deficits in social functioning in BDD, we expected that BDD would be characterized by low basal serum oxytocin concentrations, relative to healthy controls, and that low oxytocin levels would be associated with BDD symptom severity as well as poor performance on measures of social cognition. Twenty individuals with BDD and 28 healthy controls completed a fasting blood draw consisting of frequent sampling every five minutes for one hour to measure pooled levels of oxytocin. Contrary to our hypotheses, people with BDD displayed higher concentrations of oxytocin, compared to their healthy control counterparts, and their oxytocin levels were positively correlated with BDD symptom severity. There were no associations between oxytocin levels and measures of social cognition. These findings suggest increased production of endogenous oxytocin in BDD. Prospective research is needed to determine whether this contributes to or is a consequence of BDD symptomatology.

Personality as a Predictor of Treatment Response to Escitalopram in Adults With Body Dysmorphic Disorder.

OBJECTIVE: Serotonin reuptake inhibitors (SRIs) are the first-line pharmacotherapy for body dysmorphic disorder (BDD), a common and severe disorder. However, predictors and correlates of treatment response are not well understood. A closer examination of baseline personality dimensions and disorders and of changes in personality during SRI treatment is needed to advance knowledge of this clinically important issue. METHOD: We conducted a secondary analysis of data from a pharmacotherapy relapse prevention trial of the SRI escitalopram in adults with BDD to examine personality dimensions and traits, as well as whether these variables predict and correlate with treatment response. A total of 65 participants with BDD completed the Revised NEO Personality Inventory (NEO PI-R) before starting open-label treatment with escitalopram and 42 participants completed the NEO PI-R after treatment. RESULTS: At baseline, participants with BDD displayed higher levels of neuroticism and lower levels of extraversion than a normed reference group. Higher baseline neuroticism was a significant predictor of nonresponse to escitalopram treatment, even when baseline depression severity was controlled for. Changes in neuroticism were not associated with treatment response. CONCLUSION: Our findings underscore the relationship between BDD and neuroticism, and they suggest a link between neuroticism and SRI treatment response.

Working hard for oneself or others: Effects of oxytocin on reward motivation in social anxiety disorder.

There is some evidence to suggest that oxytocin promotes social behavior, especially for disorders characterized by social dysfunction, such as social anxiety disorder (SAD). The goal of this study was to examine the effect of oxytocin on reward motivation in SAD. We tested whether oxytocin promotes prosocial, or antisocial, self-directed decisions, and whether its effects depended on social anxiety severity and attachment. Fifty-two males with SAD received 24 international units of oxytocin or placebo, and completed a reward motivation task that measured willingness to work for self vs. other monetary rewards. Although there was no main drug effect, social anxiety severity moderated the effect of oxytocin. Less socially anxious individuals who received oxytocin worked harder for other vs. own rewards, compared to high socially anxious individuals. Attachment did not moderate this effect. Among people with SAD, oxytocin enhances prosocial behaviors in individuals with relatively lower levels of social anxiety. National Institutes of Health ClinicalTrials.gov Registry #NCT01856530. https://clinicaltrials.gov/ct2/show/NCT01856530?term=oxytocin+pro-social&rank=2.