Separating signal from noise in wastewater data: An algorithm to identify community-level COVID-19 surges in real time.

Wastewater monitoring has provided health officials with early warnings for new COVID-19 outbreaks, but to date, no approach has been validated to distinguish signal (sustained surges) from noise (background variability) in wastewater data to alert officials to the need for heightened public health response. We analyzed 62 wk of data from 19 sites participating in the North Carolina Wastewater Monitoring Network to characterize wastewater metrics around the Delta and Omicron surges. We found that wastewater data identified outbreaks 4 to 5 d before case data (reported on the earlier of the symptom start date or test collection date), on average. At most sites, correlations between wastewater and case data were similar regardless of how wastewater concentrations were normalized and whether calculated with county-level or sewershed-level cases, suggesting that officials may not need to geospatially align case data with sewershed boundaries to gain insights into disease transmission. Although wastewater trend lines captured clear differences in the Delta versus Omicron surge trajectories, no single wastewater metric (detectability, percent change, or flow-population normalized viral concentrations) reliably signaled when these surges started. After iteratively examining different combinations of these three metrics, we developed the Covid-SURGE (Signaling Unprecedented Rises in Groupwide Exposure) algorithm, which identifies unprecedented signals in the wastewater data. With a true positive rate of 82%, a false positive rate of 7%, and strong performance during both surges and in small and large sites, our algorithm provides public health officials with an automated way to flag community-level COVID-19 surges in real time.

Lower Intent to Comply with COVID-19 Public Health Recommendations Correlates to Higher Disease Burden in Following 30 Days.

OBJECTIVES: We sought to determine whether self-reported intent to comply with public health recommendations correlates with future coronavirus disease 2019 (COVID-19) disease burden. METHODS: A cross-sectional, online survey of US adults, recruited by snowball sampling, from April 9 to July 12, 2020. Primary measurements were participant survey responses about their intent to comply with public health recommendations. Each participant's intent to comply was compared with his or her local COVID-19 case trajectory, measured as the 7-day rolling median percentage change in COVID-19 confirmed cases within participants' 3-digit ZIP code area, using public county-level data, 30 days after participants completed the survey. RESULTS: After applying raking techniques, the 10,650-participant sample was representative of US adults with respect to age, sex, race, and ethnicity. Intent to comply varied significantly by state and sex. Lower reported intent to comply was associated with higher COVID-19 case increases during the following 30 days. For every 3% increase in intent to comply with public health recommendations, which could be achieved by improving average compliance by a single point for a single item, we estimate a 9% reduction in new COVID-19 cases during the subsequent 30 days. CONCLUSIONS: Self-reported intent to comply with public health recommendations may be used to predict COVID-19 disease burden. Measuring compliance intention offers an inexpensive, readily available method of predicting disease burden that can also identify populations most in need of public health education aimed at behavior change.

Inflammatory cytokines in major depressive disorder: A case-control study.

INTRODUCTION: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. METHODS: Subjects aged 18-70 years, diagnosed with major depressive disorder and presenting with chronic course of illness, as well as matched controls ( n = 236), were evaluated by trained raters and provided blood for cytokine measurements. Cytokine levels in EDTA plasma were measured with the MILLIPLEX Multi-Analyte Profiling Human Cytokine/Chemokine Assay employing Luminex technology. The Wilcoxon rank-sum test was used to compare cytokine levels between major depressive disorder subjects and healthy volunteers, before (interleukin [IL]-1ß, IL-6, and tumor necrosis factor-α) and after Bonferroni correction for multiple comparisons (IL-1α, IL-2, IL-3, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IFN-γ-inducible protein 10, Eotaxin, interferon-γ, monotype chemoattractant protein-1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor and vascular endothelial growth factor). RESULTS: There were no significant differences in cytokine levels between major depressive disorder subjects and controls, both prior to and after correction for multiple analyses (significance set at p ⩽ 0.05 and p ⩽ 0.002, respectively). CONCLUSION: Our well-characterized examination of cytokine plasma levels did not support the association of major depressive disorder with systemic inflammation. The heterogeneity of major depressive disorder, as well as a potential sampling bias selecting for non-inflammatory depression, might have determined our findings discordant with the literature.

Examining the Role of Anxiety Sensitivity in Sleep Dysfunction Across Anxiety Disorders.

Anxiety Sensitivity (AS) has been associated with sleep difficulties in certain anxiety disorder populations, but no studies have examined cross-diagnostically the role of anxiety sensitivity in sleep dysfunction. Three hundred one participants with generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD) completed an ancillary questionnaire-based study. Linear regression was used to examine AS and sleep dysfunction, and mediation analyses were used to examine whether AS was a mediator of the effect of primary diagnosis on sleep. AS was associated with increased sleep dysfunction across anxiety disorders, and primary anxiety disorder diagnosis was significantly associated with sleep dysfunction. However, after controlling for AS, primary diagnosis was no longer significant. AS significantly mediated the effects of PD versus SAD and of PD versus GAD on sleep dysfunction, but did not significantly mediate the effect of GAD versus SAD on sleep dysfunction. Taken together, AS appears to be a more important predictor of sleep dysfunction overall, emphasizing the cross-diagnostic nature of AS and bolstering the RDoC initiative approach for treating psychological dysfunction.

Re-examining premature mortality in anorexia nervosa: a meta-analysis redux.

Anorexia nervosa (AN) is reported to have the highest premature mortality of any psychiatric disorder, but recent meta-analyses may have inflated estimates. We sought to re-estimate mortality after methodological corrections and to identify predictors of mortality. We included 41 cohorts from 40 peer-reviewed studies published between 1966 and 2010. Methods included double data extraction, log-linear regression with an over-dispersed Poisson model, and all-cause and suicide-specific standardized mortality ratios (SMRs), with 95% Poisson confidence intervals. Participants with AN were 5.2 [3.7-7.5] times more likely to die prematurely from any cause, and 18.1 [11.5-28.7] times more likely to die by suicide than 15-34 year old females in the general population. Our estimates were 10% and 49% lower, respectively, than previously reported SMRs. Risk of premature mortality was highest in studies with older participants, although confounding by treatment was present. Gender, ascertainment, and diagnostic criteria also impacted risk.

Binge/purge thoughts in nonsuicidal self-injurious adolescents: an ecological momentary analysis.

OBJECTIVE: Adolescents who self-injure often engage in bingeing/purging (BP). Ecological momentary assessment (EMA) has potential to offer insight into the relationship between self-injury and BP. The aims of this study were to examine the frequency and context of BP using EMA in a sample of nonsuicidal self-injurious (NSSI) adolescents. METHOD: Thirty adolescents with a history of NSSI responded to questions regarding self-destructive thoughts/behaviors using a palm-pilot device. Descriptive analyses compared thought/behavior contexts during reports of BP and NSSI thoughts/behaviors (occurring together vs. individually). RESULTS: BP thoughts were present in 22 (73%) participants, occurring on 32% of the person-days recorded; 59% of these participants actually engaged in BP behavior. Seventy-nine percent of BP thoughts co-occurred with other self-destructive thoughts. Adolescents were more often with friends/peers than alone or with family when having BP thoughts. Worry and pressure precipitated both BP and NSSI thoughts, but perceived criticism and feelings of rejection/hurt were associated more often with BP thoughts than with NSSI thoughts. DISCUSSION: BP thoughts and behaviors were common in this sample, often occurring with other self-destructive thoughts. Future EMA research is needed to address the function of BP symptoms, the contextual variables that increase risk for BP thoughts, and the factors that predict the transition of thoughts into behaviors in adolescents with and without self-injury.

Two weeks of pretreatment with escitalopram facilitates extinction learning in healthy individuals.

OBJECTIVE: We aimed to examine whether pretreatment with escitalopram would be associated with reduced fear acquisition and enhanced extinction learning in a fear conditioning paradigm, compared with placebo. METHODS: Healthy volunteers were randomized in double-blind fashion, to 14 days of escitalopram 10 mg/day (n = 18) or placebo (n = 20) prior to a classical fear conditioning paradigm. RESULTS: Although escitalopram was associated with a smaller skin conductance (SC) orienting response during habituation, no medication effects on fear acquisition were found. Escitalopram was associated with faster extinction of SC responses, compared with placebo, as revealed by a significant drug × conditioned stimulus × trial interaction for early extinction (F(3, 30) = 3.26, p = 0.035) and late extinction (F(3, 30) = 3.27, p = 0.035) trials. After adjustment for age, orienting response, and acquisition, results from linear contrast remained significant for early extinction (F(1, 29) = 5.43, p = 0.027). CONCLUSIONS: Escitalopram administered for 14 days prior to a fear conditioning paradigm did not influence acquisition of a conditioned fear response but did facilitate extinction learning. Impairments in extinction learning have been identified as a key component of posttraumatic stress disorder; our preliminary findings suggest that additional experimental and clinical studies assessing the efficacy of selective serotonin reuptake inhibitors for posttraumatic stress disorder prevention are warranted.

Wastewater monitoring can anchor global disease surveillance systems.

To inform the development of global wastewater monitoring systems, we surveyed programmes in 43 countries. Most programmes monitored predominantly urban populations. In high-income countries (HICs), composite sampling at centralised treatment plants was most common, whereas grab sampling from surface waters, open drains, and pit latrines was more typical in low-income and middle-income countries (LMICs). Almost all programmes analysed samples in-country, with an average processing time of 2·3 days in HICs and 4·5 days in LMICs. Whereas 59% of HICs regularly monitored wastewater for SARS-CoV-2 variants, only 13% of LMICs did so. Most programmes share their wastewater data internally, with partnering organisations, but not publicly. Our findings show the richness of the existing wastewater monitoring ecosystem. With additional leadership, funding, and implementation frameworks, thousands of individual wastewater initiatives can coalesce into an integrated, sustainable network for disease surveillance-one that minimises the risk of overlooking future global health threats.

Plasma oxytocin immunoreactive products and response to trust in patients with social anxiety disorder.

BACKGROUND: Generalized Social Anxiety Disorder (GSAD) is characterized by excessive fear and avoidance of several types of social and performance situations. The pathophysiology is not well understood, but research in animals and humans has provided evidence that oxytocin helps regulate normal social affiliative behavior. Previous work in healthy male subjects demonstrated a rise in plasma oxytocin after receiving a high trust signal. To examine the oxytocin system in GSAD, we measured plasma oxytocin in GSAD patients and controls, before and after the social "Trust Game," a neuroeconomic test examining trust behavior and reaction to trust using real monetary incentives. METHODS: Thirty-nine subjects with GSAD and 28 healthy controls provided three blood samples for oxytocin measurement before the Trust Game, and one sample after the game. Plasma estradiol was also measured at baseline. The Trust Game protocol version prioritized the sending of a signal of high cooperation and trust to all participants. All analyses controlled for gender and estradiol levels. RESULTS: Mean oxytocin levels post-Trust Game (P = .025), and overall (area under the curve, P = .011) were lower in GSADpatients compared to controls, after controlling for sex and estradiol. There was no significant change in oxytocin levels after the game in either group. CONCLUSIONS: We report low plasma oxytocin levels in patients with GSAD during a prosocial laboratory task paradigm. Additional research will be important to further examine the relationship between oxytocin and social behavior in GSAD.

Predictors of treatment outcome in modular cognitive therapy for obsessive-compulsive disorder.

BACKGROUND: The present study sought to identify predictors of outcome for a comprehensive cognitive therapy (CT) developed for patients with obsessive-compulsive disorder (OCD). METHODS: Treatment was delivered over 22 sessions and included standard CT methods, as well as specific strategies designed for subtypes of OCD including religious, sexual, and other obsessions. This study of 39 participants assigned to CT examined predictors of outcomes assessed on the Yale-Brown Obsessive Compulsive Scale. A variety of baseline symptom variables were examined as well as treatment expectancy and motivation. RESULTS: Findings indicated that participants who perceived themselves as having more severe OCD at baseline remained in treatment but more severe symptoms were marginally associated with worse outcome for those who completed therapy. Depressed and anxious mood did not predict post-test outcome, but more Axis I comorbid diagnoses (mainly major depression and anxiety disorders), predicted more improvement, as did the presence of sexual (but not religious) OCD symptoms, and stronger motivation (but not expectancy). A small rebound in OCD symptoms at 1-year follow-up was significantly predicted by higher scores on personality traits, especially for schizotypal (but not obsessive-compulsive personality) traits. CONCLUSIONS: Longer treatment may be needed for those with more severe symptoms at the outset. CT may have positive effects not only on OCD symptoms but also on comorbid depressive and anxious disorders and associated underlying core beliefs. Findings are discussed in light of study limitations and research on other predictors.

Informing the symptom profile of complicated grief.

BACKGROUND: Complicated Grief (CG) is under consideration as a new diagnosis in DSM5. We sought to add empirical support to the current dialogue by examining the commonly used Inventory of Complicated Grief (ICG) scale completed by 782 bereaved individuals. METHODS: We employed IRT analyses, factor analyses, and sensitivity and specificity analyses utilizing our full sample (n = 782), and also compared confirmed CG cases (n = 288) to noncases (n = 377). Confirmed CG cases were defined as individuals bereaved at least 6 months who were seeking care for CG, had an ICG ≥ 30, and received a structured clinical interview for CG by a certified clinician confirming CG as their primary illness. Noncases were bereaved individuals who did not present with CG as a primary complaint (including those with depression, bipolar disorder, anxiety disorders, and controls) and had an ICG<25. RESULTS: IRT analyses provided guidance about the most informative individual items and their association with CG severity. Factor analyses demonstrated a single factor solution when the full sample was considered, but within CG cases, six symptom clusters emerged: (1) yearning and preoccupation with the deceased, (2) anger and bitterness, (3) shock and disbelief, (4) estrangement from others, (5) hallucinations of the deceased, and (6) behavior change, including avoidance and proximity seeking. The presence of at least one symptom from three different symptom clusters optimized sensitivity (94.8%) and specificity (98.1%). CONCLUSIONS: These data, derived from a diverse and predominantly clinical help seeking population, add an important perspective to existing suggestions for DSM5 criteria for CG.

Complicated grief and related bereavement issues for DSM-5.

Bereavement is a severe stressor that typically incites painful and debilitating symptoms of acute grief that commonly progresses to restoration of a satisfactory, if changed, life. Normally, grief does not need clinical intervention. However, sometimes acute grief can gain a foothold and become a chronic debilitating condition called complicated grief. Moreover, the stress caused by bereavement, like other stressors, can increase the likelihood of onset or worsening of other physical or mental disorders. Hence, some bereaved people need to be diagnosed and treated. A clinician evaluating a bereaved person is at risk for both over-and under-diagnosis, either pathologizing a normal condition or neglecting to treat an impairing disorder. The authors of DSM IV focused primarily on the problem of over-diagnosis, and omitted complicated grief because of insufficient evidence. We revisit bereavement considerations in light of new research findings. This article focuses primarily on a discussion of possible inclusion of a new diagnosis and dimensional assessment of complicated grief. We also discuss modifications in the bereavement V code and refinement of bereavement exclusions in major depression and other disorders.

Correlates of quality of life and functional disability in individuals with body dysmorphic disorder.

OBJECTIVE: Body dysmorphic disorder (BDD) is a chronic mental illness characterized by low quality of life and functional disability across multiple domains. Despite the clinical importance of understanding impairment in BDD, there has been little research examining the factors that contribute to these constructs. The present study was designed to examine sociodemographic and clinical correlates of quality of life and disability (work, social, and family) in a sample of individuals with moderately severe BDD symptoms. METHOD: Participants completed an internet survey with questions about demographics, BDD phenomenology, treatment, and impairment. Only participants who completed all study measures and received a score≥16 on the 10-item Yale-Brown Obsessive Compulsive Scale, Modified for BDD (BDD-YBOCS), indicating the presence of clinical BDD symptoms, were included in the analysis (n=256). Multivariate regression with backwards variable selection was used to identify significant predictors of quality of life and functional disability, assessed with the Quality of Life Enjoyment and Satisfaction Scale-Short Form (QLESQ-SF) and the Sheehan Disability Scale (SDS), respectively. RESULTS: BDD symptom severity was inversely associated with quality of life and directly associated with disability in all domains. After controlling statistically for BDD symptom severity, sociodemographic and clinical factors such as age, gender, ethnicity, marital status, insurance, body parts of concern, depression symptoms, and anxiety symptoms were significantly associated with impairment. CONCLUSION: Results suggest a multidimensional nature of quality of life and functional disability and underscore the importance of developing holistic treatment strategies to address impairment in BDD.

Developing a Flexible National Wastewater Surveillance System for COVID-19 and Beyond.

BACKGROUND: Wastewater testing offers a cost-effective strategy for measuring population disease prevalence and health behaviors. For COVID-19, wastewater surveillance addresses testing gaps and provides an early warning for outbreaks. As U.S. federal agencies build a National Wastewater Surveillance System around the pandemic, thinking through ways to develop flexible frameworks for wastewater sampling, testing, and reporting can avoid unnecessary system overhauls for future infectious disease, chronic disease, and drug epidemics. OBJECTIVES: We discuss ways to transform a historically academic exercise into a tool for epidemic response. We generalize lessons learned by a global network of wastewater researchers around validation and implementation for COVID-19 and opioids while also drawing on our experience with wastewater-based epidemiology in the United States. DISCUSSION: Sustainable wastewater surveillance requires coordination between health and safety officials, utilities, labs, and researchers. Adapting sampling frequency, type, and location to threat level, community vulnerability, biomarker properties, and decisions that wastewater data will inform can increase the practical value of the data. Marketplace instabilities, coupled with a fragmented testing landscape due to specialization, may require officials to engage multiple labs to test for known and unknown threats. Government funding can stabilize the market, balancing commercial pressures with public good, and incentivize data sharing. When reporting results, standardizing metrics and contextualizing wastewater data with health resource data can provide insights into a community's vulnerability and identify strategies to prevent health care systems from being overwhelmed. If wastewater data will inform policy decisions for an entire community, comparing characteristics of the wastewater treatment plant's service population to those of the larger community can help determine whether the wastewater data are generalizable. Ethical protocols may be needed to protect privacy and avoid stigmatization. With data-driven approaches to sample collection, analysis, and interpretation, officials can use wastewater surveillance for adaptive resource allocation, pandemic management, and program evaluation. https://doi.org/10.1289/EHP8572.

Predictors and moderators of symptom change during cognitive-behavioral therapy or supportive psychotherapy for body dysmorphic disorder.

BACKGROUND: Research on predictors of treatment outcome in body dysmorphic disorder, a common and severe disorder, is very limited, and no prior studies have examined moderators of outcome. Because treatment is often but not always efficacious, it is important to identify who is more likely to benefit. We examined predictors and moderators of improvement with therapist-delivered cognitive-behavioral therapy versus supportive psychotherapy in the only study of these treatments for body dysmorphic disorder. This report presents secondary analyses from a study whose primary findings have previously been published (Wilhelm et al., 2019). METHODS: Participants (N=120) with DSM-IV body dysmorphic disorder were randomized to therapist-delivered weekly cognitive-behavioral therapy or supportive therapy for 24 weeks. Using reliable and valid measures, we tested baseline body dysmorphic disorder severity, insight/delusionality, and depression severity as predictors and moderators of overall and treatment modality-specific symptom change. We explored additional variables as predictors and moderators of outcome. RESULTS: Greater treatment credibility (p=0.02) and presence of obsessive-compulsive personality disorder (p=0.03) predicted greater improvement. Serotonin-reuptake inhibitor treatment at baseline (unchanged during the study) (p=0.01) predicted less improvement. No other variables predicted or moderated outcome (all p>0.05). LIMITATIONS: The study was not powered a priori to detect predictor or moderation effects, which limited our ability to detect them unless they were strong. CONCLUSIONS: Because greater treatment credibility predicted better outcomes, fostering credibility during therapy may maximize gains. Improvement was not impeded by more severe body dysmorphic disorder, depressive symptoms, or poorer insight. No variables moderated treatment-specific improvement.

Developing and testing an automated qualitative assistant (AQUA) to support qualitative analysis.

Qualitative research remains underused, in part due to the time and cost of annotating qualitative data (coding). Artificial intelligence (AI) has been suggested as a means to reduce those burdens, and has been used in exploratory studies to reduce the burden of coding. However, methods to date use AI analytical techniques that lack transparency, potentially limiting acceptance of results. We developed an automated qualitative assistant (AQUA) using a semiclassical approach, replacing Latent Semantic Indexing/Latent Dirichlet Allocation with a more transparent graph-theoretic topic extraction and clustering method. Applied to a large dataset of free-text survey responses, AQUA generated unsupervised topic categories and circle hierarchical representations of free-text responses, enabling rapid interpretation of data. When tasked with coding a subset of free-text data into user-defined qualitative categories, AQUA demonstrated intercoder reliability in several multicategory combinations with a Cohen's kappa comparable to human coders (0.62-0.72), enabling researchers to automate coding on those categories for the entire dataset. The aim of this manuscript is to describe pertinent components of best practices of AI/machine learning (ML)-assisted qualitative methods, illustrating how primary care researchers may use AQUA to rapidly and accurately code large text datasets. The contribution of this article is providing guidance that should increase AI/ML transparency and reproducibility.

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.

Anxiety Symptoms Questionnaire (ASQ): development and validation.

BACKGROUND: The Anxiety Symptoms Questionnaire (ASQ) is a brief self-report questionnaire which measures frequency and intensity of symptoms and was developed to improve assessment of anxiety symptoms in a clinical setting. We examined the reliability and validity of the ASQ in patients with anxiety disorders and/or depression, non-clinical control subjects and college students. METHODS: 240 outpatients with generalised anxiety disorder, social anxiety disorder, panic disorder or major depressive disorder were administered the ASQ and additional questionnaires measuring depression and anxiety, as were 111 non-clinical control subjects and 487 college students. Factor analysis, Pearson's correlation coefficients and logistic regression were used to assess reliability and validity. Test-retest reliability of the ASQ was measured using a subset who were re-administered the ASQ after 4 weeks. RESULTS: Factor analysis revealed measurement of a single dimension by the ASQ. Internal consistency and test-retest reliability were strong. The ASQ total score also significantly distinguished patients with an anxiety disorder from the clinical controls above and beyond the clinician-rated Hamilton Anxiety Scale. CONCLUSIONS: The ASQ is a valid, reliable and effective self-rated measure of anxiety and may be a useful tool for screening and assessing anxiety symptoms in psychiatric as well as college settings.

Efficacy and Posttreatment Effects of Therapist-Delivered Cognitive Behavioral Therapy vs Supportive Psychotherapy for Adults With Body Dysmorphic Disorder: A Randomized Clinical Trial.

Importance: Cognitive behavioral therapy (CBT), the best-studied treatment for body dysmorphic disorder (BDD), has to date not been compared with therapist-delivered supportive psychotherapy, the most commonly received psychosocial treatment for BDD. Objective: To determine whether CBT for BDD (CBT-BDD) is superior to supportive psychotherapy in reducing BDD symptom severity and associated BDD-related insight, depressive symptoms, functional impairment, and quality of life, and whether these effects are durable. Design, Setting, and Participants: This randomized clinical trial conducted at Massachusetts General Hospital and Rhode Island Hospital recruited adults with BDD between October 24, 2011, and July 7, 2016. Participants (n = 120) were randomized to the CBT-BDD arm (n = 61) or the supportive psychotherapy arm (n = 59). Weekly treatments were administered at either hospital for 24 weeks, followed by 3- and 6-month follow-up assessments. Measures were administered by blinded independent raters. Intention-to-treat statistical analyses were performed from February 9, 2017, to September 22, 2018. Interventions: Cognitive behavioral therapy for BDD, a modular skills-based treatment, addresses the unique symptoms of the disorder. Supportive psychotherapy is a nondirective therapy that emphasizes the therapeutic relationship and self-esteem; supportive psychotherapy was enhanced with BDD-specific psychoeducation and treatment rationale. Main Outcomes and Measures: The primary outcome was BDD symptom severity measured by the change in score on the Yale-Brown Obsessive-Compulsive Scale Modified for BDD from baseline to end of treatment. Secondary outcomes were the associated symptoms and these were assessed using the Brown Assessment of Beliefs Scale, Beck Depression Inventory-Second Edition, Sheehan Disability Scale, and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form. Results: Of the 120 participants, 92 (76.7%) were women, with a mean (SD) age of 34.0 (13.1) years. The difference in effectiveness between CBT-BDD and supportive psychotherapy was site specific: at 1 site, no difference was detected (estimated mean [SE] slopes, -18.6 [1.9] vs -16.7 [1.9]; P = .48; d growth-modeling analysis change, -0.25), whereas at the other site, CBT-BDD led to greater reductions in BDD symptom severity, compared with supportive psychotherapy (estimated mean [SE] slopes, -18.6 [2.2] vs -7.6 [2.0]; P < .001; d growth-modeling analysis change, -1.36). No posttreatment symptom changes were observed throughout the 6 -months of follow-up (all slope P ≥ .10). Conclusions and Relevance: Body dysmorphic disorder severity and associated symptoms appeared to improve with both CBT-BDD and supportive psychotherapy, although CBT-BDD was associated with more consistent improvement in symptom severity and quality of life. Trial Registration: ClinicalTrials.gov identifier: NCT01453439.