Racial Implicit Associations in Child Psychiatry.

OBJECTIVE: Racial disparities in diagnosis and treatment are prevalent in child psychiatry, including disparate diagnosis rates of internalizing and externalizing disorders in Black and White children. However, limited research has investigated mechanisms that contribute to these disparities. This study examined child racial implicit associations in psychiatric clinicians and medical students to address this gap. METHOD: Psychiatrists and trainees completed an online survey including 2 race Implicit Association Tests (IATs) pairing child faces to words with either positive or negative valence, and words related to internalizing or externalizing behavioral problems. We further investigated psychiatrists' and trainees' demographic predictors of implicit associations. RESULTS: Data were analyzed from 235 psychiatrists and trainees (112 child and adolescent psychiatrists and fellows) who met inclusion criteria. Psychiatrists and trainees demonstrated greater moderate-to-strong association between Black child faces and "bad" words (44.3%) vs "good" words (6.4%), and between externalizing words (41.7%) and internalizing words (7.2%). Psychiatrists' and trainees' demographic characteristics including being female (ß = -0.12; 95% CI = -0.23 to -0.01; p < .05), Black (ß = -0.36; 95% CI = -0.54 to -0.18; p < .001), or an attending physician (ß = -0.26; 95% CI = -0.45 to -0.06; p = .01) were significant predictors of decreased association between Black child faces and negative valence words. Being female was a significant predictor of decreased association between Black child faces and externalizing words (ß = -0.26; 95% CI = -0.45 to -0.06; p = .01). CONCLUSION: Participating psychiatrists and trainees demonstrated bias toward associating Black rather than White child faces with negative words and externalizing behavioral problems. Future research should examine the following: (1) racial implicit associations in a more generalizable sample, (2) the relationship between race IATs and provider behavior, and (3) interventions to reduce racial inequities in psychiatry, including individual and systemic solutions. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science.

Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci.

Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder.

The effects of Shaoma Zhijing granules and its main components on Tourette syndrome.

BACKGROUND: Tourette syndrome (TS) represents a neurodevelopmental disorder characterized by an uncertain etiology and influencing factors. Frequently, it co-occurs with conditions such as attention deficit hyperactivity disorder, obsessive-compulsive disorder, and sleep disturbances, which have garnered substantial attention from the research community in recent years. Clinical trials have demonstrated that Shaoma Zhijing Granules (SMZJG, 5-ling granule, also known as TSupport or T92 under U.S. development), a traditional Chinese medicine compound, is an effective treatment for TS. PURPOSE: To conduct scientometric analysis on developing trends, research countries and institutions, current status, hot spots of TS and discuss the underlying mechanisms of SMZJG and its main components on TS. The aim is to provide valuable reference for ongoing clinical and basic research on TS and SMZJG. STUDY DESIGN & METHODS: Using Tourette syndrome, SMZJG and its main components along with their synonyms as keywords, we conducted a comprehensive search across major scientific databases including the Web of Science Core Collection, PubMed and China National Knowledge Infrastructure (CNKI) databases. A total of 5952 references and 99 patents were obtained. Among these, 5039 articles and reviews, as well as 54 patents were analyzed by Citespace and VOSviewer software. RESULTS: The available evidence indicates that the SMZJG's components likely exert their mechanisms in treating TS by regulating the dopaminergic pathway system, neurotransmitter imbalances, reducing neuroinflammation, promoting the repair of nerve damage and improving sleep disorders. CONCLUSION: This comprehensive analysis lays the foundation for an extensive exploration of the feasibility and clinical applications of SMZJG in TS treatment.

Editorial: Adolescent Eating Disorders Are Increasing and We Need to Do More.

The negative effects of the COVID-19 pandemic on youth mental health have been significant.1,2 The impact of the pandemic on eating disorders has been particularly notable, given the numerous risk factors exacerbated during the pandemic, such as increased social isolation and body image concerns associated with amplified virtual and social media exposure.3 Although the rise of eating disorder presentations have been documented by increased pediatric hospital admissions4 at an earlier ages of onset,5 there has, until this time, not been a meta-analytical approach to understanding the full scope of this impact on health care use. In our ever-burdened pediatric mental health care systems, it is crucial for the field to understand how health care use for eating disorders has been affected. As such, we read with keen interest the article by Madigan et al.6 This meta-analysis fills a gap in the field, analyzing the health care visits of close to 150,000 children and adolescents across more than 300 sites. This study highlights an important theme that has been observed across our mental health systems: there has been a significant increase in severe eating disorder symptom expression since the start of the pandemic. This article provides the empirical evidence to support what has been anecdotally and qualitatively observed across sites-namely, an increased use of higher levels of care, such as emergency rooms and inpatient units, in addition to outpatient care. This increase in service use for eating disorders has been particularly sharp among girls, adolescents, and those presenting with restricting presentations such as anorexia nervosa.6.

An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis.

INTRODUCTION: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. METHODS: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. RESULTS: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. CONCLUSION: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

Post-event rumination and social anxiety: a systematic review and meta-analysis.

Post-event rumination, the extent to which one engages in persistent, detailed, and negative thinking following social situations, serves as a risk process in the pathophysiology of social anxiety. Although a substantial body of research has assessed post-event rumination and social anxiety, this literature has produced inconsistent results. We conducted a systematic review and meta-analysis to examine whether the magnitude of the association between post-event rumination and social anxiety varied as a function of questionnaire and/or task utilized. We included all studies reporting a correlation between post-event rumination and social anxiety symptomatology. Fisher's z correlation coefficients were calculated through random-effect meta-analyses. Results indicated a moderate association between post-event rumination and social anxiety symptomatology (r = 0.45, p < 0.001, 95%CI [0.40-0.50]). Subgroup meta-analyses indicated that the type of questionnaire used to assess post-event rumination (Q = 44.36, df = 3, p < 0.001) and social anxiety (Q = 26.44, df = 8, p < 0.001), as well as the task conducted prior to assessing post-event rumination (Q = 14.31, df = 2, p < 0.001), influenced the effect size. This study demonstrates a moderate relation between post-event rumination and social anxiety across the anxiety spectrum, illustrating the importance of treatments specifically targeting post-event rumination. Moreover, we highlight the importance of taking care when designing studies to explore relations between post-event rumination and social anxiety.

Exploring Predictors of Ketamine Response in Adolescent Treatment-Resistant Depression.

Objective: Ketamine has proved effective as a rapid-acting antidepressant agent, but treatment is not effective for everyone (approximately a quarter to a half of patients). Some adult studies have begun to investigate predictors of ketamine's antidepressant response, but no studies have examined this in adolescents with depression. Methods: We conducted a secondary data analysis of adolescents who participated in a randomized, single-dose, midazolam-controlled crossover trial of ketamine for adolescents with treatment-resistant depression. We examined the relationship between 19 exploratory demographic and clinical variables and depression symptom improvement (using the Montgomery-Åsberg Depression Rating Scale [MADRS]) at 1 and 7 days postinfusion. Results: Subjects who had fewer medication trials of both antidepressant medications and augmentation treatments were more likely to experience depression symptom improvement with ketamine. Subjects with shorter duration of their current depressive episode were more likely to experience depression symptom improvement with ketamine. Subjects currently being treated with selective serotonin reuptake inhibitor medications, and not being treated with serotonin-norepinephrine reuptake inhibitor medications, also experienced greater symptom improvement with ketamine. When receiving the midazolam control, less severe depressive symptoms, as measured by the Children's Depression Rating Scale (CDRS) (but not MADRS), and a comorbid attention-deficit/hyperactivity disorder diagnosis were associated with increased response. Conclusions: Findings should be viewed as preliminary and exploratory given the small sample size and multiple secondary analyses. Identifying meaningful predictors of ketamine response is important to inform future therapeutic use of this compound, however, considerably more research is warranted before such clinical guidance is established. The trial was registered in clinicaltrials.gov with the identifier NCT02579928.

Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program.

BACKGROUND: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials. METHODS: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used. RESULTS: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT (P=0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients (P=0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P=0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P<0.001) and -5.2 mm Hg (-7.1, -3.3; P<0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups. CONCLUSIONS: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.

Treatment Outcomes With Licensed and Unlicensed Stimulant Doses for Adults With Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis.

Importance: Stimulants (methylphenidate and amphetamines) are often prescribed at unlicensed doses for adults with attention-deficit/hyperactivity disorder (ADHD). Whether dose escalation beyond US Food and Drug Administration recommendations is associated with positive risk benefits is unclear. Objective: To investigate the impact, based on averages, of stimulant doses on treatment outcomes in adults with ADHD and to determine, based on averages, whether unlicensed doses are associated with positive risk benefits compared with licensed doses. Data Sources: Twelve databases, including published (PubMed, Cochrane Library, Embase, Web of Sciences) and unpublished (ClinicalTrials.gov) literature, up to February 22, 2023, without language restrictions. Study Selection: Two researchers independently screened records to identify double-blinded randomized clinical trials of stimulants against placebo in adults (18 years and older) with ADHD. Data Extraction and Synthesis: Aggregate data were extracted and synthesized in random-effects dose-response meta-analyses and network meta-analyses. Main Outcome Measures: Change in ADHD symptoms and discontinuations due to adverse events. Results: A total of 47 randomized clinical trials (7714 participants; mean age, 35 (SD, 11) years; 4204 male [56%]) were included. For methylphenidate, dose-response curves indicated additional reductions of symptoms with increments in doses, but the gains were progressively smaller and accompanied by continued additional risk of adverse events dropouts. Network meta-analyses showed that unlicensed doses were associated with greater reductions of symptoms compared with licensed doses (standardized mean difference [SMD], -0.23; 95% CI, -0.44 to -0.02; very low certainty of evidence), but the additional gain was small and accompanied by increased risk of adverse event dropouts (odds ratio, 2.02; 95% CI, 1.19-3.43; moderate certainty of evidence). For amphetamines, the dose-response curve approached a plateau and increments in doses did not indicate additional reductions of symptoms, but there were continued increments in the risk of adverse event dropouts. Network meta-analysis did not identify differences between unlicensed and licensed doses for reductions of symptoms (SMD, -0.08; 95% CI, -0.24 to 0.08; very low certainty of evidence). Conclusions and Relevance: Based on group averages, unlicensed doses of stimulants may not have positive risk benefits compared with licensed doses for adults with ADHD. In general, practitioners should consider unlicensed doses cautiously. Practitioners may trial unlicensed doses if needed and tolerated but should be aware that there may not be large gains in the response to the medication with those further increments in dose. However, the findings are averages and will not generalize to every patient.

Protocol description for a randomized controlled trial of fMRI neurofeedback for tics in adolescents with Tourette Syndrome.

This article describes the protocol for a randomized, controlled clinical trial of a neurofeedback (NF) intervention for Tourette Syndrome (TS) and chronic tic disorder. The intervention involves using functional magnetic resonance imaging (fMRI) to provide feedback regarding activity in the supplementary motor area: participants practice controlling this brain area while using the feedback as a training signal. The previous version of this NF protocol was tested in a small study (n = 21) training adolescents with TS that yielded clinically promising results. Therefore, we plan a larger trial. Here we describe the background literature that motivated this work, the design of our original neurofeedback study protocol, and adaptations of the research study protocol for the new trial. We focus on those ideas incorporated into our protocol that may be of interest to others designing and running NF studies. For example, we highlight our approach for defining an unrelated brain region to be trained in the control group that is based on identifying a region with low functional connectivity to the target area. Consistent with a desire for transparency and open science, the new protocol is described in detail here prior to conducting the trial.

Editorial: Developmental considerations in addressing the earlier age of severe eating disorder onset.

The deleterious impact of the COVID-19 pandemic on youth mental health has garnered much attention (Newlove-Delgado et al., 2023). It has been a topic of interest in both research and academic writing, as well as in the public press (e.g., Tanner, 2023). Disorders and mental health concerns of focus have been wide-ranging, with some of the most severe presentations, such as suicidality, highlighted (Asarnow and Chung, 2021). Eating disorders are among the most life-threatening and prominent mental health concerns that have been exacerbated by the pandemic, and our current models of youth mental health care cannot keep up. Given this context, our team read and reviewed the manuscript, 'Shifting age of child eating disorder hospitalizations during the Covid-19 pandemic' (Auger et al., 2023), eagerly. While the increasing severity of eating disorder presentations and increase in pediatric hospitalization has been an area of research (Asch et al., 2021), including at our own institution (Shum et al., 2022), the impact of age of onset, and the consequential impact on current systems of care, requires much greater attention.

The genetic epidemiology of obsessive-compulsive disorder: a systematic review and meta-analysis.

The first systematic review and meta-analysis of obsessive-compulsive disorder (OCD) genetic epidemiology was published approximately 20 years ago. Considering the relevance of all the studies published since 2001, the current study aimed to update the state-of-art knowledge on the field. All published data concerning the genetic epidemiology of OCD from the CENTRAL, MEDLINE, EMBASE, BVS, and OpenGrey databases were searched by two independent researchers until September 30, 2021. To be included, the articles had to fulfill the following criteria: OCD diagnosis provided by standardized and validated instruments; or medical records; inclusion of a control group for comparison and case-control, cohort or twin study designs. The analysis units were the first-degree relatives (FDRs) of OCD or control probands and the co-twins in twin pairs. The outcomes of interest were the familial recurrence rates of OCD and the correlations of OCS in monozygotic compared with dizygotic twins. Nineteen family, twenty-nine twin, and six population-based studies were included. The main findings were that OCD is a prevalent and highly familial disorder, especially among the relatives of children and adolescent probands, that OCD has a phenotypic heritability of around 50%; and that the higher OCS correlations between MZ twins were mainly due to additive genetic or to non-shared environmental components.

Pharmacological and Somatic Treatment Effects on Suicide in Adults: A Systematic Review and Meta-Analysis.

Background: Suicide is a public health crisis. We conducted a systematic review and meta-analysis of the effects of psychopharmacologic and somatic therapies on suicide risk. Methods: A systematic search of MEDLINE for studies evaluating the effects of pharmacologic (excluding antidepressants) or somatic interventions on suicide risk was conducted. Studies were included if they used a comparison group, reported on suicide death, assessed a psychopharmacological or somatic intervention, and included adults. Study quality was assessed using the Newcastle-Ottawa scale. Fifty-seven studies were included from 2940 reviewed citations. Results: In bipolar disorder, lithium was associated with a reduction in the odds of suicide compared to active controls (odds ratio [OR] = .58, p = .005; k = 12) and compared to placebo/no lithium (OR = .46, p = .009; k = 9). In mixed diagnostic samples, lithium was associated with a reduction in the odds of suicide compared to placebo/no lithium (OR = .27, p < .001; k = 12), but not compared to active controls (OR = .89, p = .468; k = 7). In psychotic disorders, clozapine was associated with a reduction in the odds of suicide (OR = .46, p = .007; k = 7). Associations between suicide death and electroconvulsive therapy (OR = .77, p = .053; k = 11), non-clozapine antipsychotics in bipolar disorder (OR = .73, p = .090; k = 6) and antipsychotics in psychotic disorders (OR = .39, p = .069; k = 6) were not significant. There was no consistent relationship between antiepileptic mood stabilizers and suicide. There were insufficient studies to meta-analyze associations of suicide risk with vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, or transcranial direct current stimulation. Conclusion: Lithium and clozapine have consistent data supporting protective effects against suicide in certain clinical contexts.Reprinted from Depress Anxiety 2022; 39:100-112, with permission from John Wiley and Sons. Copyright © 2022.

Prevalence and gender distribution of excoriation (skin-picking) disorder: A systematic review and meta-analysis.

Epidemiological studies of excoriation disorder have reported different prevalence estimates for this condition, limiting our understanding of its public health impact. We performed a systematic review and meta-analysis to collate epidemiological studies of excoriation disorder. We aimed to estimate the pooled prevalence and the female-to-male ratio of excoriation disorder in the general population. We searched Embase, PsycInfo, and PubMed up to May 2020 and updated the PubMed search in October 2021. Studies which reported the frequency of excoriation disorder in a sample from the general population were included in our meta-analyses. We made no restrictions regarding the definition or assessment of excoriation disorder. Data were pooled through random-effects meta-analyses. Of the 677 records identified through database searches, 19 studies involving 38,038 participants met our inclusion criteria. Meta-analyses demonstrated that excoriation disorder has an overall prevalence of 3.45% (95% CI 2.55, 4.65%) and impacts women more than men (female-to-male OR = 1.45; 95% CI 1.15, 1.81, p = 0.001). These findings underscore the public health impact of excoriation disorder, which will hopefully motivate future research focused on advancing our understanding and management of this condition.

Endovascular Ultrasound Renal Denervation to Treat Hypertension: The RADIANCE II Randomized Clinical Trial.

Importance: Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. Objective: To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. Design, Setting, and Participants: Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. Interventions: Ultrasound renal denervation vs a sham procedure. Main Outcomes and Measures: The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. Results: Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, -7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, -1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, -6.3 mm Hg [95% CI, -9.3 to -3.2 mm Hg], P < .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group. Conclusions and Relevance: In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT03614260.

Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials.

Importance: Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important. Objective: To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy. Data Sources: A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials. Study Selection: Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up. Data Extraction and Synthesis: Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials. Main Outcomes and Measures: The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups. Results: A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mean difference, -6.4 mm Hg; 95% CI, -9.1 to -3.6 mm Hg; home SBP: -8.4 mm Hg vs -1.4 mm Hg; mean difference, -6.8 mm Hg; 95% CI, -8.7 to -4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups. Conclusions and Relevance: Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260.

The Relationship Between Acute Dissociative Effects Induced by Ketamine and Treatment Response in Adolescent Patients with Treatment-Resistant Depression.

Objective: Ketamine has proven effective as a rapid-acting antidepressant agent. Several adult studies have investigated the association between ketamine's acute dissociative effects and depression response, but no studies have examined the association in adolescents with treatment-resistant depression (TRD). Methods: We conducted a secondary data analysis of 16 adolescent participants who participated in a randomized, single-dose, midazolam-controlled crossover trial of ketamine in adolescents with depression. We examined the association between the acute dissociative symptoms (measured at 60 minutes following start of infusion using the Clinician-Administered Dissociative States Scale [CADSS], and its three subscales: depersonalization, derealization, amnesia) and response and depression symptom improvement at 1'day (using the Montgomery-Åsberg Depression Rating Scale). Results: Within the ketamine group, there were no significant associations between dissociation symptoms or CADSS subscale scores and magnitude of depression symptom improvement or likelihood of ketamine response. When receiving midazolam, there was no significant association between overall dissociation symptoms and magnitude or likelihood of response of depressive symptoms. Higher levels of symptoms on the 'depersonalization' CADSS subscale when receiving midazolam were associated with less improvement in depression symptoms at 1 day following infusion. Conclusions: In contrast to some adult literature, the current data do not show a relationship between acute dissociative effects and antidepressant response to ketamine in pediatric patients with TRD. Interpretation may be limited by the small sample size, reducing the power to detect small or medium associations. Future research should utilize larger samples to more definitively measure the magnitude of association between acute dissociative symptoms and later antidepressant response to ketamine and to assess the relationship to trial design (e.g., crossover vs. parallel trial, comparison condition utilized and number of infusions) within both adult and pediatric populations. ClinicalTrials.gov identifier: NCT02579928.

Characteristics of trichotillomania and excoriation disorder across the lifespan.

Trichotillomania (hair-pulling disorder) and excoriation (skin-picking) disorder are body-focused repetitive behaviors, which often first present in adolescence and cause distress and impairment into adulthood. Few studies have examined the clinical characteristics of the co-occurrence of these conditions across the lifespan. We examined cross-sectional survey responses collected from April 2018-February 2020 to evaluate the relationship between trichotillomania, excoriation disorder, and their co-occurrence. Responses from individuals with trichotillomania (n = 50), excoriation disorder (n = 52), and both conditions (n = 50) ages 4-67 years old were compared for co-occurring conditions and current symptoms. Self-report measures of hair-pulling and skin-picking severity and subtypes were assessed. Gender, race, and co-occurring conditions were generally similarly distributed across the three groups with high rates of self-reported anxiety (63-82%), depression (34-50%), obsessive-compulsive disorder (16-29%), and attention-deficit/hyperactivity disorder (12-32%). Among individuals with both trichotillomania and excoriation disorder, significant positive correlations were observed between hair-pulling and skin-picking severity scores as well as hair-pulling and skin-picking subtypes. Hair-pulling and skin-picking severity peaked at the transition from adolescence to adulthood and hair-pulling/skin-picking styles appeared to shift across the lifespan. Our results support several similarities between trichotillomania and excoriation disorder, providing new insight into the clinical characteristics of these conditions.