Contextual Triggers and Tic Severity Across Life Periods: A Retrospective Analysis in Adults with Tic Disorders.

In tic disorders (TD), tic expression varies across the lifespan and as a function of contextual factors. This study explored connections between tic expression and contextual triggers across life periods in 74 adults (Mage = 23.2) with TDs. The Tic History and Coping Strategies form assessed retrospective self-reports of contextual antecedents, consequences, and tic severity during four life periods (middle school; 9th/10th grade; 11th/12th grade; college/work) and past month. Tics reportedly worsened during and after school in school-aged years and worsened in the evening during college/work years. Stress and anxiety were reported to consistently trigger tics across time. The impact of activities, places, and emotions did not differ across life periods. Attention-based consequences, most prevalent during middle school, were more common than escape- or avoidance-related consequences across all periods. Findings illuminate how contextual factors may influence tics across life periods and underscore the consistent impact of tic-triggering emotions and attention-related consequences.

Brief Report: Relationships Between Caregiver-Reported Externalizing and Internalizing Behaviors and the Modified Checklist for Autism in Toddlers.

PURPOSE: Early detection and intervention are associated with improved outcomes for autistic children. Thus, it is important to understand factors influencing early screening tools designed to detect autism. This study examined the relationship between caregiver-reported emotional and behavioral symptoms and children's scores on a commonly used autism screening questionnaire, the Modified Checklist for Autism in Toddlers-Revised with Follow-Up (M-CHAT-R/F). METHODS: Toddlers were recruited from four primary care clinics between 2018 and 2021. Their caregivers completed the M-CHAT-R/F as well as the Child Behavior Checklist (CBCL), a well-validated, normed measure of emotional and behavioral functioning. Correlational and group analyses were evaluated to examine relationships between CBCL scales and M-CHAT-R/F scores. RESULTS: 1765 toddlers were recruited for the study. CBCL scores for the internalizing, externalizing, autism, ADHD, and anxiety scales were all modestly positively correlated with M-CHAT-R/F scores. Compared to toddlers with elevated autism scale scores only, toddlers with elevations in both autism and ADHD/externalizing scales had higher M-CHAT-R/F scores. In contrast, no significant difference in scores were found between toddlers with elevated autism scale scores only compared to those with elevated scores on both autism and internalizing scales. CONCLUSION: Findings suggest that, for children with elevated autism behaviors, the presence of externalizing symptoms, including ADHD-related concerns, is associated with elevated scores on the M-CHAT-R/F. In contrast, internalizing symptoms did not show an association with elevated M-CHAT-R/F scores among toddlers with elevated autism-related behaviors. Interpretation of the M-CHAT-R/F should include consideration of co-occurring psychiatric conditions, especially externalizing conditions such as ADHD.

Cognitive Disengagement Syndrome in Young Autistic Children, Children with ADHD, and Autistic Children with ADHD.

OBJECTIVE: Cognitive Disengagement Syndrome (CDS; previously called Sluggish Cognitive Tempo) refers to a constellation of cognitive and motor behaviors characterized by a predisposition toward mind wandering (cognitive subdomain) and slowed motor behavior (hypoactive). While there are a number of studies linking CDS traits to greater global impairment in children with attention-deficit/hyperactivity disorder (ADHD) and autistic children, there are few studies examining the prevalence and impact of CDS traits in autistic children with co-occurring ADHD (Autistic+ADHD). The current study explored CDS traits in autistic children with and without co-occurring ADHD, children with ADHD, and neurotypical children. METHODS: Participants were 196 children between 3- and 7-years-of-age comprising four groups: Neurotypical (N = 44), ADHD (N = 51), Autistic (N = 55), and Autistic+ADHD (N = 46). CDS traits, social and communication skills, repetitive behaviors, and sensory processing were all assessed via parent report. RESULTS: Children diagnosed with ADHD, autistic children, and Autistic+ADHD children exhibited similar levels of overall CDS traits. However, when explored separately, Autistic+ADHD children had higher cognitive CDS trait scores compared to children with ADHD alone. Both overall CDS traits and the cognitive subdomain were associated with greater social difficulties, particularly social withdrawal, higher levels of repetitive behaviors, and more sensory sensitivities, regardless of diagnosis. CONCLUSIONS: Findings suggest that CDS traits may be an additional factor directly impact functional outcomes in both autistic and ADHD children. As such, clinicians should be assessing CDS traits in addition to other clinical domains associated with ADHD and autism when developing intervention plans for young neurodiverse children.

Neurocognitive functioning in adults with trichotillomania: Predictors of treatment response and symptom severity in a randomized control trial.

Trichotillomania (TTM) is associated with impairments in response inhibition and cognitive flexibility, but it is unclear how such impairments relate to treatment outcome. The present study examined pre-treatment response inhibition and cognitive flexibility as predictors of treatment outcome, change in these domains from pre-to post-treatment, and associations with TTM severity. Participants were drawn from a randomized controlled trial comparing acceptance-enhanced behavior therapy (AEBT) to psychoeducation and supportive therapy (PST) for TTM. Adults completed assessments at pre-treatment (n = 88) and following 12 weeks of treatment (n = 68). Response inhibition and cognitive flexibility were assessed using the Stop Signal Task and Object Alternation Task, respectively. Participants completed the MGH-Hairpulling Scale. Independent evaluators administered the NIMH-Trichotillomania Severity Scale and Clinical Global Impressions-Improvement Scale. Higher pre-treatment TTM severity was associated with poorer pre-treatment cognitive flexibility, but not response inhibition. Better pre-treatment response inhibition performance predicted positive treatment response and lower post-treatment TTM symptom severity, irrespective of treatment assignment. Cognitive flexibility did not predict treatment response. After controlling for age, neither neurocognitive variable changed during treatment. Response inhibition and cognitive flexibility appear uniquely related to hair pulling severity and treatment response in adults with TTM. Implications for treatment delivery and development are discussed.

Perceived Negative Effects of Tic Management Strategies in Adults With Tic Disorders.

Behavior therapy is a well-established and empirically supported treatment for tic disorders (TDs). However, concerns have been expressed about the negative effects of behavioral interventions, such as tic worsening, tic substitution, and excessive effort. This study explored perceived negative effects of tic management strategies in adults with TDs and predictors of these experiences. Participants (N = 72) completed semi-structured interviews 11 years after receiving behavior therapy or supportive therapy in a randomized clinical trial. We examined responses to interview questions about managing tics and predictors of reported negative effects. Most participants did not experience tic worsening (84%) or tic substitution (75%) from tic management strategies. The majority felt they could manage tics while participating in their environment (87%) and did not report life interference from tic management (77%). About half (45%) felt less present when managing tics. Treatment non-responders in the original trial were more likely to report negative effects of tic management strategies. No differences in reported negative consequences were found between those who received behavior therapy versus supportive therapy, suggesting that behavior therapy specifically does not lead to such adverse effects. These findings could reduce misconceptions about behavior therapy for TDs and enhance its acceptability and utilization.

Long-term follow-up of acceptance-enhanced behavior therapy for trichotillomania.

Acceptance-enhanced behavior therapy for trichotillomania (AEBT-TTM) is effective in reducing trichotillomania (TTM) symptoms, but the durability of treatment effects remains in question. This study analyzed 6-month follow-up data from a large randomized clinical trial comparing AEBT-TTM to an active psychoeducation and supportive therapy control (PST). Adults with TTM (N=85; 92% women) received 10 sessions of AEBT-TTM or PST across 12 weeks. Independent evaluators assessed participants at baseline, post-treatment, and 6 months follow-up. For both AEBT-TTM and PST, self-reported and evaluator-rated TTM symptom severity decreased from baseline to follow-up. TTM symptoms did not worsen from post-treatment to follow-up. At follow-up, AEBT-TTM and PST did not differ in rates of treatment response, TTM diagnosis, or symptom severity. High baseline TTM symptom severity was a stronger predictor of high follow-up severity for PST than for AEBT-TTM, suggesting AEBT-TTM may be a better option for more severe TTM. Results support the efficacy of AEBT-TTM and show that treatment gains were maintained over time. Although AEBT-TTM yielded lower symptoms at post-treatment, 6-month follow-up outcomes suggest AEBT-TTM and PST may lead to similar symptom levels in the longer term. Future research should examine mechanisms that contribute to long-term gain maintenance.

Substance use outcomes from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS).

BACKGROUND: Substance use problems and anxiety disorders are both highly prevalent and frequently cooccur in youth. The present study examined the benefits of successful anxiety treatment at 3-12 years after treatment completion on substance use outcomes (i.e. diagnoses and lifetime expected use). METHODS: The sample was from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS), a naturalistic follow-up study to the Child/Adolescent Anxiety Multimodal Study (CAMS) which randomized youth to cognitive behavioral therapy (CBT; Coping cat), medication (sertraline), their combination, or pill placebo. The first CAMELS visit occurred an average of 6.5 years following CAMS randomization. Participants were 319 youth (65.4% of the CAMS sample), aged 7-17 years at CAMS baseline assessment with a mean age of 17.6 years (range: 11-26 years) at the time of the first CAMELS follow-up. Substance use outcomes included diagnoses as well as lifetime substance use (i.e. alcohol and tobacco use). RESULTS: Eleven of 319 (3.4%) CAMELS participants were diagnosed with a substance use disorder at the initial follow-up visit. When compared to the population lifetime rate of 11.4%, the rate of diagnoses in the posttreated sample was significantly lower. Additionally, rates of lifetime alcohol use were lower than population rates at the initial and final follow-up visits. Rates of lifetime tobacco use were similarly lower than lifetime population rates at the initial visit (driven by significantly lower rates in the CBT treatment condition), but higher by the final visit. Furthermore, treatment remission (but not treatment response) was associated with a lower rate of substance use diagnoses at the initial follow-up visit, although rates of lifetime alcohol and tobacco use did not differ by treatment outcome. CONCLUSIONS: Anxiety treatments confer a beneficial impact on problematic substance use (i.e. diagnoses) as well as on expected substance use (i.e. alcohol and tobacco use) for on average, a period of 6.5 years.

The impact of human cadaveric dissection on professional identity formation in medical students.

BACKGROUND: As technology advances, some schools are moving away from human cadaveric dissection to teach anatomy, leading to concern regarding the possible loss of a professional identity building experience. This study explored the role of dissection in students' professional identity formation. METHODS: A mixed-methods study was conducted using survey methodology and semi-structured interviews of medical students at an American-style graduate-entry medical school in Singapore. The questionnaire adopted the conceptual framework of the Ring Theory of Personhood and the MacLeod-Clark Professional Identity Scale was used to measure professional identity, followed by semi-structured interviews of students using Braun and Clarke's six-phase reflexive thematic analysis. RESULTS: Respondents did not differ substantively from non-respondents by age, nationality, or ethnicity, and year of entering medical school, however, they were slightly more female dominant. The number of hours of hands-on participation in dissection showed no significant relationship (r2 = 0.010; p = 0.424) with professional identity formation measured by the MacLeod-Clark Professional Identity Scale. Despite the survey results, semi-structured interviews revealed rich and nuanced findings suggesting the influence of dissection in participants' professional identity formation through deepening students' appreciation of humanistic values and enhancing their notions of patients' personhood. Notably, students without dissection experience did not express these sentiments and were orientated towards knowledge acquisition. CONCLUSION: While our findings do not suggest that dissection strongly impacts students' professional identity formation, students shared thought-provoking experiences which suggest some level of its contribution. Careful consideration of this phenomenon should be exercised prior to removing dissection in favour of technological alternatives.

Asthma and anxiety in children and adolescents: characteristics and treatment outcomes.

OBJECTIVE: This study (a) examined anxious youth with and without asthma on measures of negative self-talk, parental psychopathology, worry content, physical symptoms, panic symptoms, generalized symptoms, and separation anxiety symptoms, and (b) tested if outpatient CBT or medication were differentially effective in reducing anxiety for youth with asthma and anxiety. METHODS: This secondary analysis separated youth with an anxiety disorder into asthma and non-asthma groups. Youth were also compared on response to treatments (i.e. CBT, sertraline, combined, and placebo). RESULTS: A total of 488 participants participated in the original study, with an average age of 10 years (SD 2.87). Youth with comorbid asthma and anxiety demonstrated higher rates of negative self-talk. Youth with comorbid asthma and anxiety did not differ from the non-asthma group on measures of physical symptoms, anxiety disorder specific symptoms, parental psychopathology, or worry content. Youth with asthma and anxiety responded similarly to the non-asthma group to treatment across treatment conditions. CONCLUSIONS: Treatment was comparably effective for youth with comorbid asthma and anxiety and youth with anxiety. Future research could examine the effects of psychopharmaceuticals on asthma and anxiety comorbidity.

Early detection of autism using digital behavioral phenotyping.

Early detection of autism, a neurodevelopmental condition associated with challenges in social communication, ensures timely access to intervention. Autism screening questionnaires have been shown to have lower accuracy when used in real-world settings, such as primary care, as compared to research studies, particularly for children of color and girls. Here we report findings from a multiclinic, prospective study assessing the accuracy of an autism screening digital application (app) administered during a pediatric well-child visit to 475 (17-36 months old) children (269 boys and 206 girls), of which 49 were diagnosed with autism and 98 were diagnosed with developmental delay without autism. The app displayed stimuli that elicited behavioral signs of autism, quantified using computer vision and machine learning. An algorithm combining multiple digital phenotypes showed high diagnostic accuracy with the area under the receiver operating characteristic curve = 0.90, sensitivity = 87.8%, specificity = 80.8%, negative predictive value = 97.8% and positive predictive value = 40.6%. The algorithm had similar sensitivity performance across subgroups as defined by sex, race and ethnicity. These results demonstrate the potential for digital phenotyping to provide an objective, scalable approach to autism screening in real-world settings. Moreover, combining results from digital phenotyping and caregiver questionnaires may increase autism screening accuracy and help reduce disparities in access to diagnosis and intervention.

Relationship between quantitative digital behavioral features and clinical profiles in young autistic children.

Early behavioral markers for autism include differences in social attention and orienting in response to one's name when called, and differences in body movements and motor abilities. More efficient, scalable, objective, and reliable measures of these behaviors could improve early screening for autism. This study evaluated whether objective and quantitative measures of autism-related behaviors elicited from an app (SenseToKnow) administered on a smartphone or tablet and measured via computer vision analysis (CVA) are correlated with standardized caregiver-report and clinician administered measures of autism-related behaviors and cognitive, language, and motor abilities. This is an essential step in establishing the concurrent validity of a digital phenotyping approach. In a sample of 485 toddlers, 43 of whom were diagnosed with autism, we found that CVA-based gaze variables related to social attention were associated with the level of autism-related behaviors. Two language-related behaviors measured via the app, attention to people during a conversation and responding to one's name being called, were associated with children's language skills. Finally, performance during a bubble popping game was associated with fine motor skills. These findings provide initial support for the concurrent validity of the SenseToKnow app and its potential utility in identifying clinical profiles associated with autism. Future research is needed to determine whether the app can be used as an autism screening tool, can reliably stratify autism-related behaviors, and measure changes in autism-related behaviors over time.

Exploring Complexity of Facial Dynamics in Autism Spectrum Disorder.

Atypical facial expression is one of the early symptoms of autism spectrum disorder (ASD) characterized by reduced regularity and lack of coordination of facial movements. Automatic quantification of these behaviors can offer novel biomarkers for screening, diagnosis, and treatment monitoring of ASD. In this work, 40 toddlers with ASD and 396 typically developing toddlers were shown developmentally-appropriate and engaging movies presented on a smart tablet during a well-child pediatric visit. The movies consisted of social and non-social dynamic scenes designed to evoke certain behavioral and affective responses. The front-facing camera of the tablet was used to capture the toddlers' face. Facial landmarks' dynamics were then automatically computed using computer vision algorithms. Subsequently, the complexity of the landmarks' dynamics was estimated for the eyebrows and mouth regions using multiscale entropy. Compared to typically developing toddlers, toddlers with ASD showed higher complexity (i.e., less predictability) in these landmarks' dynamics. This complexity in facial dynamics contained novel information not captured by traditional facial affect analyses. These results suggest that computer vision analysis of facial landmark movements is a promising approach for detecting and quantifying early behavioral symptoms associated with ASD.

Blink rate and facial orientation reveal distinctive patterns of attentional engagement in autistic toddlers: a digital phenotyping approach.

Differences in social attention are well-documented in autistic individuals, representing one of the earliest signs of autism. Spontaneous blink rate has been used to index attentional engagement, with lower blink rates reflecting increased engagement. We evaluated novel methods using computer vision analysis (CVA) for automatically quantifying patterns of attentional engagement in young autistic children, based on facial orientation and blink rate, which were captured via mobile devices. Participants were 474 children (17-36 months old), 43 of whom were diagnosed with autism. Movies containing social or nonsocial content were presented via an iPad app, and simultaneously, the device's camera recorded the children's behavior while they watched the movies. CVA was used to extract the duration of time the child oriented towards the screen and their blink rate as indices of attentional engagement. Overall, autistic children spent less time facing the screen and had a higher mean blink rate compared to neurotypical children. Neurotypical children faced the screen more often and blinked at a lower rate during the social movies compared to the nonsocial movies. In contrast, autistic children faced the screen less often during social movies than during nonsocial movies and showed no differential blink rate to social versus nonsocial movies.

The role of psychological flexibility in acceptance-enhanced behavior therapy for trichotillomania: Moderation and mediation findings.

Trichotillomania is characterized by recurrent pulling out of one's hair, leading to significant hair loss and accompanied by clinically significant distress and/or functional impairment. The current study used data from a randomized controlled trial comparing the effectiveness of acceptance-enhanced behavior therapy (AEBT) to psychoeducation plus supportive therapy (PST; active control) for trichotillomania in an adult sample. The objectives were to examine the moderating and mediating influence of trichotillomania-specific psychological flexibility in treatment for trichotillomania. Participants with lower baseline flexibility performed better in AEBT than PST in terms of greater symptom reduction and quality of life. Lower baseline flexibility also predicted higher likelihood of disorder recovery in AEBT relative to PST. In addition, relative to PST, symptom reduction in AEBT was mediated by psychological flexibility, controlling for anxiety and depression. These findings suggest that psychological flexibility is a relevant process of change in the treatment of trichotillomania. Clinical implications and directions for future research are discussed.

Anxiety symptom trajectories from treatment to 5- to 12-year follow-up across childhood and adolescence.

OBJECTIVE: The current study examined trajectories of anxiety during (a) acute treatment and (b) extended follow-up to better characterize the long-term symptom trajectories of youth who received evidence-based intervention for anxiety disorders using a person-centered approach. METHOD: Participants were 319 youth (age 7-17 years at enrollment), who participated in a multicenter randomized controlled trial for the treatment of pediatric anxiety disorders, Child/Adolescent Anxiety Multimodal Study, and a 4-year naturalistic follow-up, Child/Adolescent Anxiety Multimodal Extended Long-term Study, an average of 6.5 years later. Using growth mixture modeling, the study identified distinct trajectories of anxiety across acute treatment (Weeks 0-12), posttreatment (Weeks 12-36), and the 4-year-long follow-up, and identified baseline predictors of these trajectories. RESULTS: Three nonlinear anxiety trajectories emerged: "short-term responders" who showed rapid treatment response but had higher levels of anxiety during the extended follow-up; "durable responders" who sustained treatment gains; and "delayed remitters" who did not show an initial response to treatment, but showed low levels of anxiety during the maintenance and extended follow-up periods. Worse anxiety severity and better family functioning at baseline predicted membership in the delayed remitters group. Caregiver strain differentiated short-term responders from durable responders. CONCLUSIONS: Findings suggest that initial response to treatment does not guarantee sustained treatment gains over time for some youth. Future follow-up studies that track treated youth across key developmental transitions and in the context of changing social environments are needed to inform best practices for the long-term management of anxiety.

Computer Vision Analysis of Caregiver-Child Interactions in Children with Neurodevelopmental Disorders: A Preliminary Report.

We report preliminary results of computer vision analysis of caregiver-child interactions during free play with children diagnosed with autism (N = 29, 41-91 months), attention-deficit/hyperactivity disorder (ADHD, N = 22, 48-100 months), or combined autism + ADHD (N = 20, 56-98 months), and neurotypical children (NT, N = 7, 55-95 months). We conducted micro-analytic analysis of 'reaching to a toy,' as a proxy for initiating or responding to a toy play bout. Dyadic analysis revealed two clusters of interaction patterns, which differed in frequency of 'reaching to a toy' and caregivers' contingent responding to the child's reach for a toy by also reaching for a toy. Children in dyads with higher caregiver responsiveness had less developed language, communication, and socialization skills. Clusters were not associated with diagnostic groups. These results hold promise for automated methods of characterizing caregiver responsiveness in dyadic interactions for assessment and outcome monitoring in clinical trials.

Do youth anxiety measures assess the same construct consistently throughout treatment? Results are...complicated.

Interventionists interpret changes in symptoms as reflecting response to treatment. However, changes in symptom functioning and the measurement of the underlying constructs may be reflected in reported change. Longitudinal measurement invariance (LMI) is a statistical approach that assesses the degree to which measures consistently capture the same construct over time. We examined LMI in measures of anxiety severity/symptoms [i.e., Pediatric Anxiety Rating Scale (PARS), Multidimensional Anxiety Scale for Children (MASC), Screen for Child Anxiety and Related Disorders (SCARED)] in anxious youth at baseline and posttreatment. Initial fit was inadequate for 27 of 38 baseline and posttreatment models, but model modifications resulted in acceptable fit. Tests of LMI supported scalar invariance for the PARS and many, but not all, MASC and SCARED subscales. Findings suggest that the PARS, and many MASC and SCARED subscales can accurately be used to measure change over time, however, others may reflect changes in measurement properties.

A tablet-based game for the assessment of visual motor skills in autistic children.

Increasing evidence suggests that early motor impairments are a common feature of autism. Thus, scalable, quantitative methods for measuring motor behavior in young autistic children are needed. This work presents an engaging and scalable assessment of visual-motor abilities based on a bubble-popping game administered on a tablet. Participants are 233 children ranging from 1.5 to 10 years of age (147 neurotypical children and 86 children diagnosed with autism spectrum disorder [autistic], of which 32 are also diagnosed with co-occurring attention-deficit/hyperactivity disorder [autistic+ADHD]). Computer vision analyses are used to extract several game-based touch features, which are compared across autistic, autistic+ADHD, and neurotypical participants. Results show that younger (1.5-3 years) autistic children pop the bubbles at a lower rate, and their ability to touch the bubble's center is less accurate compared to neurotypical children. When they pop a bubble, their finger lingers for a longer period, and they show more variability in their performance. In older children (3-10-years), consistent with previous research, the presence of co-occurring ADHD is associated with greater motor impairment, reflected in lower accuracy and more variable performance. Several motor features are correlated with standardized assessments of fine motor and cognitive abilities, as evaluated by an independent clinical assessment. These results highlight the potential of touch-based games as an efficient and scalable approach for assessing children's visual-motor skills, which can be part of a broader screening tool for identifying early signs associated with autism.

Effects of Long-Term Sertraline Use on Pediatric Growth and Development: The Sertraline Pediatric Registry for The Evaluation of Safety (SPRITES).

Objective: To describe the results of the Sertraline Pediatric Registry for The Evaluation of Safety (SPRITES) outcome measures of cognitive, emotional, and physical development following long-term treatment with sertraline (for up to 3 years) in children and adolescents aged 6-16 years. Methods: SPRITES was a long-term, multicenter, open-label, prospective observational study designed to compare physical and psychological development in pediatric patients exposed to sertraline (with or without psychotherapy) or psychotherapy alone in usual care settings. Data were summarized descriptively, and outcomes were evaluated using a marginal structural model. Results: Between April 2012 and September 2020, 941 patients across 44 U.S. sites participated in the study. At baseline, 695 participants were exposed to sertraline (physician prescribed) with or without psychotherapy, and 245 participants were exposed to psychotherapy alone. Of these, 432 participants (46.0%) completed the full 3-year study follow-up. No significant changes across time were found in standardized height, BRIEF (Behavior Rating Inventory of Executive Function), Trails B, and Tanner stage based on cumulative sertraline exposure or exposure since the last visit. Change in mean standardized weight across time was positively associated with both cumulative sertraline exposure (p = 0.02) and exposure since the last visit (p = 0.029). The mean changes from baseline across time in standardized weight were standard deviations of 0.02, 0.03, 0.16, and 0.17 at months 3, 6, 30, and 36, respectively. However, this finding was not observed in the mean change across time in standardized body mass index, which was not statistically significant. Conclusions: Results are consistent with normal development. Although a statistically significant finding for standardized weight was observed in comparative analyses, the magnitude of the change is small and observed at higher doses of sertraline only. No other significant differences were observed between the "sertraline" group and the "no pharmacological therapy" group on other primary outcome measures. ClinicalTrials.gov identifier: NCT01302080.