Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

CONTEXT: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. OBJECTIVE: To evaluate safety and efficacy of intranasal carbetocin in PWS. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. SETTING: Twenty-four ambulatory clinics at academic medical centers. PARTICIPANTS: A total of 130 participants with PWS aged 7 to 18 years. INTERVENTIONS: Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. MAIN OUTCOME MEASURES: Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). RESULTS: Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. CONCLUSIONS: Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. CLINICAL TRIALS REGISTRATION NUMBER: NCT03649477.

Neural correlates of cognitive behavioral therapy response in youth with negative valence disorders: A systematic review of the literature.

BACKGROUND: Cognitive-behavioral therapy (CBT) is the gold-standard psychotherapeutic treatment for pediatric negative valence disorders. However, some youths do not respond optimally to treatment, which may be due to variations in neural functioning. METHODS: We systematically reviewed functional magnetic resonance imaging studies in youths with negative valence disorders to identify pre- and post-treatment neural correlates of CBT response. RESULTS: A total of 21 studies were identified, of overall weak to moderate quality. The most consistent findings across negative valence disorders consisted of associations of treatment response with pre- and post-treatment task-based activation and/or functional connectivity within and between the prefrontal cortex, the medial temporal lobe, and other limbic regions. Associations of CBT response with baseline and/or post-treatment activity in the striatum, precentral and postcentral gyri, medial and posterior cingulate cortices, and parietal cortex, connectivity within and between the default-mode, cognitive control, salience, and frontoparietal networks, and metrics of large-scale brain network organization, were also reported, although less consistently. LIMITATIONS: The poor quality and limited number of studies and the important heterogeneity of study designs and results considerably limit the conclusions that can be drawn from this literature. CONCLUSIONS: Despite these limitations, these findings provide preliminary evidence suggesting youths presenting certain patterns of brain function may respond better to CBT, whereas others may benefit from alternative or augmented forms of treatment.

Assessing Symptom Accommodation of Social Anxiety Symptoms Among Chinese Adults: Factor Structure and Psychometric Properties of Family Accommodation Scale Anxiety-Adult Report.

OBJECTIVE: Symptom accommodation is an important interpersonal construct associated with more severe symptoms, lower levels of functioning, and worse treatment outcomes across various mental health conditions, including social anxiety. Research on this phenomenon is surprisingly absent in Chinese culture, where interpersonal relationships are highly emphasized. This may be due to the absence of a valid Chinese symptom accommodation measure for individuals with social anxiety symptoms. The current study aimed to examine the factor structure and psychometric properties of the Family Accommodation Scale Anxiety-Adult Report (FASA-AR) in Chinese adults. METHODS: Three hundred and seventy-five Chinese undergraduate students with social anxiety symptoms completed a battery of self-report measures assessing symptom accommodation in relation to social anxiety symptoms and related impairments, as well as overall symptoms of anxiety and depression. RESULTS: Confirmatory factor analysis supported a two-factor model of symptom accommodation, with factors named Participation in symptom-related behaviors and Modification of functioning. The multiple indicators multiple causes model indicated the indicators of the FASA-AR, mainly the participation in symptom-related behaviors subscale, were not invariant across gender. Internal consistency for the FASA-AR total score and subscale scores was good. Convergent validity of the FASA-AR was evidenced by significant positive association with ratings of social anxiety symptoms, social anxiety related impairments, and anxiety symptoms. Divergent validity was supported by non-significant relation with depression symptoms. Nearly all participants (94.7%) endorsed being accommodated to some extent in the past month. CONCLUSION: Symptom accommodation is an important construct and is related to social anxiety symptoms among Chinese adults. The FASA-AR demonstrated a clear two-factor latent structure and possessed good psychometric properties that can validly and reliably assess symptom accommodation of social anxiety among Chinese adults.

Practical Applications for Maintenance of Certification Products in Child and Adolescent Residency Training.

OBJECTIVE: The authors evaluated whether Maintenance of Certification (MOC) Performance-in-Practice products in training increases trainee knowledge of MOC processes and is viewed by trainees as a useful activity. METHODS: Six child and adolescent psychiatry fellowships used MOC products in continuity clinics to assess their usefulness as training tools. Two surveys assessed initial knowledge of MOC and usefulness of the activity. RESULTS: Forty-one fellows completed the initial survey. A majority of first-year fellows indicated lack of awareness of MOC in contrast to a majority of second-year fellows who indicated some awareness. Thirty-five fellows completed the second survey. A majority of first- and second-year fellows found the activity easy to execute and would change something about their practice as a result. CONCLUSIONS: Using MOC products in training appears to be a useful activity that may assist training programs in teaching the principles of self- and peer-learning.

The development of a mentalization-based outcomes and research protocol for an adolescent inpatient unit.

The authors describe the development of a theory-driven assessment and research protocol at the Adolescent Treatment Program of The Menninger Clinic. First, the theoretical framework behind a mentalization-based model for assessment and treatment is described. Next, the process whereby measures were selected to operationalize key components of the mentalization-based model is discussed, including a brief discussion of each measure and assessment procedure. The next section describes the clinical and research use of the data collected. Here, the authors describe how outcomes assessment information is integrated into the clinical decision-making process, and they outline the research questions they aim to answer through the assessment protocol. The authors conclude with a section on the challenges, pitfalls, and future directions of the project.

The good-enough mentoring relationship.

OBJECTIVE: This study aimed to describe the state of mentoring in today's academic environment. METHODS: Resident focus groups from across the nation discussed their opinions about mentoring and experiences with mentoring, and individual faculty members were videotaped discussing the same. RESULTS: Sixty-six residents and five faculty members participated in the project. There was consensus among residents and faculty regarding important qualities of a mentoring relationship, obstacles to forming a mentorship, and methods to improve the mentorship experience in psychiatric training. CONCLUSION: Mentoring is still believed to be a vital component of a successful residency experience. Specific components that warrant further research include boundaries within the relationship, ethnicity and gender factors, and potential need for resident and faculty curricula on the topic of mentoring.