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Antidepressants are standardly used to treat moderate to severe symptoms of depression and/or anxiety in youth but may also be associated with rare but serious psychiatric adverse events such as irritability, agitation, aggression, or suicidal ideation. Adverse events are especially common in youth with a family history of bipolar disorder (BD) who are at heightened risk for dysfunction in neurobiological systems that regulate emotion and arousal. To further understand this phenomenon, this study will examine (a) baseline risk factors associated with dysfunctional arousal in a sample of youth at high-risk for BD treated with or without an antidepressant, (b) whether antidepressant-related changes in arousal are mediated by changes in prefrontal-limbic circuitry, and (c) whether pharmacogenetic factors influence antidepressant-related changes in arousal. High-risk youth (aged 12-17 years with moderate to severe depressive and/or anxiety symptoms and at least one first-degree relative with bipolar I disorder) will be randomized to receive psychotherapy plus escitalopram or psychotherapy plus placebo. Neuroimaging and behavioral measures of arousal will be collected prior to randomization and at 4 weeks. Samples for pharmacogenetic analysis (serum escitalopram concentration, CYP2C19 metabolizer phenotype, and HTR2A and SLC6A4 genotypes) will be collected at 8 weeks. Youth will be followed for up to 16 weeks to assess change in arousal measures.

Previous studies have suggested that girls with Turner syndrome (TS) exhibit symptoms of social anxiety during interactions with others. However, few studies have quantified these behaviors during naturalistic face-to-face social encounters. In this study, we coded observational markers of social anxiety in prepubertal girls with TS and age-matched controls during a 10-min social encounter with an unfamiliar examiner. Results showed that girls with TS exhibited significantly higher levels of gaze avoidance compared to controls. Impairments in social gaze were particularly increased in girls with a maternally retained X chromosome (Xm), suggesting a genomic imprinting effect. These data indicate that social gaze avoidance may be a critical behavioral marker for identifying early social dysfunction in young girls with TS.

Adolescence is characterized by rapid brain development in white matter (WM) that is attributed in part to surges in gonadal hormones. To date, however, there have been few longitudinal investigations relating changes in gonadal hormones and WM development in adolescents. We acquired diffusion-weighted MRI to estimate mean fractional anisotropy (FA) from 10 WM tracts and salivary testosterone from 51 females and 29 males (ages 9-14 years) who were matched on pubertal stage and followed, on average, for 2 years. We tested whether interactions between sex and changes in testosterone levels significantly explained changes in FA. We found positive associations between changes in testosterone and changes in FA within the corpus callosum, cingulum cingulate, and corticospinal tract in females (all ps

ObjectiveThis exploratory study is the first to examine family-based treatment (FBT) adherence and association to treatment outcome in the context of a large-scale, multi-centre study for the treatment of adolescents with anorexia nervosa.MethodOne hundred and ninety recorded FBT sessions from 68 adolescents with anorexia nervosa and their families were recruited across multiple sites (N = 6). Each site provided 1-4 tapes per family over four treatment time points, and each was independently rated for therapist adherence.ResultsThere were differences in adherence scores within and between sites. ANOVA produced a main effect for site, F(5, 46) = 8.6, p

ObjectiveFamily-based treatment (FBT) for adolescent anorexia nervosa (AN) promotes faster weight restoration when compared to other treatments. However, the mechanisms through which this occurs are not clarified. This study explored the trajectories of parental self-efficacy and perceived family flexibility during FBT and systemic family therapy (SyFT). We also explored whether parental self-efficacy mediates the effects of treatment on weight gain early in treatment.Method158 adolescents (12-18 years old; 89% girls) and their parents were randomized to FBT or SyFT. Parental self-efficacy as well as adolescents' and parental perceptions of the family's flexibility were collected at baseline and at sessions 2, 4, 6, and 8.ResultsOver time, only parents in FBT reported significantly greater self-efficacy. The change in maternal self-efficacy over the first 8 weeks of treatment was a significant mediator of session 10 weight gain. There were no significant group differences in perceived flexibility by session 8.DiscussionBoth parents in FBT and mothers in SyFT understand early the need to change their family's rules and roles. However, the specific strategies of FBT appear to mediate early weight gain in AN.

ObjectiveThere is a paucity of randomized clinical trials (RCTs) for adolescents with bulimia nervosa (BN). Prior studies suggest cognitive-behavioral therapy adapted for adolescents (CBT-A) and family-based treatment for adolescent bulimia nervosa (FBT-BN) could be effective for this patient population. The objective of this study was to compare the relative efficacy of these 2 specific therapies, FBT-BN and CBT-A. In addition, a smaller participant group was randomized to a nonspecific treatment (supportive psychotherapy [SPT]), whose data were to be used if there were no differences between FBT-BN and CBT-A at end of treatment.MethodThis 2-site (Chicago and Stanford) randomized controlled trial included 130 participants (aged 12-18 years) meeting DSM-IV criteria for BN or partial BN (binge eating and purging once or more per week for 6 months). Outcomes were assessed at baseline, end of treatment, and 6 and 12 months posttreatment. Treatments involved 18 outpatient sessions over 6 months. The primary outcome was defined as abstinence from binge eating and purging for 4 weeks before assessment, using the Eating Disorder Examination.ResultsParticipants in FBT-BN achieved higher abstinence rates than in CBT-A at end of treatment (39% versus 20%; p = .040, number needed to treat [NNT] = 5) and at 6-month follow-up (44% versus 25%; p = .030, NNT = 5). Abstinence rates between these 2 groups did not differ statistically at 12-month follow-up (49% versus 32%; p = .130, NNT = 6).ConclusionIn this study, FBT-BN was more effective in promoting abstinence from binge eating and purging than CBT-A in adolescent BN at end of treatment and 6-month follow-up. By 12-month follow-up, there were no statistically significant differences between the 2 treatments.Clinical trial registration informationStudy of Treatment for Adolescents With Bulimia Nervosa; http://clinicaltrials.gov/; NCT00879151.

ObjectiveAdolescents with Anorexia Nervosa (AN), treated with family-based treatment (FBT) who fail to gain 2.3 kg by the fourth week of treatment have a 40-50% lower chance of recovery than those who do. Because of the high risk of developing enduring AN, improving outcomes in this group of poor responders is essential. This study examines the feasibility and effects of a novel adaptive treatment (i.e., Intensive Parental Coaching-IPC) aimed at enhancing parental self-efficacy related to re-feeding skills in poor early responders to FBT.Method45 adolescents (12-18 years of age) meeting DSM TR IV criteria for AN were randomized in an unbalanced design (10 to standard FBT; 35 to the adaptive arm). Attrition, suitability, expectancy rates, weight change, and psychopathology were compared between groups.OutcomesThere were no differences in rates of attrition, suitability, expectancy ratings, or most clinical outcomes between randomized groups. However, the group of poor early responders that received IPC achieved full weight restoration (>95% of expected mean BMI) by EOT at similar rates as those who had responded early.ConclusionsThe results of this study suggest that it is feasible to use an adaptive design to study the treatment effect of IPC for those who do not gain adequate weight by session 4 of FBT. The results also suggest that using IPC for poor early responders significantly improves weight recovery rates to levels comparable to those who respond early. A sufficiently powered study is needed to confirm these promising findings.

ImportanceAnorexia nervosa (AN) is a serious disorder with high rates of morbidity and mortality. Family-based treatment (FBT) is an evidence-based therapy for adolescent AN, but less than half of those who receive this approach recover. Hence, it is important to identify other approaches to prevent the development of the chronic form of AN for which there is no known evidence-based treatment.ObjectiveTo compare FBT with systemic family therapy (SyFT) for the treatment of adolescent-onset AN.Design, setting, and participantsResearch in Anorexia Nervosa (RIAN) is a 2-group (FBT and SyFT) randomized trial conducted between September 2005 and April 2012. Interviewers were blinded to the treatment condition. A total of 564 adolescents receiving care at 6 outpatient clinics experienced in the treatment of AN were screened. Of these, 262 adolescents did not meet the inclusion criteria and 138 declined to participate; hence, 164 adolescents (aged 12-18 years) of both sexes meeting the criteria for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, AN (except for amenorrhea) were enrolled. Three participants were withdrawn from FBT and 7 were withdrawn from SyFT after serious adverse events occurred.InterventionsTwo manualized family therapies with 16 one-hour sessions during 9 months. Family-based therapy focuses on the facilitation of weight gain, whereas SyFT addresses general family processes.Main outcomes and measuresThe primary outcomes were percentage of ideal body weight (IBW) and remission (≥95% of IBW). The a priori hypothesis was that FBT would result in faster weight gain early in treatment and at the end of treatment (EOT).ResultsThere were no statistically significant differences between treatment groups for the primary outcome, for eating disorder symptoms or comorbid psychiatric disorders at the EOT or follow-up. Remission rates included FBT, 33.1% at the EOT and 40.7% at follow-up and SyFT, 25.3% and 39.0%, respectively. Family-based therapy led to significantly faster weight gain early in treatment, significantly fewer days in the hospital, and lower treatment costs per patient in remission at the EOT (FBT, $8963; SyFT, $18 005). An exploratory moderator analysis found that SyFT led to greater weight gain than did FBT for participants with more severe obsessive-compulsive symptoms.Conclusions and relevanceThe findings of this study suggest that FBT is the preferred treatment for adolescent AN because it is not significantly different from SyFT and leads to similar outcomes at a lower cost than SyFT. Adolescents with more severe obsessive-compulsive symptoms may receive more benefits with SyFT.Trial registrationclinicaltrials.gov Identifier NCT00610753.

With a randomized field experiment of 433 preschoolers, we tested a tablet mathematics program designed to increase young children's mathematics learning. Intervention students played Math Shelf, a comprehensive iPad preschool and year 1 mathematics app, while comparison children received research-based hands-on mathematics instruction delivered by their classroom teachers. After 22 weeks, there was a large and statistically significant effect on mathematics achievement for Math Shelf students (Cohen's d = 0.94). Moderator analyses demonstrated an even larger effect for low achieving children (Cohen's d = 1.27). These results suggest that early education teachers can improve their students' mathematics outcomes by integrating experimentally proven tablet software into their daily routines.