Booil Jo

COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome

Although schizophrenia is strongly hereditary, there are limited data regarding biological risk factors and pathophysiological processes. In this longitudinal study of adolescents with 22q11.2 deletion syndrome, we identified the catechol-O-methyltransferase low-activity allele (COMTL) as a risk factor for decline in prefrontal cortical volume and cognition, as well as for the consequent development of psychotic symptoms during adolescence. The 22q11.2 deletion syndrome is a promising model for identifying biomarkers related to the development of schizophrenia.

Outcome from a randomized controlled trial of group therapy for binge eating disorder: comparing dialectical behavior therapy adapted for binge eating to an active comparison group therapy.

Dialectical Behavior Therapy for Binge Eating Disorder (DBT-BED) aims to reduce binge eating by improving adaptive emotion-regulation skills. Preliminary findings have been promising but have only compared DBT-BED to a wait-list. To control for the hypothesized specific effects of DBT-BED, the present study compared DBT-BED to an active comparison group therapy (ACGT). Men and women (n=101) meeting DSM-IV BED research criteria were randomly assigned to 20 group sessions of DBT-BED (n=50) or ACGT (n=51). DBT-BED had a significantly lower dropout rate (4%) than ACGT (33.3%). Linear Mixed Models revealed that posttreatment binge abstinence and reductions in binge frequency were achieved more quickly for DBT-BED than for ACGT (posttreatment abstinence rate=64% for DBT-BED vs. 36% for ACGT) though differences did not persist over the 3-, 6-, and 12-month follow-up assessments (e.g., 12-month follow-up abstinence rate=64% for DBT-BED vs. 56% for ACGT). Secondary outcome measures revealed no sustained impact on emotion regulation. Although both DBT-BED and ACGT reduced binge eating, DBT-BED showed significantly fewer dropouts and greater initial efficacy (e.g., at posttreatment) than ACGT. The lack of differential findings over follow-up suggests that the hypothesized specific effects of DBT-BED do not show long-term impact beyond those attributable to nonspecific common therapeutic factors.

Moderators and Mediators of Remission in Family-Based Treatment and Adolescent Focused Therapy for Anorexia Nervosa

Few of the limited randomized controlled trails (RCTs) for adolescent anorexia nervosa (AN) have explored the effects of moderators and mediators on outcome. This study aimed to identify treatment moderators and mediators of remission at end of treatment (EOT) and 6- and 12-month follow-up (FU) for adolescents with AN (N = 121) who participated in a multi-center RCT of family-based treatment (FBT) and individual adolescent focused therapy (AFT). Mixed effects modeling were utilized and included all available outcome data at all time points. Remission was defined as ≥ 95% IBW plus within 1 SD of the Eating Disorder Examination (EDE) norms. Eating related obsessionality (Yale-Brown-Cornell Eating Disorder Total Scale) and eating disorder specific psychopathology (EDE-Global) emerged as moderators at EOT. Subjects with higher baseline scores on these measures benefited more from FBT than AFT. AN type emerged as a moderator at FU with binge-eating/purging type responding less well than restricting type. No mediators of treatment outcome were identified. Prior hospitalization, older age and duration of illness were identified as non-specific predictors of outcome. Taken together, these results indicate that patients with more severe eating related psychopathology have better outcomes in a behaviorally targeted family treatment (FBT) than an individually focused approach (AFT).

Adaptive Designs for Randomized Trials in Public Health

In this article, we present a discussion of two general ways in which the traditional randomized trial can be modified or adapted in response to the data being collected. We use the term adaptive design to refer to a trial in which characteristics of the study itself, such as the proportion assigned to active intervention versus control, change during the trial in response to data being collected. The term adaptive sequence of trials refers to a decision-making process that fundamentally informs the conceptualization and conduct of each new trial with the results of previous trials. Our discussion below investigates the utility of these two types of adaptations for public health evaluations. Examples are provided to illustrate how adaptation can be used in practice. From these case studies, we discuss whether such evaluations can or should be analyzed as if they were formal randomized trials, and we discuss practical as well as ethical issues arising in the conduct of these new-generation trials.

Estimation of Intervention Effects with Noncompliance: Alternative Model Specifications

This study examines alternative ways of specifying models in the complier average causal effect (CACE) estimation method, where the major interest is in estimating causal effects of treatments for compliers. A fundamental difficulty involved in the CACE estimation method is in dealing with missing compliance information among study participants. Given that, the assumption of the exclusion restriction plays a critical role in separating the distributions of compliers and non-compliers. If no pretreatment covariates are available, assuming the exclusion restriction is unavoidable to obtain unique ML estimates in CACE models, although the assumption can be often unrealistic. One disadvantage of assuming the exclusion restriction is that the CACE estimate can be biased if the assumption is violated. Another disadvantage is that the assumption limits the flexibility of CACE modeling in practice. However, if pretreatment covariates are available, more modeling options other than strictly forcing the exclusion restriction can be considered to establish identifiability of CACE models. This study explores modeling possibilities of CACE estimation within an ML-EM framework in the presence of covariate information.

Causal inference in randomized experiments with mediational processes.

This article links the structural equation modeling (SEM) approach with the principal stratification (PS) approach, both of which have been widely used to study the role of intermediate posttreatment outcomes in randomized experiments. Despite the potential benefit of such integration, the 2 approaches have been developed in parallel with little interaction. This article proposes the cross-model translation (CMT) approach, in which parameter estimates are translated back and forth between the PS and SEM models. First, without involving any particular identifying assumptions, translation between PS and SEM parameters is carried out on the basis of their close conceptual connection. Monte Carlo simulations are used to further clarify the relation between the 2 approaches under particular identifying assumptions. The study concludes that, under the common goal of causal inference, what makes a practical difference is the choice of identifying assumptions, not the modeling framework itself. The CMT approach provides a common ground in which the PS and SEM approaches can be jointly considered, focusing on their common inferential problems.

An MRI and proton spectroscopy study of the thalamus in children with autism

Thalamic alterations have been reported in autism, but the relationships between these abnormalities and clinical symptoms, specifically sensory features, have not been elucidated. The goal of this investigation is to combine two neuroimaging methods to examine further the pathophysiology of thalamic anomalies in autism and to identify any association with sensory deficits. Structural MRI and multi-voxel, short echo-time proton magnetic resonance spectroscopy ((1)H MRS) measurements were collected from 18 male children with autism and 16 healthy children. Anatomical measurements of thalamic nuclei and absolute concentration levels of key (1)H MRS metabolites were obtained. Sensory abnormalities were assessed using a sensory profile questionnaire. Lower levels of N-acetylaspartate (NAA), phosphocreatine and creatine, and choline-containing metabolites were observed on the left side in the autism group compared with controls. No differences in thalamic volumes were observed between the two groups. Relationships, although limited, were observed between measures of sensory abnormalities and (1)H MRS metabolites. Findings from this study support the role of the thalamus in the pathophysiology of autism and more specifically in the sensory abnormalities observed in this disorder. Further investigations of this structure are warranted, since it plays an important role in information processing as part of the cortico-thalamo-cortical pathways.

Prediction of children's reading skills using behavioral, functional, and structural neuroimaging measures.

The ability to decode letters into language sounds is essential for reading success, and accurate identification of children at high risk for decoding impairment is critical for reducing the frequency and severity of reading impairment. We examined the utility of behavioral (standardized tests), and functional and structural neuroimaging measures taken with children at the beginning of a school year for predicting their decoding ability at the end of that school year. Specific patterns of brain activation during phonological processing and morphology, as revealed by voxel-based morphometry (VBM) of gray and white matter densities, predicted later decoding ability. Further, a model combining behavioral and neuroimaging measures predicted decoding outcome significantly better than either behavioral or neuroimaging models alone. Results were validated using cross-validation methods. These findings suggest that neuroimaging methods may be useful in enhancing the early identification of children at risk for poor decoding and reading skills.

Comparison of 2 Family Therapies for Adolescent Anorexia Nervosa: A Randomized Parallel Trial

IMPORTANCE Anorexia 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. OBJECTIVE To compare FBT with systemic family therapy (SyFT) for the treatment of adolescent-onset AN. DESIGN, SETTING, AND PARTICIPANTS Research 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. INTERVENTIONS Two 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 MEASURES The 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). RESULTS There 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,

A pilot study of an online cognitive rehabilitation program for executive function skills in children with cancer-related brain injury

8963; SyFT,