James Lock - US grants

DESCRIPTION (Adapted from the Applicant's Abstract): The overall aim of this application is to enhance the applicant's skills in clinical research through a program combining education, mentoring, and the completion of a controlled clinical trial. The objective of the controlled trial is to compare the outcome of adolescent patients with anorexia nervosa (AN) treated with intensive outpatient family therapy designed to reduce hospitalization, compared to a comparison group of adolescents with AN who receive less intensive outpatient family therapy. The intention is to test the effectiveness of intensive outpatient management as a potential alternative to hospitalization, to investigate factors predicting outcome, and provide information about the relative cost-effectiveness of more intensive compared to less intensive care. The candidate s major goal is to develop his research capacities in clinical child psychiatry with a focus on the populations treated in a clinical pediatric psychiatry program. At the end of the award period, the candidate expects to 1) possess the skills necessary to be an independent investigator in the mental health of children; 2) to have received funding as an independent investigator; and 3) to become a leader in the scientific study of patients with illnesses on the interface of pediatrics and psychiatry. The research focus of this application is on outcome and service-related issues in adolescents with AN. The candidate s broad career goal is to integrate clinical research on outcomes and service research into ongoing clinical and administrative activities in this area. In addition to the research activity, the candidate will participate in graduate course work in the School of Medicine s Department of Health Care Policy and Research and the Department of Psychiatry in the ethical conduct of research and the economics of health care. He will also take courses in the Departments of Psychology, Statistics, and Education at Stanford University in statistical and research methods related to behavioral sciences research. He will also participate in seminars and tutorials with identified educational consultants in areas related to his planned research.

This study proposes to explore the significance of prenatal psychosocial environment and prenatal mother-infant relationships in the newborn's health and development. The project's long-term aim is to facilitate early identification of high-risk families by designing new instruments that can be used prenatally to assess relational pathology and abusive tendencies toward the child. The study intends to contribute to the development of focused prenatal psychosocial interventions that would help to prevent negative consequences for the fetal and, later, the child's development and would contribute to primary prevention of perinatal complications that impose serious financial burden on the society.

DESCRIPTION (provided by applicant): Anorexia Nervosa (AN) is a serious psychological condition with a prevalence estimated at 0.48% among adolescent females between 15-19 years. In adolescents, the illness severely affects physical, emotional, and social development. To date, there are no large-scale treatment studies of adolescents with AN. Smaller scale studies, however, suggest that a specific type of family-based treatment (FT) is an effective approach to adolescent onset AN. This multi-site study aims to compare this specific family therapy (FBT) with ego oriented individual psychotherapy (EOIT) to determine which treatment is more efficacious. The study has two specific aims: (1) To compare the relative efficacy of FBT and EOIT in adolescents with AN. We will specifically examine weight gain, psychological concerns about weight and shape and changes in family functioning. (2) To examine potential predictors, mediators and moderators of outcome. To accomplish these aims the following study is proposed: at two centers (60 per center), 120 adolescents between the ages of 12-18 meeting DSM-IV criteria for AN will be randomly assigned to one of two treatment groups: 1) FBT (manualized) for 24 planned patient hours for 12 months; or 2) EOIT (manualized) for 24 planned patient hours over 12 months. All patients will be followed for 1 year after the end of treatment. Assessment will occur at baseline, end of treatment, and six months and one-year follow-up. Primary outcome will be weight change. Secondary outcomes will be changes in weight and shape concerns as measured by the Eating Disorder Examination.

DESCRIPTION (provided by candidate): This is an application for a Mid Career Development Award in patient oriented research that will take place at Stanford University School of Medicine designed to enhance research activities and to mentor future researchers in eating disorder treatment research, particularly with children and adolescents. The specific aims of the application are: 1) to continue and extend patient oriented research related to eating disorders in adolescents;and, 2) to increase my capacity to mentor young investigators in the context of patient oriented research with children and adolescents with eating disorders. Training activities will include collaborations with Dr. Christopher Fairburn in CBT-E and Marsha Linehan, MD in DBT in the areas of treatment adaptation and piloting. Mentoring activities will include clinical training, participation in ongoing research using an apprenticeship model for doctoral and post-doctoral level students, encouragement of independent research in my laboratory, and assisting students in authoring papers and presenting at research forums. The main vehicle for these mentoring activities and patient oriented research programs will be my funded R01 Treatment of Adolescents with Anorexia Nervosa as well as research projects currently under review or to be developed during the course of this award.

DESCRIPTION (provided by applicant): Anorexia Nervosa (AN) is a serious mental disorder with a prevalence rate of about 1%, a mortality rate of about 10%, and is as costly to treat as schizophrenia. No psychological or psychopharmacological treatments are known to be effective for adults with AN in part because existing studies have had difficulty retaining subjects in treatment. One potentially modifiable reason that has been suggested to assist with this problem is to address the specific cognitive impairments (inflexibility, set shifting, and weak central coherence) associated with AN through cognitive remediation therapy (CRT) prior to initiating a more specific treatment such as CBT. Evidence from the literature in schizophrenia, obsessive-compulsive disorder and traumatic brain injury indicate that CRT is an effective strategy for teaching new cognitive skills. Preliminary data suggest that CRT is both acceptable and feasible for adult AN subjects;however it has not yet been studied when added to a potentially effective psychotherapy such as cognitive behavioral therapy (CBT).The specific aims of this initial study are: Aim 1: To compare the relative efficacy of manualized CRT followed by manualized CBT-AN to manualized CBT-AN alone to retain subjects in treatment. We predict that those who receive CRT plus CBT-AN will have greater retention rates as assessed by survival curves between the treatment arms. Secondary outcomes will include changes in BMI and eating disorder psychopathology. Aim 2:To compare the relative efficacy of CRT versus CBT-AN in changing neurocognitive impairments in AN. Aim 3: To explore (post- hoc) moderators and mediators of treatment uptake, retention and outcome. To accomplish these aims, the following study is proposed: 46 subjects (ages 18 and above) meeting DSM IV criteria for AN and medically stable for outpatient treatment will be randomized to either CBT-AN (28 sessions) for 6 months or CRT (8 sessions) followed by CBT-AN for (20 sessions) for 6 months, with 23 subjects in each group. Assessments will occur at three time points: baseline, 8 weeks (end of treatment for CRT) and at 6 months follow-up. The primary outcome of the study will be time to drop out from treatment. Secondary outcomes will include changes in executive functioning (subtests of the Delis-Kaplan Executive Functioning System (D-KEFS)), the quality of the patient therapist relationship (HRQ), changes in Eating Disorder Examination (EDE) scores, and weight gain.

[unreadable] DESCRIPTION (provided by applicant): Bulimia Nervosa (BN) is a serious disorder characterized by overvalued ideas concerning body weight and shape and disinhibited eating patterns consisting of extreme dieting followed by binge eating and purging. BN occurs in approximately 1-2% of the adolescent population, while clinically significant bulimic behaviors or partial BN (specifically defined as binge eating and purging on average at least once a week for six months) occur in an additional 2-3%. However, other than frequency of binge eating and purging behaviors there appear to be few differences in the clinical severity of those with full syndrome BN and those with partial BN. Although bulimic behaviors typically onset during adolescence, there are only two published randomized clinical trials (RCTs) examining treatments for this age group. Results from our own recently published RCT of adolescent BN using a form of family-based therapy (FBT-BN) has shown that FBT-BN is superior to individual therapy for adolescents with BN. Also, recently published case series reports suggest that CBT adjusted for adolescents (CBT-A) is a promising treatment for bulimia in this age group. The Specific Aims of the proposal are: Aim 1: To compare the efficacy of CBT-A to FBT-BN in decreasing binge eating and purging episodes in adolescents with BN and partial BN (defined as binge eating and purging at least one time per week for the past six months). We predict that subjects randomized to CBT-A will achieve abstinence (as assessed by the Eating Disorder Examination) at significantly higher rates than those who receive FBT- BN. Aim 2: To explore potential moderators of outcome. We predict that symptom severity at baseline will moderate outcome; specifically, those subjects with greater symptom severity (higher EDE subscale scores) will have better outcomes with CBT-A than FBT-BN. Aim 3: To explore potential mediators of outcome. We predict that early changes in the restraint subscale of the EDE-Q) will mediate outcome in both treatments. Aim 4: If there are no differences between the two specific treatments, we will explore abstinence differences between specific treatments (CBT-A and FBT-BN) compared to a non-specific treatment (Supportive Psychotherapy - SPT) in order to examine nonspecific treatment effects (passage of time and nonspecific therapeutic influences). To accomplish these aims the following two-site study is proposed: 158 adolescents (79 at each site) between the ages of 12-18 years who meet DSM- IV criteria for BN or partial BN will be randomized to CBT-A (66 subjects), FBT-BN (66 subjects) or SPT (26 subjects), a non-specific treatment for BN for a 20 session/six month treatment period. The study is powered for the analysis of the primary aim of comparing the two specific treatments (FBT-BN and CBT-A); however, we are randomizing a smaller cohort to SPT to allow a post-hoc examination of non-specific treatment factors should no differences be found between the two specific treatments. [unreadable] [unreadable] [unreadable]

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Adolescents with anorexia and bulimia exhibit clinical symptoms suggesting abnormalities in executive function, including inhibition of responses. Functional MRI data have been collected from 23 subjects, including 6 with anorexia, 8 with bulimia, and 9 healthy control subjects, while performing the Go-NoGo task. This is a classic test of the ability to inhibit a prepotent response.

DESCRIPTION (provided by applicant): This application is a competitive renewal for a Mid-Career Development Award (K24-MH074457) designed to promote the continued development of the applicant (James Lock, MD, Ph.D) in conducting novel research and mentoring students and other investigators in the area of child and adolescent eating disorders. The applicant is active in developing and testing new treatments for eating disorders, mentoring new investigators, and developing his capacities to conduct neurocognitive and neurofunctional research as outlined in his previous award. This expansion of the scale and focus of Dr. Lock's research and mentoring activities was the direct result of having had the Mid-Career Development Award. In order to make continued progress in patient oriented research in the area of child and adolescent eating disorders and to continue to mentor young investigators, support for an additional 5 years is proposed in this application. Dr. Lock's own development as a research scientist would benefit from an additional period of Mid-Career Development by obtaining further training in neuroimaging research and in genetic research methods to be applied to eating disorder populations and by providing resources for additional mentoring for future scientists in the area of eating disorder research. This application has the following specific aims: 1) To continue to develop and test novel treatments for child and adolescent eating disorders, including enhancing a research network for anorexia nervosa research and dissemination; 2) To promote translational research in the neurosciences in patient oriented research related to eating disorders through advanced training in imaging research and new training in psychiatric genetic research; 3) To increase the number of trained researchers capable of conducting clinical research and translational research in child and adolescent eating disorders through mentoring and research training. The range of currently funded research and planned research provides an essential scaffold for research training. PUBLIC HEALTH RELEVANCE: This application is a proposal to continue to provide the applicant with support to mentor investigators and develop scientists in patient oriented research in eating disorders. The applicant's current research activities and his base in the Department of Psychiatry at Stanford University provide the platform for providing this type of scientific mentoring. In addition, this application proposes to support the development of the applicant's translational neuroscience training through advanced training in neuroimaging and initiating training in psychiatric genetics. Didactic, consultative, and experiential learning activities are proposed. A pilot project is proposed to investigate family aggregation of cognitive inefficiencies in eating disorders.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: Behavioral and personality characteristics associated with excessive inhibition and disinhibition are observed in patients with eating disorders. This study examined the neural correlates of inhibitory control in adolescents with these disorders. We hypothesized that patients with symptoms of binge eating and purging would show aberrant activation in regions associated with response inhibition, and that this pattern would differ from patients with restricting eating behaviors. Methods: Thirteen adolescents with binge eating and purging, i.e., bulimia nervosa or anorexia nervosa, binge-purge subtype ,14 with anorexia nervosa, restricting subtype, and 13 healthy controls performed a rapid jittered event related Go-NoGo task. FMRI images were collected using a 3T GE scanner and a spiral pulse sequence. A whole-brain 3-group ANOVA in SPM5 was used to identify significant activation associated with the Main Effect of Group, for the comparison of correct NoGo versus Go trials. The mean activation in these clusters was extracted for further comparisons in SPSS. To read about other projects ongoing at the Lucas Center, please visit http://rsl.stanford.edu/ (Lucas Annual Report and ISMRM 2011 Abstracts)

DESCRIPTION (provided by applicant): Anorexia Nervosa (AN) is a serious disorder associated with significant psychiatric and medical morbidity and mortality and high treatment costs due to the use of intensive treatment. Evidence suggests that FBT for adolescent AN is an effective outpatient treatment both at the end of treatment and 4-5 year follow-up. Using FBT, about 50% of participants remit (%IBW>95 + EDE >1SD of the mean) and 90% of those fully remitted at post-treatment, remain so at 12-month follow-up. In contrast, 75% of those not fully remitted at post-treatment are still not remitted at follow-up. Because there are no known effective treatments for adults with AN, and adolescents with AN appear to be more responsive to treatment, efforts to improve outcomes in this age group are critical to prevent the development of a chronic and unremitting course. However, when response to FBT is inadequate, more intensive programmed treatment (e.g. day treatment, residential care, or psychiatric hospitalization) is often recommended. Despite the common use of such programs, available data do not suggest that these interventions are more effective than outpatient interventions in adolescents. An alternative strategy to improve outcomes for those that do not respond to FBT would be to provide additional and targeted outpatient help directly to families themselves. Data suggest that families that are not likely to be successful in FBT can be identified as early as one month into treatment. Consequently, providing an alternative therapy early in the treatment course may enhance overall outcome. To develop a new treatment - Intensive Family-Focused Treatment (IFT) to improve outcomes in those who do not show an early response to FBT we propose a 2-phase treatment development study which aims to (1) identify modifiable family factors/behaviors that interfere with accomplishing weight restoration, and (2) develop a new family treatment (IFT) targeting unhelpful behaviors and promoting helpful ones (Phase 1 - Iterative case series (n=40)), and (3) pilot IFT (for those not responding early to FBT) vs. FBT alone in a small RCT, and (4) explore familial and individual factors as predictors, moderators, and mediators of treatment (Phase 2 - Small RCT (n=50)). To achieve these aims, this study will recruit 90 adolescents with AN (DSM-IV, exclusive of amenorrhea) and their families at two sites (45 participants at The University of Chicago and 45 at Stanford University). Primary outcome will be full remission from AN (%IBW>95 + EDE >1SD of the mean). Assessment of primary outcome as well as potential predictors, moderators and mediators will occur at baseline and at the end of treatment and will include eating related psychopathology in the parent and child (Eating Disorder Examination), Yale- Brown-Cornell-Eating Disorder, height/weight, general psychopathology in parent and child, family status, and family functioning.

DESCRIPTION (provided by applicant): Anorexia Nervosa (AN) is a life-threatening psychiatric disorder characterized by severe weight loss, distorted thinking about weight and appearance, and minimization of health and emotional problems. Typically, patients with AN also display a thinking style that is avoidant, rigid, and obsessive, which often limits the abilit of patients to respond to treatment. A growing body of literature demonstrates that this cognitive style is reflected in neuropsychological deficits in several domains, particularly, impaired set shifting (inflexibility), weak central coherence (exaggerated focus on detail to the neglect of the whole), and heightened sensitivity to reward and punishment. These inefficiencies may increase risk for AN given underlying brain abnormalities, and influence response to treatments. A comprehensive investigation of the neural basis of core cognitive inefficiencies in AN may suggest targets for cognitive treatments that enhance response to therapy and prevent relapse. There are a limited number of neuroimaging studies of cognitive function in AN. This application proposes a multimodal neuroimaging analysis, leveraging existing neuroimaging data collected with seed monies, to investigate the neural correlates of cognitive processes in AN. Twenty-four females with AN, ages 16-25, were previously recruited as part of an NIMH funded treatment trial. Structural and functional brain images were collected from these subjects at baseline, along with a matched group of 14 healthy female controls. This application requests funding needed to collect neuroimaging data from an additional 8 patients with AN, and to perform a comprehensive multimodal neuroimaging analysis of these existing data. State-of-the-art analyses will include multivariate pattern analysis of functional MRI acquired during standard tasks of set- shifting, central coherence, and reward processing. High resolution anatomical brain images will be subjected to a FreeSurfer analysis of regional volumes and cortical thickness throughout the brain. Diffusion tensor imaging data will be used to investigate white matter integrity throughout the brain, and tractography of fibers of interest. These analyses will contribute the most comprehensive assessment of the neural basis of neuropsychological processes in the existing AN literature.

DESCRIPTION (provided by applicant): This application responds to RFA-MH-12-050 Optimizing Fidelity of Empirically-Supported Behavioral Treatments for Mental Disorders. There is a critical need to disseminate effective psychosocial treatments for mental disorders as there is a significant gap between evidenced-based approaches and common clinical practice. One factor that contributes to this gap is low therapist fidelity to manualized treatments in clinial settings. Anorexia Nervosa (AN) is a serious disorder associated with significant psychiatric and medical morbidity, mortality, and high treatment costs. The only evidence based treatment available for adolescent AN is Family-Based Treatment (FBT). However, the role of key components of FBT that lead to clinical success (e.g., promoting parental alliance, externalization, use of a family meal, and psycho-education about the life-threatening nature of AN), have not been evaluated in relation to outcome. Moreover, it is important that more efficient training strategies be developed to promote adoption of evidence based treatments. Although therapists can likely be trained to use FBT, the key interventions needed, the most reliable methods for assessing these interventions, efficient strategies for identifying fidelity, he relationship of fidelity to outcome, and how best to train therapists efficiently in FBT are all unanswered questions. To address these gaps in knowledge, we propose the following aims in a 2-Phase design. In Phase 1 (R21): 1) To refine an existing fidelity assessment instrument for FBT and examine its psychometric properties; 2) To examine the relationship of FBT fidelity and its components to patient outcome; 3) To explore predictors of fidelity in FBT; 4) To develop a Focused Training (FT) and supervision program for FBT. During Phase 2 (R33) we plan to 1) To assess the feasibility of conducting a comparison study of two types of training in FBT by conducting a small pilot RCT of FT versus Standard Training (ST); and, explore the comparative outcomes of the patients treated by therapists in each group. To accomplish the aims of Phase 1 (R21) we will code and analyze archival data from tapes selected from previous studies using FBT. During Phase 2 (R33) we plan to compare FT to ST by randomizing 30 therapists (15 therapists with 3 subjects nested in each therapist) to receive either one of the two training programs. The primary outcome will be feasibility (e.g., recruitment, attrition, assessment battery, resource costs) to conduct a sufficiently powered comparative study.

DESCRIPTION (provided by applicant): Anorexia Nervosa (AN) usually begins during adolescence and is a serious psychiatric disorder associated with high morbidity, mortality, and economic cost. Although Family-Based Treatment (FBT) leads to full and stable recovery in about 50% of adolescents with short duration AN, there are no evidence based interventions for those who do not respond and who, as a result, are at approximately 33% risk for becoming chronically ill. Therefore, it is imperative to intervene to change the trajectory of young patient at risk for becoming chronically ill while there is a reasonable opportunity for success. This application in response to PA-12-279 (R34) proposes to study the feasibility of combining Cognitive Remediation Therapy (CRT) with FBT for future use in an adequately powered RCT to reduce the risk of adolescents developing persistent AN. Two studies suggest that higher levels of obsessional features lead to poorer outcome in FBT. It is proposed that CRT addresses the cognitive underpinnings of obsessional thought by promoting more flexible and less perseverative thinking. These changes could in turn lead to an improved ability to accept the need for change in the behaviors and thoughts that maintain AN. Two small case series report significant improvement in adults with AN. In addition, case series data in adolescents with AN find CRT is acceptable and improves cognitive processes. We propose the following Specific Aims: Aim 1: To examine the feasibility of incorporating CRT in FBT. We will examine acceptability, recruitment, feasibility of assessment procedures and instruments of FBT plus CRT and the acceptability of the comparison treatment (FBT plus art therapy). Aim 2: To explore changes in cognitive style, weight, eating related cognitions, and psychosocial functioning in those who received FBT plus CRT compared to FBT plus art therapy. To accomplish Aim 1, we will recruit 30 adolescents (ages 12-18) with AN and evidence of OC features on the YBC-ED (score >14). These participants will be randomized to either FBT (15 sessions) plus art exercises (15 sessions) for 6 months or FBT plus CRT (15 sessions) for 6 months. Our primary outcomes are: feasibility of recruitment, retention rates, and viability of assessment procedures. Secondary outcomes (Aim 2) are changes in neuropsychological functioning, weight, eating related psychopathology and psychosocial functioning. Assessments will occur at four time points: baseline, 4 weeks, 8 weeks, and end of treatment (EOT).

Confirming the efficacy/mechanism of an adaptive treatment for adolescent anorexia nervosa In adolescent anorexia nervosa (AN) 30-40% fully recover with Family Based Treatment (FBT) and remain so 3-4 years after treatment, but those who do not remit have a high risk of developing enduring AN with accompanying co-morbidities, much reduced quality of life, premature death, and for which there is no evidence-based treatment. Studies of FBT find that weight gain by session 4 predicts outcome in 85-90% of cases;  thus, one way to improve outcomes in line with precision medicine is to match treatments to patients depending on weight gain at session 4 by offering an alternative treatment to meet the specific needs of poor early responders (~44%). The aim of this study in response to RFA-MH-16-425 is to determine if an adaptive outpatient treatment compatible with FBT could significantly improve outcomes by addressing poor early response and add to our understanding of the mechanisms of treatment in FBT. We developed a 3- session (Intensive Parent Coaching-IPC) intervention to increase parental skills at re-feeding for this poor early responding group demonstrating the feasibility of using a randomized adaptive design employing IPC. Compared to expected weight restoration rates in poor early responders, 50% more participants achieved weight restoration than expected with an average mean weight of 96.7% by EOT (preliminary efficacy signal of Cohen's d= 0.82). Previous studies have shown that FBT specifically targets parental self-efficacy as the mechanism to promote weight restoration in their children with AN. Consistent with these studies, data from the current pilot RCT suggest that parents whose children do not gain 2.4 kg by session 4 report lower levels of self-efficacy related to re-feeding as early as session 2; however, after receiving FBT+IPC, parental self- efficacy scores in this group improve and become indistinguishable from those of parents of early responders. While these preliminary data are promising, a sufficiently powered and controlled RCT using an adaptive randomized design employing FBT+IPC as the adaptive intervention for poor early responders is needed to understand the role of parental efficacy and re-feeding behaviors in FBT before recommending an adaptive approach. To conduct an adequately powered study (0.87 (alpha=.05, two-tailed)), 150 adolescents (75 per site) will be randomized at 2 sites (Stanford University and the University of California, San Francisco) to either standard FBT or an adaptive treatment arm (FBT+IPC) where those who do not gain 2.4 kg by session 4 will receive additional treatment (FBT+IPC). Assessments (blinded to treatment condition) will be conducted at baseline, 3, 9 (EOT) and at 6 and 12-month follow-up. Our primary outcome will be achievement of weight remission (>94% expected mean percent BMI adjusted for age, height and gender).  

Project Abstract Background/Description. Given our mutual interest in direct brain stimulation as an effective treatment for non-adherent eating disorders associated with refractory obesity, our multidisciplinary team at Stanford University has developed a collaboration with NeuroPace, Inc, a company that recently received FDA approval for a responsive neurostimulator. We previously found that electrically stimulating the nucleus accumbens (NAc) of mice attenuates binge-like eating. In addition, increased power in low frequency oscillations appears to temporally correlate with anticipation of food reward and predict the onset of a binge. There is increasing awareness that obese individuals frequently lose control over food, which leads to binge-like eating. We hypothesize that a responsive neurostimulator could be used to identify low frequency oscillations that represent loss of control over eating and deliver responsive stimulation to the NAc to prevent a binge. Objective. To test stimulation parameters and detection algorithms for responsive neurostimulation in humans in an Early Feasibility Study. Methods. All needed regulatory avenues will be pursued, and an Early Feasibility Study will be performed in human subjects with refractory obesity due to loss of control eating. We will primarily assess device function and safety, but will utilize multimodal controlled and ambulatory measures to test the potential of this clinical program for LOC eating in obesity.

This application responds to RFA-MH-18-706 Pilot Effectiveness Trials for Treatment, Preventive, and Services Interventions. There is a critical need to disseminate efficacious psychosocial treatments for mental disorders as there is a significant gap between evidenced-based approaches and common clinical practice. One example of the need to improve dissemination and implementation of psychosocial treatments is for adolescent Anorexia Nervosa (AN), a serious mental disorder with an incidence rate of about 1%.that can become life- threatening. Based on outcomes from a series of randomized clinical trials (RCTs), the first line treatment for adolescent AN is Family-based Treatment (FBT; however, most therapists are not trained to use it. Further, while approximately 45-50% of US mental health outpatient providers are in private practice, little attention has been paid to how best to train this group. We propose to use an online training strategy to study adoption of FBT to better understand factors that limit or enhance uptake and implementation of this treatment in private practice. We propose to build on these findings using a pre-post design to examine the feasibility of new methods to retain therapists, assess training mechanisms, and collect patient outcomes from clinicians in private practice. The primary significance of this study is its potential to increase the availability FBT--the most effective treatment for adolescent AN. A major innovation of the study is assessing the feasibility of training clinicians in private practice in FBT who provide significant treatment for adolescent AN. These data would provide support for a go/no-go decision about a large scale study to train therapists in private practice using online ET-FBT.

Avoidant restrictive food intake disorder (ARFID) is a new psychiatric disorder in the Diagnostic and Statistical Manual 5 (DSM-5). ARFID has an estimated prevalence of 7.2 to 17.4 percent thus making it a significant mental health concern. ARFID is characterized by a range of dysfunctional eating behaviors including a lack of interest in eating, sensory related eating concerns (such as taste, color or texture) and a fear of adverse consequences of eating (i.e., fear of choking or vomiting). There is no evidence-based treatment for ARFID. Preliminary data from a feasibility study comparing FBT-ARFID to Usual Care (UC) provide evidence that manualized FBT adapted for patients with ARFID is feasible and effective. Recruitment and randomization averaged 1.87 participants per month over a 15 month period with an overall attrition rate of 21%, comparable to rates in fully powered studies of FBT-AN. The feasibility study also identified an efficacy signal on the difference between groups on the primary outcome (change in percent Estimated Body Weight (%EBW)) of a large effect size (ES) favoring FBT-ARFID Studies suggest that improvements in parental self-efficacy related to changing feeding and eating behaviors early in treatment is a likely mechanism of FBT for other eating disorders in youth. Our feasibility study showed a striking difference between conditions in parental self-efficacy favoring FBT-ARFID compared to UC. In addition to this promising evidence of target engagement In addition, target validation was demonstrated by the change in parental self-efficacy being significantly correlated with improvements in % EBW. Aim 1: To conduct an RCT involving children and adolescents between the ages of 6 and 12 years of age with DSM 5 ARFID and weight below 88% of EBW comparing FBT-ARFID with medical management to manualized Non-Specific Treatment UC with medical management. Treatments will be matched for time and therapist attention. We hypothesize that participants randomized to FBT-ARFID will have significantly greater change in %EBW at EOT. Aim 2: To examine early change in parental self-efficacy as a mediator of treatment effect (FBT-ARFID vs. UC on outcome). We hypothesize that positive changes due to FBT-ARFID in parental self-efficacy related to feeding behaviors using the Parents vs ARFID Scale (PvsARFID) will be associated with positive changes in %EBW at EOT. Secondarily, we will explore whether objective changes in parental re-feeding behavior is a possible mechanism of FBT-ARFID using a mediator analysis. Aim 3: To explore moderators of treatment outcome. To conduct an adequately powered study, 100 children (ages 6-12 years) will be randomized to manualized FBT-ARFID plus medical management (n=50) or manualized Non- Specific Treatment plus medical management (n=50). Assessments (blinded to treatment condition) of primary and secondary outcomes will be conducted at baseline, 1 month, 2 months, and 4 months (EOT).