Effect of Internet-Based Cognitive Behavioral Humanistic and Interpersonal Training vs Internet-Based General Health Education on Adolescent Depression in Primary Care A Randomized Clinical Trial

Importance Although 13% to 20% of American adolescents experience a depressive episode annually, no scalable primary care model for adolescent depression prevention is currently available. Objective To study whether competent adulthood transition with cognitive behavioral humanistic and interpersonal training (CATCH-IT) lowers the hazard for depression in at-risk adolescents identified in primary care, as compared with a general health education (HE) attention control. Design, Setting, and Participants This multicenter, randomized clinical trial, a phase 3 single-blind study, compares CATCH-IT with HE. Participants were enrolled from 2012 to 2016 and assessed at 2, 6, 12, 18, and 24 months postrandomization in a primary care setting. Eligible adolescents were aged 13 to 18 years with subsyndromal depression and/or history of depression and no current depression diagnosis or treatment. Of 2250 adolescents screened for eligibility, 446 participants completed the baseline interview, and 369 were randomized into CATCH-IT (n = 193) and HE (n = 176). Interventions The internet-based intervention, CATCH-IT, is a 20-module (15 adolescent modules and 5 parent modules) online psychoeducation course that includes a parent program, supported by 3 motivational interviews. Main Outcomes and Measures Time to event for depressive episode; depressive symptoms at 6 months. Results Of 369 participants (mean [SD] age, 15.4 [1.5] years; 251 women [68%]) included in this trial, 193 were randomized into CATCH-IT and 176 into HE. Among these participants, 28% had both a past episode and subsyndromal depression; 12% had a past episode only, 59% had subsyndromal depression only, and 1% had borderline subsyndromal depression. The outcome of time to event favored CATCH-IT but was not significant with intention-to-treat analyses (unadjusted hazard ratio [HR], 0.59; 95% CI, 0.27-1.29; P = .18; adjusted HR, 0.53; 95% CI, 0.23-1.23; P = .14). Adolescents with higher baseline Center for Epidemiologic Studies Depression scale (CES-D10) scores showed a significantly stronger effect of CATCH-IT on time to event relative to those with lower baseline scores (HR 0.82; 95% CI, 0.67-0.99; P = .04). For example, the hazard ratio for a CES-D10 score of 15 was 0.20 (95% CI, 0.05-0.77), compared with a hazard ratio of 1.44 (95% CI, 0.41-5.03) for a CES-D10 score of 5. In both CATCH-IT and HE groups, depression symptoms declined and functional scores increased. Conclusions and Relevance For preventing depressive episodes CATCH-IT may be better than HE for at-risk adolescents with subsyndromal depression. Also CATCH-IT may be a scalable approach to prevent depressive episodes in adolescents in primary care. Trial Registration ClinicalTrials.gov Identifier: NCT0189374

Prevention of Adolescent Depression in Primary Care: Barriers and Relational Work Solutions

Background and Purpose: Depression affects millions of adolescents in the United States each year. This population may benefit from targeted preventive interventions. We sought to understand the internal factors that affect the ability of healthcare organizations to implement an intervention that involves mental health screening and depression prevention treatment of at-risk adolescents in primary care settings. Methods: From November 2011 to July 2016 we conducted a study of the implementation of a multisite (N=30) phase 3 randomized clinical trial of an Internet-based depression prevention intervention program (CATCH-IT). We describe the prevalence of internal barriers on the screening and enrollment process by reporting REACH (the proportion of target audience exposed to the intervention). Results: A total of 369 adolescents were randomized into the intervention or control program. Mean REACH values for the study clinics were 0.216 for screening and 0.181 for enrollment to CATCH-IT. Mean REACH enrollment lost due to internal barriers was 0.233. This translated to 4,691 adolescents lost at screening and 2,443 adolescents lost at enrollment due to internal barriers. Conclusion: We propose a model of the implementation process that emphasizes the importance of positive relational work that assists in overcoming internal barriers to REACH. We also provide implications for policy and practice

Effect of Internet-Based Cognitive Behavioral Humanistic and Interpersonal Training vs Internet-Based General Health Education on Adolescent Depression in Primary Care

Importance: Although 13% to 20% of American adolescents experience a depressive episode annually, no scalable primary care model for adolescent depression prevention is currently available. Objective: To study whether competent adulthood transition with cognitive behavioral humanistic and interpersonal training (CATCH-IT) lowers the hazard for depression in at-risk adolescents identified in primary care, as compared with a general health education (HE) attention control. Design, Setting, and Participants: This multicenter, randomized clinical trial, a phase 3 single-blind study, compares CATCH-IT with HE. Participants were enrolled from 2012 to 2016 and assessed at 2, 6, 12, 18, and 24 months postrandomization in a primary care setting. Eligible adolescents were aged 13 to 18 years with subsyndromal depression and/or history of depression and no current depression diagnosis or treatment. Of 2250 adolescents screened for eligibility, 446 participants completed the baseline interview, and 369 were randomized into CATCH-IT (n = 193) and HE (n = 176). Interventions: The internet-based intervention, CATCH-IT, is a 20-module (15 adolescent modules and 5 parent modules) online psychoeducation course that includes a parent program, supported by 3 motivational interviews. Main Outcomes and Measures: Time to event for depressive episode; depressive symptoms at 6 months. Results: Of 369 participants (mean [SD] age, 15.4 [1.5] years; 251 women [68%]) included in this trial, 193 were randomized into CATCH-IT and 176 into HE. Among these participants, 28% had both a past episode and subsyndromal depression; 12% had a past episode only, 59% had subsyndromal depression only, and 1% had borderline subsyndromal depression. The outcome of time to event favored CATCH-IT but was not significant with intention-to-treat analyses (unadjusted hazard ratio [HR], 0.59; 95% CI, 0.27-1.29; P = .18; adjusted HR, 0.53; 95% CI, 0.23-1.23; P = .14). Adolescents with higher baseline Center for Epidemiologic Studies Depression scale (CES-D ) scores showed a significantly stronger effect of CATCH-IT on time to event relative to those with lower baseline scores (HR 0.82; 95% CI, 0.67-0.99; P = .04). For example, the hazard ratio for a CES-D score of 15 was 0.20 (95% CI, 0.05-0.77), compared with a hazard ratio of 1.44 (95% CI, 0.41-5.03) for a CES-D score of 5. In both CATCH-IT and HE groups, depression symptoms declined and functional scores increased. Conclusions and Relevance: For preventing depressive episodes CATCH-IT may be better than HE for at-risk adolescents with subsyndromal depression. Also CATCH-IT may be a scalable approach to prevent depressive episodes in adolescents in primary care

CRISPR-on for activation of endogenous SMARCA4 and TFAP2C expression in bovine embryos

CRISPR-mediated transcriptional activation, also known as CRISPR-on, has proven efficient for activation of individual or multiple endogenous gene expression in cultured cells from several species. However, the potential of CRISPR-on technology in preimplantation mammalian embryos remains to be explored. Here, we report for the first time the successful modulation of endogenous gene expression in bovine embryos by using the CRISPR-on system. As a proof of principle, we targeted the promoter region of either SMARCA4 or TFAP2C genes, transcription factors implicated in trophoblast lineage commitment during embryo development. We demonstrate that CRISPR-on provides temporal control of endogenous gene expression in bovine embryos, by simple cytoplasmic injection of CRISPR RNA components into one cell embryos. dCas9VP160 activator was efficiently delivered and accurately translated into protein, being detected in the nucleus of all microinjected blastomeres. Our approach resulted in the activation of SMARCA expression shortly after microinjection, with a consequent effect on downstream differentiation promoting factors, such as TFAP2C and CDX2. Although targeting of TFAP2C gene did not result in a significant increase in TFAP2C expression, there was a profound induction in CDX2 expression on day 2 of development. Finally, we demonstrate that CRISPR-on system is suitable for gene expression modulation during the preimplantation period, since no detrimental effect was observed on microinjected embryo development. This study constitutes a first step toward the application of the CRISPR-on system for the study of early embryo cell fate decisions in cattle and other mammalian embryos, as well as to design novel strategies that may lead to an improved trophectoderm development.Fil: Savy, Virginia. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; ArgentinaFil: Alberio, Virgilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; ArgentinaFil: Canel, Natalia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; ArgentinaFil: Ratner, Laura Daniela. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; ArgentinaFil: Gismondi, Maria Ines. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion En Ciencias Veterinarias y Agronomicas. Instituto de Agrobiotecnologia y Biologia Molecular. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Agrobiotecnologia y Biologia Molecular; ArgentinaFil: Ferraris, Sergio Raúl. Universidad Maimónides. Centro de Ciencias Veterinarias; ArgentinaFil: Fernández y Martín, Rafael. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; ArgentinaFil: Knott, Jason G.. Department Of Animal Science; Estados UnidosFil: Bevacqua, Romina Jimena. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; Argentina. University of Stanford; Estados UnidosFil: Salamone, Daniel Felipe. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentin

An internet-based adolescent depression preventive intervention: study protocol for a randomized control trial

Background: The high prevalence of major depressive disorder in adolescents and the low rate of successful treatment highlight a pressing need for accessible, affordable adolescent depression prevention programs. The Internet offers opportunities to provide adolescents with high quality, evidence-based programs without burdening or creating new care delivery systems. Internet-based interventions hold promise, but further research is needed to explore the efficacy of these approaches and ways of integrating emerging technologies for behavioral health into the primary care system. Methods/Design We developed a primary care Internet-based depression prevention intervention, Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training (CATCH-IT), to evaluate a self-guided, online approach to depression prevention and are conducting a randomized clinical trial comparing CATCH-IT to a general health education Internet intervention. This article documents the research framework and randomized clinical trial design used to evaluate CATCH-IT for adolescents, in order to inform future work in Internet-based adolescent prevention programs. The rationale for this trial is introduced, the current status of the study is reviewed, and potential implications and future directions are discussed. Discussion The current protocol represents the only current, systematic approach to connecting at-risk youth with self-directed depression prevention programs in a medical setting. This trial undertakes the complex public health task of identifying at-risk individuals through mass screening of the general primary care population, rather than solely relying on volunteers recruited over the Internet, and the trial design provides measures of both symptomatic and diagnostic clinical outcomes. At the present time, we have enrolled N = 234 adolescents/expected 400 and N = 186 parents/expected 400 in this trial, from N = 6 major health systems. The protocol described here provides a model for a new generation of interventions that blend substantial computer-based instruction with human contact to intervene to prevent mental disorders such as depression. Because of the potential for broad generalizability of this model, the results of this study are important, as they will help develop the guidelines for preventive interventions with youth at-risk for the development of depressive and other mental disorders. Trial registration Clinical Trial Registry: NCT01893749 date 6 May 2012

PATHway: Intervention optimization of a prevention program for adolescents at-risk for depression in the primary care setting

With as many as 13% of adolescents diagnosed with depressive disorders each year, prevention of depressive disorders has become a key priority for the National Institute of Mental Health (NIMH). Currently, we have no widely available interventions to prevent these disorders. To address this need, we developed a multi-health system collaboration to develop and evaluate the primary care based technology behavioral vaccine, Competent Adulthood Transition with Cognitive-Behavioral Humanistic and Interpersonal Therapy (CATCH-IT). The full CATCH-IT program demonstrated evidence of efficacy in prevention of depressive episodes in clinical trials. However, CATCH-IT became larger and more complex across trials, creating issues with adherence and scalability. We will use a multiphase optimization strategy approach to optimize CATCH-IT. The theoretically grounded components of CATCH-IT include: behavioral activation, cognitive-behavioral therapy, interpersonal psychotherapy, and parent program. We will use a 4-factor (2x2x2x2) fully crossed factorial design with N = 16 cells (25 per cell, after allowing 15% dropout) to evaluate the contribution of each component. Eligible at-risk youth will be high school students 13 through 18 years old, with subsyndromal symptoms of depression. The study design will enable us to eliminate non-contributing components while preserving efficacy and to optimize CATCH-IT by strengthening tolerability and scalability by reducing resource use. By reducing resource use, we anticipate satisfaction and acceptability will also increase, preparing the way for an implementation trial

Effect of Internet-Based Cognitive Behavioral Humanistic and Interpersonal Training vs Internet-Based General Health Education on Adolescent Depression in Primary Care: A Randomized Clinical Trial

Importance: Although 13% to 20% of American adolescents experience a depressive episode annually, no scalable primary care model for adolescent depression prevention is currently available. Objective: To study whether competent adulthood transition with cognitive behavioral humanistic and interpersonal training (CATCH-IT) lowers the hazard for depression in at-risk adolescents identified in primary care, as compared with a general health education (HE) attention control. Design, Setting, and Participants: This multicenter, randomized clinical trial, a phase 3 single-blind study, compares CATCH-IT with HE. Participants were enrolled from 2012 to 2016 and assessed at 2, 6, 12, 18, and 24 months postrandomization in a primary care setting. Eligible adolescents were aged 13 to 18 years with subsyndromal depression and/or history of depression and no current depression diagnosis or treatment. Of 2250 adolescents screened for eligibility, 446 participants completed the baseline interview, and 369 were randomized into CATCH-IT (n = 193) and HE (n = 176). Interventions: The internet-based intervention, CATCH-IT, is a 20-module (15 adolescent modules and 5 parent modules) online psychoeducation course that includes a parent program, supported by 3 motivational interviews. Main Outcomes and Measures: Time to event for depressive episode; depressive symptoms at 6 months. Results: Of 369 participants (mean [SD] age, 15.4 [1.5] years; 251 women [68%]) included in this trial, 193 were randomized into CATCH-IT and 176 into HE. Among these participants, 28% had both a past episode and subsyndromal depression; 12% had a past episode only, 59% had subsyndromal depression only, and 1% had borderline subsyndromal depression. The outcome of time to event favored CATCH-IT but was not significant with intention-to-treat analyses (unadjusted hazard ratio [HR], 0.59; 95% CI, 0.27-1.29; P =.18; adjusted HR, 0.53; 95% CI, 0.23-1.23; P =.14). Adolescents with higher baseline Center for Epidemiologic Studies Depression scale (CES-D10) scores showed a significantly stronger effect of CATCH-IT on time to event relative to those with lower baseline scores (HR 0.82; 95% CI, 0.67-0.99; P =.04). For example, the hazard ratio for a CES-D10score of 15 was 0.20 (95% CI, 0.05-0.77), compared with a hazard ratio of 1.44 (95% CI, 0.41-5.03) for a CES-D10score of 5. In both CATCH-IT and HE groups, depression symptoms declined and functional scores increased. Conclusions and Relevance: For preventing depressive episodes CATCH-IT may be better than HE for at-risk adolescents with subsyndromal depression. Also CATCH-IT may be a scalable approach to prevent depressive episodes in adolescents in primary care. Trial Registration: ClinicalTrials.gov Identifier: NCT01893749</p