2/4-PREVENTION OF DEPRESSION: IMPACT ON THE TRANSITION TO EARLY ADULTHOOD
G Tracy
Judge Baker Children´s Centercity: Boston country: United States (us)
Grant 5R01MH064717-09 from National Institute Of Mental Health
Keywords: 17 year old; Absenteeism; Adolescence; Adolescent; Adoption; Adult; Age; Angiotensins; Anxiety; Area; Behavioral; Benchmarking; Biological; Candidate Disease Gene; cardiovascular risk factor; Child Abuse; Cognitive; Competence; cost; cost effectiveness; Data; depressive symptoms; Development; Diet; DNA; economic outcome; Economics; Educational aspects; emerging adult; emerging adulthood; Employment; Enrollment; Environmental Risk Factor; Enzymes; Evaluation; Event; Family member; follow-up; Foundations; Future; Genes; Genetic; Genetic Polymorphism; global health; Goals; Health; high risk; Hostility; human capital; Hypertension; Hypotension; Impairment; improved; Incidence; indexing; Individual; innovation; Intervention; intervention program; Intervention Studies; Interview; Knowledge; Life; Link; Long-Term Effects; Longitudinal Studies; Mediating; Medical; meetings; Mental Depression; Mental Health; Mood Disorders; National Institute of Mental Health (U.S.); Neurotic Disorders; next generation; novel; Outcome; Overweight; Parents; Participant; Patient Self-Report; Personality; Physical activity; physical conditioning; prevent; Prevention; Prevention program; Prevention strategy; Preventive Intervention; proband; Productivity; programs; Promotor (Genetics); Psyche structure; psychologic; psychosocial; public health medicine (field); Randomized; Recording of previous events; Recurrence; Relative (related person); Relative Risks; response; Risk; Risk Behaviors; Role; Sampling; Schools; serotonin transporter; Services; Site; Sleep; Smoking; Stress; stressor; Substance abuse problem; Suicide; Teenagers; trait; treatment as usual; treatment effect; Unemployment; Unipolar Depression; Workplace; young adult; Youth
Relevance: In our original study, we found that we can prevent depression among at-risk youth, but we do not yet know if this prevention lasts and whether it improves youths´ schooling, employment, and relationships with others. The proposed study will be the first to examine whether depression continues to be prevented as these teens become young adults. This study also will identify youth who are most likely to benefit from this program, and will inform us about how to create future prevention programs that help those youth who did not benefit
Project start date: 2001-12-01
Project end date: 2012-12-31
Budget start date: 1-JAN-2012
Budget end date: 31-DEC-2012
5R01MH064717-09 (2012): $228863
Sponsored Links Excellgen http://Excellgen.com
2/4-PREVENTION OF DEPRESSION: IMPACT ON THE TRANSITION TO EARLY ADULTHOOD
G Tracy, Professor Of Psychiatry
Judge Baker Children´s Centercity: Boston country: United States (us)
Grant 5R01MH064717-08 from National Institute Of Mental Health
Abstract: This A1competitive renewal is one of four collaborative, linked R01s that proposes to examine the long-term effects of a Cognitive Behavioral Program (CBP) for preventing depression provided when adolescents were 13-17 years old. The sample is at high risk by virtue of familial (parental depression) and individual factors (past history of depression and/or current subsyndromal depressive symptoms). In the original study, we successfully enrolled 99% (N=316) of our proposed target recruitment of 320 adolescents, with equal recruitment across the 4 sites. Participants were randomized into either CBP or treatment as usual (TAU), with equally high retention (92%) in both conditions. Results through the 8-month follow-up indicated a significant prevention effect of CBP with regard to depressive episodes (HR=.60, 95% CI, .38-.96; effect size, d=.25), thus replicating and extending the earlier, single site study by Clarke et al., (2001). The aims of the current proposal are to (a) study the longer term impact of CBP on preventing depression during the critical developmental transition to early adulthood, a period of multiple new life challenges and stressors; (b) assess potential biological (e.g., genetic) and psychosocial (e.g., childhood abuse, stressful life events) moderators of response to the intervention; (c) examine the broader impact of the CBP program on sequelae of depression including other mental and medical health problems, health risk behaviors, and impairment in the attainment of developmental competencies; and (d) assess the long-term cost-efficacy of CBP, identify markers of the impact of CBP on key economic outcomes (e.g., workplace productivity), and examine the longer-term economic benefits of preventing or delaying the onset of mood disorders in adolescents with CBP. We will explore the potential role of adolescent depression in mediating these outcomes in young adulthood. These aims are consistent with the areas of highest priority for the NIMH Division of Services and Intervention Research (DSIR) insofar as this project will evaluate the durability and broader effects as well as cost-efficacy of an innovative prevention strategy, will potentially reduce the burden of suicidality by increasing depression-free days, and will both aid in the personalization of the intervention and the identification of new prevention targets through our study of biological and psychosocial moderators of treatment effects. Knowledge gained from this study will be used to identify individuals who are most and least likely to benefit from this prevention program, and will provide an empirical foundation for novel and innovative strategies for the prevention of depression. In our original study, we found that we can prevent depression among at-risk youth, but we do not yet know if this prevention lasts and whether it improves youths´ schooling, employment, and relationships with others. The proposed study will be the first to examine whether depression continues to be prevented as these teens become young adults. This study also will identify youth who are most likely to benefit from this program, and will inform us about how to create future prevention programs that help those youth who did not benefit
Keywords: 0-11 years old; 12-20 years old; 17 year old; 21+ years old; 5HT transporter; 5HTT protein; abnormal psychology; Absenteeism; abuse neglect; abuse of substances; Active Follow-up; Acute; Address; Adolescence; adolescence (12-20); Adolescent; adolescent trauma; Adolescent Youth; Adoption; Adult; adult human (21+); adult youth; Affective Disorders; Age; Age of Onset; Angiotensins; Anxiety; Area; at risk behavior; Behavioral; Benchmarking; Best Practice Analysis; Biological; Blood Pressure, High; Blood Pressure, Low; BMI percentile; BMI z-score; Body mass index; Boston; Candidate Disease Gene; Candidate Gene; cardiovascular disease risk; cardiovascular disorder risk; cardiovascular risk; cardiovascular risk factor; Child; Child Abuse; Child Youth; Childhood Abuse; childhood trauma; children; Children (0-21); Chronic; City of Boston; Cognitive; cohort; Competence; cost; cost effective; cost effectiveness; Costs and Benefits; critical period; Data; Data Collection; Data Coordinating Center; Data Coordination Center; Deoxyribonucleic Acid; depressed; Depressed mood; Depression; depressive; Depressive disorder; depressive symptoms; design; designing; Development; Diet; disability; Disease; disease prevention; disease/disorder; Disorder; disorder prevention; Divorce; DNA; Doctor of Philosophy; early childhood; early detection; Early Diagnosis; economic impact; economic outcome; Economics; Education; Educational aspects; effect of intervention; Effectiveness of Interventions; Effects, Longterm; emerging adult; emerging adulthood; Emotional Depression; Employment; enroll; Enrollment; Environment; Environmental Factor; environmental risk; Environmental Risk Factor; Enzymes; Epidemiology, Family Medical History; Evaluation; Event; experience; Family; Family history of; Family Medical History; Family member; fatal attempt; fatal suicide; follow-up; Foundations; Funding; Future; Genes; Genetic; Genetic analyses; genetic analysis; Genetic Markers; Genetic Polymorphism; Genetic Risk; global health; Goals; Health; Health Benefit; Health Care Costs; health care organization; health care service organization; Health Costs; Health Psychology; Health Status; Healthcare Costs; heavy metal lead; heavy metal Pb; high risk; History; Hostility; human capital; Human, Adult; Human, Child; hyperpiesia; hyperpiesis; Hypertension; hypertensive disease; Hypotension; Impairment; improved; Incidence; indexing; Individual; Individual Differences; innovate; innovation; innovative; intent to die; Intervention; intervention development; intervention effect; intervention program; Intervention Strategies; Intervention Studies; interventional strategy; Interview; Job Environment; Job Location; Job Place; Job Setting; Job Site; jobless; joblessness; juvenile; juvenile human; Knowledge; Lead; Level of Health; Life; Link; Literature; Long-Term Effects; long-term study; Longitudinal Studies; Measures; Mediating; Medical; meetings; mental; Mental Depression; Mental disorders; Mental Health; Mental health disorders; Mental Hygiene; mental illness; Methods; Modeling; Molecular; Mood Disorders; Morbidity; Morbidity - disease rate; multi-site trial; National Institute of Mental Health; National Institute of Mental Health (U.S.); neglect and abuse; Neuroses; Neurosis, Depressive; neurotic; Neurotic Disorders; neuroticism; next generation; NIMH; novel; Occupational; offspring; out of work; Outcome; Over weight; Overweight; Parenting; Parenting behavior; Parents; Participant; Patient Self-Report; Pb element; pediatric trauma; performance site; Personality; Ph.D.; PhD; Phone; Physical activity; physical conditioning; polymorphism; Polymorphism (Genetics); Polymorphism, Genetic; Population; Prevalence; prevent; preventing; Prevention; Prevention program; Prevention strategy; preventional intervention strategy; Preventive; Preventive Intervention; Preventive strategy; proband; Procedures; Productivity; Program Development; programs; Programs (PT); Programs [Publication Type]; Progress Reports; Promoter; Promoters (Genetics); Promotor; Promotor (Genetics); Psyche structure; Psychiatric Disease; Psychiatric Disorder; psychologic; psychological; psychological disorder; Psychological Health; Psychoneuroses; Psychopathology; psychosocial; Psychosocial Factor; psychosocial variables; Public Health; public health medicine (field); Quetelet index; R01 Mechanism; R01 Program; randomisation; randomization; Randomized; randomly assigned; Recording of previous events; Recurrence; Recurrent; Relative; Relative (related person); Relative Risks; Reporting; Research; Research Grants; Research Project Grants; Research Projects; Research Projects, R-Series; response; Risk; Risk Behaviors; Risk Factors; Risky Behavior; Role; RPG; sadness; sample collection; Sample Size; Sampling; Schools; Self-Report; serotonin transporter; Services; seventeen year old; Severities; Site; Sleep; Smoking; Social Policies; social role; sodium-dependent serotonin transporter; Source; Specific qualifier value; Specified; specimen collection; Stress; stressor; SUBGP; Subgroup; substance abuse; Substance abuse problem; suicidal risk; suicidality; Suicide; suicide risk; Symptoms of depression; Technical Report; technical report; Technical Report (PT); Technical Report [Publication Type]; Teen; teen years; teenage; Teenagers; Teens; Telephone; therapy development; Training; trait; treatment as usual; treatment development; treatment effect; unemployed; Unemployment; Unipolar Depression; United States National Institute of Mental Health; Universities; Unspecified Mental Disorder; Vascular Hypertensive Disease; Vascular Hypertensive Disorder; Vascular Hypotensive Disorder; Work; work environment; Work Location; Work Place; work setting; Work-Site; Workplace; Worksite; young adult; youngster; Youth; Youth 10-21
Relevance: In our original study, we found that we can prevent depression among at-risk youth, but we do not yet know if this prevention lasts and whether it improves youths´ schooling, employment, and relationships with others. The proposed study will be the first to examine whether depression continues to be prevented as these teens become young adults. This study also will identify youth who are most likely to benefit from this program, and will inform us about how to create future prevention programs that help those youth who did not benefit
Project start date: 2001-12-01
Project end date: 2012-12-31
Budget start date: 1-JAN-2011
Budget end date: 31-DEC-2011
PFA/PA: PA-07-070
5R01MH064717-08 (2011): $232401
Grants awarded to G Tracy
PRIMARY CARE INTERNET-BASED DEPRESSION PREVENTION FOR ADOLESCENTS (CATCH-IT)
G Tracy, Assistant Professor Of Medicine
University Of Chicagocity: Chicago country: United States (us)
Grant 1R01MH090035-01A1 from National Institute Of Mental Health
Abstract: Developing new interventions that incorporate the "diverse needs and circumstances of people with mental illness," particularly in primary care and community settings, is a key NIMH strategic objective. Prevention of mental disorders has become a priority for the NIMH, which emphasizes the importance of developing "new and better interventions" to "...preempt the occurrence of disease." These interventions must (1) work in multiple and diverse settings (e.g. primary care); (2) be suitable for delivery outside of traditional mental health systems (3) use new technologies; (4) build on previous clinical trials; (5) reduce identified disorders/enhance functional outcomes; (6) include families and (7) be tailored to the individual. Despite these NIMH guidelines, while primary care physicians remain the first line providers for at-risk adolescents, there is no widely available, low cost and culturally acceptable preventive approach that targets depression in primary care settings. To address this gap and specified NIMH priority, Dr. Van Voorhees developed and conducted a phase 2 clinical trial of a primary care Internet-based depression prevention intervention (CATCH-IT, Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training). In this study, the high intensity arm (i.e., motivational interview + internet site) demonstrated significant reductions in depressed mood and increases in protective factors (social support, motivation) and lower incidence of depressive episodes over 12 months (7% versus 28%), compared to the low intensity arm (internet site referral + only physician brief advice). We now propose the next step study, a phase 3 efficacy study. In this 5-year, two-site randomized clinical trial, we propose to test the efficacy of the CATCH-IT primary care/Internet based depression prevention intervention against Attention Monitoring Psychoeducation (AMPE) in preventing the onset of depressive episodes in an intermediate to high risk group of adolescents aged 13-17. We plan to (a) identify high risk adolescents based on elevated scores on the PHQ-A, a screening measure of depressive symptoms; (b) recruit 400 (200 per site) of these at-risk adolescents to be randomized into either the CATCH-IT or the AMPE group; (c) assess outcomes at 2, 8, 12, 18, and 24 months post intake on measures of depressive symptoms, depressive diagnoses, other mental disorders, and on measures of role impairment in education, quality of life, attainment of educational milestones, and family functioning; and (d) conduct exploratory analyses to examine the effectiveness of this intervention program, moderators of protection, and potential ethnic and cultural differences in intervention response. This a randomized clinical trial to determine if a primary care internet-based depression prevention intervention (CATCH-IT 2R) can build resiliency and protect adolescents (ages 13-17) against depression and strengthen their ability to attain their life goals. The intervention includes a motivational interview with the adolescent´s primary care physician and learning coping skills through stories, videos and games on-line. Adolescents, who will be randomly assigned to the intervention or an education control groups, will be evaluated for progress over two years
Keywords: 0-11 years old; 21+ years old; abnormal psychology; Active Follow-up; Address; Adherence; Adherence (attribute); Adolescent; Adolescent Youth; Adult; adult human (21+); Adverse event; Adverse Experience; Age; aged; Alcohol consumption; Alcohol Drinking; alcohol ingestion; alcohol intake; alcohol product use; alcohol use; alcoholic beverage consumption; alcoholic drink intake; Anxiety; arm; Attention; Award; base; Behavioral; brief advice; Care, Health; Chicago; Child; Child Youth; children; Children (0-21); clinical investigation; Clinical Trials; Clinical Trials, Phase II; Clinical Trials, Unspecified; Cognition; Cognitive; college; community setting; Control Groups; Coping Skills; cost; cost effective; depressed; Depressed mood; Depression; depressive; depressive symptoms; Diagnosis; Disease; disease/disorder; Disorder; Education; Education for Intervention; Educational aspects; Educational Intervention; effect of intervention; Effectiveness of Interventions; efficacy testing; Emotional Depression; ethanol consumption; ethanol drinking; ethanol ingestion; ethanol intake; ethanol product use; ethanol use; ethnic minority; ethnic minority population; Ethnic Origin; Ethnicity; Ethnicity aspects; EtOH drinking; etoh use; Exhibits; Family; follow-up; Foundations; functional outcomes; Future; Generalized Growth; Generations; Goals; Grant; Growth; Guidelines; hazard; health related quality of life; Health system; Healthcare; high risk; Human, Adult; Human, Child; Impairment; improved; Incidence; Individual; innovate; innovation; innovative; Instruction Intervention; instructional intervention; Intake; Internet; Intervention; intervention program; Intervention Strategies; interventional strategy; Investigators; juvenile; juvenile human; Learning; Life; Major Depression, single episode; Major Depressive Disorder, Single Episode; Major depressive disorder, single episode, unspecified degree; major depressive episode; Manuals; Measures; Mediating; Mediator; Mediator of Activation; Mediator of activation protein; meetings; Mental Depression; mental disorder prevention; Mental disorders; Mental Health; Mental health disorders; Mental Hygiene; mental illness; Modeling; Monitor; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Motivation; motivational enhancement therapy; motivational interview; Music; Musics; National Institute of Mental Health; National Institute of Mental Health (U.S.); new technology; NIMH; ontogeny; Outcome; Parents; Participant; Phase; Phase 2 Clinical Trials; phase 2 study; phase 2 trial; Phase II Clinical Trials; phase II trial; Physicians; Population; preempt; prevent; preventing; Prevention; Prevention strategy; preventional intervention strategy; Preventive; Preventive Intervention; Preventive strategy; Primary Care; Primary Care Physician; primary care setting; Primary Health Care; Primary Healthcare; programs; Programs (PT); Programs [Publication Type]; protocol, phase II; PROV; Provider; Psychiatric Disease; Psychiatric Disorder; psychoeducation; psychological disorder; Psychological Health; Psychopathology; Psychotherapy; Public Health; public health medicine (field); public health relevance; QOL; Quality of life; randomisation; randomization; Randomized; Randomized Clinical Trials; randomly assigned; recruit; Recruitment Activity; Reporting; Research Personnel; Researchers; response; Risk; Role; sadness; Sampling; screening; Screening procedure; screenings; Sensitivity and Specificity; single episode major depressive disorder; Single Episode of Major Depressive Disorder; Single major depression; Single major depressive episode; Site; social role; Social support; social support network; Specific qualifier value; Specified; study, phase II; Symptoms; Symptoms of depression; Tissue Growth; Training; Training Intervention; United States National Institute of Mental Health; Universities; Unspecified Mental Disorder; Video Games; web; Work; world wide web; WWW; youngster; Youth; Youth 10-21
Relevance: This a randomized clinical trial to determine if a primary care internet-based depression prevention intervention (CATCH-IT 2R) can build resiliency and protect adolescents (ages 13-17) against depression and strengthen their ability to attain their life goals. The intervention includes a motivational interview with the adolescent´s primary care physician and learning coping skills through stories, videos and games on-line. Adolescents, who will be randomly assigned to the intervention or an education control groups, will be evaluated for progress over two years
Project start date: 2011-01-15
Project end date: 2015-11-30
Budget start date: 15-JAN-2011
Budget end date: 30-NOV-2011
PFA/PA: PA-10-067
1R01MH090035-01A1 (2011): $689869
MOLECULAR MECHANISMS OF ADVERSE METABOLIC EVENTS BY ASPARAGINASE.
G Tracy, Assistant Professor
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Grant 1R01HD070487-01 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: Asparaginase is an integral part of the treatment for acute lymphoblastic leukemia, the most common childhood cancer. Asparaginase produces hepatotoxicity resulting in treatment-related metabolic complications that include fatty liver, reduced plasma proteins, and coagulation problems that lead to thromboembolism and cerebrovascular events. Our long-term goal is to increase the safety and efficacy of asparaginase. The objective of this proposal is to discover mechanisms by which asparaginase causes adverse metabolic effects. To accomplish this, we propose to identify key molecular events that modulate hepatic dysfunction by asparaginase. Our preliminary data demonstrate that asparaginase increases phosphorylation of the translation factor, eIF2, by GCN2. Deletion of GCN2 precludes adaptive responses to asparaginase and enhances endoplasmic reticulum (ER) stress, leading to induction of another eIF2 kinase called PKR-like ER- resident Kinase (PERK). The central hypothesis is that activation of eIF2 kinases prevent and/or mitigate hepatic dysfunction by asparaginase. We plan to test our hypothesis and accomplish the objective of this application by pursuing the following specific aims Aim 1) Identify the role of GCN2 in liver during asparaginase treatment; Aim 2) Determine the role of PERK in liver during asparaginase treatment; Aim 3) Characterize age differences in eIF2 kinase signaling in liver by asparaginase. To accomplish the above aims, asparaginase will be administered to both wild-type mice and mice deleted for the eIF2 kinases, GCN2 and/or PERK. Time course analysis will focus on how modulation of eIF2 kinase signaling and activation of ER stress relates to development of liver dysfunction. In addition, asparaginase will be administered to mice of varying ages and key molecular and metabolic responses to asparaginase will be assessed. This proposal is innovative in that it seeks to identify the progression of molecular events that lead to liver dysfunction by asparaginase at different ages. The work proposed is significant as it will help identify pediatric patients at risk for adverse metabolic events by asparaginase during the developmental continuum. The results will also be used to develop and test new methods of prevention and/or treatment. The proposed project is relevant to public health as it seeks to improve the treatment regimen for acute lymphoblastic leukemia, the most common childhood cancer. This proposal aims to reduce and prevent adverse metabolic events caused by asparaginase by identifying the molecular events that cause liver dysfunction
Keywords: Address; Adolescent; Adverse event; Affect; Age; age difference; Amino Acids; asparaginase; Asparagine; base; Blood; Blood coagulation; Blood Coagulation Disorders; Cell Survival; cerebrovascular; Chemicals; Child; Childhood; Chronic; Clinical; Coagulation Process; Cytoplasm; Data; Development; Diagnosis; Drug Kinetics; Endoplasmic Reticulum; endoplasmic reticulum stress; Ensure; Environment; Eukaryotic Initiation Factor-2; Event; experience; Fatty Liver; Functional disorder; Gene Expression; Genetic Translation; Glutamine; Goals; Hepatic; Hepatocyte; Hepatotoxicity; Homeostasis; Hyperglycemia; improved; innovation; insight; Knowledge; Lead; Left; Leukemia, Lymphocytic, Acute; Liver; Liver Dysfunction; Liver Failure; liver function; liver metabolism; Malignant Childhood Neoplasm; Metabolic; Methods; Molecular; Molecular Chaperones; Molecular Mechanisms of Action; Morbidity - disease rate; Mus; Outcome; Pancreas; Pancreatitis; Pathway interactions; patient population; Patients; Pattern; Pharmacodynamics; Phosphorylation; Phosphotransferases; Plasma Proteins; Play; premature; prevent; Prevention; protein aggregation; Protein Biosynthesis; protein expression; protein folding; Protein Kinase; Proteins; public health medicine (field); Publishing; Regimen; Research; Research Personnel; response; Risk; Role; Safety; Seizures; Serpins; Signal Transduction; skills; Stress; Testing; therapy development; Thromboembolism; Time; Tissues; Toxic effect; translation factor; Treatment Protocols; United States; Wild Type Mouse; Work
Relevance: The proposed project is relevant to public health as it seeks to improve the treatment regimen for acute lymphoblastic leukemia, the most common childhood cancer. This proposal aims to reduce and prevent adverse metabolic events caused by asparaginase by identifying the molecular events that cause liver dysfunction
Project start date: 2011-07-25
Project end date: 2016-04-30
Budget start date: 25-JUL-2011
Budget end date: 30-APR-2012
PFA/PA: RFA-HD-10-010
1R01HD070487-01 (2011): $306856