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Integrating Methodologic Advances into Prevention Research
Grant Abstracts
| Designs
and Analyses for Mental Health Preventive Trials, 5R01MH040859-14,
P.I. C Hendricks Brown, Co-P.I. Bengt Muthen. This project is co-funded by the National Institute of Mental Health and the National Institute on Drug Abuse, and is in its 14th year of funding with budget of $1,989,805. As core funding for the Prevention Science and Methodology Group, this is a continuation of the previous grant entitled Statistical Methods for Mental Health Preventive Trials. The project involves developing designs and analytical methods |
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| (1)
to handle selection bias, variations in implementation, participation,
and adherence, and differential attrition in preventive trials,
(2) to develop efficient designs for preventive trials addressing questions of efficacy as well as effectiveness, implementation, dissemination and scalability, and (3) to merge biostatistical, psychometric, and epidemiologic methods regarding intervention impact, to elucidate variation in intervention impact. |
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| These latter models include mediation and effect modification as well as growth curve modeling of the impact of an intervention on differential trajectories. The data used in this project comes from the following sources: the American Institutes for Research Center Integrating Education and Prevention Research in Schools, the Oregon Social Learning Center, the Johns Hopkins Prevention Research Center, and the University of Michigan. | |
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Understanding and Preventing Adolescent Drug Abuse (MERIT award,
NIDA; Working title: Project Alliance, May 1, 2001-April 30, 2006) The application is proposes a five-year extension of the MERIT award status of the research entitled ?Understanding and Preventing Adolescent Drug Abuse.? The previous funding period resulted in over 20 publications on modeling and prevention research using the Adolescent Transitions Project (ATP) sample of 220 high-risk adolescents and the Project Alliance (PA) sample of 999. The ATP family-based intervention has been found to be effective in reducing substance use and problem behavior, which has been replicated by another group of investigators (Irvine et al., 1999). In addition, the multilevel family-based intervention located within public schools has been found to reduce growth in deviant peer association, substance use and antisocial behavior in the PA sample during the middle school years. This application requests an increase in funding level as needed to staff the continuance of this ongoing longitudinal experimental field trial using a family-centered prevention strategy. Specifically, increased funds will be used to track, retain, and assess a multicultural, urban sample of families through the adolescent years. We propose to conduct a major follow-up assessment of the PA sample in high school to include direct observations of family interaction and peer interaction, to provide an adolescent version of the Family Check-Up and an Adolescent Check-Up, and to assess the families yearly on all major dependent variables through the end of high school. We plan to extend our evaluations to include all t he PA youth and families through adolescence, to model the influence of family management and peer deviance in adolescence, and to study the consequences of early-onset substance use on the progression to drug abuse, academic failure, relationship problems, and emotional adjustment. |
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Enhancing Family-Based Prevention of Adolescent Drug Use (NIDA;
Working title: The Next Generation, October 1, 2000-September 20,
2003) This application proposes to study the impact of school-based family interventions for preventing substance abuse and other problem behavior in young adolescents. The Adolescent Transitions Program (ATP) has been found to be effective in improving the observed parentchild interaction process, as well as reducing tobacco use and antisocial behavior among high-risk young adolescents (Dishion & Andrews, 1995; Dishion, Andrews, Kavanagh, & Soberman, 1996; Irvine, Biglan, Smolkowski, Metzler, & Ary, 1999). The research to date has used experimental designs with random assignment at the individual level to test program effectiveness. The next generation of this program of research is to systemically study the ecological conditions necessary to maximally engage families in need of intervention support in early adolescence, in the context of the public school system. By randomly assigning 8 middle schools to an ecologically0enhanced versus standard intervention model, we specifically propose to examine the effectiveness of family and parenting programs administered as school-based services. The proposed research will measure family engagement in services, as well as target specific outcomes for adolescents (e.g., substance use). The program will target the school population, resulting in about 1200 participants each year across the 8 middle schools. The results of this research have implications for the future family services at the school level, as well as future prevention programs aimed at reducing substance use among early adolescents. |
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Multicultural Interventions for Adolescent Substance Use (NIAAA;
Working title: The Shadow Project, September 1, 1999-August 31,
2002) This is a 3-year project to be conducted with 60 Native American adolescents referred for drug and alcohol intervention (AOD). The participants will be randomly assigned to family-enhanced intervention versus community services (services as usual). The family-enhanced intervention will include services as usual for the adolescent, with the addition of a family-based enhancement to increase participation of the family in the adolescent's treatment. The Family Wellness Intervention implements motivational interviewing techniques and services focusing on parent monitoring and peer clustering that are culturally relevant to Native American (NA) family contexts. In addition, participants in the family-enhanced condition will be encouraged to engage in parenting groups throughout the course of the adolescent's treatment. Families will be assessed using a multiagent, multimethod assessment battery, including teacher, parent, and peer report, and will participate in the videotaped family interaction task. The first year of the study will consist of consultation and extensive piloting. The next year will consist of intervention implementation and follow-up assessments. To determine the long-term impact of the intervention program on reducing adolescent alcohol and other drug use, all families will be followed and assessed one year following treatment. |
| A
Family-Based Prevention for Early Conduct Problems (; Working title:
Early Intervention, September 1, 2000-August 31, 2003) In response to this RFA that requests innovative and developmentally-based intervention projects that stem from knowledge gained from studies of risk, etiology, and basic behavioral processes, this application proposes to test a family-based preventive intervention with two-year-old children at risk for developing significant conduct problems, providing the necessary pilot data to test the model¹s applied efficacy. The Investigative team¹s programs of research have identified specific parenting factors and family profiles that are associated with early onset and persistence of serious conduct problems from infancy to the school-age period that have yet to be tested as an intervention. Despite prior longitudinal research that has shown that early-starter children go on to show the most chronic and severe forms of antisocial behavior, a developmentally-based, ecologically sensitive intervention initiated during the toddler period has yet to be tested with extreme-risk families to examine if antisocial trajectories are preventable before the child¹s and family¹s behaviors are less malleable to change. This project will test the efficacy of Dishion¹s Family Check Up intervention package with a group of 120 extreme-risk families recruited from WIC sites in Pittsburgh, PA. As well as drawing on a well-established evidence base, the intervention will incorporate novel preventive strategies into the Family Check Up package from Shaw¹s and Gardner¹s developmentally based research. ; Extreme-risk status will be based on the presence of child, parent, and sociodemographic risk factors. It is expected that early intervention will be associated with improvement in parenting and child behavior, whereas families in the nonintervention group are likely to show decreases in parental functioning and growth in child conduct problems. |
| Genetic
Linkage Study of Children with ADHD 5R01HD037694-03 (Stephen Faraone,
P.I.) An Ecogenetic Study of ADHD (Stephen Faraone, P.I.) Abstract: The main goal of the proposed program of research is to use specific gene variants and environmental measures to clarify the nature of gene-environment interactions in Attention Deficit Hyperactivity Disorder (ADHD) and to improve our ability to predict which children require preventive interventions for ADHD and its associated adverse outcomes. We will accomplish this goal by collecting DNA samples from subjects who have already participated in two ongoing longitudinal family studies of ADHD. Our basic strategy is to use the ecogenetic approach described by Khoury et al. This method improves risk prediction by examining genetically mediated differences in susceptibility to environmental agents. In the proposed work, we will collect DNA samples from the ADHD proband and their family members who have participated in our two longitudinal family studies comprising 1,040 subjects in families ascertained through ADHD children. The proposal has three main aims: |
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| 1)
to predict adverse outcomes among ADHD children and their siblings;
2) to assess the accuracy of risk prediction and 3) to create a genetics resource for ecogenetic studies. |
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| There
can be little doubt that ADHD is caused by the confluence of genes
and environment. Because some susceptibility genes have been found
and some environmental causes identified, ADHD is an ideal disorder
for the application of ecogenetic models. Moreover, because ADHD children are at high risk for multiple adverse outcomes, they are a clinically meaningful target group for prevention studies seeking to prevent these outcomes. Predicting adverse outcomes among ADHD children has clinical, scientific and public health implications. Such efforts can help identify etiologic risk factors associated with more impaired outcome in ADHD and can characterize early predictors of persistence and morbidity of this disorder. Moreover, predicting the course of ADHD could help design improved secondary prevention programs aimed at reducing the morbidity of ADHD throughout childhood and adolescence. From a public health perspective, the ability to predict course and clinical complications could help focus societal resources on those at higher risk for persistent illness with complicated outcomes. One strength of the proposed study is that we have also collected data on the siblings of ADHD probands. Using ecogenetic methods, we will be able to predict which siblings are at highest risk for ADHD. Such data would be useful for clinicians faced with parents of ADHD children who are concerned with the future of their non-ADHD children. Ecogenetic prediction models could one day provide a rational method for clinicians to recommend preventive interventions for siblings of ADHD children. Although longitudinal studies of ADHD have provided some evidence that outcome can be predicted from clinical assessments, the accuracy of prediction is low, suggesting that variables from other domains should be entered into the prediction equation. Our plan is to use genes as new predictors of outcome is innovative because no prior studies have used specific gene variants to predict course and outcome among ADHD children. Furthermore, no studies have used an ecogenetic approach to sharpen the accuracy of risk prediction. |
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| Testing
the Validity of Adult Attention Deficit Disorder 5R01MH057934-04
(Stephen Faraone, P.I.). Abstract: DESCRIPTION (Adapted from applicant's abstract): Despite increasing media attention, adult Attention-deficit-hyperactivity disorder (ADHD) has not been systematically studied in large samples. As a result, there has been a debate in the field about the validity of ADHD in adults presenting at mental health clinics. To shed light on this debate, we propose to test hypothesis in one domain of adult ADHD that has received scant attention: its genetic epidemiology. As we review in the background section, there have been only two small pilot studies of the genetic epidemiology of ADHD. Such data are essential to validating the syndrome, creating developmentally appropriate diagnostic algorithms and laying the clinical foundation for genetic linkage studies. To fill this gap in the research literature, we will address the validity of adult ADHD from the genetic epidemiological perspective by testing the following hypothesis for the five main aims of our proposal: |
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| 1)
Assessing the Familial Transmission of Adult ADHD; 2) Validating Adult ADHD with Molecular Genetic Data; 3) Assessing the Divergent Validity of Adult ADHD; 4) Using Family Study Data to Validate Diagnostic Models of Adult ADHD; AND 5) Creating a Resource for Future Follow-up and Molecular Genetic Studies of Adult ADHD. |
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| To achieve these aims, we will complete a double- blind family study of 140 ADHD families and 120 control families. We view our family study strategy as being a valuable investment for several reasons. A large double-blind study of adult ADHD has never been done before. Moreover, because consistent positive associations have been reported between childhood ADHD and two dopamine related genes, the collection of molecular genetic data will allow us to validate adult ADHD at the molecular level. Because we are collecting data about lifetime psychiatric diagnoses, we will be able to determine if other disorders can account for the familial transmission of ADHD or its molecular genetic associations. We will also be able to assess what age at onset criterion and what set of symptom thresholds should be used for the diagnosis of adult ADHD and will be able to define phenotypes and sample selection rules that will maximize the yield of future linkage studies. To maximize the scientific yield of this proposal, we will create a resource for future molecular genetic and follow-up studies of adult ADHD. We will set the stage for these studies by | |
| 1)
providing a comprehensive baseline assessment for a follow-up study
and 2) clarifying the nature of phenotypes and the sample sizes that will be needed for molecular genetic studies. |
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| Thus, if founded, we expect that the proposed work will lead to a program of research that can both clarify the nosological complexities of adult ADHD and clarify the nature of genes that are risk factors for the disorder. | |
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Alcohol Expectancies: Mediators of Biopsychological Risk, (PI: Mark
S. Goldman) $239,801, NIAAA R37AA08333-10 The purpose of this study was to explore changes in alcohol consumption during the first year of college. Daily drinking records were generated for the entire academic year from monthly Timeline Followback assessments of 308 college freshmen (49% male, M age = 18.4). Using weekly (t = 32) summaries of consumption, general growth mixture modeling (GGMM) identified five latent classes of drinking trajectories and tested a variety of baseline measures as predictors of class membership. Alcohol expectancies assessed at baseline were the strongest predictor of class membership. |
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Mapping Substance Abuse Service Use, (PI: Paul E. Greenbaum), $50,000,
NIDA RO3DA14250-01 The purpose of this study is to explore the relationship between substance use (SU) involvement and receipt of substance use services among adolescents with serious emotional disorders. GGMM will be used to examine trajectory class membership for both SU involvement and service use, to relate class membership to contextual factors (e.g., family cohesion, gender), and to assess cross-domain associations among the growth trajectories of SU involvement and service use classes. The study uses existing data from approximately 800 children with serious emotional disorders, who participated in the 7-year National Adolescent and Child Treatment Study (NACTS). |
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Evaluation of the Comprehensive Community Mental Health Services
for Children and their Families Program-Evidenced-Based Treatment,
(PIs: Robert M. Friedman, Paul E. Greenbaum, & Mario Hernandez)
$64,724, ORC MACRO award #35064-OS-336. This study used GGMM and propensity analysis to evaluate an integrated mental health services demonstration project. Results indicated that there was no significant intervention effect when all participants were included in a single latent growth curve model, however, when growth mixtures were considered, at least one class of participants showed a significant intervention effect. |
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Alcohol Expectancies: Mediators of Biopsychological Risk,
(PI: Mark S. Goldman) $458,987, Under review, NIAAA RO1AA08333-11 The purpose of this study is to use GGMM to model drinking and alcohol expectancy trajectories during young adulthood, when alcohol consumption patterns typically diverge. Primary research questions include whether changes, (and particularly decreases) in expectancies mediate changes in drinking and how an understanding of the cross-domain relationship between expectancy trajectories and drinking trajectories might lead to more effective prevention and intervention effects. |
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Followup of Two Universal Preventive Intervention 5R01DA011796-03
(Nick Ialongo, P.I.) This grant extends through the transition to high school the evaluation of the impact of the second randomized trial conducted by the Baltimore Prevention Project, of two universal, first grade preventive interventions on the early risk behaviors of poor achievement and aggressive and shy behaviors and their distal correlates: substance use, antisocial behavior, and anxious and depressive symptoms. In extending the evaluation into high school, we expect to broaden our understanding of normal and pathogenic developmental paths and their variation and malleability in response to the preventive interventions from school entry through early adolescence. We will build on the scientific evaluate of an existing, prospective, developmental epidemiological data base involving a defined population of urban first-graders, whose psychological well-being (PWB) and social adaptational status (SAS) in the classroom, peer group, and family social fields have been assessed periodically from ages 6-11. This representative population of urban first graders is comprised of 678 children from 9 elementary schools in predominantly low to lower middle income areas in Baltimore. Within each of the nine schools, first grade children and their teachers were randomly assigned to either a standard setting (i.e., control) classroom or to a classroom featuring one of two universal preventive interventions. Each intervention specifically targeted two confirmed antecedents of later antisocial behavior, psychiatric symptoms and substance use: |
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| 1)
aggressive and shy behaviors, and 2) poor school achievement. |
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| One intervention, the classroom-centered intervention (C), sought to reduce the early risk behaviors of poor achievement and aggressive and shy behaviors through the enhancement of classroom curricula and teacher instructional and behavior management practices. The second intervention, the family-school partnership intervention (FSP), sought to reduce to reduce their early risk behaviors by improving by improving parent-teacher collaboration and by enhancing parents' teaching and behavior management skills. Extension of the data set through ages 12-15 will enable us to assess the effectiveness of the CC and FSP interventions in terms of the reduced risk for substance use, antisocial behavior and anxious and depressive symptoms in early adolescence. The data set will also allow us to assess variation in the malleability of developmental paths as a function of the initial and evolving characteristics of the child, and the social fields of family, peer group, classroom/school, and neighborhood. Continued follow-up will enable us to determine the incidence and prevalence of substance use, antisocial behavior, and anxious, and symptoms in early adolescence. | |
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NIMH K25-MH01880 Statistical Methods for economic analysis
in prevention 8/01-7/05 Abstract: The economic consequences of mental illness prevention programs often span multiple years into another stage of life beyond the period of intervention. This is particularly true of prevention programs targeting children. The interventions are aimed at proximal targets (mediators) thereby altering the developmental trajectory of mental health outcomes. This statistical design issue alone makes economic analysis for prevention programs more complex. Thus, prevention scientists need suitable methods to permit both efficacy and economic evaluations in the design and analyses of studies of preventive interventions. The methods for long-term benefits need to include developmental trajectories. The research plan integrates training and mentoring by addressing the question: What are the short and long-term benefits of mental health interventions and how do they vary across clusters of individuals with distinct developmental trajectories of long-term outcomes? Our approach is to use a new statistical method called general growth mixture models (GGMM) to identify distinct clusters of individuals using time invariant and time varying covariates using mixture models and developmental trajectories of distal outcomes. A cost-effectiveness analysis will be conducted using data from an ongoing federally funded longitudinal childhood mental health intervention study at the Johns Hopkins Prevention Center. |
Sheppard Kellam, American Institutes for Research
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Reducing Violence by Joining Education and Prevention, 5R21HD040051-02.
P.I., Sheppard G. Kellam, Co-PI's C Hendricks Brown, Kiberly T.
Kendziora, Jeanne M. Poduska, and John B. Reid. This grant is funded by the National Institute on Child Health and Human Development to develop new interventions as part of a cross-NIH Violence Prevention Consortium. This intervention will focus on a highly integrated whole day program in first grade to teach reading skills and behavior management in the classroom as well as to connect parents and teachers. This developmental grant involves formalizing manuals of the intervention, developing community and institutional partnerships to support a full field trials, as well as assessing statistical power for a more extensive randomized trial. |
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K02 AA00230 (Muthen) 8/1/01-7/31/06 80% PHS/NIAAA Advanced Analysis of the Development of Alcohol Problems The proposed research has three major aims. The first is to develop new statistical methods to better answer substantive questions in alcohol research related to the development and prevention of alcohol problems. The second aim is to collaborate with alcohol researchers on advanced statistical analysis of their data using these new methods. And the third aim is to disseminate information on the new methods so that others in the alcohol and related fields can benefit from them. The development of new statistical methods will focus on five areas of statistics integral to the study of the development and prevention of alcohol problems: mixture data analysis, categorical and other non-normal data analysis, multilevel data analysis, missing data analysis, and longitudinal data analysis. The first four areas of statistics are building blocks for both cross-sectional and longitudinal data analysis. The research results in these four areas will be used to enhance longitudinal data analysis, the primary focus of the project. In addition, research on problems unique to longitudinal data analysis will be carried out. The five areas can be studied efficiently within the framework of latent variable modeling, which has the advantage of providing a powerful general model that allows new combinations of data problems to be handled within a single analytic framework. The specific aims are as follows. In the area of mixture data analysis, model specification and identification will be carefully thought out for a new, general latent variable mixture model. The aim is for this general mixture model to include a set of new features: continuous latent variables influencing categorical outcomes, path analysis model behind the latent class variable, latent class variables influenced by continuous latent variables, relationships involving several latent class variables, multiple-group analysis, multi-level analysis, and longitudinal data. The estimation of such a general latent variable mixture model will be developed using a variety of estimators and numerical techniques, and studied in real and simulated data. In the area of categorical and other non-normal data analysis, maximum likelihood and Bayesian estimation will be studied for the general models envisioned above. Gauss-Hermite, Laplace, and importance sampling approaches will be studied as well as Bayesian MCMC techniques. Non-parametric maximum-likelihood (NPML) estimation of random effects distributions will be developed for these models as well as methods for semicontinuous outcomes. In the area of multilevel data analysis, estimation will be approached by maximum-likelihood and Bayesian analysis. Models will include multilevel latent variable analyses for categorical observed variables, as well as for models involving a combination of categorical and continuous latent variables. In the area of missing data analysis, project work will develop missing data techniques for general latent variable models that combine features of mixtures, categorical outcomes, and multilevel data. Maximum-likelihood and Bayesian analysis will be used. Non-ignorable missing data with missingness influenced by latent classes will be incorporated. In the area of longitudinal analysis, project work concerns three sub areas. First, discrete-time survival analysis with latent variable mixtures will be studied, alone and in combination with growth models. Second, latent variable methods for randomized trials will be studied, considering new latent variable models to take into account noncompliance, screening designs, multilevel data, and non-ignorable missing data situations. Third, for the new models of the project, power estimation and design choices will be studied for mixture data analysis, categorical and other non-normal data analysis, multilevel data analysis, missing data analysis, and randomized preventive interventions. Collaboration with researchers on the analysis of their alcohol data will involve advanced analyses of several longitudinal datasets concerned with alcohol problems. These analyses will draw on extensive interactions with the substantive experts regarding the questions they are attempting to answer and the corresponding examples of the above statistical problems in analyzing their data. Dissemination of information on the new methods developed within the project will take place through the publication of substantively-oriented articles in collaboration with the substantive researchers as well as methodologically-oriented articles, and training sessions describing these new advances. |
Jose Szapocznik, Univ. of Miami
| Structural
Ecosystems Tx with Drug-Using Minority Youth 5R01DA010574-05 (Jose Szapocznik,
P.I.) Abstract: DESCRIPTION: (Applicant's Abstract) The primary aims of the proposed study are to: |
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| 1)
investigate the efficacy of Structural Ecosystems Therapy (SET) in reducing
adolescent drug use and conduct problems, and 2) examine it's theoretical mechanisms of action. |
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| SET is a culturally sensitive comprehensive ecosystemic intervention that systematically targets maladaptive patterns of interaction at three levels of the adolescent's social ecology: microsystem (family, peers, school, and justice system), mesosystem (family-peer, family-school, and family-justice system), and exosystem (parental support system). It is hypothesized that improvements in functioning at these three levels will lead to: | ||
| 1) reductions in symptomatic behaviors of | ||
| a)
drug use, and b) conduct, delinquent, and antisocial behaviors; and |
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| 2) improvements in psychosocial functioning. | ||
| An experimental design is achieved by randomly assigning 312 (156 African-American, 156 Hispanic) drug using, behavior problem adolescents to one of three treatment conditions: SET, Structural family therapy (FAM), and community control (CC). FAM represents one standard of care in the treatment of drug using, behavior problem adolescents, and CC is intended to replicate the typical range of services currently provided in our community. Three rigorous procedures are designed to ensure fidelity to conditions. Comprehensive assessments of adolescent drug use, conduct problems, and functioning at each of the three ecosystemic levels are conducted at baseline, and 6, 12, and 18 months post-baseline. Analyses investigate the intervention's direct effects on behavioral outcomes (drug use, conduct problems, and psychosocial functioning), and hypothesized mediators (micro-, meso-, and exosystemic functioning), as well as the contribution of each mediator to outcome. Proposed analyses include RMANOVA, structural equations modeling, and Hierarchical Linear Modeling. Additional analyses explore the moderating effects of race/ethnicity, culture, treatment adherence, and treatment dosage. | ||
| Families
Preventing HIV in Hispanic Adolescents 5R01MH063042-02 (Jose Szapocznik,
P.I.) Abstract: DESCRIPTION (adapted from the applicant's abstract): There are currently no published studies specifically documenting the efficacy of HIV prevention interventions with Hispanic adolescents. This study proposes to test the efficacy of 2 HIV prevention interventions with an urban poor, recent immigrant Hispanic population. All interventions have been constructed to build on Hispanic cultural values by validating the central role of the family as protector and change agent of its youth. 300 families with an eighth grade adolescent will be randomized into 3 conditions: Experimental Condition A = HEPI to improve parenting + PATH for HIV prevention; Experimental Condition B = English classes + PATH for HIV prevention; Condition C = English classes + a cardiovascular prevention intervention. English classes are used as a control for nonspecific factor of the parenting intervention, and the cardiovascular intervention for control of nonspecific factors in HIV prevention. The proposed study investigates if providing HIV prevention in the context of a parenting intervention significantly increases the efficacy of the HIV prevention intervention. The parenting intervention has been shown to significantly increase/improve parental investment, parent-adolescent communication, parental monitoring skills, problem behaviors, and alcohol use in recent immigrant Hispanic adolescents. The HIV prevention intervention has been shown to significantly positively influence parent-adolescent communication about HIV, increase parents' and adolescents' knowledge about HIV, and increase adolescents' intentions to use condoms. Dosage has been equalized across interventions and control. Stratified urn randomization along 7 variables will be used. Efficacy will be assessed in relation to: (H1) ultimate outcomes of risky sexual behavior and drug use; (H2) ecodevelopmental mediators (parental investment, parent-adolescent communication, parental monitoring); and, (H3) social cognitive mediators (attitudes, subjective norms, perceived control, and behavioral intentions). Multi-method, multi-reporter assessments will allow the construction of latent constructs using SEM. HLM will be used for growth curve analysis of the three conditions over the 5 time points (Baseline, 6, 12, 24, and 36 months post baseline). |
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| Built
Environment & Hispanic Elders' Behavioral Health 5R01MH063709-02 (Jose
Szapocznik, P.I.) Abstract: DESCRIPTION (Taken from the Investigator's Abstract) The proposed project seeks to understand how, and to what extent, an elder's built environment is mediated by the elder's social behaviors and effective support systems to affect behavioral health changes for elderly Hispanic residents in a low-socioeconomic (SES) Urban Neighborhood: East Little Havana, Florida. An elder's built environment is defined by a set of architectural features of the buildings on the elder's residential street. A residential street is defined by two block faces bounded either by two intersections or by one intersection and a street ending. There are 226 such residential streets in East Little Havana. The proposed study will test a model that predicts that the architectural features of an elder's built environment are sequentially mediated by the elder's social behaviors and effective social supports to influence the trajectory of change in their cognitive functioning and their affective symptoms over a 36-month period. The method involves evaluating and coding the buildings on each of East Little Havana's 226 residential streets to describe the residential streets that support social connectedness. A household survey (covering 3,900 properties) will be conducted to locate the elders 70 years or older on each residential street. Then, two or more elders are to be randomly selected from each residential street, recruited, and engaged to participate in the study, and assessed at baseline and again at 12, 24 and 36 months after baseline. Hierarchical Linear Modeling and Multilevel Latent Growth Curve Analysis will be used to examine the effects of the built environment and the mediating effects of individual social behaviors and effective social supports on the trajectory of change in cognitive functioning and change in affective symptoms in elders over a 36-month time period. Findings will be disseminated at three conferences focusing on the project in addition to submitting technical papers to be presented at professional meetings and to referred journals. |
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| Structural
Ecosystems Therapy with HIV+ Women 5R37MH055796-07 (Jose Szapocznik, P.I.) Abstract: DESCRIPTION (Adapted from applicant's abstract): Structural Ecosystems Therapy (SET) is a theoretically derived intervention that builds on the basic tenets of human ecology and structural family therapy. The term ecosystems reflects a belief in the influence of the context on the individual, with family comprising the most significant system in human ecology. "Structural" concepts refer to a focus on patterns of interactions that occur within and between systems. The major focus of the (SET) intervention is to identify patterns of interactions--and then to strengthen those interactions that support the individual and her family and correct those interactions that are problematic. SET is thus targeted at the social systems (or more precisely interactions with these ecosystems), which are the most relevant contexts for these women: intrapersonal, family, and environment, as well as the interactions among these systems. The model builds on over two decades of family-oriented research with minority families by the investigators. The primary aims of this study are to investigate the efficacy of Structural Ecosystems Therapy, and to describe some of its theoretical mechanisms. This will be achieved by randomizing 264 HIV+ African American women to one of three conditions: SET, Attention Control, or Community Control. The Attention Control condition is operationalized in the form of Person-Centered Therapy. The Community Control is intended to reflect the baseline level and mix of services usually utilized by these women. Considerable rigor is introduced into four levels of controls to ensure fidelity to conditions. Outcomes are linked to family processes derived from observational ratings. SET is hypothesized to have a beneficial effect on family functioning and supportiveness, distress, maladaptive coping, perceived control, and perceptions of hassles. Proposed analyses include RMANOVA, RANOVAS, multiple regression, and structural equations modeling. |
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| Florida
Node of the Drug Abuse Clinical Trials Network 5U10DA013720-02 (Jose Szapocznik,
P.I.) Abstract: This is a proposal to establish the Florida Regional Node of the National Drug Abuse Treatment Clinical Trials Network (CTN). Four major research centers at the University of Miami have joined to provide the Regional Research and Training Center (RRTC) with their considerable clinical trials, multi-site, and drug abuse treatment expertise: Center for Family Studies, Comprehensive Drug Research Center, Center for Treatment Research on Adolescent Drug Abuse, and Behavioral Medicine Research Center. The Community Treatment Programs (CTPs) elected are among the largest and most respected in the State, representing the north(Gateway in Jacksonville), central (PAR in Tampa; Center for Drug Free Living in Orlando) and south (The Village in Miami; Spectrum in Broward County) pats of the State. They offer exceptional diversity of treatment modalities, ethnic profiles, and drug abusing and addicted populations. In the first year, The Florida Node has the capacity of serving up to 20,000 drug abusing and addicted patients. The Florida Node Steering Committee includes the leaders of the 5 CTPs, the P.I., and the Co-P.I/Operations Director. Each of the other teams also include RRTC and CTP representation: Clinical Trials Training and Implementation Monitoring, Concept Development, and Biostatistics/Data Management. In this partnership both the RRTC and the CTPs are eager to learn from each other, and eager to learn about efficacious treatment models that can be transported from other nodes to Florida's treatment programs. The Florida Node RRTC has developed and published efficacious family- based treatment models and brings considerable strength in family-based interventions with drug abusing populations (adolescent drug abusers, drug addicted new mothers, HIV+ women using drugs intermittently) and with HIV+ populations (HIV transmission prevention, family ecological therapy to improve individual and family functioning). The Node's interests in these areas range from transportability of interventions to statistical methodological issues in aggregating family data in longitudinal designs. Particular challenges to the work of the Florida Node include communication and collaboration across geographic distance. Facilitators include eagerness to provide quality services, interest in using outcome data to update state treatment funding policies, recognition of a zeitgeist in the state and the nation of accountability, and prior collaboration among the CTP under the New Century Institute umbrella to promote the group's treatment and research competence. |
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Molecular Genetics of Heroin Dependence 1R01DA012846-01 (Ming
Tsuang, P.I.) Abstract: Our proposal is a response to NIDA's Request for Applications entitled `Molecular Genetics of Drug Addiction Vulnerability. The main goal of the proposed study is to detect one or more genes responsible for the genetic transmission of heroin dependence. Our Specific Aims respond to those specified in the RFA: |
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| 1)
To collect and clinically characterize a large sib-pair sample with adequate
statistical power for identifying genomic regions that may harbor loci
conferring susceptibility to heroin dependence; 2) To conduct a whole-genome scan to establish the chromosomal localization of such loci; 3) To follow-up regions of interest from the whole-genome scan and evaluate candidate genes; and 4) To make the clinical and genotypic data quickly available to other investigators in the scientific community. |
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| To accomplish our aims, we have established a collaboration with two psychiatrists in Yunnan Province, China. This province, which borders the "Golden Triangle" -- the source of much of the world's heroin -- has a comprehensive drug abuse registration system to which our colleagues have access. About 30,000 heroin addicts are in the registry and can be easily located by our Chinese collaborator, the Director of the Yunnan Institute for Drug Abuse. We will collect blood and diagnostic information (using a structured diagnostic interview) from 1000 sib-pairs having DSM-IV defined heroin dependence as well as from their parents and other affected and unaffected siblings. Blood samples will be sent to a cell repository at Coriell Laboratories for creation of lymphoblastoid cell lines. In collaboration with a colleague at Washington University, we will complete a genome scan using 350 markers spaced at an average of 10 cM intervals. Genotype and clinical data will be entered using database software. We will conduct a multipoint linkage analysis using the guidelines of Lander and Kruglyak to assert statistical significance. We will follow-up regions of interest with a denser set of markers and evaluate candidate genes. All clinical data will be made available to the scientific community by the end of the funding period. All genotypes will be available one year after they are generated, but no later than a year after the end of the funding period. We are submitting this proposal using the RO1 mechanism. | |
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Schizophrenia - Psychopathology and Heterogeneity 5R01MH043518-14
(Ming Tsuang, P.I) Abstract: We propose to continue a line of research, enabled by an NIMH Merit Award, which has been testing hypotheses about neurobiologic manifestations of schizotaxia (the predisposition to schizophrenia) among schizophrenic patients and the nonpsychotic adult relatives of schizophrenic patients. Our work-showing that schizotaxia is associated with negative symptoms, neuropsychological dysfunction and structural brain abnormalities-converges with data from other centers to show that schizotaxia is a subtle brain disorder affecting about 20 to 50 percent of the nonpsychotic relatives of schizophrenic patients. The data collected during prior funding periods have allowed us to demonstrate |
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| a)
neuropsychological deficits in schizophrenic patients and their relatives,
b) gender differences in the expression of these deficits, c) stability of these deficits over time, d) structural brain abnormalities in patients and relatives, e) functional MRI abnormalities in patients and relatives, and f) how the psychometric features of neuropsychological tests make them useful for assessing phenotypes in genetic linkage studies of schizophrenia. |
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| We have decided to pursue three major aims in this continuation proposal that will help us better understand the neural substrates of schizotaxia and how they lead to schizophrenia. First, we will identify predictors of social dysfunction and psychopathology in adolescent children of schizophrenia patients. Second, we will better describe the neural substrate of schizophrenia prior to the onset of psychosis and lay the foundation for work that will examine if neurodegeneration occurs after illness onset. Third, we will establish the infrastructure required to monitor adolescents at risk for psychosis so that future proposals can select adolescents at risk for schizophrenia for prevention protocols. To accomplish these aims, we will assess 300 adolescent children of schizophrenic patients (ACSZ) and 50 normal controls with neuropsychological, psychosis proneness, psychosocial functioning, and family adversity measures. All controls and 150 randomly selected ACSZ will also be evaluated with magnetic resonance imaging. All 350 subjects will be monitored for adverse outcomes at six month intervals. Given the wide age range for the onset of schizophrenia, we plan to follow this sample for many years. Thus, we will also lay the foundation for future proposals that will monitor the incidence of psychosis in this sample through young adulthood. This will eventually allow us to assess | |
| 1) the predictive validity of schizotaxia measures and environmental adversity for subsequent psychosis and 2)longitudinal changes in neuro-psychological functioning and brain structure in subjects who do not become psychotic. | |
| Achievement of the second goal will help clarify which brain abnormalities in schizophrenic patients can be attributed to neurodevelop-mental events prior to onset and which are due to neurodegeneration after onset. | |
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Neurodevelopmental Study of Schizophrenia - Phase III 5R01MH050647-09
(Ming Tsuang, P.I.). Abstract: This is a proposed Phase III of our Neurodevelopmental Study of Schizophrenia, in which we intend to assess the consequences of genetic and/or pre- and perinatal complications (PPCs) using high resolution structured magnetic resonance imaging (MRI). Studies of schizophrenia have implicated gray and white matter abnormalities in limbic-diencephalic, paralimbic, and prefrontal brain regions. These brain abnormalities result from genetic and/or environmental (i.e., obstetric) factors. Further, some nonpsychotic relatives of patients with schizophrenia suffer from similar, milder, ("subsyndromal") dysfunctions. We are proposing a 5-year study to continue a 40-year prospective high risk study to directly test the consequences of genetic vulnerability (assessed by psychosis in the parent) and specific PPCs (i.e., chronic fetal hypoxia and infections in the second trimester), on cortical and subcortical brain volumes in adult offspring of parents with schizophrenia or affective psychoses. We have a unique opportunity to re-evaluate subjects that we have carefully studied by clinical and neuropsychological evaluations in Phase II of the study. The sample was originally ascertained from a community cohort of pregnancies drawn from the Providence and Boston cohorts of the National Collaborative Perinatal Project. At these sites, 17,741 pregnancies were followed prospectively and systematically recorded, and the offspring's mental and physical development were assessed at 4 and 8 months, and 1,4, and 7 years of age. We have systematically located, recruited, and diagnosed 200 parents with psychotic disorders, and 200 normal comparison parents, individually-matched on specific parent and offspring characteristics. 403 of their adult offspring, ages 31-37, have been identified in Phase II. We estimate that we will ascertain 85 percent of these 403 offspring for MRI. This study is unique in that we can specify developmental predictors of structural brain abnormalities and their functional consequences due to risk and obstetric status, for offspring who become psychotic, or exhibit subsyndromal expressions of the genetic diathesis. Further, we will identify the contribution of PPCs and/or genetic vulnerability to neural circuit abnormalities and demonstrate the specificity for schizophrenia versus affective psychosis. We will use a high resolution MRI and highly detailed, reliable image analysis techniques programs to link etiological predisposition to adult brain volumes (i.e., in limbic-diencephalic, paralimbic and cortical regions, and white matter tracts). This study has important implications for understand2ing the etiology and development of schizophrenia. |
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Genetic Linkage Study of Schizophrenia 5R01MH059624-04 (Ming Tsuang,
P.I.). Abstract: It is proposed to study 90 sib-pairs with the disorder. Specific aims are: |
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| (1)
to clinically assess a pedigree sample having adequate power to detect
genes for schizophrenia; (2) to conduct a genome scan to find such loci; and (3) to transmit all data to the NIMH designated cell repository and data management centers. |
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| The goals will be attained by achieving the following: | |
| (1)
from Taiwan and China, 900 Han Chinese sib- pairs having DSM-IV schizophrenia
will be collected. (2) The investigators will examine all family members using the Diagnostic Interview for Genetic Studies and the Family Interview for Genetic Studies. The PI participated in the development and field testing of these interviews and has an already established training program for their use. They have been translated into Mandarin by the Taiwanese investigators, who have used them in prior studies. (3) Blood samples will be sent to the NIMH designated cell repository for creation of lymphoblastoid cell lines. (4) Clinical data will be entered using the database software created for the NIMH Human Genetics Initiative. Data will be vetted and sent to the NIMH designated data management center. (5) The investigators will complete a genome scan using 450 markers spaced at an average of 10 cM intervals using markers that have been optimized for use in the Han Chinese population. The scan will be completed with no cost to the NIMH through an agreement with Millenium Pharmaceuticals, a biotechnology company in the Boston area that the PI has worked with on a prior genetic linkage study of schizophrenia. All genetic analyses will be approved by the consultant, Eric Lander, Ph.D. (6) all clinical data will be made available to the scientific community by the end of the funding period. |
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| All genotypes will be available on year after they are created but no later than a year after the funding period. This project is feasible because: | |
| (1)
The PI has already coordinated one multi-site genetic linkage study of
schizophrenia and has participated in a second. (2) The investigators have a longstanding relationship with the Taiwanese collaborators and an effective, albeit, more recent working relationship with the Chinese collaborator. (3) The investigators have conservatively estimated that each site has access to more than enough available families having two schizophrenic siblings. (4) The PI's Harvard team has had prior experience collaborating on genotyping and linkage analysis projects with Millennium Pharmaceuticals. |
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| This, and Millennium's prior genotyping experience shows that the genotyping phase of the work is feasible. | |