Neil Schneiderman - US grants

health science research support; university;

Black people in the United States have a much higher prevalence of essential hypertension than whites. Causes of this difference are speculative but, differences in diet, renal physiology and socioecologic factors have been implicated. A high level of autonomic nervous system (ANS) reactivity to emotionally challenging stimuli has also been related to the development of essential hypertension. The presently proposed project will focus upon the propostion that black-white differences in renal function, an elevated intake of sodium, a high level of psychosocial and socioecologic stress, and a high level of ANS reactivity to emotionally stressful situations interact to produce the very high, disproportionate prevalence of borderline hypertension that has been reported for poor inner-city blacks. In order to study this proposition the proposed project would examine in 320 25-44 year old Miami residents, cardiovascular (i.e., heart rate, blood pressure, rate-pressure product) and hormonal (i.e., plasma epinephrine, norepinephrine, renin, cortisol) responses to standardized, laboratory, biobehavioral challenges (i.e., bicycle ergometer, competitive video game, cold pressor test, Type A structured interview). Cardiovascular and hormonal responses to the biobehavioral challenges will be specifically compared as a function of race, sex, socioeconomic status and normal blood pressure versus borderline hypertension. The results will be further analyzed as a function of dietary (e.g., sodium, potassium, and calcium intake), genetic, (i.e., family history of hypertension), organismic (i.e., urinary sodium, potassium, calcium; plasma renin, cortisol, catecholamines, aerobic fitness; obesity), and psychological (e.g., alienation; anger expression; chronic anxiety) variables. Extent to which the reactivity findings obtained in the laboratory generalize to everyday life will be examined using ambulatory electrocardiographic and blood pressure monitoring.

DESCRIPTION (provided by applicant): The purpose of the training program is to provide systematic multidisciplinary predoctoral and postdoctoral research training into the biobehavioral and psychosocial factors involved in the pathogenesis and treatment of cardiovascular diseases as well as the prevention of such diseases in high risk populations. Research training is also offered for study of neural, hormonal and immunological mechanisms that may link biobehavioral variables to cardiovascular pathology. Training is closely coordinated with several extramurally funded NIH NHLBI grants including a program project, "Biobehavioral Bases of CHD Risk and Management," a large multi-center longitudinal epidemiological study, "Hispanic Community Health Study/Study of Latinos (HCHS/SOL)" and multiple RO1 grants. The program project consists of integrated, multidisciplinary projects examining the clinical and/or preclinical markers of CHD risk associated with type 2 diabetes (Project 1), metabolic syndrome (Project 2) or hyperlipidemia (Project 3) and their involvement in the progression or amelioration of atherosclerotic CHD processes. In each project we examine modification of risk factors through interventions such as dietary restriction, exercise, stress management and/or manipulation of social environment. Outcome variables include measures of glycemic control/insulin resistance and/or dyslipidemia, oxidative stress, inflammation and overt manifestations of disease. Projects 1 and 2 recruit patients from a large community health center serving low income Blacks and Hispanics/Latinos and Project 3 examines Watanabe heritable hyperlipidemic rabbits and knockout mice. In the HCHS/SOL study the Miami field center is conducting physical exams and interviews as well as follow- ups of 4000 Cuban, South and Central Americans drawn from 24 census tracts to assess health, health risks and practices. Trainees will include 5 predoctoral and 2 postdoctoral fellows who are expected to spend at least two years in the program. Although emphasis at both the pre- and post-doctoral level is upon research, available didactic training includes multiple courses in advanced statistics as well as epidemiology, behavioral medicine, mechanisms of disease, neuroscience and molecular biology. Trainees usually undergo rotations through our program project cores in Biochemistry and Metabolism, Cardiovascular Measurement, and Data Management and Statistics. All trainees receive individual mentoring and participate in relevant program project and other research meetings.

The objective is to conduct an integrated, multidisciplinary inquiry into the psychophysiology of cardiovascular reactivity. Our goal is to use psychophysiological, neurobiological, and behavioral methods to study cardiovascular regulatory processes, relationships between behavior and chronic disorders, and the development of efficacious treatments. The Project consists of four major areas, together with Core facilities supporting the program with biochemical urinary and plasma assays, computation/instrumentation, and psychophysiological data collection. The Cores contribute substantially to the implementation of each Project by using common methodological approaches. Project 1 will examine why black Americans have double the prevalence of hypertension as whites. The manner in which biobehavioral and psychosocial factors influence cardiovascular adjustments and neuroregulatory processes as a function of sex, race, and blood pressure level (normotension vs. borderline hypertension) will be examined during psychophysiological reactivity tasks in the laboratory and during ambulatory heart rate, blood pressure, and hormonal monitoring in natural settings. Project 2 will examine in mild or moderate hypertensives how beta blockers differing in selectivity, lipophilicity, and intrinsic sympathetic activity influence as a function of race and sex: (a) hemodynamic and hormonal reactivity to standardized behavioral challenges in the laboratory; (b) heart rate, blood pressure, and hormonal activity during ambulatory monitoring, (c) cognitive performance, (d) mood, and (e) fatigue. Project 3 will use psychophysiological reactivity tasks, autonomic function tests, and ambulatory monitoring in Type 1 diabetics to investigate: (a) interrelationships among autonomic function, glycemia, cardiovascular and neurohormonal reactivity, and behavior; (b) putative pathophysiological mechanisms responsible for autonomic neuropathy; (c) influences of psychosocial stressors and personality factors on pharmacologic, and/or behavioral interventions designed to exert glycemic control and moderate autonomic reactivity; and (d) influences of anti-hypertensive therapies upon glycemia, autonomic function, reactivity, and behavior. Project 4 will examine in rabbits, the CNS mechanisms underlying cardiovascular reactivity, and will assess the degree to which sympathetic nervous system induced reactivity is attenuated by behavioral conditioning or direct activation of sympathoinhibitory CNS pathways.

particle counter; biomedical equipment resource;

biomedical equipment purchase;

biomedical equipment purchase;

The objective of this 5 yr program project is to extend findings of our previous NIMH supported studies of responses to psychological stressors and their attenuation by behavioral interventions in HIV-1+ gay men. Our previous research documented that changes in affect, endocrine and/or immune function occur in response to psychological stressors such as anticipation or actual diagnosis of HIV status and that responses to diagnosis in HIV+ men can be attenuated by aerobic exercise of cognitive behavioral stress management (CBSM). Project 1 would analyze cardiovascular, endocrine and immunologic reactivity and recovery from acute stressors by: (a) moving our focus from correlational field observations to controlled laboratory manipulation; and (b) extending our previous observations on HIV- and asymptomatic HIV+ White-American gay men to African- and Hispanic-Americans, to symptomatic HIV-1 infected but pre-AIDS (WHO Stage 3B) individuals and to women. Thus, the project would examine autonomic, neuroendocrine and immune responses to an evaluative speech stressor in 306 subjects using a 3 (ethnicity) x 2 (gender) x 3 (HIV status) design. Project 2 would also extend our previous research by examining the effects of a 10 week CBSM group intervention and 6 month post-maintenance program on 100 Hispanic- and 100 nonHispanic White-American WHO Stage 3B gay men randomized into the CBSM intervention condition or an assessment only control condition. The CBSM intervention is designed to enhance psychological adjustments to symptomatic HIV-1 infection and reduce sexual risk and substance use behaviors by teaching anxiety reduction and self-management techniques, enhancing interpersonal coping skills and increasing social support. The maintenance program combines group support and reinforcement of treatment adherence by using well-documented relapse prevention strategies. Psychological, endocrine and immune measures would be assessed at study entry, immediately after the 10 wk intervention period, and after a 6 month maintenance period. Project 3 would extend our previous research in which we found that moderate aerobic exercise prior to HIV-1 diagnosis lowered self-report levels of distress following news of seropositivity. The proposed project would extend our research conducted on asymptomatic HIV+ gay White men to WHO Stage 3B African- and nonHispanic White- American men and women coping with HIV-1 related symptoms and stressors. Relapse prevention strategies will be used to assess feasibility of aerobic exercise as a long-term intervention in symptomatic HIV-1 infection. The project would randomize 176 men (88 African-American, 88 nonHispanic White-American) and 88 women to either the intervention condition or an assessment-only control condition and would conduct aerobic fitness, psychosocial, endocrine and immune assessments at study entry as well as 3- and 12-months post entry. Cross-project analyses will be conducted on psychosocial, psychiatric, endocrine and immune data.

human therapy evaluation; social support network; isolation /deprivation; depression; myocardial infarction; psychosocial rehabilitation; quality of life; therapy compliance; health behavior; clinical trials; relapse /recurrence; health education; gender difference; psychosocial separation; racial /ethnic difference; psychological stressor; behavioral /social science research tag; human subject; electrocardiography;

[unreadable] DESCRIPTION (provided by applicant): [unreadable] This program project competitive renewal application consists of an integrated, multidisciplinary program including 3 closely related projects examining the preclinical and/or clinical markers of coronary heart disease (CHD) risk associated with type 2 diabetes, metabolic syndrome or hyperlipidemia and their involvement in the progression or amelioration of atherosclerotic CHD processes. In each project we will examine the modification of risk factors through the use of behavioral interventions such as dietary restriction, exercise, stress management and/or manipulations of social environment. Outcome variables will include measures of glycemic control/insulin resistance and/or dyslipidemia, oxidative stress, inflammation and overt manifestations of disease. The first Project will determine if compared to Standard Care (SC), a Community Approach to Lifestyle Modification for Diabetes (CALM-D) program including diet, physical activity and coping skills training, can decrease depression, weight and HbA1c and improve medication adherence in low income, minority, depressed, overweight, type 2 diabetic patients seen in a large comprehensive community health center. The second Project will determine if compared to SC, a Community Health and Risk-reduction in Metabolic Syndrome (CHARMS) program also including diet, physical activity and coping skills training, can decrease weight, increase physical activity and reduce the frequency and severity of metabolic syndrome. The third project will assess the role of behavior in the progression of atherosclerosis in the Watanabe Heritable Hyperlipidemic Rabbit by examining the influence of social environment on hyperlipidemic, oxidative, and inflammatory disease processes. The projects will interact with and rely heavily on, the Biochemical Analyses Core, the Cardiovascular Measurement Core and the Data Management and Statistical Analyses Core.

This proposed research will determine whether a behavioral intervention involving stress management, dietary supervision and self-directed exercise, when superimposed upon standard pharmacological treatment, can further reduce coronary heart disease (CHD) risk in post-myocardial infarction (MI) patients. The major mechanistic hypothesis to be investigated is that behavioral procedures can decrease sympathetic nervous system (SNS) activation and insulin resistance (IR), thereby impacting favorably on CHD risk factors such as obesity, glucose intolerance, high blood pressure and dyslipidemia. The Project will use a randomized study design to compare in recent post-M.I. patients, who are not scheduled for nor have had coronary artery bypass graft (CABG) surgery: (1) a standard pharmacological treatment (standard care) condition; and (2) an enhanced care condition in which subjects will receive both standard pharmacotherapy plus behavioral treatment. The 102 subjects ina the standard care condition will generally receive thrombolytic therapy (aspirin), an angiotensin converting enzyme (ACE) inhibitor (if tolerated), a beta blocker (if tolerated) and a lipid lowering agent (if needed). The 102 subjects in the enhanced care condition will also receive pharmacological treatment as well as behavioral self-management skills training to decrease stress, improve diet and increase walking activity. Subjects ina the enhanced care condition will meet in small groups weekly during the first 12 weeks and monthly for the next 9 months. All subjects will be tested (echocardiography, brachial artery ultrasound, euglycemic-hyperinsulinemic clamp, oral glucose tolerance test, 12 lead electrocardiogram, blood pressure, urinary catecholaminns, serum lipids, adiposity, medical history, psychosocial assessments, quality of life assessment) before and after one year. All measures except echocardiographic, euglycemic-hyperinsulinemic clamp, and brachial artery ultrasound measurements will also be assessed 12 weeks after athe first assessment session.

stress management; stress; mental disorder diagnosis; case history; HIV infections; psychological tests; physical fitness; biomedical facility; stressor; functional ability; social support network; self concept; lifestyle; health behavior; disease /disorder classification; disease /disorder proneness /risk; coping; sex behavior; clinical depression; personality disorders; substance abuse related disorder; aerobic exercise; cardiovascular stress test; behavioral /social science research tag; personality tests; human subject; alternative medicine; clinical chemistry; electrocardiography; behavior test; neuropsychological tests;

Recent advances in pharmacotherapy that have helped contain the AIDS virus, have dramatically increased the need for psychosocial interventions that can concurrently facilitate drug adherence, promote harm reduction, decrease anxiety and depressed affect, improve quality of life, and explore possibilities for optimizing immune functioning in diverse and often hard to reach populations. These populations include low socioeconomic status minority and/or substance abuse individuals. This 5 year program project continuation would meet these objectives using cognitive-behavioral stress management (CBSM) as the intervention, primarily in Black, Hispanic and non-Hispanic White men and women. Projects 0002 and would examine the effects of CBSM in symptomatic HIV+ gay men and in women, respectively, as a function of psychosocial, endocrine, immune and health status variables. Because chronic physiological arousal may adversely impact immune function and disease progression and because we have found that HIV+ versus HIV- individuals differ in their endocrine and immune responses to acute stressors, Project 0002 will conduct pre- versus post-CBSM psychophysiological laboratory studies to examine the effects that the CBSM program and the implementation of trained relaxation responses have on acute stress responses in HIV+ individuals. The projects will each be supported by administrative, health, psychosocial, endocrinology, immunology, and data management and statistics core units.

This project will involve participation of 200 men aged 50 and older who have been diagnosed and treated (radical prostatectomy, beam radiation) for localized prostate cancer. The study will use a 2x4 randomized experimental design with experimental condition (10-wk Cognitive- Behavioral Stress Management, CBSM; 1-day CBSM seminar) as the between-group factor and time point (pre-psychosocial intervention, post- psychosocial intervention, 6-month and 12-month follow-up) as the within-group factor. We intend to test the effects of the 10-wk CBSM program on quality of life (QOL), indicators (general QOL; prostate cancer specific QOL; positive growth negative affect, fatigue, sexuality) and immune system status (natural killer [NK] cell number, NK cell cytotoxicity) across the study period. We also intend to assess mediators of the 10 wk CBSM program effects on QOL by associating QOL changes with the following intervention process: (a) changes in cognitive appraisals (increased optimism, increased positive reframing); (b) increases in coping self-efficacy; (c) increases in emotional processing (increased emotional awareness and emotional expression); (d) increases in social support provisions; (e) increases in free testosterone and DHEA- S; (f) decreases in physiological arousal as induced by 24-hour output of norepinephrine, epinephrine and cortisol; and (g) decreases in neuropeptide Y. Finally, we intend to determine the mediators of CBSM on immune system status (NK cell number; NK cell cytotoxicity) by associating immune system changes with psychosocial (QOL indicators) and neurohormonal )catecholamines, cortisol, reproductive hormones, neuropeptide Y) intervention induced changes.

DESCRIPTION (provided by applicant): Depression and inadequate social support are risk factors for medical morbidity and morality after acute myocardial infarction (AMI). The Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial is a multicenter, randomized, controlled clinical study of cognitive-behavioral treatment (CBT) for depression and inadequate social support in post-AMI patients. Because the ENRICHD trial did not focus on biological risk factors (e.g., lipoproteins, lipids, glucose tolerance, adiposity, insulin, inflammatory markers, coagulation factors), possible subclinical markers of disease (e.g., coronary calcification, elevated intima-media thickness [IMT] of carotid artery, decreased brachial artery vasodilation, increased left ventricular mass) or putative mediators (e.g., cortisol, catecholamines) of increased coronary heart disease (CHD) risk or putative subclinical markers of disease, we propose to study further some 200 Miami patients previously enrolled in ENRICHD as well as 210 (180 completors) newly-recruited post-acute MI patients. Thus, approximately 100 previously studied ENRICHD patients, who received CBT, and 100 ENRICHD patients who received usual care, would be compared in terms of post-treatment cardiovascular risk factors, possible subclinical markers of disease and other biological and psychosocial variables to determine the effects of CBT. These patients would then be compared with 210 (180 completors) newly recruited post-acute MI patients. Half of these newly recruited subjects would be randomized into the CBT condition and half into usual care. These newly recruited post-MI patients would be assessed both before and after treatment (i.e., CBT or usual care) in terms of psychosocial variables (e.g., depression and social support), putative biological mediators (e.g., elevated cortisol), risk factors (e.g., elevated triglycerides) and possible subclinical markers of disease (e.g., coronary calcification) as well as demographic and medical characteristics. The project would use all of the core units.

Recent advances in pharmacotherapy that have helped contain the AIDS virus, have dramatically increased the need for psychosocial interventions that can concurrently facilitate drug adherence, promote harm reduction, decrease anxiety and depressed affect, improve quality of life, and explore possibilities for optimizing immune functioning in diverse and often hard to reach populations. These populations include low socioeconomic status minority and/or substance abuse individuals. This 5 year program project continuation would meet these objectives using cognitive-behavioral stress management (CBSM) as the intervention, primarily in Black, Hispanic and non-Hispanic White men and women. Projects 0002 and would examine the effects of CBSM in symptomatic HIV+ gay men and in women, respectively, as a function of psychosocial, endocrine, immune and health status variables. Because chronic physiological arousal may adversely impact immune function and disease progression and because we have found that HIV+ versus HIV- individuals differ in their endocrine and immune responses to acute stressors, Project 0002 will conduct pre- versus post-CBSM psychophysiological laboratory studies to examine the effects that the CBSM program and the implementation of trained relaxation responses have on acute stress responses in HIV+ individuals. The projects will each be supported by administrative, health, psychosocial, endocrinology, immunology, and data management and statistics core units.

combination therapy; counseling; human therapy evaluation; male; AIDS therapy; drug abuse; antiviral agents; combination chemotherapy; intravenous drug abuse; HIV infections; therapy compliance; substance abuse related behavior; coping; helper T lymphocyte; blood cell count; psychological adaptation; virus load; safe sex /sex abstinence; health services research tag; behavioral /social science research tag; human subject; clinical research;

behavioral /social science research tag; clinical trial phase II; heart dimension /size; insulin sensitivity /resistance; noninsulin dependent diabetes mellitus; serotonin inhibitor

The Hispanic Community Health Study (HCHS)/Study of Latinos (SOL) is a 6.5 year study made up of four (4) field centers and one (1) coordinating center. Each field center will examine and follow 4000 study participants. The NIDCR provides funds for this project to support the planning, implementation and analysis of oral health / dental data collected on subject participants enrolled in the HCHS/SOL. It was specified that the HCHS/SOL exam be conducted in the same manner as the dental component of the NHANES studies run by the National Center for Health Statistics. While not all of the NHANES oral measures are included in the HCHS/SOL exam, those components that are included follow the NHANES protocol so that these data can be compared with national findings. The HCHS/SOL examiners are trained by and calibrated using NHANES methodology.

The Hispanic Community Health Study / Study of Latinos (HCHS/SOL) is a multi-center epidemiologic study in Hispanic/Latino populations to determine the role of acculturation in the prevalence and development of disease, and to identify risk factors playing a protective or harmful role in Hispanics/Latinos. The study is sponsored by the National Heart, Lung, and Blood Institute (NHLBI) and six other institutes, centers, and offices of the National Institutes of Health (NIH). Study goals include studying the prevalence and development of disease in Hispanics/Latinos, the role of acculturation, and to identify risk factors that play protective or harmful roles in Hispanics/Latinos. The target population of 16,000 persons of Hispanic/Latino origin, specifically Cuban, Puerto Rican, Mexican, and Central/South American, to be recruited through four Field Centers affiliated with San Diego State University, Northwestern University in Chicago, Albert Einstein College of Medicine in the Bronx area of New York, and the University of Miami. Seven additional academic centers serve as scientific and logistical support centers. Study participants aged 18-74 years will undergo an extensive clinic exam and assessments to determine baseline risk factors. Annual follow-up interviews will be conducted for 2-4 years to determine health outcomes of interest. Study results will be disseminated through scientific journals and also conveyed to the communities involved in the study in order to improve public health at the local level.