Robert F. Krueger, Ph.D. - US grants

DESCRIPTION (provided by applicant): Rationale- The emergence of a biological revolution in psychopathology research is now strongly solidified, leaving most clinical psychology students inadequately trained in biological concepts and methods, contributing to a void of creative young psychologists equipped to study normal and abnormal personality and psychopathological syndromes across varying levels of analysis. Most graduate programs in clinical psychology are primarily oriented toward cognitive and psychosocial approaches to behavior. A training program that integrates behavioral neurobiology and behavior genetics in the study of psychopathology and personality, taking advantage of the unique perspectives on emotional-behavioral systems offered by psychology, is critically needed. Such a training program is described herein. Six components of a 2-year training program are described: 1) coursework in behavioral neurobiology, concepts of behavioral genetics, the structure of personality, and psychopathology; 2) a two-year association with a designated lab for apprenticeship training in research; 3) participation in research seminars led by training program mentors; 4) lecture series composed of invited scholars and a year-end research conference featuring student presentations; 5) neuropsychology practicum; and 6) travel to national conferences to present research findings. Trainees- Five years of support is sought for four predoctoral positions. Trainees are selected from our clinical psychology doctoral program, most at the conclusion of their second year of graduate study. The success of the training program is evidenced by the productivity of trainees in scholarly publication, and their success in securing post-doctoral appointments indicative of continuing development as research scientists.

DESCRIPTION (provided by applicant): The central objective of the proposed research is to launch a new era of molecular genetics in a large national study of American adults, known as MIDUS (Midlife in the U.S.). Begun in 1995, MIDUS has become a major forum for multidisciplinary research on aging from early adulthood through later life, with a huge following from the scientific community (most frequently downloaded dataset at the national Archive of Computerized Data on Aging). Scientific productive from the study is extensive (about 400 publications), key themes of which clarify that the primary competitive advantage of MIDUS for molecular genetics is its comprehensive and cumulative assessments of environmental exposures. We will focus on two key exposures, socioeconomic status (SES) and social relationships (SR), which constitute well established influences on morbidity and mortality from social epidemiology. We build our specific aims around an explicit gene by environment approach to three outcomes: emotional distress, cognition, and inflammation. In each (Aims 1 through 3), we target primary genetic markers (i.e., those receiving the lion's share of attention in prior research as well as those for which there are functional rationales with regard to underlying neurobiological mechanisms) and examine the role of SES and SR environmental exposures as moderators of their influence on outcomes. Incorporating both risk and protective moderators, we will focus on cumulative SES disadvantage and cumulative SR advantage. An additional set of provisional genetic markers will also be included as supplemental analyses. The proposed work will be carried out with members of the MIDUS Refresher sample (newly recruited respondents) and the existing longitudinal sample (projected sample size for testing key gene by environment hypotheses is 5,400 adults). Embedded within MIDUS is also a national sample of twins for which additional gene by environment analyses will be conducted as well as analyses guided by a co-twin control design. A final aim of the proposed research is to create a genetic repository from the saliva-based DNA extraction and to then hold workshops in the final two years of the grant drawing on scientists from around the country to discuss plans to optimally leverage the use of this repository in a national study with unprecedented depth in assessment of diverse environmental exposures, only two of which are investigated in the proposed research. Overall, the future scientific inquiry that will emanate from the proposed plans to bring molecular genetics to MIDUS is of exceptional scope.

Age-related decline in physical health is one of the most pressing concerns our country faces. In the context of this important societal challenge, one of the major contributions of health psychology has been to demonstrate that variation in physical health is reliably associated with aspects of the person (i.e., individual differences in personality traits) as well as the key social contexts in which the person is embedded (i.e., the quality and nature of adults? interpersonal experiences). For example, in predicting mortality, the effect size for the personality traits of conscientiousness and neuroticism are equal to, if not greater than low SES or low IQ1. Similarly, it has been noted that ?social relationships?constitute a major risk factor for health?rivaling the effect of well established health markers such as cigarette smoking, blood pressure, blood lipids, obesity and physical activity?2 (p. 1). In short, that key intra- and interpersonal resources are reliably associated with health status is now not in dispute. Nevertheless, the degree to which these associations emerge from environmentally mediated processes amenable to intervention remains largely unknown because existing research cannot rule out the possibility that some of these associations might reflect the impact of confounds, including especially evocative genetic processes, that produce correlations between personality/interpersonal experiences and physical health3, 4. We propose to use an innovative co-twin control design to rule out potential genetic and family background confounds and thereby identify environmentally mediated connections linking both personality and interpersonal experiences in advancing age with physical health outcomes. To sidestep problems with correlated measurement error, we will use a multiple-levels-of-analysis approach to assessment, including: (a) self- and romantic partner-reports of personality, social support, and relationship satisfaction, (b) observations of marital interactions while participants? autonomic nervous system responses are monitored continuously, and (c) measurement of health-related behaviors and both standard and early biological markers of health status. Moreover, we intend to do all of this in the context of a genetically informed research design. Though this has never before been done, it is critical in properly targeting interventions to improve health among older adults. More specifically, we will study whether the relation between individual/interpersonal differences and physical health is environmentally mediated by working with participants in the Minnesota Twin Registry (MTR) now in late life (800 twin pairs with their romantic partners, as applicable), a group that completed an assessment of personality previously (~28 years ago, when they were ~38 years old). The acquisition of these new measures from the MTR will allow us to address our specific aims: (Aim 1) to determine whether associations between both personality and relationship experiences in late life and physical health are environmentally mediated, (Aim 2) to identify mechanisms in the environmental pathways connecting personality and health, and (Aim 3) to test whether the effects of personality and relationship qualities extend to biological indicators of health risk.