Theodore P. Beauchaine, Ph.D. - US grants

DESCRIPTION (Adapted from Applicant's Abstract): The proposed research will examine differential patterns of electrodermal and cardiac reactivity among conduct-disordered (CD), attention deficit hyperactivity-disordered (ADHD), and control groups of adolescents. Research by Fowles (1980, 1988) and others suggests that electrodermal reactivity during extinction, and heart rate reactivity during reward, represent the functioning of Gray's (1982a, 1982b, 1987a, 1987b) behavioral inhibition (BIS and behavioral activation (BAS) systems, respectively. According to this model, the disinhibition characteristic of both CD and ADHD results from an underactive BIS, an overactive BAS, or both. While deficits in electrodermal reactivity have been demonstrated in both CD and ADHD samples, heart rate is a contaminated measure of the sympathetically-mediated BAS, because it is also determined by parasympathetic input. This is particularly problematic given recent reports of deficits in parasympathetic functioning in CD samples. In the proposed research, electrodermal activity and appropriate measures of both sympathetic (pre-ejection period) and parasympathetic (vagal tone) influences on cardiac functioning will be assessed during reward, extinction, and passive coping. The pattern of results yielded is expected to provide an increment in specificity over Gray's model, with ADHD group exhibiting deficits in sympathetic functioning, and the CD group exhibiting deficits in both sympathetic and parasympathetic functioning compared to controls. This pattern would suggest a modification of Gray's model toward accounting for the aggression that accompanies behavioral disinhibition on CD but not ADHD samples.

DESCRIPTION (provided by applicant): Conduct Disorder (CD) and depression are highly comorbid conditions in childhood and adolescence. This comorbidity is associated with increased risk for several adverse outcomes, including social rejection, substance use, anxiety disorders, and suicide. However, because much of the extant research in this area has been conducted at the symptom level, relatively little is known about the mechanisms of action that are responsible for the observed rates of comorbidity. Moreover, a number of plausible alternatives obtain. Identifying which of these mechanisms is at work is likely to require the application of several strategies that have generally not been employed in the comorbidity literature to date. These include (a) distinguishing between childhood-onset and adolescent-onset CD, (b) expanding the scope of comorbidity research to include biological and physiological measures, (c) generating and testing mechanistic theories of comorbidity, and (d) studying the development of comorbidity and its associated symptoms longitudinally. In the proposed research, each of these issues will be addressed in a study including childhood-onset conduct-disordered, depressed, comorbid (conduct-disordered + depressed), and control preadolescents, ages 8-12. Studies conducted within this age range are critical, as it represents a period of escalating delinquency, depression, and substance use, which often co-occur. Following from theories of emotion regulation (Porges, 1995) and motivation (Gray, 1 982a, 1 982b, 1 987a, 1 987b), patterns of psychophysiological responding will be assessed in participants during conditions of reward, punishment, and social threat. In addition, extensive family history interviews with be conducted with parents, and measures of child delinquency, symptoms of depression, and substance use will be obtained at each of three one-year intervals. Using these data, the following Specific Aims will be pursued: (1) elucidate patterns of autonomic nervous system activity within and across groups through assessment of appropriate psychophysiological markers of behavioral inhibition (electrodermal responding during punishment), behavioral activation (cardiac pre-ejection period during reward), and emotion regulation (respiratory sinus arrhythmia during social threat); (2) assess developmental trajectories in autonomic responding within and across disorders, and relate these trajectories to parental background characteristics and parenting practices; and (3) assess developmental trajectories in child substance use patterns, and examine the potential mediating roles of autonomic responding in relations between parental and child use. Findings obtained should further our understanding of the autonomic substrates of CD, depression, and their comorbidity, and may have differential treatment implications for depressed probands who do and do not present with comorbid CD.

This award provides funds to permit the University of Washington to acquire a 3T magnetic resonance imaging (MRI) scanner for basic-science brain imaging research. This instrument will be housed in a dedicated MRI research facility in the Health Sciences building where it will support a primary group of over 30 basic-science MRI users at UW whose ongoing research success depends critically on access to a 3T MRI scanner. These multidisciplinary researchers originate from multiple different departments that include Psychology, Speech and Hearing Science, Music, Computer Science, Physiology and Biophysics, Linguistics, Neurosurgery, Neurology, Bioengineering and Radiology. Thus, this 3T facility will provide campus-wide support to neuroscience researchers in the Schools of the Arts and Sciences, Education, Engineering, Medicine, the Health Sciences, the School of Public Health and the Graduate School (Psychology). In addition to the current MR researchers, there are many other neuroscientists at UW who have expressed interest in using the 3T facility for their research when available. Thus, addition of a 3T MRI facility will expand the functional brain MRI research efforts at UW in the future. It will also be a resource accessible to researchers from other regional institutions.

Functional brain imaging (fMRI) is an important new research tool used to define how the brain operates to control motor and cognitive tasks and how these functions may be affected by abnormal development or disease. The 3T MRI will be utilized for many fMRI studies some of which include visual system analysis to understand how the brain operates to simultaneously process diverse types of visual input that includes spatial information (location) as well as feature information (color, shape, motion, direction, etc) to interpret a visual scene. Studies of fMRI involving language and cognition will investigate how the brain codes successes and errors during trial-and-error learning to see whether these neural coding events can be used to predict how well people learn. Neuroimaging using structural MRI and MR spectroscopy (MRS) to measure brain metabolite changes will be used to compare brains of young children with normal development to those with Autism. Quantitative MRI/MRS analyses of grey matter and regional volumetric and chemical changes over time (age 3 to age 10) will be correlated with behavioral developmental changes to address questions regarding the time course of brain development and its relationship to typical and atypical behavior.

The University of Washington is strongly committed to interdisciplinary science and education, as evidenced by strong cross-campus research ties, interdisciplinary training programs such as the Graduate Program in Neurobiology and Behavior, and discipline-spanning research centers such as the Integrated Brain Imaging Center (IBIC), Institute for Learning and Brain Science (ILABS), Virginia Merrill Bloedel Hearing Research Center (VMBHRC), Center on Human Development and Disability (CHDD), and Washington National Primate Research Center (WaNPRC). The proposed 3T facility will operate in this tradition, providing new opportunities not only for disciplinary and cross-disciplinary research, but also for graduate and post-graduate training, educational outreach, recruitment of new faculty in neuroimaging, and involvement by female students and researchers, and those from underrepresented groups.

? DESCRIPTION (provided by applicant): Corrosive couple conflict (CCC) and coercive parent-child conflict constitute a ubiquitous, potent, and destructive (but modifiable) interpersonal poison to a wide range of adult and children's health outcomes. Such patterns are also linked with poor parent-child relationships and with more harsh punishment, which is associated with disturbed responses to environmental stresses (e.g., disruption in sympathetic nervous system and hypothalamic-pituitary-adrenocortical responses), a wide variety of adverse health outcomes in childhood, including dental caries, obesity, and diabetes related metabolic markers. This phase of NIH's Science of Behavior Change program emphasizes an experimental medicine approach to behavior change necessitating identification of central interpersonal/social targets for maximal impact on far-reaching panoply of health outcomes. This project will focus on factors associated diabetes and oral health (though the processes affect many other disease outcomes). Both are associated with pain, distress, expense, loss of productivity, and even mortality. They share overlapping medical regimens, are driven by overlapping proximal health behaviors, and affect a wide developmental span, from early childhood to late adulthood. As requested by the RFA, we will isolate three proximal health behaviors: (a) medical regimen adherence; (b) eating and drinking high sugar/calorie items; and (c) self-care behaviors. CCC/coercive parent-child conflicts are marked by an interrelated set of affective, behavioral, and physiological signatures. In the UH2 phase, we will identify/develop/validate assays. We will also identify/develop, and test interventions to reduce CCC/coercion targets. In the UH3 phase, we expect to conduct at least 2 studies to test whether reduction in targets results in improvement in adherence and other health behaviors of interest. One study will focus on parents and children, the other on adults in intimate relationships. Health behaviors related to diabetes and oral health problems will serve as dependent variables as will self-care behaviors in both diabetes and oral health. To place these health behaviors in the context of disease conditions and medical regimen adherence, we expect to focus one study on a sample of children with early childhood caries and the other study on an adult sample with diabetes.