2005 — 2009 |
Abercrombie, Heather C |
K08Activity Code Description: To provide the opportunity for promising medical scientists with demonstrated aptitude to develop into independent investigators, or for faculty members to pursue research aspects of categorical areas applicable to the awarding unit, and aid in filling the academic faculty gap in these shortage areas within health profession's institutions of the country. |
Hpa &Emotional Information Processing in Depression @ University of Wisconsin Madison
[unreadable] DESCRIPTION (provided by applicant): Alterations in hypothalamic pituitary adrenal (HPA) functioning in Major Depressive Disorder (MDD) have been studied for decades. However, relatively little is known about the role of cortisol in psychological features of MDD. Extensive basic research shows that cortisol modulates core affective and cognitive processes (especially learning and memory) and their neural substrates. As of yet, little clinical research has applied this basic knowledge to the study of neural underpinnings of cognition and affect in depression. HPA alterations in depression are often characterized by deficient negative feedback, in which cortisol elevations are relatively ineffective in suppressing further HPA activation. Research from a number of sources suggests that in depressed individuals, brain glucocorticoid receptors (GR) in certain key regions may be relatively insensitive to the effects of cortisol. The proposed project will use pharmacological manipulation of cortisol in combination with functional magnetic resonance imaging (fMRI) to determine whether cortisol's effects on regional brain activity differ for depressed and healthy individuals, and how these effects on brain functioning mediate cortisol's effects both on psychological functioning and on HPA negative feedback. Furthermore, using pharmacological blockade of GR in depressed and healthy individuals, the proposed projects will test whether the effects of cortisol are mediated by GR. The candidate is a Clinical Psychologist, and has research background in 1) positron emission tomography studies of regional brain functioning in MDD and 2) the effects of cortisol on memory in healthy individuals. The candidate has proposed a training program that includes implementation of the proposed program of research, which requires training in each of the following areas: in depth HPA axis biology, corticosteroid receptor biology, pharmacological probes of corticosteroid functioning in clinical samples, pharmacological fMRI, and professional development and leadership skills. [unreadable] [unreadable]
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0.958 |
2012 — 2016 |
Abercrombie, Heather C |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Learning, Neural Signaling of Cortisol, and Early Adversity in Depression @ University of Wisconsin-Madison
DESCRIPTION (provided by applicant): The stress hormone cortisol has been studied in depression for decades. However, relatively little is known about the role of cortisol in psychological features of depression. Basic research shows that cortisol modulates brain processes that are highly relevant to depression (especially the neural substrates of negative biases in learning and memory formation). However, very few studies have directly examined the effects of cortisol on neural circuitry of learning in depressed humans. In addition, basic research shows that the effects of cortisol on the neural substrates of learning differ for males and females. The toll of depression is especially high in women, who are roughly twice as likely as men to suffer from depression. Thus, the primary goal of this project is to investigate the effects of cortisol on the neural circuitry of learning in depressed women. A secondary goal is to investigate whether early life adversity moderates cortisol's effects on neural circuitry of learning. Animal data suggests that early life adversity causes life-long biases toward learning in threatening conditions associated with elevated cortisol. In addition, new data from humans suggests that alterations in cortisol traditionally ascribed to depression may stem in part from early adversity rather than depression per se. Thus, this study will examine effects of cortisol on neural circuitry of learning in depressed and healthy women with and without history of early life adversity. The study will use pharmacological manipulation of cortisol levels (compared to placebo) during measurement of brain activity at rest and during memory encoding of emotional and neutral stimuli. The study will also measure whether cortisol exacerbates (or instills) the negative biases in emotional memory often seen in depression. In doing so, the study will examine the role of cortisol in neural networks associated with emotional learning that are often implicated in depression. Medications that target cortisol receptors in the brain may be beneficial in the treatment of depression. However, this knowledge has yet to inform clinical practice, and mechanisms of action of these medications are not well understood. This project is significant because it provides the prerequisite knowledge (and develops a paradigm) that can be used in the development of more effective targeted intervention strategies. The project is innovative because it brings the vast literature of cortisol's effects on learning to research on depression. Learning broadly refers to acquisition of relevant knowledge and the capacity to adaptively alter one's behavior to meet demands of the environment. At the core of depression is difficulty adapting to and engaging with one's environmental context, especially in the face of stressors. Recovery from depression (whether treated medically or behaviorally) requires neural changes supporting adaptation to one's environment. Thus, the project translates information from animal to human research suggesting that recovery from depression entails amelioration of stress-related alterations in neural processes underlying learning. PUBLIC HEALTH RELEVANCE: Depressive disorders are a major public health concern, and the toll of depression is especially high for women. The proposed research will 1) contribute novel information about the relation between neurophysiological and cognitive mechanisms in women with depression, and 2) contribute knowledge regarding the differentiation of depressive subtypes. The project will provide basic information and a research paradigm that can be used in the development of more effective targeted intervention strategies.
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0.958 |