2007 — 2009 |
Foland-Ross, Lara C |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Brain Function and Structure in Bipolar Euthymia @ University of California Los Angeles
[unreadable] DESCRIPTION (provided by applicant): The goal of this proposal is to assess abnormalities in brain structure and function in patients diagnosed with type I bipolar disorder (history of manic episode) who are currently euthymic. Patients and healthy volunteers will undergo structural and functional magnetic resonance imaging. Functional imaging will take place during the performance of a neuropsychological task known to activate ventral prefrontal cortex and amygdala, known components of the emotion regulatory system. Advanced surface based processing algorithms will be used on high resolution structural images to measure gray matter thickness in frontal cortex and other brain regions. A correlation analysis will then be used to assess, at every point along the cortex, the relationship between cortical thickness and fMR signal intensity. Because ventral frontal regions of cortex send direct inhibitory projections to the amygdala, the relationship between ventral prefrontal cortical thinning and the response level of the amygdala will also be examined. These studies represent the first attempt at characterizing the thickness of the frontal cortex in bipolar disorder and how structural abnormalities in this region impact functioning of fronto-limbic mood regulatory circuits. Results from the proposed experiments will help to advance our understanding of the pathophysiology of bipolar disorder and identify phenotypic brain abnormalities that predispose an individual to extreme liabilities in mood. Future studies that examine the emergence and progression of these brain abnormalities and the associated impact of medications and treatments will serve to have profound prognostic consequences for patients. [unreadable] [unreadable] [unreadable] [unreadable]
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1 |
2010 — 2012 |
Foland-Ross, Lara C |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
An Integrative Examination of Brain Structure and Function in Major Depression
DESCRIPTION (provided by applicant): Major Depressive Disorder (MDD) is among the most prevalent of psychiatric disorders, affecting as many as 20% of the American population. Yet, the neurobiologic basis of this disorder has not been elucidated. Structural neuroimaging studies of depressed individuals have documented neuroanatomic abnormalities in subgenual prefrontal cortex (PFC), dorsal PFC, and amygdala, known components of emotion regulatory networks. Findings from this literature, however, are mixed, with some, but not all investigators reporting volumetric reductions in these structures. Further, it is possible that these abnormalities may relate to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system that, when hyper- reactive as in MDD, results in high and likely neurotoxic levels of the glucocorticoid hormone, cortisol. The goal of this research is to assess abnormalities in brain structure and function in individuals diagnosed with MDD using structural MRI in conjunction with self-report measures, functional neuroimaging assessments, indicators of HPA-axis reactivity, and genotyping. Specific goals include (1) assessing whether there are regionally specific neuroanatomic abnormalities in MDD patients using newly developed tools for measuring gray matter thickness;and (2) examining associations among disease-specific alterations in brain structure, HPA-axis dysregulation, and activation level of the amygdala, a limbic structure that receives direct inhibitory cortical input. To achieve these objectives, all participants will undergo functional and structural neuroimaging. Structural MRI data will be processed to provide thickness measurements of cortical gray matter at each point along the cortical surface. To assess HPA-axis reactivity, salivary cortisol levels will be measured during the performance on a laboratory stress task. The association between cortical gray matter thickness and cortisol will be examined at each point along the cortical surface to assess whether structural integrity of cortical regions is, in part, dependent on HPA-axis dysregulation and, thus, whether it is related to susceptibility to becoming frequently hypercortisolemic. Additional analyses examining whether the interaction of brain structure and neuroendocrine function is influenced by genetic (serotonin transporter gene polymorphisms) and environmental (history of trauma) factors will be conducted using salivary DNA and self-report measures. Finally, to examine whether heightened amygdala activation in MDD individuals is related to cortical thickness, fMRI data will be processed to provide percent signal change in this region for use as a covariate for linkage with local gray matter distribution. Negative associations between these measures will be examined, and analyses will address whether regulation of the amygdala, and in a broader sense affect, is dependent on prefrontal gray matter integrity and on the inhibitory/executive functions that this prefrontal region subserves. This program of research will provide the applicant with training in several new methodologies, including the collection and interpretation of genetic, neuroendocrine, and event-related fMRI data, as well as in the diagnosis and clinical assessment of MDD. PUBLIC HEALTH RELEVANCE: Results from the proposed experiments will help to advance our understanding of the neurobiological characteristics of MDD, to elucidate the structural and functional brain abnormalities that are associated with MDD, and to identify phenotypic brain abnormalities that may predispose individuals to extreme labilities in mood. These findings will also serve to inform future projects examining the emergence of these abnormalities in depression, their progression, and the impact of various pharmacological and psychological interventions for MDD.
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0.954 |