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Functional and neurochemical brain changes in first episode

第一集大脑功能和神经化学变化

基本信息

批准号：
8099705
负责人：
STEPHEN M STRAKOWSKI
金额：
$ 17.96万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8099705
关键词：
Acute Address Affective Aftercare Anterior Antimanic Agents Area Behavior Behavioral Bipolar Disorder Brain Brain region Brodmann&apos s area Choline Chronic Cognition Cognitive Corpus striatum structure Development Disease Progression Emotional Energy Metabolism Exhibits Financial compensation Frequencies Functional Imaging Functional Magnetic Resonance Imaging Functional disorder Future Glutamates Glycolysis Goals Homeostasis Human Inositol Lithium Magnetic Resonance Spectroscopy Manic Measurement Measures Metabolic Metabolism Mind Modeling Mood stabilizers Moods N-acetylaspartate Neurobehavioral Manifestations Neurons Onset of illness Oxidative Phosphorylation Patients Pattern Pharmaceutical Preparations Phospholipid Metabolism Prefrontal Cortex Recurrence Reporting Risk Sampling Structure Subgroup Symptoms System Task Performances Time Work cingulate cortex excitotoxicity experience myoinositol neurochemistry neurophysiology neurotoxicity neurotransmission olanzapine prevent response response marker restoration standard care treatment response

项目摘要

Bipolar disorder is a dynamic condition with symptomatic fluctuations throughout its course. These fluctuations suggest that bipolar neurophysiology involves dysfunction of brain networks that maintain emotional homeostasis. Human emotional behavior appears to be modulated by ventral prefrontal cortical and subcortical brain regions that form the 'anterior limbic network.' Consequently, we hypothesize that the symptoms of bipolar disorder arise from dysfunction within this network. Specifically, functional imaging (fMRI) studies suggest that the anterior limbic network may be over-activated in bipolar patients, thereby producing the symptoms of this condition. Additionally, magnetic resonance spectroscopy (MRS) studies suggest that this over-activation results from anterior limbic hypermetabolism. Moreover, during mania, MRS studies report elevated glutamate (Glx) concentrations; excessive glutamatergic neurotransmission may underlie the excessive anterior limbic metabolism and activation of bipolar disorder. Bipolar disorder is progressive with increasing episode frequency early in the illness course, leading to an established, recurrent illness. Repeated increases in excitatory neurotransmission associated with manic episodes may cause glutamatergic neurotoxicity, thereby initiating neurophysiologic changes that produce progressive emotional instability. It is not known whether any of the standard treatments for bipolar disorder prevent these changes. Nonetheless, perhaps by decreasing excitatory glutamatergic neurotransmission, these medications might correct the hypothesized excessive anterior limbic activation and hypermetabolism, and diminish the risk of neurotoxicity, thereby preventing disease progression. Studies of early course patients, prior to significant disease progression, are needed to make these determinations. With these consideration in mind, the goals of this study are: 1) To use 1H-MRS to identify neurometabolic abnormalities in bipolar disorder at the time of the first manic episode, and then determine how these abnormalities change in response to lithium and olanzapine treatment; 2) To identify corresponding changes in fMRI brain activation to a cognitive probe (CRT-END) while receiving lithium and olanzapine therapy; and 3) To demonstrate that regional brain activation changes are associated with regional metabolic changes. To accomplish these aims, we will acquire integrated neurometabolic (MRS) and functional neuroanatomic (fMRI) measurements in first-episode manic bipolar and healthy subjects in order to refine neurophysiological models of bipolar disorder (Center goal 1); to identify MRS and fMRI markers of treatment response of acute mania to two mechanistically different medications (Center goal 2); and to identify potential predictors of treatment response for future studies (Center goal 3).

双相情感障碍是一种动态状态，在整个过程中有症状波动。这些