NEUROANATOMY OF TREATMENT RESPONSE IN BIPOLAR DEPRESSION

双相抑郁症治疗反应的神经解剖学

• 批准号: 7627541
• 负责人: JAIR C SOARES
• 金额: $ 7.31万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627541
• 关键词: Accounting; Bipolar Depression; Bipolar Disorder; Brain; Brain imaging; Chronic; Combined Modality Therapy; Computer Retrieval of Information on Scientific Projects Database; DSM-IV; Depressed mood; Development; Disease remission; Functional disorder; Funding; Grant; Impairment; Institution; Light; Lithium; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Medial; Methods; Mood stabilizers; Moods; N-acetylaspartate; Neuroanatomy; Neurons; Patients; Pharmaceutical Preparations; Phase; Prefrontal Cortex; Process; Research; Research Personnel; Resources; Role; Scanning; Score; Source; Stabilizing Agents; Symptoms; Temporal Lobe; Testing; Therapeutic; Therapeutic Intervention; United States National Institutes of Health; Week; base; brain volume; clinically relevant; depressive symptoms; follow-up; improved; in vivo; lamotrigine; neurochemistry; novel; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: Bipolar depression, the depressive phase of bipolar disorder (BD), is a major therapeutic challenge and frequent cause of chronic impairment. Patients suffering from bipolar depression are often non-responsive to various therapeutic interventions. Abnormalities in fronto-limbic brain (FLB) mechanisms could account for their pathophysiology and relate to treatment response. We propose to test specific hypotheses about the involvement of FLB circuits in bipolar depression in BD type I patients, and the relationship of FLB abnormalities to symptom remission and treatment response to mood stabilizing agents. RESEARCH PLAN: Ninety (90) untreated depressed DSM-IV BD type I patients will undergo MRI and MRS scans at entry to the study, and after 4 and 16 weeks of medication treatment. 60 matched healthy controls will undergo MRI/MRS scan at entry, of which 20 will repeat these measures at weeks 4 and 16. The BD patients will be stratified into 3 groups, based on their responsiveness to treatments (50% improvement in HAMD-21 item scores) during the 16-week period: (i) those who improve following 4 weeks of monotherapy with lithium, and remain improved until the end of the 16-week follow-up period, (ii) monotherapy non-responders who subsequently are responsive to an additional 12 weeks of combination treatment lithium lamotrigine and lithium, and (iii) patients with bipolar depression who do not respond to either monotherapy or combination therapy. METHODS: In vivo brain imaging methods (magnetic resonance imaging, MRI, and MR-spectroscopy, MRS) will be utilized to measure and compare regional brain volumes and regional levels of N-Acetyl Aspartate (NAA), a non-specific marker of neuronal viability and function, in prefrontal cortex and medial temporal lobe regions. CLINICAL RELEVANCE: Our proposed study will examine the role of FLB abnormalities in the mechanisms involved in bipolar depression and treatment response. It will be the first controlled longitudinal study to investigate the relevance of morphometric and neurochemical FLB abnormalities in course of illness and response to treatment with mood stabilizers in BD patients. The elucidation of involved mechanisms could begin to shed light into the specific processes underlying treatment response and refractoriness in bipolar depression. These studies have considerable potential to elucidate the pathophysiology of BD and ultimately contribute to the development of novel and more effective treatments for this severe psychiatric illness.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 目的：躁郁症（BD）的抑郁阶段躁郁症抑郁症是主要的治疗挑战，并且经常引起慢性损害的原因。 患有躁郁症抑郁症的患者通常对各种治疗干预措施无反应。 额膜脑（FLB）机制的异常可能解释其病理生理学，并且与治疗反应有关。 我们建议测试有关FLB电路在BD I型患者中参​​与双相抑郁症的特定假设，以及FLB异常与症状缓解和治疗对情绪稳定剂的治疗反应的关系。 研究计划：90（90）未经治疗的DSM-IV BD I型患者将在进行研究时接受MRI和MRS扫描，并在接受治疗4和16周后。 60个匹配的健康对照将在入口时进行MRI/MRS扫描，其中20个将在第4和第16周重复这些措施。基于他们对治疗的反应能力（在HAMD-21项目得分中提高50％）在16周期间的治疗能力（50％提高）在16周期间：（i）在MON ORTHIPAIN中进行了改善，直到16周（ii）（ii）（ii）均在16周中进行了改善（II），直到16周（ii），直到16周（ii），直到II，并在16周内进行。随后对另外12周的组合治疗锂三硫嗪和锂的组合治疗以及（iii）双极抑郁症患者对单一疗法或联合疗法无反应的患者的无反应者。 方法：将使用体内脑成像方法（磁共振成像，MRI和MR光谱镜，MRS）来测量和比较N-乙酰天冬氨酸（NAA）的区域脑体积和区域水平，这是一种非特异性的神经元纤维固定性和功能的非特异性标记，在胸膜前胸腔和衍生过程中。 临床相关性：我们提出的研究将研究FLB异常在二极性抑郁症和治疗反应中的机制中的作用。 这将是首次研究形态和神经化学FLB异常在疾病过程中的相关性以及BD患者对情绪稳定剂治疗的反应的相关性。 阐明所涉及的机制可以开始阐明双相抑郁症的治疗反应和难治性的特定过程。 这些研究具有巨大的潜力，可以阐明BD的病理生理学，并最终有助于为这种严重的精神疾病开发新颖，更有效的治疗方法。