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: 6870508
• 负责人: JAIR C SOARES
• 金额: $ 36.16万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-16 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6870508
• 关键词: amygdala; anticonvulsants; aspartate; biomarker; bipolar depression; brain imaging /visualization /scanning; brain morphology; central nervous system depressants; clinical research; combination chemotherapy; human subject; human therapy evaluation; limbic system; lithium; magnetic resonance imaging; mental disorder chemotherapy; neuroanatomy; neuropathology; neuropharmacology; nuclear magnetic resonance spectroscopy; pathologic process; patient oriented research; prefrontal lobe /cortex; psychopathology; psychotropic drugs; temporal lobe /cortex

DESCRIPTION (provided by applicant): 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 1patients, and the relationship of FLB abnormalities to symptom remission and treatment response to mood stabilizing agents. Study Design and Methods: In vivo brain imaging methods (magnetic resonance imaging, MRI, and MRspectroscopy, MRS) will be utilized to measure and compare regional brain volumes and regional levels of Nacetyl Aspartate (NAA), a non-specific marker of neuronal viability and function, in prefrontal cortex and medial temporal lobe regions. 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 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 with lamotrigine and lithium, and (iii) patients with bipolar depression who do not respond to either monotherapy or combination therapy. Specific Hypotheses: I: Bipolar depression arises from impairment in neuronal survival in FLB circuits. II: Treatment with a mood-stabilizing agent has detectable effects of ameliorating or reversing prefrontal cortex (PFC) abnormalities. III: Amygdala abnormalities are related to decreased PFC inhibitory drive. IV: Therapeutic response to mood stabilizing agents is related to amelioration or reversal of FLB abnormalities.

描述（由申请人提供）：躁郁症（BD）的抑郁阶段（BD）是一个主要的治疗性挑战，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电路在双相抑郁症中参与BD型1pationt的特定假设，以及FLB异常与症状缓解和对情绪稳定剂的治疗反应的关系。研究设计和方法：将使用体内脑成像方法（磁共振成像，MRI和MRSPECTROSCOPOCOPOP能，MRS）来测量和比较nacetyl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的生存能力和功能。 90个未经治疗的DSM-IV BD I型患者将在进行研究时进行MRI和MRS扫描，并在接受治疗4和16周后。 60 matched healthy controls will undergo 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随后，他对与拉莫三嗪和锂进行了另外12周的联合治疗，以及（iii）双极抑郁症患者对单一疗法或联合疗法不反应。 特定的假设：I：双极抑郁症是由FLB电路中神经元存活损害引起的。 II：用稳定剂的治疗具有改善或逆转前额叶皮层（PFC）异常的可检测作用。 III：杏仁核异常与PFC抑制驱动的降低有关。 IV：对情绪稳定剂的治疗反应与FLB异常的改善或逆转有关。