1H-MR Spectroscopy of Bipolar Depression Before and After Lamotrigine Treatment

描述（由申请人提供）：抑郁症是双相情感障碍的主要极点，它与大量的发病率和死亡率相关。然而，与急性躁狂症相比，双相抑郁症在病理生理学、临床试验和fda批准的治疗方面的研究都不足。由于缺乏指导，临床医生和患者对于双相抑郁症的循证治疗是有限的。质子磁共振波谱（1H-MRS）是一种有价值的、无创的脑生化研究方法。在新的成像范式中，MRS在研究药物作用的生化机制方面具有独特的定位，这是客观可测量的和临床相关的。随着人们对情绪障碍中谷氨酸能失调的兴趣越来越大，本项目将利用3T时的h - mrs来研究与双相情感障碍相关的大脑区域中的谷氨酸和谷氨酰胺水平[前扣带（Brodmann's区24a/b和32）和背外侧前额叶皮层（Brodmann's区9/46）]。该项目的目的是评估前扣带和前额叶皮层谷氨酰胺是否与抗谷氨酰胺情绪稳定剂拉莫三嗪的临床缓解（MADRS=12）有关，以csf校正的绝对浓度百分比从基线变化进行量化。在基线，大约80名双相抑郁症受试者和30名年龄匹配的对照组将在位于梅奥诊所校园查理顿北成像设施的GE 3.0特斯拉LX MRI系统上接受前扣带和左背外侧前额皮质的1H- MRS检查。双相抑郁受试者将进入为期12周的拉莫三嗪单药治疗评估。12周后，双相患者将接受第二次1H-MRS扫描。

DESCRIPTION (provided by applicant): Depression is the predominant prevailing pole in bipolar disorder and it is associated with substantial morbidity and mortality. However, in comparison to acute mania, bipolar depression is understudied both from the standpoint of its pathophysiology as well as clinical trials and FDA-approved treatments. With little guidance, clinicians and patients are limited as to what evidence-based treatment is available for bipolar depression. Proton magnetic resonance spectroscopy (1H-MRS) is a valuable, non-invasive method to study in-vivo brain biochemistry. Of the novel imaging paradigms, MRS is uniquely positioned to investigate biochemical mechanism of drug action that is objectively measurable and clinically relevant. As there is increasing interest in glutamatergic dysregulation in mood disorders, this project will utilize 1H-MRS at 3T to study glutamate and glutamine levels in brain regions implicated in bipolar disorder [anterior cingulate (Brodmann's areas 24a/b and 32) and dorsolateral prefrontal cortex (Brodmann's 9/46)]. The goal of this project is to evaluate whether anterior cingulate and prefrontal cortex glutamine, quantified as a CSF-corrected absolute concentration percent change from baseline, is associated with clinical remission (MADRS=12) to the anti-glutamatergic mood stabilizer lamotrigine. At baseline, approximately 80 bipolar depressed subjects and 30 age-matched controls will undergo 1H- MRS of the anterior cingulate and left dorsolateral prefrontal cortex on a GE 3.0 Tesla LX MRI system located in the Charlton North Imaging Facility on the Mayo Clinic campus. The bipolar depressed subjects will then enter a 12-week evaluation of lamotrigine monotherapy. After 12 weeks the bipolar subjects will undergo a second 1H-MRS scan. PUBLIC HEALTH RELEVANCE: This study will evaluate what biochemical changes are associated with effective lamotrigine treatment, a drug which has been shown to be helpful for many patients with bipolar depression. A better understanding as to how the drug is effective may enable more specific individualized treatment (i.e. identifying the particular patient who should receive lamotrigine based on a MR spectroscopy biochemical picture of the brain). By doing so, we may be able to increase the likelihood of treatment response and decrease the number of ineffective treatments and/or serious side effects for patients with bipolar depression.