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优势，它与相当大的发病率和死亡率有关。然而，与急性躁狂相比，双相抑郁从其病理生理学以及临床试验和FDA批准的治疗的角度来看都没有得到充分的研究。在缺乏指导的情况下，临床医生和患者对于双相抑郁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、无创的研究活体脑生化的方法。在新的成像范例中，MRS在研究药物作用的生化机制方面是独一无二的，这是客观可测量和临床相关的。随着人们对情绪障碍中谷氨酸能失调的兴趣与日俱增，该项目将利用3T的1H-MRS来研究与双相情感障碍有关的脑区[前扣带回(Brodmann‘s Area24a/b和32)和背外侧前额叶皮质(Brodmann’s 9/46)]中的谷氨酸和谷氨酰胺水平。该项目的目标是评估前扣带回和前额叶皮质谷氨酰胺是否与抗谷氨酸情绪稳定剂拉莫三嗪的临床缓解(MADRS=12)有关。谷氨酰胺被量化为脑脊液校正的绝对浓度与基线的百分比变化。在基线水平，大约80名双相抑郁受试者和30名年龄匹配的对照组将在位于梅奥诊所园区查尔顿北部成像设施的GE 3.0Tesla LX磁共振系统上对前扣带回和左侧背外侧前额叶皮质进行1H-MRS检查。然后，双相抑郁的受试者将进入为期12周的拉莫三嗪单一疗法评估。12周后，双相受试者将接受第二次1H-MRS扫描。 公共卫生相关性：这项研究将评估有效的拉莫三嗪治疗与哪些生化变化有关，拉莫三嗪已被证明对许多双相抑郁患者有帮助。更好地了解药物是如何有效的，可能会实现更具体的个体化治疗(即根据脑部的磁共振波谱生化图像确定应该接受拉莫三嗪治疗的特定患者)。通过这样做，我们可能能够增加治疗反应的可能性，减少双相抑郁患者无效治疗和/或严重副作用的数量。

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.