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

描述（由申请人提供）：抑郁是双相情感障碍的主要流行极，与大量发病率和死亡率相关。然而，与急性躁狂症相比，双相抑郁症的病理生理学以及临床试验和FDA批准的治疗方法都研究不足。由于缺乏指导，临床医生和患者对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，非侵入性的方法来研究在体脑生化。在新的成像范例中，MRS独特地定位于研究客观可测量且临床相关的药物作用的生化机制。由于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3 T的1H-MRS研究与双相情感障碍有关的脑区[前扣带回（Brodmann区24 a/B和32）和背外侧前额叶皮层（Brodmann区9/46）]中的谷氨酸和谷氨酰胺水平。本项目的目的是评价前扣带回和前额皮质谷氨酰胺（定量为CSF校正的绝对浓度较基线的百分比变化）是否与抗谷氨酸能情绪稳定剂拉莫三嗪的临床缓解（MADRS=12）相关。在基线时，约80名双相抑郁受试者和30名年龄匹配的对照者将在位于马约诊所园区查尔顿北成像设施的GE 3.0 Tesla LX MRI系统上接受前扣带回和左背外侧前额叶皮质的1H-MRS。然后，双相抑郁受试者将进入为期12周的拉莫三嗪单药治疗评价。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：这项研究将评估哪些生化变化与有效的拉莫三嗪治疗有关，拉莫三嗪已被证明对许多双相抑郁症患者有帮助。更好地了解药物如何有效可能使更具体的个体化治疗（即确定特定的患者谁应该接受拉莫三嗪的基础上，磁共振波谱生化图片的大脑）。通过这样做，我们可能能够增加治疗反应的可能性，减少双相抑郁症患者无效治疗和/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.