区分双相与单相抑郁障碍的神经化学标志物：磁共振频谱法纵向观察及机制研究

Bipolar disorders (BD) is a severe mental disorder featured with the alternative occurance of depression and mania. The patients with depression as the first symptom of BD is often misdiagnosed as unipolar depression (UD). Studies have shown a different glutamate (GLU)/GABA imbalance in both BD and UD. Our previous study also found significant differences between BD and UD patients in GLU levels in anterior cingulate area. On the basis of the existent findings and literature, we hypothesized that the pathogenesis of BD mainly involve GABAergic neurons whereas UD may be due to damages to both astrocytes and glutamatergic neurons. With this hypothesis, this project will employ hydrogen proton magnetic resonance spectroscopy to quantitatively detect the levels of GLU and GABA in the prefrontal cortex and anterior cingulate area of patients with BD, UD, or those with first-episode depression while the healthy subjects will be used as controls. And the three groups of patients will be followed up for two years while regular treatments are given to them. Concurrent analysis and comparison of the levels of GLU and GABA in the four groups will allow us to determine if these two variables can be used as biomarkers differnetiating BD from UD, if they vary over the disease courses, and if the changes are associated with the corresponding drug therapies. The data resulted from this research project will be of help in differentiating BD from UD, understanding the pathogenesis of them, and providing new insights into the development of new medical interventions for these two mental disorders.

双相障碍(BD)是一种以躁狂、抑郁交替发作为主要表现的重性精神疾病，在疾病早期难以及时识别，很难与单相抑郁(UD)区分。研究显示BD和UD患者脑内均存在谷氨酸(GLU)和GABA失衡。我们前期研究也发现BD和UD患者的前扣带回GLU水平有显著性差异。我们假设，BD主要累及GABA能神经元，UD主要累及星型胶质细胞和谷氨酸能神经元，导致二者的GLU和GABA水平变化方向相反。本题拟利用MEGA-PRESS序列检测处于抑郁发作期的BD、反复发作的UD、首发抑郁及正常对照前额叶和前扣带回GLU和GABA的含量。对三组患者进行为期两年的追踪观察和比较，明确GLU和GABA联动分析是否可用作区分BD和UD的生物学标志，GLU和GABA是否随BD和UD的病程演变而变化，以及变化是否与药物治疗相关。研究结果将有助于鉴别BD和UD，帮助阐明BD和UD的发病机制，为研发新的抗抑郁药和心境稳定剂提供新线索。

双相障碍(BD)是一种以躁狂、抑郁交替发作为主要表现的重性精神疾病，在疾病早期难以及时识别，很难与单相抑郁(UD)区分。研究显示BD和UD患者脑内均存在谷氨酸(GLU) 和GABA失衡。本研究围绕单双相抑郁障碍客观生物学鉴别诊断指标问题进行研究，建立抑郁发作患者数据库，收集了36例单相抑郁发作，24例双相抑郁发作患者，首发抑郁患者10例，37例正常对照，收集了受试者一般资料、抑郁量表评分、童年创伤问卷的评定、MRS、DTI、DKI、VBM等神经影像学数据，主要研究内容及结果有：1）伴有童年创伤的抑郁组CTQ评分明显高于不伴童年创伤的抑郁组及健康对照组，在前扣带回处我们发现伴有童年创伤抑郁组与健康对照组相比NAA水平降低。我们的研究结果提示伴有童年创伤的抑郁症患者NAA水平与健康对照组有显著差异。童年创伤可以加重抑郁症患者疾病的进展，伴有童年创伤的抑郁症患者在前扣带回存在特殊的代谢物的改变。2）单相、双相抑郁患者不同脑区出现了较一致的NAA、Ins降低的改变，但是单相及双相抑郁Cho、Glu值的改变在不同脑区则有所不同，双相抑郁患者前、后扣带回Cho升高，双相抑郁患者双侧背外侧额叶白质Glu及左侧背外侧额叶白质Cho升高，可能是单相及双相抑郁在代谢物改变上的的重要鉴别点。3）本研究结果提示初发抑郁患者已经出现前扣带回、双侧额叶白质、双侧丘脑包含NAA、Glu等脑代谢物水平的降低，随着病程的进展，出现更广泛脑区脑代谢物降低。4）单相抑郁患者不同脑区出现了较一致的GLUCEST%降低，而双相抑郁患者GLUCEST%改变则不一致，单相抑郁和双相抑郁在前扣带回、左、右侧背外侧额叶白质脑区GLUCEST%相反的变化模式可能有助于对二者进行鉴别。5）首发抑郁患者部分脑区已经出现谷氨酸水平的降低，复发抑郁患者谷氨酸水平降低的脑区更加广泛，而且随着病程进展，各脑区谷氨酸水平有降低的趋势。