Structural Brain Abnormalities In Depression

海马体、杏仁核和腹侧前扣带回都与情绪障碍的病理生理学有关。抑郁症和双相情感障碍患者海马下托体积异常减小。先前一些情绪障碍的MRI研究报告了海马体积的细微减少，尽管许多其他研究无法证实这种差异。两项研究的海马进行死后提供的线索，体积的减少可能仅限于离散的子区域的海马，即下托和相邻的CA1区。已知下托在引导奖励导向行为和调节对压力的内分泌反应方面起着重要作用，并且是海马体的一部分，与涉及调节情绪行为的其他大脑区域共享最重的解剖学连接。NIMH和NINDS合作开发的一种以非常高的空间分辨率对人脑进行成像的方法，允许对下托和邻近的CA1皮质进行可靠的体积测量。该技术的应用揭示了在情绪障碍中存在明显的下托体积减少，并证明这种异常可以使用MRI无创检测。其次，在重度抑郁症（MDD）中杏仁核有异常减少的胶质细胞。神经胶质细胞先前被证明在前额叶皮层的其他脑区减少，这些脑区与MDD和双相情感障碍患者的杏仁核有广泛的解剖学联系。神经胶质细胞在协助神经元的功能方面发挥着各种重要作用，神经元负责将信号从一个大脑区域传递到另一个区域。因此，这种异常可能会干扰杏仁核的正常功能，而杏仁核在调节情绪行为方面起着重要作用。最后，双相情感障碍受试者的锂治疗与左腹侧前扣带皮层体积的增加（向正常方向）相关，该结构的灰质体积先前被证明在双相情感障碍中异常减少。在实验动物或人类身上进行的研究表明，这种大脑结构在抑制或调节对威胁或压力的自主和内分泌反应，以及对内部产生的悲伤或焦虑的想法和记忆做出反应时产生的情绪感受方面起着重要作用。体积的异常减少可能表明该区域的功能在双相情感障碍中受损，情绪表达和体验失调。锂已被证明可以增加发挥神经保护和神经营养作用的蛋白质的基因表达，因此纠正这种大脑异常可能在锂的情绪稳定作用中发挥不可或缺的作用。目前正在研究其他精神药物（如普拉克索）的影响。

The hippocampus, amygdala, and ventral anterior cingulate are each implicated in the pathophysiology of mood disorders. The volume of the subiculum of the hippocampus is abnormally decreased in MDD and bipolar disorder. Subtle decreases in hippocampal volume were previously reported by some MRI studies of mood disorders, although many other studies were unable to confirm this difference. Two studies of the hippocampus performed post mortem provided clues that the reduction in volume may be confined to only discreet subregions of the hippocampus, namely the subiculum and the adjacent CA1 region. The subiculum is known to play major roles in guiding reward-directed behavior and in modulating endocrine responses to stress, and is the portion of the hippocampus that shares the heaviest anatomical connections with other brain regions implicated in regulating emotional behavior. A method for imaging the human brain at a very high spatial resolution, developed by a collaboration between NIMH and NINDS, permitted reliable volumetric measures of the subiculum and adjacent CA1 cortex. Application of this technique revealed a marked reduction in the volume of the subiculum exists in mood disorders, and demonstrated this abnormality can be noninvasively detected using MRI. Secondly, the amygdala has an abnormal reduction of glial cells in major depressive disorder (MDD). Glial cells were previously shown to be decreased in other brain regions of the prefrontal cortex which share extensive anatomical connections with the amygdala in both MDD and bipolar disorder. The glial cells play a variety of important roles in assisting the function of the neurons, the cells responsible for carrying signals from one brain region to another. This abnormality could thus interfere with the normal functioning of the amygdala, which plays major roles in the regulation of emotional behavior. Finally, lithium treatment of bipolar disordered subjects is associated with increases (toward normal) in the volume of the left ventral anterior cingulate cortex, a structure where the grey matter volume was previously shown to be abnormally reduced in bipolar disorder. Studies performed in experimental animals or humans have suggested that this brain structure plays a major role in inhibiting or regulating the autonomic and endocrine responses to threat or stress, and the emotional feelings that occur in response to internally generated sad or anxious thoughts and memories. The abnormal reduction in volume may indicate this region's function is impaired in bipolar disorder, dysregulating emotional expression and experience. Lithium has been shown to increase the genetic expression of proteins that exert neuroprotective and neurotrophic effects, so correcting this brain abnormality may play an integral role in lithium's mood stabilizing effect. Effects of other psychotropic medications such as pramipexole are currently being persued.