Drevets Wayne C, Bogers Wendy, Raichle Marcus E
Neuroimaging in Mood and Anxiety Disorders Section, National Institutes of Health, NIMH/MIB, Bethesda, MD 20892, USA.
Eur Neuropsychopharmacol. 2002 Dec;12(6):527-44. doi: 10.1016/s0924-977x(02)00102-5.
Neurophysiological studies of major depression performed using PET imaging have shown abnormalities of regional cerebral blood flow (CBF) and glucose metabolism in multiple prefrontal cortical and limbic structures that have been more generally implicated in emotional processing. The current study investigated the effects of antidepressant drug treatment in these regions using PET measures of glucose metabolism. Subjects with primary MDD (n=27) were imaged while unmedicated and depressed, and, of these, 20 were rescanned following chronic antidepressant drug treatment. Regional metabolism was compared between unmedicated depressives and controls and between the pre- and post-treatment conditions in regions-of-interest (ROI) where metabolism or flow had previously been shown to be abnormal in unmedicated depressives. At baseline, the mean metabolism was increased in the left and right lateral orbital cortex/ventrolateral prefrontal cortex (PFC), left amygdala, and posterior cingulate cortex, and decreased in the subgenual ACC and dorsal medial/dorsal anterolateral PFC in the unmedicated depressives relative to controls, consistent with the results of previous studies. Following treatment, metabolism significantly decreased in the left amygdala and left subgenual ACC, and corresponding changes in the orbital and posterior cingulate cortices approached significance. The metabolic reduction in the amygdala and right subgenual ACC appeared largely limited to those subjects who both responded to treatment and remained well at 6 months follow-up, in whom the reduction in amygdala metabolism tightly correlated with the reduction in HDRS scores. The magnitude of the treatment-associated, metabolic change in the amygdala also correlated positively with the change in the stressed plasma cortisol levels measured during scanning. These data converge with those from other PET studies to indicate that primary MDD is associated with abnormal metabolism in limbic and paralimbic structures of the mesiotemporal and prefrontal cortices. Chronic antidepressant drug treatment reduces metabolism in the amygdala and ventral ACC in subjects showing a persistent, positive treatment response. In contrast, the persistence of the abnormal metabolic deficits in the dorsomedial/dorsal anterolateral PFC in MDD during treatment may conceivably relate to the histopathological changes reported in these regions in post mortem studies of MDD.
使用正电子发射断层扫描（PET）成像对重度抑郁症进行的神经生理学研究表明，多个前额叶皮质和边缘结构存在局部脑血流量（CBF）和葡萄糖代谢异常，这些结构更普遍地参与情绪加工。本研究使用PET葡萄糖代谢测量方法，调查了抗抑郁药物治疗对这些区域的影响。对患有原发性重度抑郁症（MDD，n = 27）的受试者在未服药且抑郁状态下进行成像，其中20名受试者在接受慢性抗抑郁药物治疗后再次进行扫描。在感兴趣区域（ROI）比较了未服药抑郁症患者与对照组之间以及治疗前后的区域代谢情况，这些区域的代谢或血流在未服药抑郁症患者中先前已显示异常。在基线时，相对于对照组，未服药抑郁症患者的左、右侧眶外侧皮质/腹外侧前额叶皮质（PFC）、左侧杏仁核和后扣带回皮质的平均代谢增加，而膝下前扣带回皮质以及背内侧/背外侧前PFC的代谢降低，这与先前研究结果一致。治疗后，左侧杏仁核和左侧膝下前扣带回皮质的代谢显著降低，眶皮质和后扣带回皮质的相应变化接近显著水平。杏仁核和右侧膝下前扣带回皮质的代谢降低似乎主要限于那些对治疗有反应且在6个月随访时仍状况良好的受试者，其中杏仁核代谢的降低与汉密尔顿抑郁量表（HDRS）评分的降低紧密相关。扫描期间测量的应激血浆皮质醇水平的变化与杏仁核中与治疗相关的代谢变化幅度也呈正相关。这些数据与其他PET研究的数据一致，表明原发性MDD与颞内侧和前额叶皮质的边缘及边缘旁结构的代谢异常有关。慢性抗抑郁药物治疗可降低显示持续、积极治疗反应的受试者杏仁核和腹侧前扣带回皮质的代谢。相比之下，MDD患者在治疗期间背内侧/背外侧前PFC中异常代谢缺陷的持续存在可能与MDD死后研究中这些区域报道的组织病理学变化有关。
