A preliminary study of resting brain metabolism in treatment-resistant depression before and after treatment with olanzapine-fluoxetine combination
A preliminary study of resting brain metabolism in treatment-resistant depression before and after treatment with olanzapine-fluoxetine combination
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DOI：
10.1101/624288
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发表时间：
2019-05
期刊：
影响因子：
3.7
通讯作者：
J. Pardo;S. Sheikh;G. Schwindt;Joel T. Lee;D. Adson;Barry R. Rittberg;F. Abuzzahab
中科院分区：
文献类型：
--
作者：
J. Pardo;S. Sheikh;G. Schwindt;Joel T. Lee;D. Adson;Barry R. Rittberg;F. Abuzzahab
难治性抑郁症（TRD）发生在许多患者中，并导致高发病率和死亡率。由于TRD受试者特别难以研究，特别是纵向研究，生物学数据仍然非常有限。在初步的可行性和有效性研究中，25例TRD患者转诊自专业精神科。所有人都是严重和慢性抑郁症，大多数人都有精神疾病的合并症，这是典型的TRD。9名患者能够完成所有必需的方案组成部分，包括诊断性访谈；等级量表;临床磁共振成像；药物冲刷;最大耐受奥氮平-氟西汀联合治疗8周；和前后处理氟脱氧葡萄糖正电子发射断层扫描。这种药物组合是公认的TRD治疗标准。辍学的原因是抑郁、失眠和焦虑加剧。一名患者病情缓解；三个反应。先验感兴趣的区域包括杏仁核和亚属扣带皮层（sgACC; BA25）。反应者表现出治疗后右侧杏仁核代谢降低，这与临床反应相关；BA25无明显变化；BA25基线代谢水平越高，治疗反应越好；治疗后右腹内侧前额叶代谢（VMPFC；大于BA25）下降，与抑郁评分无关。与规范的代谢数据库相比，所有个体的基线代谢显示出不同的模式。虽然样本量是初步的，但本研究强调了几个对未来工作重要的问题：本研究设计中的显着辍学率；需要大样本量以获得足够的功率；TRD的基线代谢异质性需要仔细的受试者表征，以便未来的干预研究；杏仁核活动随反应降低；以及sgACC和VMPFC基线活动与反应之间的关系。奥氮平-氟西汀联合治疗TRD成功后，脑代谢的变化与治疗反应性重度抑郁症相似。
Treatment-resistant depression (TRD) occurs in many patients and causes high morbidity and mortality. Because TRD subjects are particularly difficult to study especially longitudinally, biological data remain very limited. In a preliminary study to judge feasibility and power, 25 TRD patients were referred from specialty psychiatric practices. All were severely and chronically depressed and mostly had comorbid psychiatric disorders as is typical in TRD. Nine patients were able to complete all required components of the protocol that included diagnostic interview; rating scales; clinical magnetic resonance imaging; medication washout; treatment with maximally tolerated olanzapine-fluoxetine combination for 8 weeks; and pre- and post-treatment fluorodeoxyglucose positron emission tomography. This drug combination is an accepted standard of treatment for TRD. Dropouts arose from worsening depression, insomnia, and anxiety. One patient remitted; three responded. A priori regions of interest included the amygdala and subgenual cingulate cortex (sgACC; BA25). Responders showed decreased metabolism with treatment in the right amygdala that correlated with clinical response; no significant changes in BA25; better response to treatment the higher the baseline BA25 metabolism; and decreased right ventromedial prefrontal metabolism (VMPFC; broader than BA25) with treatment which did not correlate with depression scores. The baseline metabolism of all individuals showed heterogeneous patterns when compared to a normative metabolic database. Although preliminary given the sample size, this study highlights several issues important for future work: marked dropout rate in this study design; need for large sample size for adequate power; baseline metabolic heterogeneity of TRD requiring careful subject characterization for future studies of interventions; relationship of amygdala activity decreases with response; and the relationship between baseline sgACC and VMPFC activity with response. Successful treatment of TRD with olanzapine-fluoxetine combination shows changes in cerebral metabolism similar to those seen in treatment-responsive major depression.