Division of Bipolar Disorder Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45219-0516, USA.
J Clin Psychopharmacol. 2013 Aug;33(4):528-32. doi: 10.1097/JCP.0b013e3182905b77.
Although the neurophysiology underlying pharmacotherapy for bipolar disorder remains poorly understood, recent studies suggest that therapeutic mechanisms may be reflected in changes in concentrations of N-acetylaspartate (NAA), a putative measure of neuronal integrity and metabolism. In this study, we used magnetic resonance spectroscopy (MRS) to examine prefrontal NAA in patients receiving quetiapine for bipolar mania. On the basis of previous findings, we hypothesized that remission would be associated with increased NAA concentrations in the prefrontal cortex. Thirty-one manic bipolar patients and 13 healthy subjects were recruited to participate in this prospective study. All subjects participated in MRS at baseline and after 8 weeks of treatment. Bipolar subjects received open-label quetiapine monotherapy (mean dose [SD], 584 [191] mg). Fourteen patients remitted (Young Mania Rating Scale ≤ 12) ("remitters"), 11 patients did not ("nonremitters"), and 6 patients were lost to follow-up. Bipolar and healthy subjects did not significantly differ in baseline NAA or degree of change during the 8 weeks. Remitters showed greater mean baseline NAA concentrations in the right ventrolateral prefrontal cortex compared with nonremitters (P < 0.05). In the anterior cingulate, remitters showed near significantly decreased baseline NAA concentrations at baseline (P < 0.06), and significant differences in NAA change during the 8 weeks of treatment (P < 0.03). Manic patients who remitted with quetiapine treatment in the course of this study exhibited distinct patterns of baseline prefrontal NAA concentration, coupled with decreased NAA in the anterior cingulate with treatment; the latter possibly reflecting disparate effects of quetiapine on neuronal metabolism. These data support suggestions that therapeutic effects of quetiapine involve metabolic effects on specific prefrontal regions.
虽然双相情感障碍的药物治疗的神经生理学基础仍知之甚少，但最近的研究表明，治疗机制可能反映在 N-乙酰天门冬氨酸 (NAA) 浓度的变化中，NAA 是神经元完整性和代谢的一种推测性测量指标。在这项研究中，我们使用磁共振波谱 (MRS) 检查接受喹硫平治疗的双相躁狂患者的前额叶 NAA。基于先前的发现，我们假设缓解与前额叶皮层 NAA 浓度增加有关。招募了 31 名躁狂双相情感障碍患者和 13 名健康对照者参与这项前瞻性研究。所有受试者均在基线和 8 周治疗后进行 MRS 检查。双相情感障碍患者接受开放标签喹硫平单药治疗（平均剂量 [SD]，584 [191]mg）。14 名患者缓解（Young 躁狂评定量表≤12）（“缓解者”），11 名患者未缓解（“未缓解者”），6 名患者失访。缓解者的右侧腹外侧前额叶皮层的基线 NAA 或 8 周内的变化程度与未缓解者无显著差异。与未缓解者相比，缓解者的右侧腹外侧前额叶皮层的基线 NAA 浓度平均值较高（P <0.05）。在前扣带皮层，缓解者的基线 NAA 浓度明显较低（P <0.06），且在 8 周的治疗过程中 NAA 变化显著（P <0.03）。在这项研究中，接受喹硫平治疗后缓解的躁狂患者表现出明显的基线前额叶 NAA 浓度模式，同时在前扣带皮层中，NAA 浓度随治疗而降低；后者可能反映了喹硫平对神经元代谢的不同影响。这些数据支持了喹硫平的治疗效果涉及对特定前额叶区域的代谢作用的观点。
