A Longitudinal Study of the Effects of Lithium Treatment on Prefrontal and Subgenual Prefrontal Gray Matter Volume in Treatment-Responsive Bipolar Disorder Patients
A Longitudinal Study of the Effects of Lithium Treatment on Prefrontal and Subgenual Prefrontal Gray Matter Volume in Treatment-Responsive Bipolar Disorder Patients
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DOI：
10.4088/jcp.07m03745
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发表时间：
2009-05-01
影响因子：
5.3
通讯作者：
Manji, Husseini K.
中科院分区：
文献类型：
--
作者：
Moore, Gregory J.;Cortese, Bernadette M.;Manji, Husseini K.
目的：最近的分子、临床前和初步临床研究表明，情绪稳定剂的治疗效果可能通过调节有效的神经营养和神经保护因子的表达来介导，这些因子具有逆转细胞弹性损伤、脑体积减少和细胞死亡或萎缩的潜力。我们的主要目标是调查潜在的临床意义，这些研究结果在有关双相disorder.Methods：在良好的特征（DSM-IV标准）双相抑郁症受试者（N = 28）在基线（无药物治疗）和锂管理后（4周），锂对脑灰质体积的纵向影响进行了研究。全脑灰质前额叶灰质，左膝下前额叶灰质体积确定使用有效的半自动分割和感兴趣的区域的方法。该研究于1997年11月至2004年4月在密歇根州底特律市的韦恩州立大学医学院进行。（1）（143）.此外，双相情感障碍受试者的区域分析显示，应答者之间存在显著差异（汉密尔顿抑郁量表总分下降> 50%）和无应答者;只有应答者显示前额叶皮层灰质体积显著增加（p = 0.003）和左膝下前额叶皮质体积的趋势水平增加（p = .0786）.结论：这些区域灰质体积的增加，各种神经影像学和死后神经病理学研究表明，与双相情感障碍的神经病理生理学有关，这表明观察到的效果可能与临床反应有关。这些发现也支持了这样一种观点，即未来的治疗方法更直接地靶向调节细胞可塑性的关键中枢神经系统通路中的分子，有望成为情绪障碍以及一些神经退行性疾病（如阿尔茨海默病）的新型、改进的长期治疗方法。clinicaltrials.gov J Clin Psychiatry 2009;70（5）：699-705（C）版权所有2009年医师研究生出版社。Inc.
Objective: Recent molecular, preclinical, and preliminary clinical studies suggest that the therapeutic effects of mood stabilizers may be mediated by modulating expression of potent neurotrophic and neuroprotective factors having the potential to reverse impairments of cellular resilience, reductions in brain volume, and cell death or atrophy. Our main goal was to investigate the potential clinical significance of these findings in relation to bipolar disorder.Methods: The longitudinal effect of lithium on brain gray matter volume was investigated in well-characterized (DSM-IV criteria) bipolar depressed subjects (N = 28) at baseline (medication-free) and after lithium administration (4 weeks). Total brain gray matter prefrontal gray matter, and left subgenual prefrontal gray matter volumes were determined using validated semiautomated segmentation and region of interest methodology. The study was conducted from November 1997 until April 2004 at Wayne State University School of Medicine, Detroit, Mich.Results: Significant increases in total brain gray matter volume in bipolar subjects were observed after 4 weeks of lithium administration (p =.(1(143). Moreover, regional analyses in the bipolar subjects revealed significant differences between responders (> 50% decrease in Hamilton Depression Rating Scale total score) and nonresponders; only responders showed a significant increase in gray matter volume in the prefrontal cortex (p = .003) and an increase at trend level in the left subgenual prefrontal cortex volume (p = .0786).Conclusions: The increase in gray matter volume in these areas, which various neuroimaging and postmortem neuropathology studies have implicated in the neuropathophysiology of bipolar disorder, suggests that the observed effects may be linked to clinical response. The findings also support the notion that future treatments that more directly target molecules in critical central nervous system pathways that regulate cellular plasticity hold promise as novel, improved, long-term treatments for mood disorders as well as some neurodegenerative conditions, such as Alzheimer's disease.Trial Registration: clinicaltrials.gov Identifier NCT00870311. J Clin Psychiatry 2009;70(5):699-705 (C) Copyright 2009 Physicians Postgraduate Press. Inc.