Investigation of postmortem brain polyunsaturated fatty acid composition in psychiatric disorders: limitations, challenges, and future directions.
Investigation of postmortem brain polyunsaturated fatty acid composition in psychiatric disorders: limitations, challenges, and future directions.
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精神疾病中死后大脑多不饱和脂肪酸成分的调查：局限性、挑战和未来方向。
DOI：
10.1016/j.jpsychires.2010.04.029
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发表时间：
2011
影响因子：
4.8
通讯作者：
Jandacek,Ronald
中科院分区：
文献类型：
--
作者：
McNamara,RobertK;Jandacek,Ronald
越来越多的病例对照研究已经调查了来自患有精神障碍（包括精神分裂症）的患者的死后脑组织的脂肪酸组成（Hamazaki等人，2010; Horrobin等人，1991; Landen等人，2002; McNamara等人，2007 a; Yao等人，2000）、双相情感障碍（Hamazaki等人，2010; Igarashi等人，2010年; McNamara等人，2008 a）、重度抑郁症（Conklin et al.，2010; Lalovic等人，2007; McNamara等人，2007 b）和自杀（Lalovic等人，2007; McNamara等人，2009年）。特别令人感兴趣的是主要的脑ω-3和ω-6多不饱和脂肪酸，二十二碳六烯酸（DHA，22：6 n-3）和花生四烯酸（AA，20：4 n-6），因为先前的病例对照研究已经观察到精神病患者中显著的红细胞膜DHA和/或AA缺陷。然而，不同的死后大脑研究的结果并不一致，一些研究发现DHA和/或AA缺乏，而另一些则没有。这些不同的发现突出了一些重要的外来变量和方法问题，往往没有考虑，可能会直接影响死后皮质DHA和AA的组成，并帮助这些结果的解释。此外，考虑这些变量将有助于指导未来死后脂肪酸研究的设计，而死后组织变量的匹配组，包括死后间隔，冷冻储存时间和pH值，是至关重要的，潜在的差异，在死后脑组织的氧化防御精神病患者可能仍然人为地导致死后较低的DHA和AA水平，尽管匹配这些变量。此外，从冷冻皮质组织块中解剖组织可能会引入高度的变异性。例如，DHA集中在突触膜中，额叶白色物质DHA成分（~ 2%）是额叶灰质DHA成分（~ 15%）的一小部分。因此，重要的是获得在灰色和白色物质含量方面尽可能均匀的皮质样品。此外，影像学研究发现，精神疾病与加速灰质损失有关。因此，在死后脑组织中观察到的DHA成分的减少可能仅仅反映了
A growing number of case-control studies have investigated the fatty acid composition of postmortem brain tissue from patients with psychiatric disorders, including schizophrenia (Hamazaki et al., 2010; Horrobin et al., 1991; Landen et al., 2002; McNamara et al., 2007a; Yao et al., 2000), bipolar disorder (Hamazaki et al., 2010; Igarashi et al., 2010; McNamara et al., 2008a), major depressive disorder (Conklin et al., 2010; Lalovic et al., 2007; McNamara et al., 2007b), and suicide (Lalovic et al., 2007; McNamara et al., 2009). Of particular interest are the principal brain omega-3 and omega-6 polyunsaturated fatty acids, docosahexaenoic acid (DHA, 22: 6n-3) and arachidonic acid (AA, 20: 4n-6) respectively, because prior case-control studies have observed significant erythrocyte membrane DHA and/or AA deficits in psychiatric patients. However, results from different postmortem brain studies have been inconsistent, with some studies finding DHA and/or AA deficits whereas others have not. These disparate findings serve to highlight a number of important extraneous variables and methodological issues, frequently not accounted for, that may directly influence postmortem cortical DHA and AA composition, and help inform interpretation of these findings. Furthermore, accounting for such variables will help guide the design of future postmortem fatty acid studies.While matching groups for postmortem tissue variables, including postmortem interval, freezer storage duration, and pH, is critical, potential differences in oxidative defenses in postmortem brain tissue from psychiatric patients may nevertheless artificially lead to lower postmortem DHA and AA levels despite matching these variables. Additionally, tissue dissection from frozen cortical tissue blocks may introduce a high degree of variability. For example, DHA is concentrated in synaptic membranes, and frontal white matter DHA composition (~ 2%) is a small fraction of frontal gray matter DHA composition (~ 15%). It is therefore important to obtain cortical samples that are as uniform as possible in terms of gray and white matter content. Additionally, imaging studies have found that psychiatric disorders are associated with accelerated gray matter loss. Therefore, the observed reductions in DHA composition in postmortem brain tissue may simply reflect reductions in