最新试验显示，抑郁症与诱发狼疮的一种特异性自身抗体及中枢神经系统功能障碍存在相关性。系统性红斑狼疮(SLE)，通常简称为狼疮，是一种主要以关节疼痛、皮疹、极度疲劳和抑郁为特征的复杂性自身免疫性疾病。 既往研究发现，SLE最严重的精神病症状表现（重性精神病）可能与中枢神经系统的抗核糖体P蛋白抗体有关。
特拉维夫（Tel Aviv）大学的研究人员通过制造小鼠抑郁症模型，研究自身抗体与大脑相互作用刺激行为改变的机制。2007年3月份出版的《关节炎&风湿症》(http://www.interscience.wiley.com/journal/arthritis)将刊载此次的研究结果。 狼疮可导致周围神经和中枢神经系统功能障碍，该项研究旨在弄清楚这两个神经系统中与抑郁行为产生有关的大脑通路。
试验中，给予健康母鼠大脑直接注射从SLE 患者血样中提取的抗核糖体P蛋白抗体；给予对照组中同样数量的小鼠注射来自正常人的免疫球蛋白G。接着对全部小鼠进行一系列测试：强迫游泳测试，即将小鼠放进半满的玻璃烧杯中，评估其试图站立或跃起的逃生行为；旋转和握力测试，评估运动功能；阶梯测试；游泳T-maze测试，评估认知功能；被动回避测试，评估小鼠对24小时前的足底电击的记忆力。
抗核糖体P蛋白抗体注射组小鼠在接受强迫游泳测试时表现出明显的抑郁样行为，该组小鼠的静态时间是对照组的两倍，表明处于一种绝望状态。两组在认知功能和运动功能方面无显著性差异，排除神经学损伤。
在此基础上进行另一个试验，将"抑郁"的小鼠随机分成盐酸氟西汀（商品名为百忧解的抗抑郁药）治疗组和氟派啶醇（治疗焦虑、成瘾和抑郁的精神治疗药物）治疗组。重复对两组进行强迫游泳测试、阶梯测试和旋转测试，以确定药物疗效。长期盐酸氟西汀治疗可明显减少抑郁样行为，但短期或长期氟派啶醇治疗则效果都不明显。
试验最后阶段，通过免疫染色细致观察小鼠大脑的组织切片。观察结果发现，染色图案勾勒出的是能够调节自主神经系统的压力应答的大脑边缘系统以及与嗅觉相关的大脑区域。
此项研究结果为研究大脑边缘系统通路和嗅觉通路刺激抑郁样行为产生的机制提供了一条崭新的思路。对有
临床表现的抑郁症患者和SLE患者进行影像学研究，将有助于确定人脑的这些通路是否同样受累及。
该研究报告的主要作者，耶胡达·肖恩费尔德博士强调应扩大临床研究规模深入研究，同时指出，"此项研究的另一个令人感兴趣的方面在于发现抑郁与SLE的中枢神经系统功能障碍存在关联性"， "弄清楚抗核糖体P蛋白抗体诱导行为改变的机制，将有可能为抑郁的SLE 患者带来治疗上的新进展。"
http://www.eurekalert.org/pub_releases/2007-02/jws-nii022307.php
Public release date: 27-Feb-2007
New insights into autoimmunity and depression
Novel experiment links depression with a specific autoantibody and central nervous system dysfunction in lupus
Systemic lupus erythomatosus (SLE), often simply called lupus, is a complex autoimmune disease marked by joint pain, skin rashes, extreme fatigue, and depression, among other symptoms. Some studies have described a possible link between SLE抯 most severe psychiatric manifestation, psychosis, and a protein autoantibody associated with the central nervous system, anti-ribosomal P.
To investigate how an autoantibody could stimulate behavioral changes by interaction with the brain, researchers at Tel Aviv University set out to induce depressive hallmarks in mice. Their findings, presented in the March 2007 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), shed light on the brain pathways of depression in general and in central nervous system dysfunction in SLE in particular.
Healthy female mice received injections, directly into the brain, of human anti-ribosomal P antibodies extracted from the blood sample of an SLE patient. For control purposes, equal numbers of mice were injected with normal human immunoglobin G. All the mice were then subjected to a series of tests: a forced swimming test in a glass beaker partially filled water to evaluate escape-oriented behaviors, such as rearing and jumping; rotarod and grip strength tests to gauge motor function; a staircase test; a swim T-maze test to assess cognitive function; and a passive avoidance test to measure the ability of mice to remember a foot shock delivered 24-hours earlier.
Depression-like behavior was strongly observed in the performance of anti-ribosomal P antibody-injected mice on the forced swimming test. The immobility time of these mice was twice as high as that of the control group, indicating a state of despair. In the remaining tests of cognitive and motor functions, there were no significant differences detected between the mice in each group, ruling out neurological damage.
In an additional experiment, the "depressed" mice were randomly divided into treatment groups. Some mice were treated with fluoxetine, the antidepressant marketed as Prozac, and some mice were treated with haloperidol, a psychotropic drug used to treat anxiety, addiction, and depression. To determine the effectiveness of each therapy, mice were subjected to repeating the forced swimming, staircase, and rotarod tests. Depression-like behavior was significantly blocked by long-term treatment with fluoxetine, but not by short- or long-term treatment with haloperidol.
At the culmination of the experiments, the brains of mice were sectioned and scrutinized through immunostaining. The staining pattern delineated the limbic system, which regulates the automatic nervous system抯 response to stress. It also highlighted areas of the brain associated with the sense of smell.
These findings provide a novel line of research into the mechanisms underlying the limbic and olfactory pathways in depression. Imaging studies both in patients with clinical depression and patients with SLE could help determine whether these pathways are similarly affected in humans.
"The relevance of the results to the involvement of the central nervous system in SLE is another intriguing aspect of the present study," notes its leading author, Yehuda Shoenfeld, M.D., while emphasizing the need for further investigation through large-scale clinical studies. "Elucidating the mechanisms by which anti-ribosomal P induces behavioral changes may lead to novel therapeutic advances for SLE patients with depression," Dr. Shoenfeld reflects.
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