首发抑郁症患者纹状体多巴胺D2受体结合力改变及其与行为学的相关分析

Non-displaceable binding potential changes of striatal dopamine D2 receptors in patients with first- episode major depressive disorder and the correlation with clinical features

目的应用11C-雷氯必利（Raclopride） PET/CT，结合汉密尔顿抑郁量表（HAM-D），探讨首发抑郁症患者纹状体多巴胺D2受体的受体结合力（BPND）改变及其与行为学改变之间的关系。方法以2014年12月至2015年12月间收治的首发抑郁症患者及与患者年龄、性别相匹配的健康志愿者为对象进行前瞻性研究，所有受试者均接受脑部MRI和11C-Raclopride PET/CT检查。应用分子影像动态分析工具箱（MIAKAT）软件计算受试者纹状体多巴胺D2受体的BPND，分析抑郁症患者纹状体多巴胺D2受体BPND的改变，并对BPND与患者HAM-D评分进行相关分析。采用配对t检验、两样本t检验及Pearson相关分析处理数据。结果共纳入首发抑郁症患者20例（抑郁组），其中男8例、女12例，平均年龄（32.80±9.76）岁；健康志愿者20名（对照组），其中男9名、女11名，平均年龄（29.25±6.93）岁。抑郁组和对照组受试者脑组织对^11C-Raclopride摄取均主要分布于纹状体区，大脑皮质和小脑分布极微。抑郁组双侧尾状核、壳核D2受体BPND差异无统计学意义（t值：0.69和0.35，均P〉0.05）；对照组双侧尾状核、壳核D2受体BPND差异无统计学意义（t值：0.28和0.24，均P〉0.05）。抑郁组双侧尾状核、壳核D2受体BPND均分别低于对照组（t值：3.13～4.41，均P〈0.05）。抑郁组双侧尾状核和（或）壳核D2受体BPND与HAM-D总分、焦虑或躯体化、认知障碍、迟滞及睡眠障碍等因子分值均有相关性（r值：－0.688～－0.453，均P〈0.05）。结论首发抑郁症患者纹状体多巴胺D2受体BPND下降，且D2受体BPND水平与抑郁症症状相关。纹状体多巴胺受体异常可能是抑郁症患者中脑-纹状体多巴胺奖赏环路异常的重要分子机制之一。

Objective To observe non-displaceable binding potential （BPND） changes of striatal dopamine D2 receptors （SDDR） in patients with first-episode major depressive disorder （MDD） using ^11C- Raclopride PET/CT, and to analyze the relationship between BPND and Hamilton rating scale for depression （HAM-D）. Methods From December 2014 to December 2015, patients with first-episode MDD and age/ gender-matched healthy controls underwent brain MRI and ^11C-Raclopride PET/CT in this prospective study. BPND of bilateral SDDR was calculated by molecular imaging and kinetic analysis toolbox （MIAKAT）. BPND changes of bilateral SDDR and their relationship with HAM-D score were analyzed. Paired t test, two-sample t test and Pearson correlation analysis were used. Results A total of 20 MDD patients （8 males, 12 females, average age： （32.80±9.76） years） and 20 healthy controls （9 males, 11 females, average age： （29.25±6.93） years） were enrolled in this study. The ^11C-Raclopride uptake in brain tissue of the MDD group and control group were mainly distributed in bilateral striatum, and very few ^11C-Raclopride was distributed in bilateral cerebral cortex and cerebellum. In MDD group, the BPND level of bilateral SDDR had no statistical differences（t values： 0.69, 0.35, both P〉0.05）, and similar results were found in the control group（t values： 0.28, 0.24, both P〉0.05）. Compared with the control group, however, the MDD group had lower BPND level of bilateral SDDR（t values： 3.13-4.41, all P〈0.05）. The BPND of bilateral caudate nucleus and/or putamen D2 receptors was correlated with HAM-D total score, anxiety/somatization factor score, cognitive impairment factor score, retardation factor score and sleep disturbance factor score （r values： from -0.688 to -0.453, all P〈0.05）. Conclusions The binding potential of SDDR in patients with first-episode MDD is declined, and the BPND level of SDDR is correlated with symptoms of depression. The abnormality of SDDR may be an important molecular mechanism of the abnormality of midbrain-striatal dopamine reward circuits in MDD patients.