品行障碍者冷漠特质的催产素干预作用及遗传机制研究

Conduct disorder(CD) refers to a pattern of repetitive rule-breaking behavior, aggression, and always associated with crimes. Callous–unemotional traits(CU) have been added to the fifth edition of the DSM (DSM-5) as a specifier for the diagnosis of conduct disorder, which include reduced guilt, callousness, uncaring behavior, and reduced empathy. CD with callous–unemotional traits have a poorer prognosis and treatment response. They also incur a considerable societal burden from interpersonal suffering and financial costs. A torrent of studies found out that oxytocin can increases trust and cooperation. These findings quickly led to speculation about clinical applications. Until now, we have not find any studies on oxytocin treatment to conduct disorder with CU traits. Therefore, we presume that: oxytocin can improve CU traits among conduct disorder, CU traits will be associated with oxytocin receptor gene. In order to confirm hypothesis, we will recruit male juvenile offenders (include 100 CD with CU , 100 CD without CU, aged 14-18) from juvenile reformatory. One hundred normal male high school students, match age and sex with offenders, will include as control group. Methylation of the CpG island on transcriptional activity of oxytocin receptor gene, 8 SNPs of oxytocin receptor gene and blood concentration of oxytocin will be detected. This is part 1 of the study, in order to explore the association between oxytocin receptor gene and conduct disorder with CU traits. Randomized, double-blind, crossover, and placebo-controlled trial is used in part 2. In this part, face expression and verbal stimuli will be used to assess participants’ face recognition before and after intervention. Participants will also play assurance game before and after intervention. We hope to find whether oxytocin have treatment efficiency to conduct disorder with CU traits, which kind of participants respond positively to the hormone, and whether the different efficiency is in association with variants and methylation of the oxytocin receptor gene.

品行障碍与违法犯罪密切相关，伴冷漠特质品行障碍者常表现出更严重的反社会行为。对冷漠特质的有效干预将显著降低其社会危险性。但目前仍缺乏有效的干预措施，有必要研究冷漠特质的病因学机制和寻找有效干预方法。增强信任感和亲社会行为有助于改善冷漠特质，现有研究证实催产素可增加人类的信任感和亲社会行为。故本研究提出假设：①催产素对冷漠特质具有改善作用；②青少年冷漠特质与催产素受体基因有关。本研究从未成年管教所选取品行障碍冷漠特质组和单纯品行障碍组作为研究组，以同龄健康中学生为对照组，比较三组间催产素浓度、催产素受体基因多态性和甲基化水平，以探寻品行障碍者冷漠特质的遗传学机制。同时采用随机、双盲、交叉和安慰剂对照方法，运用言语性和非言语性情感刺激试验和信任游戏，首次探讨催产素对品行障碍者冷漠特质的干预作用，并分析干预疗效与催产素受体基因的关系。研究成果将为伴冷漠特质品行障碍者的个体化干预提供初步证据。

品行障碍与违法犯罪密切相关，伴冷漠特质品行障碍者常表现出更严重的反社会行为。催产素受体基因是与冷漠和品行问题相关的一个重要候选基因，催产素受体基因甲基化水平可能是品行障碍冷漠特质亚型的表观遗传学基础，但相关研究仍处于初级阶段，且缺乏针对青少年个体的研究。本课题首次针对青少年罪犯中品行障碍者，研究催产素受体基因甲基化水平与品行障碍冷漠特质的关系。.课题组成员经过三年的工作完成了样本采集、DNA提取、甲基化检测及其与品行障碍冷漠特质的相关性分析。结果发现冷漠特质是品行障碍的有效分组依据。高冷漠特质和低冷漠特质品行障碍者在人格特征、行为问题、暴力风险及共病问题方面存在显著差异。相较于低冷漠特质品行障碍者，高冷漠特质品行障碍行为问题更严重，且以非攻击性行为为主，共病注意缺陷多动障碍的可能性更高，常出现注意力不集中、容易走神、缺乏条理、容易冲动的性格特点，同时伴有惹是生非、常指责他人、不守规矩等对立违抗表现。高冷漠特质品行障碍患者曾目睹或遭遇暴力的几率更高，且暴力风险更高，降低暴力风险的保护性因子更少，而增加暴力风险的危险性因子更多。高冷漠特质和低冷漠特质个体在全基因组甲基化模式上存在可区别的特征。相比于低冷漠特质组，高冷漠特质组有大量的甲基化位点显著下调，且高冷漠特质组催产素受体基因的甲基化水平显著降低。.本研究率先从人格特征、行为问题、暴力风险因素、暴力习得及共病情况等方面系统性、多层面的研究了冷漠特质和品行障碍的关系。本研究采用了自评式问卷和他评工具，分别进行定性和定量评估，且两种测量方法均得出相同的结果，使得上述结果更为可靠。另外，本研究率先使用全基因组甲基化芯片技术对品行障碍冷漠特质的表观遗传学机制进行研究。本研究为品行障碍的进一步分组提供了客观依据，为违法犯罪行为的干预和客观评估提供了一定的研究基础。