司法鉴定中精神疾病识别及刑事责任能力评定分子标记筛选研究

In recent years, under high pressure and fast-paced lifestyles, people more often suffer from mental diseases.According to statistics issued at the beginning of 2009 by National Center for Mental Health, China-CDC, there are more than 100 million people in China suffering from various mental diseases, among which 16 million people were diagnosed with severe mental disorders, and the incidence rate of violence attack among them is about 10 percent. Severe mental illness not only imposes a huge economic burden on individuals, families and society, but also pose danger to the psychoses themselves or others. People with a major mental disorder are at increased risk of committing crimes, especially violent crimes, compared with the general population. Therefore, it has been viewed as one of the leading cause of public health and social problems with significant implications for forensic psychiatry and the community. .Forensic psychiatry is concerned with the relationship between psychiatric abnormalities and legal violations and crimes. Due to the lack of available biological criteria, assessment, evaluation and therapy in forensic psychiatry has so far been restricted to psychosocial and mental criteria of offender personality. Study on evaluating mentally ill violent offenders based on biological criteria has long been a hot issue and challenge in the modern forensic psychiatry. .In this study, on the basis of epidemiological study, we plan to use a case-control design to investigate the association between violent behavior of patients with severe mental illness and 43 previously reported polymorphic loci firstly. In this screening step, single-locus association analysis, haplotype association analysis as well as gene-gene interaction analysis will be performed, and single polymorphic loci, haplotypes and multi-loci combinations showing significance will be selected as molecular marker for violence behavior of mental disorders in Chinese population. And then, after genotyping of selected markers in three sub-groups identified by capacity of criminal responsibility, we shall investigate the reliability and efficacy of assessing capacity of criminal responsibility of violent crime offenders using these markers in forensic psychiatric expertise. .The aim of our study is to screen molecular marker for the recognition of violence behavior of mental disorders and to assess their potential application value in forensic psychiatry. If the result turns out to be ideal, it would be of fundamental value! -It may well be objective biological marker for assessment of criminal responsibility in forensic psychiatric practice, meanwhile it may have potential application value in violent risk assessment and violence intervention of the mental disorder.

目前我国重性精神病患者人数超过1600万，肇事肇祸率约10％，不仅造成巨大经济负担，而且严重危害自身和他人安全，破坏社会安定和谐，已成为突出的公共卫生和社会问题。依据客观生物学标记，准确评估暴力涉案者的精神状态和刑事责任能力是当前司法精神病鉴定的难题和热点。本项目拟在前期流行病学研究和文献分析基础上，先采用病例-对照研究策略，在危险重性精神病患者和对照群体中，选择43个文献报道与暴力攻击有关的多态位点进行检测，筛选出与中国重性精神病暴力攻击显著相关的分子标记，然后研究这些分子标记在暴力涉案进行司法精神病鉴定的三个人群（无/限制/完全刑事责任能力者）中的分布差异及特征，评估其对精神疾病识别以及刑事责任能力划分的准确度和灵敏度，探讨在司法鉴定中的适用性和有效性，为司法精神病鉴定刑事责任能力评定提供客观科学的生物学依据，并为精神病危险性评估和暴力防控提供理论依据，具有重大理论意义和应用价值。

重性精神病患者肇事肇祸已成为突出的公共卫生和社会问题。本课题首先采用病例-对照研究策略，以399例精神健康个体和234例精神分裂症患者（121例无攻击行为，113例有攻击行为）为研究对象，选择促肾上腺皮质激素释放激素受体1(CRHR1)基因3个标签SNP位点（rs242924、rs4458044和 rs17689966）、促肾上腺皮质激素释放激素结合蛋白(CRHBP)基因4个标签SNP位点（rs7721799、rs32897、rs7718461和rs10062367）和盐皮质激素受体2(NR3C2 )基因4个功能SNP位点（rs2070951、rs5522、rs5525、 rs2871）进行检测，以多重连接酶检测反应（M-LDR）方法，对上述SNP多态性与精神分裂症及其攻击行为的关联性进行研究，筛选出关联显著的分子标记；对23例因攻击行为涉案，司法精神病鉴定为精神分裂症无/限制行为能力的个体在上述基因位点的分布特征进行检测比较，以验证相关分子标记对精神分裂症攻击行为关联的一致性。结果发现，CRHR1基因的rs4458044（C/G）位点C等位基因使精神分裂症患者攻击行为风险增高（OR=1.61，95%CI: 1.074-2.419, p=0.021）;NR3C2基因rs2871（C/T）位点的C等位基因使女性精神分裂症易感性降低（OR值为0.53，95%CI: 0.298-0.927,p=0.025）。单倍型分析结果表明，CRHBP基因4个标签SNP 构建的ACGG单倍型使精神分裂症患病易感性均增高，在男性中更明显，GCAG单倍型则使易感性降低，此外，GCGA单倍型携带的患者攻击风险增加；NR3C2基因CTGC单倍型使精神分裂症易感性降低，在女性中更显著。多因子降维法（MDR）分析显示,所检测的3个基因交互作用模型均无显著性差异。攻击涉案的精神分裂症与非涉案精神分裂症(有/无攻击行为)的个体在各位点等位基因、基因型以及单倍型分布均无显著性差异。综上所述，检测分析结果提示,CRHR1、CRHBP和NR3C2基因与精神分裂症及其攻击行为发生存在一定的相关性，且在不同性别中存在差异，通过验证，筛选出有关联的SNP位点和单倍型在涉案、非涉案的精神分裂症患者中具有一致性。上述研究，为依据分子标记进行精神分裂症的疾病识别和攻击行为预测提供了新的理论基础。