DRD3基因对精神分裂症研究的法医学意义

阐明精神分裂症的病因和发病机制是医学面临的重要挑战之一,同时也是法医司法鉴定的重要内容之一。精神分裂症的多巴胺假说认为多巴胺能系统的失调是精神分裂症的病因,DRD3基因在脑中的区域性高表达以及其与众多精神疾病的阳性关联提示其在精神分裂症中的潜在重要性。本文综述了DRD3基因在精神分裂症的群体遗传学、动物模型和在人源细胞表达情况的研究现状,认为DRD3基因参与精神分裂症的发病机制并且在未来可能作为一个重要的遗传学指标而应用到法医精神病学的鉴定当中。     

DRD5基因遗传多态性与精神状态的相关性及法医学意义

多巴胺是人类神经系统中重要的神经递质,通过与受体结合发挥生物学作用。当编码受体的基因异常时,可能导致精神疾病的发生。多巴胺受体有5种类型,分别为DRD1、DRD2、DRD3、DRD4、DRD5。DRD5是精神疾病的一个重要候选基因。DRD5受体基因上的rs7655090、rs1850744、(TC)n与精神疾病可能相关联;同时也存在矛盾的研究结果,表明精神疾病可能为多因素、多位点、多基因复制遗传疾病。DRD5基因的SNP具有较好的遗传多态性,可为法医学个人识别与亲权鉴定提供新的遗传标记及为司法精神病鉴定提供参考性遗传学指标。     

谷氨酸受体基因单核苷酸多态性与精神分裂症的关联

谷氨酸是人类神经系统中重要的兴奋性神经递质,通过与受体结合发挥生物学作用.当编码受体的基因异常时,可能导致精神疾病发生.本文通过回顾相关研究,发现诸如GRIN1、GRIN2B、GRM3等受体基因上的rs11146020、366C/G、rs1468412与精神分裂症相关联;同时也存在矛盾的研究结果,表明精神分裂症可能为多因素、多位点、多基因复杂遗传疾病.部分位点如GRIN2B上的366C/G、2664C/T,GRIK2上的rs1408766(C/T)的遗传多态性较好,可能成为法医学个人识别与亲权鉴定的新指标.该领域研究在司法精神病的鉴定工作中可能具有潜在的意义.     

CCK受体基因多态性及与部分精神疾病症状的相关性

胆囊收缩素(CCK)不仅存在于消化系统,而且还广泛存在于中枢及外周神经系统,并以神经递质的形式通过其受体(CCK-R)发挥着重要的生理作用。CCK-R有两种类型,CCK-AR和CCK-BR。CCK-R基因具有遗传多态性,并通过影响或改变CCK对中枢神经系统的作用强度而与酒精中毒、精神分裂症、恐慌症等人类精神疾病密切相关。CCK-R基因遗传多态性的研究可能为法医学个人识别与亲权鉴定新提供新的遗传标记及为司法精神病鉴定提供参考性遗传学指标。     

精神分裂症与司法精神病鉴定

精神分裂症在司法精神病鉴定中占首位,精神分裂症患者的作案动机、作案方式及作案后果均具有特殊性,因此精神分裂症在司法精神病鉴定中占有很重要的地位。笔者结合国内外有关文献,对精神分裂症患者所致司法案件的作案特征以及患者的责任能力、受审能力、服刑能力的研究进行综述。     

HTR1A基因与相应精神疾病的关联及法医学意义

五羟色胺受体1A基因的遗传变异通过影响受体的表达量或与配体结合的活性变化而增强或减弱5-HT的功能,在抑郁症及部分精神系统疾病的发病机制中起着重要的作用。文章通过对HTR1A基因遗传学多态性与部分精神系统疾病的关系进行综述。研究HTR1A基因与抑郁、恐慌、冲动易怒等情绪变化在法医司法精神病鉴定中的意义,并从基因-心理-社会模型的角度探讨犯罪行为的成因。     

COMT基因与精神分裂症患者暴力攻击行为关联性的研究进展

精神分裂症患者的暴力攻击行为发生率高于一般人群,暴力攻击行为在某些方面具有显著的遗传倾向性,与精神分裂症患者暴力攻击行为研究最多的是儿茶酚氧位甲基转移酶（catechol-O-methyltrans-ferase , COMT ）基因。本文从COMT Val158Met 和COMT Ala72Ser 的SNP 多态性、COMT 基因单倍型、COMT基因启动子区DNA甲基化等方面对COMT基因变异与精神分裂症患者暴力攻击行为的相关性研究进行综述,并提出精神分裂症患者暴力攻击行为的遗传学研究方向。     

MAO基因遗传多态性及与精神疾病相关性研究进展

单胺氧化酶(monoamine oxidase,MAO)是调控儿茶酚胺和5-羟色胺等单胺类氧化脱氨的一类重要酶,广泛分布于包括神经系统在内的人体各种组织中,具有多种生物学功能。MAO有两种类型,MAO-A和MAO-B。MAO基因具有遗传多态性,其中部分多态性位点与某些精神疾病如严重抑郁障碍、酒精中毒、反社会情感障碍及精神分裂症等有一定的相关性。MAO基因遗传多态性的研究,可能为法医学个人识别与亲权鉴定提供新的遗传标记,并为司法精神病鉴定提供参考性遗传学指标。     

氯胺酮致小鼠产生类精神分裂症与NRG1、ErbB4 mRNA表达的相关性

目的探讨氯胺酮连续给药致小鼠产生的类似精神分裂症症状,与精神分裂症易感基因神经调节蛋白1（neuregulin-1,NRG1）及其受体ErbB4 mRNA表达的相关性,为研究精神分裂症的可能发病机制提供参考依据。方法50只雄性昆明种小鼠,随机分为生理盐水组、氯胺酮小剂量（25 mg/kg）、中剂量（50 mg/kg）、大剂量（100 mg/kg）组和氯氮平治疗组,腹腔注射给药,1次/d,连续7 d。氯氮平组在连续腹腔注射7d氯胺酮（1次/d,每次100mg/kg）后,再用氯氮平灌胃7d（1次/d,每次20mg/kg）。HE染色观察海马神经元的变化;采用逆转录-聚合酶链反应（RT-PCR）检测海马中NRG1及ErbB4 mRNA的表达。结果注射7d氯胺酮后,大剂量组海马区NRG1及ErbB4 mRNA的表达显著减少。结论氯胺酮诱导小鼠产生类似精神分裂症的症状,可能与海马区NRG1及ErbB4 mRNA的表达减少相关联。     

多巴胺D_3受体基因遗传多态性及法医学意义

多巴胺D3受体(dopam ine D3 receptor,DRD3)基因位于人类第3号染色体上[1],主要在大脑的边缘系统表达,被认为是与精神症状有关的重要候选基因之一[2],其功能可能是影响第二信使系统,对腺苷酸环化酶有抑制作用。在DRD3基因座的第一外显子上存在一个Ser9G ly(第9密码子由丝氨酸变     

Partial Agonist Therapy in Schizophrenia: Relevance to Diminished Criminal Responsibility

Abstract: Pathological gambling (PG), classified in the DSM‐IV among impulse control disorders, is defined as inappropriate, persistent gaming for money with serious personal, family, and social consequences. Offenses are frequently committed to obtain money for gambling. Pathological gambling, a planned and structured behavioral disorder, has often been described as a complication of dopamine agonist treatment in patients with Parkinson’s disease. It has never been described in patients with schizophrenia receiving dopamine agonists. We present two patients with schizophrenia, previously treated with antipsychotic drugs without any suggestion of PG, who a short time after starting aripiprazole, a dopamine partial agonist, developed PG and criminal behavior, which totally resolved when aripiprazole was discontinued. Based on recent advances in research on PG and adverse drug reactions to dopamine agonists in Parkinson’s disease, we postulate a link between aripiprazole and PG in both our patients with schizophrenia and raise the question of criminal responsibility.     

偏执型精神分裂症患者GRIN1基因-855G/C与-1140G/A位点的遗传多态性

目的探讨GRIN1基因启动子区两个单核苷酸多态性位点-855 G/C、-1140 G/A遗传多态性与偏执型精神分裂症的相关性及法医学意义。方法采用PCR限制性片段长度多态性(restriction fragment length polymorphism,RFLP)结合PAGE法对中国北方汉族183例健康无关个体和172例偏执型精神分裂症患者GRIN1基因5′端的-855 G/C和-1140 G/A位点多态性进行检测,采用χ2检验人群中基因型分布是否符合Hardy-Weinberg平衡定律,并比较两组人群中基因型和等位基因频率分布的差异。结果两组群体基因型分布符合Hardy-Weinberg平衡定律。-855 G/C位点基因型分布在对照组女性和实验组女性间的差异具有统计学意义(P0.05),-1140 G/A位点基因型和等位基因频率分布在对照组和实验组间及两组女性间差异具有统计学意义(P0.05)。结论 GRIN1基因启动子区-1140 G/A位点单核苷酸多态性可能与精神分裂症存在相关性;精神分裂症发生的遗传学因素可能存在性别倾向,可为精神分裂症的司法鉴定提供参考。     

Disposition of quetiapine in biological specimens from postmortem cases

Quetiapine is a new atypical antipsychotic that was approved in 1997 by the U.S. Food and Drug Administration for the treatment of schizophrenia. It possesses a high affinity for 5-HT2 receptors and a low affinity for D1 and D2 dopamine receptors. Because quetiapine has only been released recently to the U.S. market, little information exists regarding therapeutic, toxic, and lethal concentrations. This study reports the detection of quetiapine in 13 postmortem cases. Following a basic liquid-liquid extraction, quetiapine was identified and quantitated by capillary gas chromatography with nitrogen phosphorus detection. Confirmation was accomplished by full scan electron impact gas chromatography/mass spectrometry. Heart blood quetiapine concentrations ranged from 0.07 to 18.37 mg/L (N = 12, mean +/- SD = 3.42 +/- 5.67, median 0.62) and femoral blood concentrations ranged from 0.06 to 19.25 mg/L (N = 10. mean +/- SD = 3.89 +/- 6.12, median 0.81). The average heart blood/femoral blood ratio was 1.31 (range 0.55 to 2.57, N = 10). Urine, bile, and gastric contents were assayed in all cases in which they were submitted. In three cases, the cause of death was determined to be quetiapine toxicity. In these cases heart blood concentrations ranged from 0.72 to 18.37 mg/L (N = 3). These data may provide a basis for establishing levels associated with quetiapine toxicity as well as therapeutic concentrations in postmortem specimens.     

Brain distribution of selected antipsychotics in schizophrenia

The brain distribution of phenothiazine antipsychotics in 22 confirmed schizophrenic and 11 control subjects were collected at autopsy. Specimens were homogenized, extracted with n-butyl chloride, and analyzed via liquid chromatography-mass spectrometry, using atmospheric pressure electrospray ionization operating in the positive mode. Drug concentrations normalized for those observed in cerebellum showed three distinct patterns of distribution corresponding to different structural features of each type of phenothiazine. Those drugs with high affinity for dopamine receptors were detected in the highest concentrations in regions with high concentrations of such receptors. However, those associated with relatively lower dopaminergic activity were found in the highest concentration in the occipital cortex, a region with a relatively low concentration of dopamine receptors. The regional brain distribution of thioridazine and its metabolites was concentration dependent. These results have implications for determining the role of these drugs in the sudden and unexpected deaths of schizophrenics.     

NMDA受体拮抗剂与精神分裂症动物模型

精神分裂症是一类常见的精神疾病之一,由于其发病机制复杂,到目前为止病因尚未完全阐明,N-甲基-D-天门冬氨酸（N-methyl-D-aspartate,NMDA）受体拮抗剂能够较好地模拟精神分裂症的阳性症状、阴性症状以及认知功能障碍,近年来被广泛用以制作精神分裂症的动物模型。本文综述了苯环利定、地佐西平和氯胺酮这3种NMDA离子通道开放阻断剂与建立精神分裂症动物模型的关系。     

National study comparing the characteristics of patients diagnosed with schizophrenia who committed homicide vs. those who died by suicide

Associations between serious mental disorder and violence are well-documented, but there is little epidemiological evidence linking these disorders and homicide risk. The reported study compares socio-demographic and clinical characteristics of people diagnosed with schizophrenia who committed homicide vs. those who died by suicide. The study is a national case series of male patients in England & Wales diagnosed with schizophrenia and convicted of homicide during 1997–2012 (n = 168), and a randomly selected comparison group of male patients with schizophrenia who died by suicide and who were matched to the homicide case series by age (n = 777). There are different patterns of behaviour in people with schizophrenia preceding homicide and suicide. Homicide perpetrators have frequently disengaged with services whilst patients who die by suicide are often in recent contact. This is important knowledge for clinical services as it indicates a different preventive emphasis despite the existence of other shared characteristics.