5-羟色胺2A受体基因-1438A/G多态性与抑郁症的关联研究

目的探讨中国汉族人群中抑郁症患者与5-羟色胺2A(5-HT2A)受体基因-1438A/G多态性之间的关系。方法采用高温连接酶检测反应法,检测254例抑郁症患者和231例正常对照者的5-HT2A受体基因-1438A/G多态性的基因型和等位基因分布。结果(1)5-HT2A受体基因-1438A/G多态性的基因型和等位基因频率在患者组和对照组的分布差异无统计学意义(P>0.05)。(2)患者组-1438A/G多态性的三种基因型之间的汉密尔顿抑郁量表总分和各因子分的差异无统计学意义(P>0.05)。(3)-1438A/G多态性基因型及等位基因在性别和有无精神病疾病家族史之间无显著差异(P>0.05)。结论在中国汉族人群中未发现5-HT2A受体基因-1438A/G多态性与抑郁症存在关联。     

5-羟色胺2A、2C受体基因多态性与难治性抑郁症的关联分析

目的：探讨中国汉族人群难治性抑郁症患者5-羟色胺2C（5-HT2C）受体基因与5-HT2A受体基因之间的关联性。方法：应用聚合酶链式反应（PCR）扩增技术及限制性片段长度多态性（RFLP）分别测定77例难治性抑郁症患者及90名正常人5-HT2C受体基因和5-HT2A受体基因的基因型和等位基因。结果：难治性抑郁症组-759野生型频率明显低于对照组。-759野生型／-697野生型频率也显著低于正常;患者组5-HT2A受体基因型杂合子组的-759野生型、-697野生型以及-759野生型／-697野生型均明显高于纯合子组。结论：-759野生型可能与难治性抑郁症的发病存在一定的相关性;5-HT2A受体基因与5-HT2C受体基因相互之间对难治性抑郁症易患性可能存在一定的关系。     

5-羟色胺转运体基因LPR及5-羟色胺1A受体C(-1019)G基因多态性的联合作用与重性抑郁症的关联研究

目的探讨5-羟色胺转运体基因LPR(5-HTT LPR)多态性和5-羟色胺1A受体(5-HT_(1A)R)C(-1019)G基因多态性的联合作用与重性抑郁症的关系。方法采用病例对照研究,以2005年10月-2007年5月在山西医科大学第一医院就诊的197例重性抑郁症患者为患者组,选取同期该院体检中心与患者组性别、年龄匹配的健康对照者197例为对照组。应用聚合酶链反应技术(PCR)、SDS-聚丙烯酰胺凝胶电泳(SDS-PAGE)及DNA直接测序法对两组的5-HTT LPR及5-HT_(1A)R C(-1019)G基因多态性进行检测。应用UNPHASED软件进行统计分析。结果患者组与对照组的5-HTT LPR和5-HT_(1A)R C(-1019)G多态性位点基因型及等位基因分布频率差异均无统计学意义(P均0.05)。多态性联合作用分析显示,患者组G-S等位基因组合频率高于对照组,差异有统计学意义(21.4%vs.12.4%,P=0.022)。结论在中国汉族人群中,5-HTT LPR和5-HT_(1A)R C(-1019)G的联合作用与重性抑郁症存在关联,G-S等位基因组合可能会增加重性抑郁症发病的危险性。     

5-羟色胺2A受体基因多态性与精神疾病

五羟色胺2A受体基因是人类精神疾病研究的重要候选基因之一,本文对其基因多态性与精神疾病的研究作了简要的文献综述。     

5-羟色胺受体与抑郁症

国外报道抑郁症的男性终生患病率为 5 %～12 % ,女性为 10 %～ 2 0 % ,其中 5 0 %～ 85 %可反复发作 ;每年有 15 %的抑郁症患者自杀[1] 。 5 羟色胺受体 (5 ＨＴＲ)在抑郁症的病因和抗抑郁剂的药理机制中发挥着重要作用。人类至少存在 7种 5 ＨＴＲ即 :5 ＨＴ1Ｒ、5 ＨＴ2 Ｒ、5 ＨＴ3Ｒ、5 ＨＴ4 Ｒ、5 ＨＴ5Ｒ、5 ＨＴ6 Ｒ、5 ＨＴ7Ｒ ,且大部分已被克隆 ,7种类型又进一步分为若干亚型。哪些5 ＨＴＲ亚型与抑郁症及抗抑郁剂的作用有关还远未完全清楚 ,可能为 5 ＨＴ1Ａ Ｒ、5 ＨＴ1ＣＲ、5 ＨＴ2 Ｒ、5 ＨＴ3Ｒ。作者单位 …     

5-羟色胺2A受体基因多态性与抑郁症的关联

目的：探讨中国汉族人群难治性抑郁症患者与5-羟色胺2A(5-HT2A)受体基因的T102C多态性之间的关系。方法：抽取79例难治性抑郁症患者作研究，以102名正常人作对照。应用聚合酶链式反应(PCR)扩增技术及限制性片段长度多态性(RFLP)分别测定所有研究对象的5-HT2A受体基因的基因型和等位基因。结果：5-HT2A受体基因的3种基因型(A1／A1，A1／A2和A2／A2)在难治性抑郁症组的分布分别为31．6％、54．4％和13．9％，在对照组分别为29．4％、45．1％和25．5％，两组间差异无显著性。结论：5-HB。受体基因的T102C多态性与难治性抑郁症之间无显著关联。     

5-羟色胺2A受体基因多态性与精神分裂症的相关性研究

目的探讨５－羟色胺２Ａ受体基因多态性与精神分裂症的相关性。方法采用Ａｍｐ－ＲＦＬＰ方法对精神分裂症患者和各对照组的５－羟色胺２Ａ受体（简称５－ＨＴ２ＡＲ）基因的相关性进行了研究。结果精神分裂症患者５－ＨＴ２ＡＲ基因Ａ２Ａ２纯合子基因型频率及等位基因Ａ２频率均高于对照组（χ２＝８．９９，８３８Ｐ均＜０．０１），对发生精神分裂症的５－ＨＴ２ＡＲ基因Ａ２Ａ２纯合子相对危险度是２３６。结论本实验结果提示５－ＨＴ２ＡＲ基因的变异与精神分裂症有密切相关性。     

5-羟色胺基因多态性与抑郁症的相关性研究

目的：探讨5-羟色胺转运体(5-HTT)基因启动子区多态性(5-HTTLPR)与抑郁症的相关性及其对抗抑郁药疗效的影响。方法：运用聚合酶链反应技术(PCR)检测51例抑郁症患者(患者组)和60名健康对照者(对照组)5-HTTLPR的分布频率；并予文拉法辛治疗，用汉密尔顿抑郁量表(HAMD)观察疗效。结果：患者组5-HTTLPR的短重复序列／短重复序列(short／short，S／S)基因型和短重复序列(short，S)等位基因频率分别为71％和81％，对照组为45％和69％差异显著。治疗4周后，长重复序列／长重复序列(long／long，L／L)基因型患者的减分率显著高于其他两型。结论：5-HTTLPR的S／S基因型可能是抑郁症的易感基因之一，L／L基因型可能和更好的选择性5-羟色胺受体阻滞剂类(SSRIs)疗效有关。     

5-羟色胺转运体基因多态性与青少年抑郁症的关联研究

目的 探讨中国汉族青少年抑郁症与5-羟色胺转运体（5-HTY）基因的启动子区多态（5-HTTLPR）之间的关系。方法 应用聚合酶链式反应（PCR）扩增技术对84例青少年抑郁症患者和85例健康者进行基因型分析。结果 5-HTYLPR基因的3种基因型S／S,L／S和L/L在青少年抑郁症组的分布分别为57．1％,36．9％,6．0％;在对照组分别为57．6％,34．1％,8．2％,两组间差异无显著性（P〉0．05）。抑郁症组中S／S基因型患者HAMD自杀因子评分明显高于L／L和L／S型患者（P〈0.01）。结论 5-HTT基因多态性与青少年抑郁症无明显关联。抑郁症中携带S／S基因型患者的自杀风险相对比L／L型、L／S型患者高。     

色氨酸羟化酶1与5-羟色胺2A受体基因对抑郁症患者额叶情绪加工的影响

目的:分析色氨酸羟化酶1 (TPH1)基因A218C多态性、5-羟色胺(5-HT)2A受体基因(HTR2A) T102C多态性对抑郁症患者额叶情绪识别功能异常的影响. 方法:28例抑郁症患者(患者组)及34名性别、年龄、受教育年限相匹配的健康对照(对照组)均进行情绪识别任务态下功能磁共振扫描,并以聚合酶链式反应-限制...     

促肾上腺皮质激素释放激素受体1基因多态与抗抑郁药物疗效的关联研究

目的探讨促肾上腺皮质激素释放激素受体1(corticotropin-releasing hormone receptor1,CRHR1)基因多态性与选择性5-羟色胺再摄取抑制剂(Selective Serotonin Reuptake Inhibitors,SSRIs)、5-羟色胺和去甲肾上腺素再摄取抑制剂(Serotonin and Norepinephrine Reuptake Inhibitors,SNRIs)抗抑郁疗效差异的相关性。方法对符合美国精神障碍诊断与统计手册第4版(Diagnostic and Statistical Manual of Mental Disorders,Fourth Edi-tion,DSM-Ⅳ)抑郁症诊断标准的271例抑郁症患者予以单一新型抗抑郁药(SSRIs或SNRIs)常规剂量治疗至少6周,以治疗前后17项汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)总分减分率作为评估疗效的指标。采用TaqMan探针法检测CRHR1基因上4个单核苷酸多态性(Single Nucleotide Polymorphism,SNP)的基因型,比较有效组(HAMD-17减分率≥50%)和无效组(HAMD-17减分率<50%)之间4个位点基因型及多位点组成单倍型的不同。结果治疗4周末:CRHR1基因rs17689966位点A等位基因及AA基因型携带者在治疗无效组的频率均显著高于有效组(88.0%vs.77.0%,P=0.004;75.8%vs.59.0%,P=0.004)。有3种单倍型在有效组和无效组之间的分布差异有统计学意义,分别是T-A/T-G(rs242924-rs17689966:86.6%vs.74.7%,P=0.002;8.1%vs.15.5%,P=0.018),G-T-G(rs4458044-rs rs242924-rs17689966:8.2%vs.15.5%,P=0.019)。治疗6周末:CRHR1基因4个SNPs的基因型、等位基因频率及单倍型分析在不同疗效患者组间分布差异均无统计学意义(均P>0.05)。结论CRHR1基因多态性可能与SSRIs、SNRIs类药物的早期疗效相关。     

Associations between LSAMP gene polymorphisms and major depressive disorder and panic disorder

The purpose of this case–control genetic association study was to explore potential relationships between polymorphisms in the limbic system-associated membrane protein (LSAMP) gene and mood and anxiety disorders. A total of 21 single-nucleotide polymorphisms (SNPs) from the LSAMP gene were analyzed in 591 unrelated patients with the diagnoses of major depressive disorder (MDD) or panic disorder (PD) and in 384 healthy control subjects. The results showed a strong association between LSAMP SNPs and MDD, and a suggestive association between LSAMP SNPs and PD. This is the first evidence of a possible role of LSAMP gene in mood and anxiety disorders in humans.     

Incident and recurrent major depressive disorder and coronary artery disease severity in acute coronary syndrome patients

There is recent evidence that acute coronary syndrome (ACS) patients with first time incident major depressive disorder (MDD) and those with recurrent MDD represent different subtypes among individuals with ACS and comorbid depression. However, few studies have examined whether or not these subtypes differ in coronary artery disease (CAD) severity. We assessed whether those with incident MDD (in-hospital MDD and negative for history of MDD) or recurrent MDD (in-hospital MDD and a positive history of MDD) differ in angiographically documented CAD severity. Within 1 week of admission for ACS, 88 patients completed a clinical interview to assess current and past diagnosis of MDD. CAD severity was assessed in all patients by coronary angiography. A hierarchical regression analysis showed that neither in-hospital MDD status, nor history of MDD were significant predictors of CAD severity, but the interaction term between in-hospital MDD status and history of MDD was a significant predictor of CAD severity, after controlling for age, sex and ethnicity. Follow-up analyses showed that patients with first time, incident MDD had significantly more severe CAD compared to patients with recurrent MDD (p=0.043). To conclude, our study adds to the growing evidence that patients with incident MDD should be considered as a clinically distinct subtype from those with recurrent MDD. Possible mechanisms for differing CAD severity by angiogram between these two subtypes are proposed and implications for prognosis and treatment are discussed.     

A 5-year prospective study of predictors for disability pension among patients with major depressive disorder

Holma IAK, Holma KM, Melartin TK, Rytsälä HJ, Isometsä ET. A 5‐year prospective study of predictors for disability pension among patients with major depressive disorder. Objective: There is a scarcity of prospective long‐term studies on work disability caused by depression. We investigated predictors for disability pension among psychiatric patients with MDD. Method: The Vantaa Depression Study followed up prospectively 269 psychiatric in‐ and out‐patients with DSM‐IV MDD for 5 years with a life chart, including 230 (91.3%) patients belonging to labour force. Information on disability pensions was obtained from interviews, patient records and registers. Results: Within 5 years, 20% of the patients belonging to labour force at baseline were granted a disability pension. In multivariate analyses, the significant baseline predictors for granted disability pension were age ≥50 years (HR = 3.91, P < 0.001), subjective inability to work (HR = 2.14, P = 0.008) and introversion (HR = 1.08, P = 0.049). When follow‐up variables were included, the predictors were age more than 50 (OR = 6.25, P < 0.001), proportion of time spent depressed (OR = 14.6, P < 0.001), number of comorbid somatic disorders (OR = 1.47, P = 0.013) and lack of vocational education (OR = 2.38, P = 0.032). Conclusion: Of psychiatric patients with depression, one‐fifth were granted a disability pension within 5 years. Future disability pension can be predicted by baseline older age, personality factors, functional disability, lack of vocational education and comorbid somatic disorders. Longitudinally, accumulation of time spent depressed appears decisive for pensioning.     

Dysbindin gene (DTNBP1) in major depressive disorder (MDD) patients: Lack of association with clinical phenotypes

Abstract

Objectives. Dystrobrevin binding protein 1 (Dysbindin) is a plausible candidate gene for major depressive disorders (MDD) due to its involvement in synaptic signaling, plasticity and localization in the brain. Methods. Two intronic SNPs of DTNBP1; rs760761 (P1320) and rs2619522 (P1763) were analyzed in 206 patients with DSM-IV MDD to investigate the functional impact of genotypes on susceptibility for depression and some clinical phenotypes. The Sequenom iPLEX assay (Sequenom, Cambridge, MA) was used for genotyping. Results and Conclusions. Despite the limited power of analysis, our results showed that these two SNPs in DTNPB1 gene were not related to clinical phenotypes such as melancholia, age at onset, suicidality and co-morbid anxiety disorders, as well as to treatment response phenotypes.     

抑郁障碍患者家庭功能的跨文化研究

目的:探讨中国和美国抑郁障碍患者的家庭功能特征.方法:采用家庭功能量表(FAD)对92例中国抑郁障碍患者(中国组)及92例美国抑郁障碍患者(美国组)进行评估及比较.结果:两组FAD各维度均分均高于健康的家庭功能临界值,为不健康的家庭功能.中国组FAD中的情感反应维度评分及行为控制维度评分明显高于美国组;中国男性组情感反...     

A logical relationship for schizophrenia,bipolar, and major depressive disorder. Part 1: Evidence from chromosome 1 high density association screen

Familial clustering of schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD) was investigated systematically (Aukes et al., Genetics in Medicine, 2012, 14, 338–341) and any two or even three of these disorders could coexist in some families. Furthermore, evidence from symptomatology and psychopharmacology also imply the existence of intrinsic connections between these three major psychiatric disorders. A total of 71,445 SNPs on chromosome 1 were genotyped on 119 SCZ, 253 BPD (type-I), 177 MDD cases and 1000 controls and further validated in 986 SCZ patients in the population of Shandong province of China. Outstanding psychosis genes are systematically revealed( ATP1A4, ELTD1, FAM5C, HHAT, KIF26B, LMX1A, NEGR1, NFIA, NR5A2, NTNG1, PAPPA2, PDE4B, PEX14, RYR2, SYT6, TGFBR3, TTLL7, and USH2A). Unexpectedly, flanking genes for up to 97.09% of the associated SNPs were also replicated in an enlarged cohort of 986 SCZ patients. F rom the perspective of etiological rather than clinical psychiatry, bipolar, and major depressive disorder could be subtypes of schizophrenia. Meanwhile, the varied clinical feature and prognosis might be the result of interaction of genetics and epigenetics, for example, irreversible or reversible shut down, and over or insufficient expression of certain genes, which may gives other aspects of these severe mental disorders.     

首发与复发抑郁症患者血清犬尿氨酸途径代谢物水平比较

背景 抑郁症发病机制至今尚未完全清楚,既往研究表明,犬尿氨酸途径（KP）在抑郁症发病中具有重要作用。目的 探讨首发和复发抑郁症患者血清KP代谢物水平的差异,并分析血清KP代谢物水平与抑郁症状严重程度的关系,为预防抑郁症复发提供参考。方法 连续纳入2016年11月-2018年12月在广州医科大学附属脑科医院门诊就诊的符合《精神障碍诊断与统计手册（第5版）》（DSM-5）诊断标准的136例抑郁障碍患者为研究组,其中首发组62例,复发组74例。同时纳入60例健康被试作为对照组。所有患者均接受汉密尔顿抑郁量表17项版（HAMD-17）评定。采用液相色谱串联质谱（LC-MS/MS）法检测抑郁障碍患者和对照组血清色氨酸（TRP）、犬尿氨酸（KYN）以及犬尿喹啉酸（KYNA）水平。采用偏相关分析考查抑郁症患者HAMD-17各因子评分及总评分与KP代谢物水平的关系。结果 与对照组相比,首发组和复发组TRP水平更低（t=-3.044、-4.477,P<0.05或0.01）,KYN/TRP更高（t=2.343、3.644,P<0.05或0.01）,差异均有统计学意义。与复发组相比,首发组和对照组KYNA水平更高（t=2.490、2.636,P<0.05或0.01）,KYNA/KYN更高（t=2.894、2.616,P均<0.01）,差异均有统计学意义。偏相关分析显示,首发抑郁症患者KYN/TRP与HAMD-17的焦虑/躯体化因子评分呈正相关（r=0.261,P<0.05）,KYNA/KYN与HAMD-17总评分及阻滞评分均呈负相关（r=-0.286、-0.282,P均<0.05）;复发抑郁症患者KYN/TRP与焦虑/躯体化评分呈正相关（r=0.280,P<0.05）。结论 首发和复发抑郁症患者血清KP代谢物水平存在差异,且复发患者KP代谢物水平异常更明显,KP代谢物可能是抑郁症辅助诊断及判断复发的潜在生物标志物。