胰岛素样生长因子1、载脂蛋白酶E基因多态性与阿尔茨海默病关系的研究

目的探讨河南省汉族人群胰岛素样生长因子1(insulin like growth factor 1,IGF-1)基因rs972936位点多态性、载脂蛋白酶E(Apo E)基因多态性与阿尔茨海默病(Alzheimer’s disease,AD)之间的相关性。方法选取58例AD患者和126例年龄、性别相匹配的健康对照(ND)者为研究对象,柱层析法提取外周血基因组DNA,采用PCR和基因测序技术检测IGF-1基因rs972936位点及Apo E基因型多态分布,并进行对比分析。结果与ND组比较,AD组IGF-1基因rs972936位点3种基因型分布总体差异有统计学意义(χ~2=6.108,P=0.047),其中AD组中GG基因型的频率高于对照组(70.7%51.6%,χ~2=5.935,P=0.015),G等位基因频率明显高于健康对照组(χ~2=6.502,P=0.011);AD组Apo Eε4等位基因频率可能增加AD的患病风险(OR=2.872,95%CI 1.542~5.351)(P=0.001);Apo Eε4等位基因不影响IGF-1基因rs972936位点的基因型或等位基因的分布频率(P0.05)。结论 IGF-1基因rs972936位点多态性与河南汉族人群AD的发病可能有相关性,其中GG基因型、G等位基因可能是AD发病的独立于Apo Eε4等位基因的危险因素。Apo Eε4等位基因是散发性AD的主要危险因素。     

脑啡肽酶基因多态性与散发性阿尔茨海默病的关系研究

目的探讨脑啡肽酶(neprilysin,NEP)基因单核苷酸多态性与中国北方汉族散发性阿尔茨海默病(sporadic Alzheimer’s disease,SAD)的关系。方法临床确诊的99例中国北方汉族SAD患者及109例正常对照,提取外周血基因组DNA,聚合酶链反应-限制性片段长度多态性结合DNA直接测序法确定NEP基因rs989692位点及rs6776185位点基因型,分析上述两个位点单核苷酸多态性与AD的关系。结果 AD组和正常对照组NEP基因rs989692位点各等位基因频率及基因型分布无显著性差异(P>0.05);AD组NEP基因rs6776185位点A等位基因频率显著高于正常对照组(88.9%vs 81.2%,P=0.029),AA基因型频率显著高于正常对照组(80.8%vs 67.0%,P=0.024);携带A等位基因者,发生AD的风险是不携带A等位基因者的1.85倍(OR=1.85,95%CI 1.07~3.20);经载脂蛋白E基因(apolipoprotein E,Apo E)ε4等位基因及年龄分层比较,携带ε4基因及年龄<75岁组,AD组A等位基因及AA基因型分布频率仍明显高于正常对照组(P<0.05)。结论 NEP基因rs6776185位点A等位基因和AA基因型可能是中国北方汉族人群SAD的危险因素,可使AD发病年龄提前,并与Apo Eε4等位基因可能具有协同作用。     

卒中后抑郁与rs1187929关联分析

目的研究酪氨酸激酶B基因多态性位点rs1187929与卒中后抑郁(post-stroke depression, PSD)之间的关联性。方法采用病例对照研究,共有78例卒中后抑郁组(PSD组)和112例卒中后非抑郁组(NPSD组)纳入此项研究。患者均使用汉密尔顿抑郁量表(HAMD)进行评估,以确定抑郁症严重程度,并完成分组(PSD组和NPSD组),所有PSD组患者符合美国精神障碍分类与诊断标准第五版(DSM-V)。应用PCR产物纯化及Sanger双脱氧终止测序法测序完成入组患者TrkB基因的rs1778929位点基因分型。结果 PSD组78人,NPSD组112人,总患病率为41.05%;男性患病率为42.86%,女性患病率为38.82%,两者差异无统计学意义(χ~2=0.316,P=0.57);PSD组CC、CT、TT频率分别为是26.92%、48.72%、24.36%;NPSD组CC、CT、TT频率分别为是42.86%、45.54%、11.61%。以CC基因型为参照,纯合突变型TT的相对危险度为3.341(χ~2=7.347,P=0.007,OR=3.341),PSD组中T等位基因频率为48.72%高于NPSD组T等位基因频率(34.38%),等位基因T相对于等位基因C相对危险度为1.814(χ~2=7.798,P=0.005,OR=1.814)。纯合突变型TT及等位基因T是卒中后抑郁的危险因素(P0.05)。结论在中国皖南地区汉族人群中,rs1778929位点基因多态性与PSD的发生具有一定关联性,未来需要进一步的研究来确认我们的发现。     

急性缺血性卒中ApoEε4等位基因与血脂和预后相关性研究

目的探讨急性缺血性卒中患者载脂蛋白E(Apo E)ε4等位基因与血脂水平及预后的关系。方法据Apo E基因分型和美国国立卫生研究院卒中量表(NIHSS)评分,将786例急性缺血性卒中患者分为携带Apo Eε4等位基因组和不携带Apo Eε4等位基因组,以及预后良好组(NIHSS评分≤10分)和预后不良组(NIHSS评分10分),分别采用单因素和前进法多因素Logistic回归分析筛查影响携带Apo Eε4等位基因急性缺血性卒中患者预后的不良因素。结果携带Apo Eε4等位基因组患者血清低密度脂蛋白胆固醇和载脂蛋白B表达水平高于不携带Apo Eε4等位基因组[(3.25±0.85)mmol/L对(3.00±0.83)mmol/L,P=0.008;(1.20±0.30)mmol/L对(1.09±0.25)mmol/L,P=0.000]。前进法多因素Logistic回归分析仅入院时NIHSS评分和出院时改良Rankin量表评分是影响急性缺血性卒中患者预后的主要危险因素(均P=0.000),而Apo Eε4等位基因并非其影响因素(P=0.343)。结论携带Apo Eε4等位基因的急性缺血性卒中患者血清低密度脂蛋白胆固醇和载脂蛋白B表达水平升高,但Apo Eε4等位基因并非预后不良的预测指标。     

四氢叶酸还原酶基因C677T突变与阿尔茨海默病有关

目的　调查一些候选基因的多态性与阿尔茨海默病 (Alzheimer disease,AD)发病的关系。方法　利用Roche公司 Roche Molecular System(RMS)提供的同时检测多种基因多态性的方法 ,检测 1 5种与脂代谢、血压和血栓形成相关基因的 2 9个多态性位点的基因型 ,比较 3 7例 AD患者和 84名健康人在这些等位基因频率方面的差别。结果　 AD组载脂蛋白 E(Apo E)常见基因多态性 (ε2、ε3、ε4)和甲烯四氢叶酸还原酶 (MTHFR)基因的 C677T多态性分布与健康对照组相比有显著不同。Apo Eε4和 MTHFR基因的 677T等位基因的频率在AD组显著高于对照组 (P <0 .0 5 )。结论　 MTHFR基因的 677T等位基因可能是除 Apo Eε4外另一个与 AD发病有关的遗传危险因素     

脂肪酰胺水解酶基因rs324420多态性与抑郁障碍及抗抑郁疗效的关系

目的:探讨脂肪酰胺水解酶(FAAH)基因rs324420多态性与抑郁障碍及抗抑郁疗效的关系。方法:采用聚合酶链反应技术检测219例抑郁障碍患者(患者组)及411名健康对照者(对照组)FAAH基因rs324420多态性;患者组中98例完成8周抗抑郁药物治疗并分别于治疗前及治疗后2、4、6、8周采用17项汉密尔顿抑郁量表(HAMD-17)进行评估;治疗后HAMD≤7分为界将患者分为缓解亚组51例与非缓解亚组47例。结果:患者组与对照组FAAH基因rs324420基因型及等位基因频率差异无统计学意义。缓解亚组与非缓解亚组间rs324420基因型频率差异无统计学意义,A等位基因频率明显高于非缓解组(χ~2=4.28,P=0.039)。不同基因型患者间,AA基因型患者治疗后2、4、6、8周HAMD总分低于AC、CC型,减分率高于AC、CC型,但差异无统计学意义。结论:FAAH基因rs324420多态性可能与抗抑郁药的疗效相关,A等位基因及AA基因型携带者的抗抑郁疗效较好。     

中国人群ApoE基因多态性与迟发性阿尔茨海默病关系的Meta分析

目的探讨中国人群载脂蛋白E(Apo E)基因多态性与迟发性阿尔茨海默病的关系。方法以载脂蛋白E基因(Apo E)、迟发性阿尔茨海默病(late onset Alzheimer's disease)、基因多态性(polymorphism)、China和Chinese等中英文词组,检索美国国立医学图书馆生物医学信息检索系统、荷兰医学文摘、EBSCO-CINAHL、Cochrane图书馆,以及中国生物医学文献数据库、中国知网中国知识基础设施工程、万方数据库等近20年发表的关于中国人群Apo E基因多态性与迟发性阿尔茨海默病关系的病例对照研究,采用Newcastle-Ottawa量表(NOS)进行文献质量评价,Rev Man 5.0统计软件进行Meta分析。结果共获得249篇文献,经剔除重复和不符合纳入标准者并补充相关文献,最终纳入13篇高质量临床研究(NOS评分≥5分),共3372例受试者(迟发性阿尔茨海默病患者1360例、对照者2012例)。Meta分析显示:携带Apo Eε4等位基因者发生迟发性阿尔茨海默病的风险高于携带Apo Eε3等位基因者(OR=3.710,95%CI:2.960~4.640;P=0.000);表现为Apo Eε3/ε4(OR=3.160,95%CI:2.390~4.180;P=0.000)、Apo Eε2/ε4(OR=3.410,95%CI:2.160~5.380;P=0.000)和Apo Eε4/ε4(OR=16.400,95%CI:8.200~32.810;P=0.000)基因型者发生迟发性阿尔茨海默病的风险高于Apo Eε3/ε3基因型者。结论携带Apo Eε4等位基因,以及Apo Eε3/ε4、Apo Eε2/ε4和Apo Eε4/ε4基因型是中国人群发生迟发性阿尔茨海默病的危险因素。     

ApoE基因多态性与血管性痴呆关系的实验研究

目的　探讨 Apo E基因多态性与血管性痴呆 ( Va D)的相互关系。方法　应用聚合酶链反应 -限制性片段长度多态性 ( PCR-RFLP)技术 ,检测脑卒中后 Va D组与未发生 Va D的对照组患者的 Apo E基因型分布及出现频率。结果　 Apo E基因的ε4 / 4基因型 ,在 Va D组的出现频率明显高于未发生 Va D的对照组 ( P<0 .0 5 ) ,其余各基因型的出现频率 ,两组间差异无显著性 ( P>0 .0 5 )。结论　Apo E基因的 ε4 / 4基因型与 Va D的发生密切相关 ;等位基因ε4可能是 Va D的一种遗传易感性因子。     

载脂蛋白E基因多态性与脑梗死的相关性分析

目的　探讨载脂蛋白 E基因多态性与脑梗死的关系。方法　通过聚合酶链反应 -限制性片段长度多态性 (PCR- RFL P)分析结合 DNA直接银染技术检测 6 6例脑梗死 (CI)患者的载脂蛋白 E(Apo E)基因型 (其中家系中有明确脑梗死先证者的家族聚集性脑梗死 (FMACI)亚组 2 6例 ,家系中无脑卒中史的非家族聚集性脑梗死 (NF-MACI)亚组 4 0例 ) ,并与 90例健康对照组比较 ,同时检测血脂、脂蛋白 (a) [L P(a) ]及部分载脂蛋白。结果　脑梗死组ε3/4基因型频率明显高于对照组 (P<0 .0 1) ,ε3/3基因型频率明显低于对照组 (P<0 .0 1) ;两脑梗死亚组之间的ε3/4/ε3/3基因型频率虽有上升 /下降趋势 ,但未发现明显的统计学差异 ;FMACI组高密度脂蛋白 (HDL )水平明显低于 NFMACI组 (P<0 .0 5 )。结论　 Apo E基因多态性与脑梗死的发生有关 ,ε4等位基因是脑梗死的易感因子 ,ε3等位基因对脑梗死的发生有保护作用 ;Apo E基因多态性和 HDL水平双重作用于家族聚集性脑梗死的发生。     

心血管危险因子与广西汉族迟发性阿尔茨海默病之间的相关性研究

目的　研究心血管危险因子载脂蛋白 E( Apo E)、载脂蛋白 C- ( Apo C- )以及低密度脂蛋白受体相关蛋白 ( LRP)与汉族迟发性阿尔茨海默病 ( LOAD)之间的相关性。方法　应用 PCR-RFLP技术或直接通过 PCR方法 ,分析了 1 5 6例正常老年人、79例 LOAD Apo E、Apo C- 与 LRP基因型。结果　在 LOAD患者组和正常对照组中 ,Apo Eε4等位基因出现的频率分别为 1 7.7%、5 .7% ,其间差异有显著性 ( x2 =1 5 .75 0 ;P=0 .0 0 1 ,OR=3 .3 96,95 % CI =1 .80 8～ 6.3 79) ;Apo Eε3等位基因频率分别为 76.0 %、84% ,前者低于后者 ( x2 =4.43 9;P=0 .0 3 5 ,OR=1 .65 9,95 % CI =1 .0 3 3～ 2 .665 ) ;LRP、Apo C- 基因的基因型频率和等位基因频率在 LOAD与对照组之间差异无显著性 ( P >0 .0 5 )。结论　 Apo Eε4等位基因是 LOAD的遗传危险因子 ,Apo Eε3等位基因则可能有保护效应 ;此研究未能证明 Apo C- 基因变异和 LRP基因 C766T多态性与 LOAD有相关关系     

Comparison of depression symptoms between primary depression and secondary-to-schizophrenia depression

Objectives: This study exclusively aimed to clinically assess which symptom pattern discriminates primary depression from depression-secondary to-schizophrenia.

Methods: A total of 98 patients with primary depression and 71 patients with secondary-to-schizophrenia depression were assessed for identifying the clinical phenomena of depression. Diagnosis of schizophrenia was confirmed by Mini International Neuropsychiatric Interview. Each participant was, however, assessed by Patient Health Questionnaire-9 as well as Calgary Depression Scale for Schizophrenia (CDSS) for possible concurrent depressive symptoms.

Results: Depressed mood, loss of interest, reduced energy and pathological guilt were more common in primary depression, whereas sleep disturbance and guilty ideas of reference were more amounting towards the diagnosis of depression secondary-to-schizophrenia.

Conclusions: It is clinically hard to differentiate primary from secondary-to-schizophrenia depression, especially in the absence of obvious psychotic symptoms. However, the classical symptoms of depression like subjective depressed mood, anhedonia, reduced energy and pathological guilt are more prominent in the primary depression.     

Cerebrovascular disease basis of depression: post-stroke depression and vascular depression

The close association between cerebrovascular disease and depression has been known for more than a century, yet much of the progress in understanding the cerebrovascular basis of depression in late life has been spurred by development of two concepts: 'post-stroke depression' and 'vascular depression'. The purpose of this review is to examine the epidemiology, diagnostic features, course, pathophysiology and prognosis of post-stroke depression and vascular depression, to highlight their common features, and to contrast the distinct aspects of these two subtypes of geriatric depression.     

Simultaneous depression

Five different strategies were used to detect cases in which depressed behaviour occurred in both spouses within the same time period (simultaneous depression). Among 7068 references on depression in the literature, only one referred to a case of simultaneous depression. Of 8008 registered individuals hospitalized in Norway from 1961-1971, none had simultaneous depression. A search of the total Scandinavian population (17.5 million) revealed only one case. The authors suggest that the result is caused by specific communication values attached to depressed behaviour and compensatory mechanisms in depressed couple relationships. The need for assessments that include the identified patient's family system in the planning of treatment for depression is discussed, with the aim to prevent cases of successful mistreatment in which the identified patient is cured while the spouse becomes depressed or commits suicide.     

Atypical depression

I have indicated that the concept of atypical depression is as confusing as the concept of atypical psychosis when discussing the “schizophrenias.” Atypical depressions must be distnguished from the typical picture of depressive experience congruent with depressive behavior and biologic or vegetative symptoms.I have divided atypical depression into two major subgroups:Atypical depressions characterized by depressive experience in the absence of biobehavioral symptoms. These atypical depressions have been identified by both British and American psychiatrists and seem to be depressions that are successfully treated by MAO inhibitors.Atypical depressions characterized by biobehavioral symptoms in the absence of depressive experience. The classical patients here include various pain patients, and patients with neurotic symptoms including presentation with anxiety as a major symptom. These patients often respond to antidepressant medication, either tricyclic antidepressants or MAO inhibitors. The third kind of patient presents with neither depressive experience nor biobehavioral symptoms or signs, and responds to antidepressive medication. I do not feel these patients should be diagnosed as atypical depressives. These patients should be considered as undiagnosed patients who have responded to the nonspecific affects of antidepressant medications.By using the diagnostic outline I have discussed, it becomes possible to highlight the typical depressions and compare and contrast them to two major subtypes of atypical depression. In this way, we can avoid confusion when we use the term depression and when we diagnose depressive syndromes.     

Atypical bipolar II depression compared with atypical unipolar depression and nonatypical bipolar II depression

Aim of the study was to find out whether atypical bipolar II depression was distinct from both atypical unipolar depression and nonatypical bipolar II depression. Seventy-nine consecutive atypical bipolar II depressed outpatients were compared with 42 consecutive atypical unipolar depressed outpatients and with 53 consecutive nonatypical bipolar II depressed outpatients. Among the variables studied (age at intake, age at onset, female gender, duration of illness, psychosis, comorbidity, chronicity, recurrences, severity), age at intake and onset were significantly lower in the atypical bipolar II group than in the other groups. The other variables, apart from psychosis, were not significantly different. Findings suggest that atypical bipolar II depression may have an age at onset different from that of atypical unipolar depression and nonatypical bipolar II depression. As different ages at onset may identify distinct subtypes of depression, this finding might suggest that atypical bipolar II depression may be distinct from both atypical unipolar depression and nonatypical bipolar II depression.     

Lithium-responsive depression

Lithium carbonate has proven effective in controlling acute mania and in reducing the frequency and severity of recurrence of both mania and depression in bipolar patients.^1–4 Several studies indicate that lithium is effective in certain unipolar depressions, but the results are inconsistent. Davis's recent review concluded that the magnitude of improvement associated with lithium was at least as great in unipolar as in bipolar depression.⁴ Mendels⁵ and Noyes et al.,⁶ using different approaches, noted that patients diagnosed as bipolar respond more frequently to lithium than do those diagnosed as unipolar. The purpose of this article is to present the problems in clarifying the kinds of depressions which do respond, and clinical guidelines for recognizing likely lithium responders.     

Post-stroke depression

Post-stroke depression (PSD) is among the most common emotional disorders afflicting stroke sufferers. Approximately one third of stroke survivors experience an early or later onset of depression. PSD impedes the rehabilitation and recovery process, jeopardizes quality of life and increases mortality. Diagnosis of PSD is challenging in the acute and chronic aftermath. Therefore, it often remains unrecognized and/or undertreated. The interaction between depression and stroke is very complex and the pathophysiological mechanisms have not as yet been fully elucidated, although an interaction between anatomical and psychosocial factors may be important in PSD development. Neurochemical changes and clinical findings are similar to endogenous depression. PSD is potentially treatable, although no conclusive benefits of antidepressant agents and nonpharmacological interventions have been observed. The efficacy of preventive strategies in PSD remains essentially undetermined.