中国北方汉族人群5-羟色胺2A受体基因的T102C多态性与重性抑郁症的关联研究

目的 探讨中国北方汉族人群重性抑郁症患者与5-羟色胺2A(5-HT2A)受体基因的T102C多态性之间的关系.方法 选取375例重性抑郁症患者作研究,以374名健康人作对照,应用聚合酶链式反应(PCR)扩增技术及直接测序法测定所有研究对象的5-HT2A受体基因T102C多态性的基因型和等位基因分布.结果 5-HT2A受体基因T102C多态性基因型和等位基因在患者组和对照组的分布差异无统计学意义(P>0.05);按照发病年龄(30岁为界)、有无家族史分层后,患者组与对照组间基因型和等位基因分布也无统计学意义(P>0.05).结论 未发现中国北方汉族人群5-HT2A受体基因T102C多态性与重性抑郁症存在关联.     

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受体基因多态性与抑郁症的关联研究

目的探讨5-羟色胺2A（5-HT2A）受体基因T102C和A-1438G多态性与抑郁症的关系。方法采用聚合酶链式反应（PCR）和限制性片断长度多态性（RFLP）技术检测123例抑郁症患者和122名健康对照的T102C和A-1438G基因多态性分布,病例-对照关联分析法分析两组间基因型频率和等位基因频率的差异。结果5-HT2A基因T102C多态性等位基因频率和A-1438G等位基因频率在患者组和对照组间的分布均有显著性差异（P〈0．05）,患者组C102等位基因频率（30．1％）明显低于对照组（41．0％）,在分层分析中,男性患者组中频率（26．2％）明显低于男性对照组（50．0oA）;患者组A-1438等位基因型频率（69．1％）明显高于对照组（56．6％）,A-1438等位基因在女性患者组中频率（69．1％）明显高于女性对照组（55．2％）。患者组中TT／AA（T102T／A-1438A）基因型组合频率（43．9％）明显高于对照组（20．5％）。结论5-HT2A基因T102C和A-1438G多态性可能与抑郁症的发病有关,其中C102等位基因可能是男性罹患抑郁症的保护因子,A-1438等位基因可能是抑郁症特别是女性抑郁症患病的危险因子,T102T和A—1438A基因型同时出现可能是抑郁症发病的重要危险因素。     

5-羟色胺2A受体基因多态性与利培酮治疗中国首发精神分裂症患者疗效关联

背景5-羟色胺2A受体基因已经证实为精神分裂症的候选易感基因,因为阐明其作为非典型抗精神病药物重要作用靶点减轻阴性症状已引起业界倍加关注.本研究试图探讨(1)5-HT2A受体基因T102C多态性在不同临床亚型之间等位基因和基因型频率的关系,(2)5-HT2A受体基因T102C在利培酮高剂量组和低剂量组之间基因型和等位基因分布频率的关系,(3)5-HT2A受体基因T102C多态性在治疗有效组与无效组之间的基因型和等位基因分布频率的关系,(4)5-羟色胺2A受体T102C基因多态性是否与中国首发精神分裂症患者利培酮疗效有关.方法对201例精神分裂症初发期患者分别进行利培酮治疗[3～5 mg/d,平均(3.2±1.3)mg/d],疗程8周.采用聚合酶链式反应扩增与限制性片段长度多态性(PCR-RFLP)技术检测5-HT2A受体基因T102C多态性.以临床亚型将精神分裂症患者划分为偏执型、瓦解型、未定型和其他型,分析不同临床亚型等位基因和基因型频率的差异;按服用利培酮剂量划分低剂量组(＜4 mg/d)和高剂量组(≥4 mg/d),经比较利培酮高剂量组和低剂量组的5-HT2A受体基因T102C基因型和等位基因分布频率差异性;同时以阴性和阳性症状量表(PANSS)总减分率＞50%有效,≤50%为无效以分析治疗有效组与无效组之间的基因型和等位基因分布频率差异有无显著性;以PANSS评定患者治疗前及治疗后2周、4周、6周和第8周末的精神症状,比较5-HT2A受体T102C各基因亚型与年龄、发病年龄、PANSS总分值、阳性症状基线分、阴性症状基线分、一般病理症状基线分、PANSS总减分率、阳性症状减分率、阴性症状减分率和一般病理症状减分率的差异.结果5-HT2A受体T102C基因型在患者组分布频率均符合H-W平衡定律(P＞0.05);不同临床诊断亚型精神分裂症患者等位基因和基因型频率无显著性差异(χ2=0.415,P=0.937;χ2=1.705,P=0.941);高剂量组与低剂量组之间的基因型和等位基因分布频率差异均无显著性(χ2=2.402,P=0.301;χ2=2.465,P=0.116);治疗有效和无效组的基因型和等位基因分布频率的差异无显著性(χ2=1.995,P=0.369;χ2=1.939,P=0.164);各基因型亚组的年龄、发病年龄及其病程差异均无显著性(P均大于0.05);但基因亚组A1/A1的治疗前PANSS总分(χ2=4.076,P=0.018)和阴性症状分(χ2=3.946,P=0.021)以及治疗结束PANSS总分减分率(χ2=4.036,P=0.019)和阴性症状减分率(χ2=3.876,P=0.022)均显著高于A1/A2及A2/A2基因型.结论(1)首发精神分裂症患者不同临床亚型5-HT2A受体基因T102C基因型和等位基因频率无显著差异.(2)利培酮高剂量组和低剂量组5-HT2A受体基因T102C基因型和等位基因分布频率没有显著性差异.(3)治疗有效组与无效组之间5-HT2A受体基因T102C基因型和等位基因分布频率也无显著性差异.(4)5-HT2A受体T102C Ai/A1基因亚型可能影响中国首发精神分裂症患者对利培酮的治疗效应.     

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。     

单相抑郁症与5-羟色胺2A受体基因多态性的关联研究

探讨中国汉族人群单相抑郁症患者与5－HT2A受体基因T102C多态性之间的关系，方法：采用AmP-RFLP方法，检测单相抑郁症患者对照组的5－HT2A受体基因频率分布。结果：单相抑郁症患者5－HT2A受体基因型频率，等位基因频率与对照组无明显差异。结论：本实验结果提示5－HT2A受体基因多态性与单相抑郁症患者未见明显相关，提示5－HT2A受体基因可能不是单相抑郁症发病的风险基因之一。     

抑郁症患者自杀行为与色氨酸羟化酶基因及单胺氧化酶A基因多态性的关联研究

目的:探讨抑郁症患者自杀行为与色氨酸羟化酶(TPH)、单胺氧化酶A(MAOA)基因多态性的相关性. 方法:符合中国精神障碍分类与诊断标准第3版抑郁症诊断标准患者212例,汉密尔顿抑郁量表评分≥17分,其中64例患者有自杀或自杀未遂行为(有自杀行为组),148例患者无自杀行为(无自杀行为组).采用聚合酶链式反应扩增及限制性片段长度多态性技术检测TPH、MAOA基因多态性,与抑郁症患者自杀行为进行关联分析. 结果:TPH基因型频数和等位基因频率上有自杀行为组与无自杀行为组差异有统计学意义(x2=6.058,P=0.048;x2=4.774,P=0.029),有自杀行为组A/A基因型和等位基因A频率分布显著高于无自杀行为组(P＜0.05).MAOA基因型频数和等位基因频率上有自杀行为组与无自杀行为组差异无统计学意义(x2=0.922,0.898;P均＞0.05). 结论:TPH基因多态性与抑郁症患者的自杀行为存在关联,MAOA基因多态性与抑郁症患者自杀行为可能无关联.     

5—羟色胺2A受体基因多态性与精神分裂症阳性症状相关性研究

目的:探讨中国汉族人群精神分裂症阳性症状患者与5-羟色胺2A受体基因T102C多态性之间的关系.方法:采用AmP-RFLP方法,检测精神分裂症患者对照组的5-HT2A受体基因频率分布.结果:精神分裂症阳性症状患者5-HT2A受体基因型频率,等位基因频率与对照组无明显差异,但有精神病家族史精神分裂症患者A1A1基因型频率,A1等位基因频率明显高于对照组.结论:实验结果提示,5-HT2A受体基因多态性与有精神病家庭史的精神分裂症阳性症状患者密切相关.A1等位基因可能是精神分裂症发病的风险基因之一.     

5-羟色胺2C受体基因多态性与抑郁症的关联

目的：探讨5-羟色胺2C（5-HT2C）受体基因-759C/T多态性与抑郁症发病机制之间的关系。方法：50例抑郁症患者作为研究组，30名正常者作为对照组，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）分别测定所有受试者的5-HT2C受体基因的基因型和等位基因，由于5-HT2C基因位于X性染色体，故对女性个体行基因鉴定，对男性患者只行半合子型鉴定。结果：与对照组相比，抑郁症组男性半合子型T、C分布频率分别为31.8%和68.2%，对照组为41.7%和58.3%，两组比较差异无显著性（χ^2=2.11，P〉0.05）。抑郁症组女性基因型TT、CC分布频率分别为46.4%和53.6%，对照组为16.7%和83.3%，无T、C杂合子基因型出现，两组比较差异有显著性（χ^2=20.4，P〈0.001）。抑郁症组T、C等位基因分布频率分别为42.3%和57.7%，对照组为22.9%和77.1%，两组比较差异有显著性（χ^2=8.72，P〈0.01）。结论：5-HT2C受体基因启动子区-759C/T单核苷酸置换多态性与女性伴自杀行为抑郁症的发病机制可能存在相关性，而男性患者的发病可能与此无关。     

5-羟色胺2A受体T102C基因多态性与卒中后抑郁的关联研究

目的 探讨5-羟色胺(5-HT)2A受体T102C基因多态性与卒中后抑郁(PSD)的关系,研究PSD的遗传发病机制.方法 选择珠江医院神经内科自2010年1月至2010年12月收治的汉族住院患者为研究对象,根据有无并发抑郁症将其分为PSD组(97例)及单纯卒中组(72例).采用PCR和限制性片断长度多态性(RFLP)技术测定2组患者5-HT2A受体T102C等位基因频率及基因型.结果 PSD组中突变型C等位基因频率(43.3％)低于单纯脑卒中组(59.0％),突变纯合子C/C基因型频率(20.6％)也低于单纯卒中组(34.7％),差异均有统计学意义(x2=0.179,P=0.004;x2=7.855,P=0.020).结论 5-HT2A受体T102C基因可能是PSD的易感基因,C等位基因是罹患PSD的保护因子.     

Efficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy

Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.     

Satellite cells and myonuclei in young and elderly women and men

The overall aim of this study was to assess the effects of aging on the satellite cell population. Muscle biopsies were taken from the tibialis anterior muscle of healthy, moderately active young (age range, 20-32 years; n = 31) and elderly (age range, 70-83 years; n = 27) women and men with comparable physical activity pattern. Satellite cells and myonuclei were visualized using a monoclonal antibody against neural cell adhesion molecule and counterstained with Mayer's hematoxylin. An average of 211 (range, 192-241) muscle fibers were examined for each individual. Compared with the young women and men, the elderly subjects had a significantly lower (P < 0.011) number of satellite cells per muscle fiber but a significantly higher (P < 0.004) number of myonuclei per muscle fiber. The number of satellite cells relative to the total number of nuclei [satellite cells/(myonuclei + satellite cells)] was significantly lower in the elderly than in the young women and men. These results imply that a reduction in the satellite cell population occurs as a result of increasing age in healthy men and women.     

Opiate and digitalis receptor assays distinguish between neuroexcitant and inactive organochlorines and between anesthetics and convulsants

Specific binding of [3H]naloxone to rat brain tissue in vitro was inhibited by the excitant organochlorinated insecticides (OCI), by ether (E) and octanol (OCT), and by the convulsant indoklon (IND) and its anesthetic isomer, isoindoklon (ISO). In the presence of 100 mM NaCl the inhibition of naloxone binding by E, OCT and ISO was greatly potentiated, whereas that by OCI and IND was attenuated. KCl (100 mM) was equally effective as NaCl on the action of anesthetics, but the effect of the excitant drugs was, in contrast to NaCl, unaffected by KCl. Specific binding of [3H]ouabain in the absence of Na, was depressed by anesthetics and enhanced by neuroexcitants. In the presence of NaCl, which by itself inhibits ouabain binding to brain, both anesthetics and excitants enhanced ouabain binding. DDE, a non-insecticidal analog of DDT, and the dimethyl derivative of the OCI, lindane, were inactive in the receptor assays. These observations point to a unique isolated system which responds consistently to anesthetic agents as a class and, in a different way, to neuroexcitant compounds.     

Learning and forgetting new names and objects in MCI and AD

We studied how subjects with mild cognitive impairment (MCI), early Alzheimer's disease (AD) and age-matched controls learned and maintained the names of unfamiliar objects that were trained with or without semantic support (object definitions). Naming performance, phonological cueing, incidental learning of the definitions and recognition of the objects were tested during follow-up. We found that word learning was significantly impaired in MCI and AD patients, whereas forgetting patterns were similar across groups. Semantic support showed a beneficial effect on object name retrieval in the MCI group 8 weeks after training, suggesting that the MCI patients’ preserved semantic memory can compensate for impaired episodic memory. The MCI group performed equally well as the controls in the tasks measuring incidental learning and recognition memory, whereas the AD group showed impairment in this respect. Both the MCI and the AD group benefited less from phonological cueing than the controls. Our findings indicate that word learning is compromised in both MCI and AD, whereas long-term retention of newly learned words is not affected to the same extent. Incidental learning and recognition memory seem to be well preserved in MCI.     

Necdin蛋白与神经元的生长分化

在神经系统 ,Necdin只在成熟神经元的细胞核中表达 ,可能与成熟神经元分裂静止状态的保持有关。近年的研究表明 ,Necdin是一种生长抑制蛋白 ,能与多种因子如SV4 0大T抗原 ,腺病毒E1A ,转录因子E2F1以及肿瘤抑制蛋白p5 3等结合 ,在功能上类似于成视网膜瘤蛋白Rb。necdin基因缺陷时 ,会引起脑内 ,特别是下丘脑神经元分化障碍。人类necdin基因位于PWS综合征的基因缺失区 ,可能与PWS的一些症状有关。本文从Necdin蛋白的基本概况 ,生物功能以及Necdin与疾病三个方面进行了综述     

Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics

We recently reviewed the status of peptide and nonpeptide agonists and antagonists for the V(1a), V(1b) and V(2) receptors for arginine vasopressin (AVP) and the oxytocin receptor for oxytocin (OT). In the present review, we update the status of peptides and nonpeptides as: (i) research tools and (ii) therapeutic agents. We also present our recent findings on the design of fluorescent ligands for V(1b) receptor localisation and for OT receptor dimerisation. We note the exciting discoveries regarding two novel naturally occurring analogues of OT. Recent reports of a selective VP V(1a) agonist and a selective OT agonist point to the continued therapeutic potential of peptides in this field. To date, only two nonpeptides, the V(2) /V(1a) antagonist, conivaptan and the V(2) antagonist tolvaptan have received Food and Drug Administration approval for clinical use. The development of nonpeptide AVP V(1a), V(1b) and V(2) antagonists and OT agonists and antagonists has recently been abandoned by Merck, Sanofi and Pfizer. A promising OT antagonist, Retosiban, developed at Glaxo SmithKline is currently in a Phase II clinical trial for the prevention of premature labour. A number of the nonpeptide ligands that were not successful in clinical trials are proving to be valuable as research tools. Peptide agonists and antagonists continue to be very widely used as research tools in this field. In this regard, we present receptor data on some of the most widely used peptide and nonpeptide ligands, as a guide for their use, especially with regard to receptor selectivity and species differences.     

Retrospective and prospective design and data

The study of the presentation, symptomatology and family characteristics of an exclusively adolescent sample of patients with borderline personality disorder (BPD) was undertaken. Twenty-four cases of borderline personality disorder, 20 females, 4 males, identified using chart review and meeting the criteria of the Diagnostic Interview for Borderlines (DIB) and DSM III-R, were matched with psychiatric controls. Adolescents with borderline personality disorder were found to have high rates of affective symptomatology with Axis I diagnosis of major depressive disorder - MDD (DSM-III-R), and high rates of interpersonal psychopathology, i.e., manipulation, devaluation, and a pervasive sense of boredom. The latter seem to be characteristic as for adults with borderline personality disorder. The families were particularly angry and volatile.     

Cortisol levels and depression in men and women using heroin and cocaine

Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are well documented in men using illicit drugs and/or infected with HIV; however, less is known about HPA function, or the health consequence of HPA dysfunction, in their female counterparts. People with depression exhibit hypercortisolemia, and depression is common in people with HIV or substance use problems. The current study investigated cortisol secretion in 209 demographically matched men and women, stratified by their HIV and drug use status. Self-reported depressive symptoms were evaluated using a standardized, validated questionnaire (CES-D). Women reported more depressive symptoms than men (p=.01). Male and female drug users exhibited higher cortisol concentrations (p=.03), and were more likely to report depressive symptoms (p=.04), than non-users. Depression was related to elevated cortisol concentrations for the study population (p=.03), and women with elevated cortisol concentrations were significantly more depressed than all other participants (p=.05). While it is unknown whether high cortisol concentrations precede depressive symptoms or vice versa, these data indicate that higher cortisol concentrations are associated with depressive symptoms in heroin and cocaine users, and that this association is more pronounced in women than men. HIV status did not act in an additive or synergistic way with drug use for either cortisol or CES-D measures in the current study. Unique therapies to treat the endocrine and mental health consequences of illicit drug use in men and women deserve consideration as depressive symptoms, and high cortisol concentrations associated with depressive symptoms, differ by gender.     

Dissociation and Counterdissociation: Nuanced and Binary Perceptions of Good and Evil

Dissociated experiences are often communicated to analysts. Clinicians may absorb patients' dissociation, thereby creating “counterdissociated” states. Counterdissociation contributes to binary thinking in the analyst similar to black- and-white thinking commonly seen in patients' dissociated states. This can have both positive and negative effects: Counterdissociation may help therapists identify with patients' experience, thereby cementing the therapeutic bond. If analysts remain counterdissociated, however, patients may remain dissociated. As analysts identify their counterdissociation, they may gain insight into patients' needs for dissociation. As they overcome counterdissociation, patients may concurrently overcome dissociation. This allows both to have a more nuanced view of inner experience. With two extended case studies of sexually abused men, this article tracks how an analyst deals with counterdissociation created through intimate contact with dissociated positive and negative introjects of victimizers, thus forming identifications or overidentifications with the patients' abused parts.     

Hemodynamic and serum cardiac markers and risk of cognitive impairment and dementia

Introduction

Cardiac function is a key player in maintaining energy homeostasis in the brain. Heart failure is closely related to higher risk of neurocognitive disorders. Recent evidence shows that this relationship might not be limited to patients with advanced heart failure, and even suboptimal cardiac functioning is associated with accelerated brain aging. Hence, hemodynamic and serum cardiac markers may provide valuable information about the risk of dementia.