孕期焦虑情绪与5-HTTLPR多态性及产后抑郁症探讨

目的对中国汉族人群中孕期焦虑情绪与5-HTTLPR多态性及产后抑郁症关系的探讨。方法应用聚合酶链式反应(PCR)扩增技术和限制性片段长度多态性(RFLP)对在妊娠36~38周施测抑郁情绪测定量表(HAD)的145例正常孕期情绪人群(对照组)和155例孕期焦虑情绪患者(试验组)中观察5-HTTLPR多态性的分布,并探讨了他们与产后抑郁症之间的关系。结果在受试人群5-HTTLPR在两组中的分布差异均有显著性,产后抑郁症组的5-HTTLPR的SS基因型及S等位基因频率均高于对照组(P<0.05),孕期有焦虑情绪的产妇较无焦虑情绪的产妇产后抑郁症的发病率高(P<0.05)。结论中国广州地区汉族人群中5-HTTLPR多态性与产后抑郁症分布存在差异,5-HTTLPR中的S等位基因可能是产后抑郁症的易感基因,产妇产后抑郁症的发生可能与其孕期的焦虑情绪有关。     

5-羟色胺转运体基因启动子区多态性与海洛因依赖的关联分析

目的:探讨云南省汉族海洛因依赖患者5-羟色胺转运体基因启动子区多态性(5-HTTLPR)和海洛因依赖的关联关系。方法:采用病例-对照研究设计,运用聚合酶链式反应检测云南省217例海洛因依赖者和102例正常对照的5-HTTLPR。探讨5-HTTLPR与海洛因依赖是否相关。结果:海洛因依赖和正常对照两组间基因型频率及等位基因频率分布无显著性差异。结论:5-HTTLPR的基因多态性与海洛因依赖无统计学关联,5-HTTLPR可能不是海洛因依赖的易感基因。     

攻击行为与儿茶酚胺氧位甲基转移酶基因多态性研究

目的：探讨精神疾病伴发的攻击行为与儿茶酚胺氧位甲基转移酶(catechol-0-methyltransferase，COMT)基因多态性的关系。方法：研究组(有攻击行为)43例，疾病对照组41例。健康对照组156例。采用聚合酶链反应-限制性片段长度多态性(PCR-KFLP)技术分析COMT基岗多态性。结果：①研究组的COMT基因型与健康对照组之间的差异有统计学意义。②研究组与疾病对照组之间的差异无统计学意义。③等位基因A携带患者在疾病症状(敌对性、情感平淡)及认知功能方面存在差异。结论：精神疾病患者其COMT基因多态性及等位基因分布频率与健康对照者不同。等位基因A携带患者的症状表现不同。攻击行为与COMT基因多态性无相关性。     

住院精神分裂症患者发生攻击行为的因素及对策

目的探讨住院精神分裂症患者发生攻击行为的因素，预测有攻击行为倾向的病例，提出防范对策。方法对我院5年来具有攻击行为的精神分裂症患者105例资料进行回顾性分析。结果精神分裂症患者攻击行为发生率高达15．8％，入院1周内最多见，攻击行为针对工作人员的占首位，攻击行为与患者年龄、职业、文化、既往史、临床特征、个性特点密切相关，与强制体检、治疗等负性刺激为诱发因素。结论做好人院评估并实施预见性护理，严格执行安全制度，建立健康教育、心理支持、行为干预为一体的护理模式是防范暴力行为发生的重要措施。     

某区居民5-HTTLPR基因多态性与血糖、三酰甘油、胆固醇的相关性研究

目的探讨湘潭城区普通中老年居民5-羟色胺转运体启动子区基因多态性(5-HTTLPR)与血清葡萄糖、胆固醇、三酰甘油的相关性。方法选取参加健康体检的湘潭中老年无糖尿病志愿者167例,检测其空腹血清葡萄糖、三酰甘油及胆固醇水平,采用聚合酶链反应(PCR)技术检测5-HTTLPR基因多态性,分析5-HTTLPR基因多态性与血糖、总胆固醇及三酰甘油之间的相关性。结果中老年男性血清葡糖糖浓度在5-HTTLPR基因型SS、SL、LL中有明显差异(P=0.028<0.05),用Nemenyi检验组间两两比较,SS型基因携带者的葡萄糖浓度水平比SL型基因携带者高(P=0.045);男性S等位基因携带者葡萄糖水平比L等位基因携带者高,P=0.011<0.05,有统计学意义。结论5-HTTLPR基因多态性与血清葡萄糖存在关联性,而与血清胆固醇及三酰甘油无关。     

精神分裂症患者的攻击行为特征及其临床护理

目的了解精神分裂症患者发生攻击行为的特征,探讨其临床护理效果。方法调查81例伴攻击行为的精神分裂症患者（研究组）的一般资料、量表资料、攻击行为表现,实施2周护理干预,并与239例不伴攻击行为分裂症患者作对照。结果攻击行为发生率为25．3％。既往有攻击行为史、病前性格不良、初发年龄较早、精神病家族史阳性率较高是发生攻击行为精神分裂症患者的主要特征。采取有针对性的护理干预措施效果较好。结论加强治疗和监护及相应的护理干预,有利于防范精神分裂症患者攻击行为的发生。     

精神病患者对医护人员的攻击行为特征分析

目的了解住院精神分裂症患者对医护人员攻击行为的临床特征。方法对38例有攻击行为患者进行临床分析。结果攻击行为发生以男性、中年、工人、农民及偏执型最常见。发生时间以上班人数少的中、晚班为主。攻击方式多种多样。受攻击对象则以经常与患者密切接触的女护士首当其冲。工作人员的态度与攻击行为的发生密切相关。结论应采取相应的自防措施,减少攻击行为的发生。     

分裂症患者的攻击行为与5-羟色胺和胆固醇水平的关系

研究发现精神分裂症的攻击行为占精神障碍的39%,其中涉及体力攻击者占11%[1]。5-HT功能下降会减少冲动行为的抑制,会刺激引出冲动行为。有研究发现血清脂质与行为有关,攻击行为的精神病患者血清胆固醇水平较低[2]。本研究将探讨精神分裂症患者的血浆5-HT水平和血清胆固醇水平与     

280例精神分裂症患者攻击行为分析与护理

精神分裂症患者常发生攻击他人危害社会的不良行为．本文调查了我院精神科1990－06～1997－05经CCMD－11或DSM－11确诊为精神分裂症的280例病人，对攻击行为的相关因素进行了分析，对护理措施进行了探讨，现报道如下．1临床资料1.1攻击发生率280例病人共发生攻击行为57例，占全部调查病例的20．36％．1．2性别与攻击行为分析见表1．年龄比敦P＜001性别比较P＞005表1结果可以看出年龄＜3o岁者攻击行为远为多见，与年轻自知能力差，性格不稳定有关，但性别间无显著伯差异．1．3文化程度及家族史与攻击行为分析见表2文化程度比较P＜001有无…     

闽南地区人群NPAS3基因表达及多态性与精神分裂症的关联

探讨NPAS3基因表达及多态性在闽南地区正常人群与精神分裂症人群中的差异。随机选择闽南地区30例正常人、30例精神分裂症患者作为研究对象,提取外周血RNA,利用RT-PCR检测NPAS3基因的表达;提取外周血DNA后利用特异性引物对其进行扩增,测序后基因分型。RT-PCR结果表明NPAS3基因表达在2组中无显著性差异（P＞0.05）,rs10483442位点经基因分型发现只有CC一种基因型,rs207474631位点经基因分型发现也只有CC一种基因型,均未发现其他基因型。 NPAS3基因表达以及rs10483442和rs207474631位点在闽南地区正常人群和精神分裂症人群中可能不存在差异。     

Serotonin transporter gene-linked polymorphic region (5-HTTLPR) influences decision making under ambiguity and risk in a large Chinese sample

Risky decision making is a complex process that involves weighing the probabilities of alternative options that can be desirable, undesirable, or neutral. Individuals vary greatly in how they make decisions either under ambiguity and/or under risk. Such individual differences may have genetic bases. Based on previous studies on the genetic basis of decision making, two decision making tasks [i.e., the Iowa Gambling Task (IGT) and Loss Aversion Task (LAT)] were used to test the effect of 5-HTTLPR polymorphism on decision making under ambiguity and under risk in a large Han Chinese sample (572 college students, 312 females). Basic intelligence and memory tests were also included to control for the influence of basic cognitive abilities on decision making. We found that 5-HTTLPR polymorphism significantly influenced performance in both IGT and LAT. After controlling for intelligence and memory abilities, subjects homozygous for s allele had lower IGT scores than l carriers in the first 40 trials of the IGT task. They also exhibited higher loss aversion than l carriers in the LAT task. Moreover, the effects of 5-HTTLPR were stronger for males than for females. These results extend the literature on the important role of emotion in decision making under ambiguity and risk, and shed additional lights on how decision making is influenced by culture as well as sex differences. Combining our results with existing literature, we propose that these effects might be mediated by a neural circuitry that comprises the amygdala, ventromedial prefrontal cortex, and insular cortex. Understanding the genetic factors affecting decision making in healthy subjects may allow us to better identify at-risk individuals, and better target the development of new potential treatments for specific disorders such as schizophrenia, addiction, and depression.     

Reduced aggression in mice lacking the serotonin transporter

Abstract Rationale. The possible role of γ-aminobutyric acid (GABA) in human aggression was evaluated by administering baclofen, a GABA-B agonist and comparing the effects on laboratory measures of aggression and escape among subjects with and without a history of conduct disorder. Methods. Twenty male subjects with a history of criminal behavior participated in experimental sessions, which measured aggressive and escape responses. Ten subjects had a history of childhood conduct disorder (CD+) and ten control subjects had no history of CD. Aggression was measured using the point subtraction aggression paradigm (PSAP), which provides subjects with aggressive, escape, and monetary-reinforced response options. Results. Acute doses (0.07, 0.14 and 0.28 mg/kg) of baclofen had remarkably different effects on aggressive responses among CD+ subjects relative to control subjects. Aggressive responses of CD+ subjects decreased, while aggressive responses of control subjects increased following baclofen administration. Baclofen decreased escape responses for both CD+ and control subjects. No changes in monetary-reinforced responses were observed, indicative of no central nervous system stimulation or sedation. Conclusions. The GABA-B agonist baclofen suppressed aggressive responses in subjects with a history of childhood CD, while producing the opposite effect in control subjects. These suggest a possible unique role for GABA in the regulation of aggression in CD+ population. Electronic Publication     

Influence of olfactory bulbectomy and the serotonergic system upon intermale aggression and maternal behavior in the mouse

Biochemical parameters in the brains of olfactory bulbectomized male and female mice were studied in two experiments, followed by three experiments in which 5-HTP was injected into bulbectomized males and females to try to block abnormal behaviors. In Experiment 1 bulbectomized male and female mice had significantly less tryptophan hydroxylase in their brains than did sham controls. Neither 5-hydroxytrptophan decarboxylase nor tyrosine hydroxylase activity was affected. In Experiment 2 the rate of synthesis of 5-HT was significantly less in bulbectomized males and females. Since bulbectomy leads to increased pup killing by female mice, the objective of Experiments 3 and 4 was to see whether the injection of 5-HTP into bulbectomized females could block this behavior. The incidence of pup killing was not influenced, but in both studies the latency to kill was significantly prolonged. Olfactory bulbectomy eliminates aggressive behavior in male mice, and the purpose of Experiment 5 was to determine whether 5-HTP treatment could restore normal levels of aggression. No significant effect was found. The data suggest that a dual mechanism is needed to explain the behavioral abnormalities seen in the two sexes; the mechanism in the female appears to be serotonergic while that in the male is still unknown.     

Serotonin transporter characteristics in lymphocytes and platelets of male aggressive schizophrenia patients compared to non-aggressive schizophrenia patients

A large body of literature indicates that disturbances of central serotonin (5-HT) function play an important role in aggressive behavior. Results from open-label and placebo-controlled trials as well as the reported inverse relationship between 5-HT function and aggression in human subjects, suggest that reduced 5-HT activity is associated with aggressive behavior. The activity of the 5-HT transporter (5-HTT), as determined by [³H]5-HT uptake to blood lymphocytes, was measured in 20 currently aggressive and 20 non-aggressive male schizophrenia patients. In addition, the pharmacodynamic characteristics of platelet 5-HTT were assessed by [³H]citalopram binding.

There were no significant differences in the density (B_max) of platelet [³H]citalopram binding sites between the two groups. Similarly, the dissociation constant (K_d) values were indistinguishable. The maximum uptake velocity (V_max) of [³H]5-HT to fresh lymphocytes and the K_m values of the 5-HT to the transporter were significantly higher in currently aggressive compared to the non-aggressive schizophrenia patients. The association of high V_max values with current aggressive behavior provides further support to the involvement of the 5-HTT in aggressive behavior as well as to the efficacy of 5-HTT blockers in the control of aggression. The role of the various components of the serotonergic system in the pathophysiology and treatment of aggressive behavior in schizophrenia needs to be further evaluated.     

Effects of chronic d-amphetamine on social behavior of the rat: Implications for an animal model of paranoid schizophrenia

Hooded rats in a social colony were given increasing daily doses of d-amphetamine up to 8 mg/kg. Time-lapse 16 mm cinematographically recorded behavior was analyzed for the following: grooming, feeding, sex, sleeping, resting, stereotypy, agonistic behavior, muricidal activity, and the location and movement of each rat. Subordinant rats receiving d-amphetamine actively withdrew from social interactions by retreating to strategically defensible locations in the environment. They remained hypervigilant of other rats and overreacted to their approaches by either fleeing or by defensively rearing and boxing. On the other hand, when the dominant rat received the maximum dose, it seemed totally oblivious to the other rats. The responses to drug treatment in subordinant rats may provide a model for the social behavior of frightened paranoid schizophrenics.NIMH Research Scientist awardee MH 1759     

Association study of a novel functional polymorphism of the serotonin transporter gene in bipolar disorder and suicidal behaviour

A serotonin transporter gene linked polymorphic region (5-HTTLPR) has been investigated in several genetic association studies, including studies of bipolar disorder (BD) and suicidality. The current study was designed to examine whether the new long (A/G) variant polymorphism of the 5-HTT gene may be associated with the suicide attempts in 305 families with at least one member having BD. No association with history of suicide attempt was found either in the multiallelic HTTLPR (LRS=0.15, df=2, P=0.92), or with the intron 2 variable number tandem repeat (VNTR) polymorphism (LRS=0.87 df=2 P=0.64). When we performed a haplotype analysis, we found no association between suicide attempt and haplotype distribution (LRS=1.84 df=4 P=0.76). These findings suggest that this new polymorphism in the 5-HTT gene may not influence suicidal behaviour in patients with bipolar disorder.     

The serotonin transporter 5-HTTLPR polymorphism in the association between sleep quality and affect

A link between sleep and affect is well-known. Serotonin (5-HT) is associated with the regulation of affective as well as sleep-related processes. A functional polymorphism in the serotonin transporter gene (5-HTTLPR) has been associated with serotonergic functioning. The present study investigated whether allelic variation of this gene moderates the association between nighttime subjective sleep quality and affect the following day. A population-based sample of 361 ethnically homogenous adult female twins underwent a five day protocol based on the experience sampling method (ESM), assessing momentary negative affect, positive affect, and subjective sleep quality repeatedly and prospectively. There was a significant interaction between sleep quality and genotype in predicting positive affect the next day: carriers of one (n=167) or two S-alleles (n=78) had a significantly steeper slope compared to LL carriers (n=116) (χ²=4.16, p=.042 and χ²=3.90, p=.048 respectively). The association between subjective sleep quality and positive affect the next day varied as a function of 5-HTTLPR: it was stronger in carriers of at least one copy of the S-allele compared to homozygous L-carriers, supporting a link between sleep and affect regulation, in which serotonin may play a role. However, these results are preliminary and require replication.     

Smoking moderates association of 5-HTTLPR and in vivo availability of serotonin transporters

Although preclinical studies clearly indicate an effect of 5-HTTLPR genotype on 5-HT transporter (5-HTT) expression, studies in humans provided inconclusive results, hypothetically due to environmental factors and differences in individual behavior. For example, nicotine and other constituents of tobacco smoke elevate serotonin (5-HT) levels in the brain and may thereby cause homeostatic adaptations in 5-HTT availability that moderate effects of 5-HTTLPR genotype. To test whether 5-HTT availability in the midbrain is affected by smoking status and 5-HTTLPR genotype, we pooled data from prior studies on in vivo 5-HTT availability (BP_ND) measured with positron emission tomography (PET) and [¹¹C]DASB. In total, we reanalyzed 5-HTT availability in 116 subjects using ANCOVA statistics. ROI analysis revealed that current smokers and non-smokers do not differ in midbrain BP_ND. Interestingly, smoking status significantly interacted with 5-HTTLPR genotype: active smoking was associated with reduced 5-HTT availability only in LL subjects but not in carriers of the S-allele. From the perspective of genotype effects, non-smokers showed the expected association with 5-HTTLPR, i.e. higher 5-HTT availability in LL subjects compared to carriers of the S-allele, whereas this pattern was actually reversed for active smokers. Our study indicates that smoking status moderates the association of 5-HTTLPR genotype and 5-HTT expression, which may help to explain inconsistent findings in previous studies. Regarding the mechanism, we suggest that smoking may induce epigenetic processes such as methylation of SLC6A4, which can differ depending on its genetic constitution.     

Effects of apomorphine on mating behavior, flank marking and aggression in male hamsters

In male rats, the dopamine agonist apomorphine (APO) generally facilitates copulatory behavior. However, disruptive effects of high APO doses have been reported. These have been interpreted in diverse ways, as products of a dopaminergic system that inhibits sexual behavior or as consequences of APO's stimulation of competing responses. To test the generality of these effects, we observed APO's impact on copulatory behavior in male hamsters. Several effects were observed, all attributable to a relatively high dose and involving the disruption of male behavior. More unexpectedly, APO treatment caused males to attack estrous stimulus females in the course of these tests. To clarify these effects, we observed the effects of APO on flank marking, a type of scent marking closely allied to aggression and dominance in hamsters. Treatment reliably decreased the latency of marking. It also increased the rate of marking when appropriate measures were taken to prevent this effect from being obscured by drug-induced cheek pouching. Together, these results confirm and extend APO's well-known ability to increase aggression. Further, they suggest that APO-induced aggression can intrude into other contexts so as to disrupt, or possibly facilitate, other forms of social behavior.     

护理门诊干预对精神分裂症患者院外遵医行为的影响

目的:探讨护理门诊对精神分裂症患者院外遵医行为的影响.方法:对168例出院的精神分裂症患者随机分为研究组及对照组各84例.研究组出院后进行精神分裂症护理门诊干预,1年后对两组患者的疾病了解、坚持服药、定期复查、适量运动、合理饮食、情绪调节等遵医行为进行问卷测评.结果:护理门诊干预后,研究组患者对疾病了解、坚持服药、定期复查、适量运动、合理饮食、情绪调节项目的遵医率明显高于对照组,差异极有统计学意义(均P＜0.01).结论:护理门诊干预能有效提高精神分裂症患者的院外遵医行为.