冠心病伴抑郁与5-羟色胺转运体基因多态性的关系

目的：探讨5-羟色胺转运体基因多态性对冠心病伴抑郁的影响。方法：选择冠心病伴抑郁患者70例，以冠心病不伴抑郁患者70例作对照。采用聚合酶链反应技术检测受试对象5-羟色胺转运体基因上游调控区多态性位点（5-HTTLPR）与内含子2区（VNRT）2种基因多态性的分布频率。均经社会支持评定量表与应对方式问卷进行心理评定。结果：抑郁组5-HTFLPR的SS基因型及S等位基因频率显著高于对照组（均P〈0．01），VNRT基因型及等位基因频率分布2组差别无统计学意义（均P〉0．05）。SS基因型冠心病患者社会支持总分和积极应对分显著低于L5型及LL型（均P〈0．01）：消极应对分显著高于15型及LL型（均P〈0．01）。多元Logistic回归分析结果显示5-HTTLPR基因SS型与冠心病伴抑郁独立相关。结论：5-HTTLPR的SS基因型可能是冠心病患者伴发抑郁的易感基因之一。     

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。     

奥氮平联合阿立哌唑治疗精神分裂症伴攻击行为的临床观察

目的 分析奥氮平联合阿立哌唑治疗精神分裂症伴攻击行为的临床效果.方法 采用前瞻性随机试验方法,选取2018年1月至2020年10月我院接收的60例精神分裂症伴攻击行为患者作为研究对象,采用双盲法将其分为两组,各30例.对照组采用奥氮平治疗,观察组采用奥氮平联合阿立哌唑治疗,均治疗6周.对比两组治疗前、治疗6周时修订版外显攻击行为量表(MOAS)评分、阳性与阴性症状量表(PANSS)评分及治疗期间不良反应发生率.结果 治疗6周,与对照组比较,观察组阳性症状、阴性症状、一般精神病理症状及PANSS总分均较低,差异有统计学意义(P＜0.05);治疗6周,与对照组比较,观察组言语攻击、对财产的攻击、自身攻击、体力攻击及MOAS加权总分均较低,差异有统计学意义(P＜0.05);两组不良反应发生率比较,差异无统计学意义(P＞0.05).结论 表明在精神分裂症伴攻击行为患者的治疗中,采用奥氮平联合阿立哌唑治疗可有效改善其阴性、阳性、病理症状及攻击行为,且不会明显增加不良反应.     

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。     

Penta D、Penta E基因座与军人被动攻击行为关联的病例对照研究

目的探讨军人被动攻击行为与Penta D、Penta E基因座的关联情况。方法采用PCR结合毛细管电泳的方法对178例男性军人被动攻击行为者（研究组）和459例健康男性（对照组）的外周静脉血样进行Penta D、Penta E基因座的基因型分析,观察两组在Penta D、Penta E基因座的等位基因及基因型分布差异。结果 Penta D、Penta E基因座均符合遗传平衡定律（Hardy-Weinberg定律）;Penta E基因座等位基因及基因型频率在两个群体中分布差异有统计学意义（P〈0.05）;在两个群体中Penta E基因座的基因型16-18的频率分布差异有统计学意义（P〈0.01,OR：6.564,95%CI：2.278～18.914）;PentaD基因座等位基因频率及基因型频率在两个群体中分布无显著差异（P〉0.05）。结论 Penta E基因座多态性与军人被动攻击行为的发生存在关联,Penta E基因座基因型16-18为军人被动攻击行为的遗传易感因素。     

多巴胺D1ξχχ受体基因多态性与精神分裂症相关性研究

目的探讨精神分裂症与多巴胺D1受体（DRD1）基因多态性之间的关联。方法应用聚合酶链反应扩增技术,对中国汉族75例精神分裂症患者（患者组）和70例正常组（对照组）PCR扩增产物多态性检测,并进行关联分析。结果①正常组与患者组等位基因频数分布无显著性差异（χ2=17．72,P〉0．05）;②在138bp等位基因片段中,女性患者相对男性患者及对照组有较高的分布频率。结论DRD,基因多态性与精神分裂症无显著性关联,但性别不同可能影响精神分裂症的易感性。     

基于logistic回归分析的康复方案对住院精神分裂症患者攻击行为的预防作用

目的　分析住院精神分裂症患者攻击行为的影响因素,探究针对性康复干预对患者攻击行为的预防效果。方法　选择2019年1月至2020年8月山东省精神卫生中心接收248例住院精神分裂症患者,其中男135例,女113例,年龄23～67（38.03±0.41）岁。根据修改版外显攻击行为量表（MOAS）总加权分划分为攻击组（MOAS≥4分）、非攻击组（MOAS<4分）。比较两组患者的一般临床资料、阴性及阳性症状量表的兴奋因子（PANSS-EC）与中文版模棱两可、目的和敌意问卷（AIHQ-C）、社会支持评定量表（SSRS）、疾病不确定感（MUIS-A）情况。多因素logistic分析患者攻击行为的独立影响因素,并制定针对性康复方案。采用随机数字表法将山东省精神卫生中心2020年9月至2021年9月接收的100例精神分裂症患者［男57例,女43例,年龄20～69（38.38±2.51）岁］划分为两组。对照组实施常规干预,研究组在对照组基础上联合实施针对性康复方案。入院两个月,比较两组干预前后的攻击行为情况以及PANSS-EC、AIHQ-C、SSRS、MUIS-A评分。研究数据应用SPSS 26.0软件处理,计量资料给予t检验,计数资料给予χ²检验,等级资料给予秩和检验。结果　多因素logistic分析显示,男性、入院前1个月有攻击行为史、非自愿住院、首次住院、PANSS-EC评分、AIHQ-C敌意偏向总分、AIHQ-C责备偏向总分、AIHQ-C攻击偏向总分、SSRS客观支持得分、SSRS主观支持得分、MUIS-A不明确性得分、MUIS-A复杂性得分是住院精神分裂症患者攻击行为的独立影响因素（均P<0.05）;患者入院两个月,实施针对性康复方案后,研究组攻击行为发生率（16.00%,8/50）低于对照组（36.00%,18/50）,MOAS评分为（2.01±0.32）分,低于对照组的（3.56±0.24）分,两组比较,差异均有统计学意义（χ²=5.198,t=27.400,均P<0.05）;干预后,研究组PANSS-EC评分为（9.20±0.32）分、AIHQ-C评分为（13.48±1.11）分、SSRS评分为（33.21±2.47）分、MUIS-A评分为（70.31±3.56）分,均优于对照组［（11.21±0.28）分、（17.46±1.29）分、（30.29±3.03）分、（85.35±3.20）分］,两组比较,差异均有统计学意义（t=33.426、16.537、5.282、22.217,均P<0.05）。结论　精神分裂症患者攻击行为受多方面因素共同影响,针对性康复方案干预可有效改善患者攻击行为诱因,降低攻击行为发生率。     

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。     

利培酮合并丙戊酸钠对精神分裂症患者攻击行为疗效的对照研究

目的：探讨丙戊酸钠对精神分裂症患者攻击行为的疗效。方法：将60例精神分裂症患者随机分为研究组、对照组,研究组采用利培酮合并丙戊酸钠治疗,对照组采用利培酮单一治疗,采用阳性和阴性症状量表（PANSS）、外显攻击行为量表（MOAS）,在入组时以及第1、2、4、8周末进行评定,并进行统计分析。结果：两组PANSS和MOAS评分在第1、2、4周末和第8周末较入组时均显著降低（P〈0.01或〈0.05）。除第1周末外,在各时点PANSS和MOAS评分,研究组均显著低于对照组（P〈0.O1）。不良反应总发生率两组间差异无统计学意义（P〉0.05）。结论：丙戊酸钠与利培酮联合治疗精神分裂症,不但能增强单一使用利培酮的疗效,而且能有效控制攻击行为。     

5-HTT基因多态性与SSRIs,SNRIs类抗抑郁药治疗抑郁症临床疗效的关系研究

目的研究中国人群中5-HTT基因多态性与抑郁症及SSRIs和SNRIs类药物临床疗效是否存在相关性。方法用聚合酶链式反应多态性分析(PCR)技术对148例抑郁症患者和100例健康者进行基因型分析;用HAMD量表评定抗抑郁药的疗效。结果抑郁症5-HTT基因型频率(LL 24.3％,LS 44.6％,SS 31.1％)、等位基因频率(L 46.6％,S 53.4％)与正常对照组基因型频率(LL29.0％,LS 47.0％,SS 24.0％)、等位基因频率(L 52.5％,S 47.5％)比较没有显著性差异(P>0.05);不同基因型抑郁症患者治疗前,HAMD总分有显著差异(P<0.01);经4周SSRIs和SNRIs类抗抑郁药治疗后,HAMD总分均显著下降,减分值有显著差异(P<0.05)。结论中国人群中5-HTT基因多态性与抑郁症的发病不存在相关性,但与抑郁症疾病严重程度和抗抑郁药治疗效存在显著的相关性,这一区域的基因型可能成为抑郁症患者实现个体化治疗的一个参考指标。     

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.     

5-HT(3) receptors, alcohol and aggressive behavior in mice

Alcohol is a positive modulator at the 5-HT(3) receptor, which has been implicated in alcohol drinking, anxiety and aggression. The reported experiments explored the role of the 5-HT(3) receptor in aggressive behavior and alcohol-heightened aggression. Male, CFW mice were trained to self-administer 1.0 g/kg of alcohol, after which they confronted an intruder. Half of the CFW mice exhibited consistently increased aggressive behavior after alcohol and were designated as showing alcohol-heightened aggression, the others showed no increase and were designated as showing alcohol non-heightened aggression. The 5-HT(3) antagonist, ondansetron (0.01-1.0 mg/kg), significantly reduced aggression in both groups of CFW mice without affecting non-aggressive behaviors. Zacopride also reduced aggression effectively in both groups of mice, but at high doses began to affect walking. Male B6SJL/F2 transgenic 5-HT(3) over-expressing mice (TG) and wild-type mice (WT) were tested for aggressive behavior in their home cage. In those individuals that fought in tests of resident-intruder aggression, no differences were found in aggression after alcohol intake. In tests of aggression without alcohol intake, zacopride reduced aggression in both TG and WT mice at a dose of 56 mg/kg. Antagonism of 5-HT(3) receptors shows promising anti-aggressive effects, although these effects depend on the genetic background of the mice.     

Resistance of androgen-mediated aggressive behavior in mice to flutamide,an antiandrogen

The effects of ethanol (0.4, 0.8, 1.6, and 2.4 g/kg p.o.) on behavior of aggressive, timid, and sociable male mice treated with the drug on paired interactions with non-aggressive males given water were investigated. Under control interactions, aggressive mice attacked their partners, timid mice showed defensive-escape activities though their partners were completely non-aggressive, and sociable mice intensively investigated their partners. A low dose of ethanol (0.4 g/kg) increased while higher doses (0.8 to 2.4 g/kg) reduced aggressive activities in aggressive mice. Ethanol (0.8 g/kg) also evoked aggressive behavior in non-aggressive timid mice but no dose of ethanol stimulated aggression in non-aggressive sociable mice. Ethanol altered timid defensive-escape activities only in the highest dose of 2.4 g/kg: this dose increased defences and escapes in aggressive males while it reduced defensive upright postures in timid mice. However, 2.4 g/kg of ethanol reduced also another upright movement (exploratory rearing) in timid mice. Sociable activities were not increased by any dose of ethanol tested. By contrast, 0.4 g/kg of ethanol reduced sniffing and following partners in sociable mice. Thus, ethanol exhibited relatively strong aggression-stimulating effects in aversively disposed subjects while the drug was not able to supress timid defensive escape behavior and to stimulate active non-aggressive contacts between strange male mice.     

抗精神病药物联合小剂量丙戊酸镁治疗精神分裂症攻击行为的临床分析

目的 研究和探讨抗精神病药物联合小剂量丙戊酸镁治疗精神分裂症患者攻击行为的临床效果和应用价值.方法 选择本院2014年11月至2015年11月收治的具有精神分裂症攻击行为的患者180例,随机分为对照组(使用抗精神药物利培酮治疗,90例)和观察组(使用利培酮联合丙戊酸镁治疗,90例),对比和分析两组临床治疗效果和应用价值.结果 治疗前,对照组阳性与阴性症状(75.6±5.6)分,外显攻击行为(7.5±0.9)分,观察组阳性与阴性症状(75.7±7.2)分,外显攻击行为(7.4±0.8)分;治疗后,对照组阳性与阴性症状(62.5±7.6)分,外显攻击行为(4.9±0.8)分,观察组阳性与阴性症状(51.2±7.9)分,外显攻击行为(2.9±1.1)分;治疗后,两组评分指标均好于治疗前,观察组评分指标明显优于对照组,差异具有统计学意义(P＜0.05).观察组不良反应发生率24.44％;对照组22.22％,差异无统计学意义(P＞0.05).结论 抗精神病药物联合小剂量丙戊酸镁药物治疗精神分裂症攻击行为临床效果佳,能够明显降低抗精神病药物带来的临床不适反应,具有推广价值.     

Polyunsaturated fatty acid status and aggression in cocaine addicts

BACKGROUND: There is mounting evidence that low levels of some polyunsaturated fatty acids (PUFAs) play a role in the pathophysiology of aggressive disorders. PUFA status is influenced by nutritional factors and because of our observation that some substance abusers have poor dietary habits, we explored the possibility that the fatty acids (FA) profiles of cocaine addicts with and without aggressive tendencies would differ. We also explored the possibility that their FA levels would change after a 2 week stay on an inpatient unit where a standard diet would be provided. METHODS: Plasma levels of FAs were measured in 24 cocaine addicts admitted to an inpatient substance abuse unit. Six patients had a past history of aggression and 18 did not. RESULTS: A comparison of the FA levels of aggressive and non-aggressive patients performed 3.7+/-2.0 days after their admission did not reveal any significant difference in saturated FAs (SFAs) or monounsaturated FAs (MFAs). Aggressive patients had significantly lower levels of the n-6 PUFA docosapentaenoic acid (DPA), of total n-3 PUFAs and of the n-3 PUFA docosahexaenoic acid (DHA), and a marginally significant increase in the ratio of n-6 to n-3 PUFAs. Measurements performed 18.4+/-1.3 days after admission showed that most FAs had increased in the two patient groups. Some PUFAs, especially those of the n-3 series, increased more sharply in the aggressive patients. As a result, PUFA differences between groups that were present shortly after admission became non-significant. CONCLUSIONS: These data suggest that patients' diets prior to their hospitalization were less than optimal and that the diet of the aggressive individuals might have been particularly deficient in n-3 rich nutrients. These data also give additional support to evidence indicating a possible link between an n-3 deficiency and aggression in humans.     

Interaction between childhood trauma and serotonin transporter gene variation in suicide.

Although the serotonin transporter promoter polymorphism (5-HTTLPR) contributes to depression and suicidality in a fashion modulated by environmental stress, 5-HTTLPR has been little examined in relation to suicidal behavior in substance dependence. Recently, a third functional allele of 5-HTTLPR was discovered enabling more of the interindividual variation in serotonin transporter expression to be predicted by genotype. We examined whether the 5-HTTLPR gene alone, or interacting with childhood trauma, was predictive of suicidal behavior in substance-dependent patients, a clinical population that is at high risk of suicide, as well as childhood trauma and other stress. We interviewed 306 abstinent male African-American substance-dependent patients about whether they had ever attempted suicide and administered the 34-item Childhood Trauma Questionnaire (CTQ). Patients and 132 male African-American controls were genotyped to determine the S, L(G), and L(A) 5-HTTLPR alleles; some analyses grouped the S and L(G) alleles on the basis of equivalent function. The distribution of 5-HTTLPR genotypes did not differ between patients and controls, nor between suicide attempters and non-attempters. However, patients with low expression 5-HTTLPR genotypes and above-median CTQ scores were more likely to have attempted suicide. Logistic regression showed increasing risk of a suicide attempt with increasing reports of childhood trauma scores; in addition, this increase was exaggerated among those with low expression forms of the 5-HTTLPR genotype. Childhood trauma interacts with low expressing 5-HTTLPR genotypes to increase the risk of suicidal behavior among patients with substance dependence.     

NMDA receptor antagonism: escalation of aggressive behavior in alcohol-drinking mice

Rationale

Memantine is a potential treatment for alcoholic patients, yet few studies investigate the effect of concurrent treatment with memantine and ethanol on aggression. We evaluated aggressive behavior following ethanol consumption and treatment with glutamatergic drugs to characterize interactions between these compounds.

Objective

This study aimed to use rodent models of aggression to examine interactions between glutamatergic compounds and ethanol.

Materials and methods

Once male CFW mice reliably self-administered 1 g/kg ethanol or water, they were assessed for aggression in resident–intruder confrontations. Alternatively, aggression was evaluated following a social-instigation procedure. Animals were then injected with memantine, ketamine, neramexane, MTEP, or LY379268 before aggressive confrontations. Effects of the pharmacological manipulations on salient aggressive and non-aggressive behaviors were analyzed.

Results

Moderate doses of memantine, neramexane, and MTEP interacted with ethanol to increase the frequency of attack bites while ketamine did not. The highest dose of LY379268, an mGluR_2/3 agonist, reduced both aggressive and non-aggressive behaviors after water and ethanol self-administration. Attack bites increased with social instigation and decreased with administration of high doses of MTEP and LY379268. Memantine and MTEP both reduced attack bite frequency in the instigation condition without reducing locomotor behavior.

Conclusions

Memantine and neramexane interacted with ethanol to heighten aggression. The binding characteristics of these compounds allow for ‘partial trapping’ by which some NMDARs are unblocked between depolarizations. We propose that this feature may contribute to the differential aggression-heightening interactions between these compounds and ethanol. MTEP also interacted with ethanol to escalate aggression, possibly through inhibition of mGluR₅ modulation of NMDARs.     

Reduced isolation-induced aggressiveness in mice following NAALADase inhibition

Rationale Long-term individual housing increases aggressive behavior in mice, a condition termed isolation-induced aggression; this aggressiveness is reduced by some antidepressants and anxiolytics. NMDA antagonists also inhibit isolation-induced aggression in mice. The enzyme N-acetylated--linked acidic dipeptidase (NAALADase) hydrolyzes the neurotransmitter N-acetylaspartylglutamate (NAAG) to form glutamate and N-acetylaspartate; NAAG acts as a partial NMDA agonist as well as a full agonist at the presynaptic metabotropic glutamate receptor 3 (mGluR3), where it acts to reduce glutamate release.Objective We postulated that NAALADase inhibition would reduce isolation-induced aggression in mice.Methods We tested whether acute exposure to the NAALADase inhibitor 2-[[hydroxy[2,3,4,5,6-pentafluorophenyl)methyl]phosphinyl]methyl] pentanedioic acid (GPI-5232), administered 30 min prior to a social interaction test, would inhibit aggressive behavior in SJL mice that had been individually housed long term.Results Administration of GPI-5232 (30 mg/kg, IP) inhibited initiation of aggressive behavior, indicated by greater latencies to display tail-rattling, attack and biting, and by fewer mice initiating aggressive behavior, compared to mice that received vehicle. In addition, GPI-5232 treated mice had fewer tail-rattling responses to a non-aggressive conspecific.Conclusions The effectiveness of GPI-5232 in this animal model suggests that NAALADase inhibition may be a novel therapeutic approach to reduce or inhibit heightened aggressiveness, and possibly to treat aggressive behavior associated with psychiatric disorders.