血清白细胞介素6、脑源性神经营养因子、甘油三酯、5-羟色胺与精神分裂症患者认知功能和攻击行为的关系分析

摘要 目的：探讨血清白细胞介素6（IL-6）、脑源性神经营养因子（BDNF）、甘油三酯（TG）、5-羟色胺（5-HT）与精神分裂症（SZ）患者认知功能的关系,并分析SZ患者攻击行为的影响因素,研究血清IL-6、TG、BDNF、5-HT与攻击行为的关系。方法：选取2020年1月～2022年1月我院收治的112例SZ患者作为SZ组,根据有无攻击行为分为有攻击行为组31例和无攻击行为组81例,另选取同期41例体检健康者作为对照组,检测血清IL-6、BDNF、TG、5-HT水平,中文版MATRICS共识认知成套测验（MCCB）评估认知功能。采用Pearson/Spearman相关性分析SZ患者血清IL-6、BDNF、TG、5-HT水平与MCCB评分的相关性,多因素Logistic回归分析SZ患者攻击行为的影响因素,受试者工作特征（ROC）曲线分析血清IL-6、BDNF、TG、5-HT水平对SZ患者攻击行为的预测价值。结果：SZ组血清IL-6、TG水平高于对照组,BDNF、5-HT水平和MCCB评分低于对照组（P＜0.05）。Pearson/Spearman相关性分析显示,SZ患者血清IL-6、TG水平与MCCB评分呈负相关（r/rs=-0.569、-0.528,均P＜0.001）,BDNF、5-HT水平与MCCB评分呈正相关（r/rs=0.587、0.602,均P＜0.001）。多因素Logistic回归分析显示,PANSS总分增加（OR=1.958,95％CI：1.035～3.704）、IL-6升高（OR=1.015,95％CI：1.041～1.172）、TG升高（OR=1.007,95％CI：1.023～1.135）为SZ患者攻击行为的独立危险因素,MCCB评分增加（OR=0.911,95％CI：0.848～0.979）、BDNF升高（OR=0.792,95％CI：0.656～0.955）、5-HT升高（OR=0.979,95％CI：0.965～0.994）为独立保护因素（均P＜0.05）。ROC曲线分析发现,血清IL-6、BDNF、TG、5-HT水平单独与联合预测SZ患者攻击行为的曲线下面积（AUC）分别为0.765、0.754、0.750、0.748、0.920,四项联合预测SZ患者攻击行为的AUC大于各指标单独预测。结论：SZ患者血清IL-6、TG水平升高和BDNF、5-HT水平降低与认知功能障碍和攻击行为有关,血清IL-6、BDNF、TG、5-HT水平可作为SZ患者攻击行为的辅助预测指标。     

跑台运动对攻击行为大鼠内侧下丘脑和中脑导水管周围灰质5-HT1A受体、5-HT2A受体蛋白表达的影响

目的:探讨跑台运动对攻击行为大鼠内侧下丘脑(MH)和中脑导水管周围灰质(PAG)5-HT1A受体、5-HT2A受体蛋白表达的影响,为研究运动对攻击行为改善的神经生物学机制提供实验基础.方法:3月龄雄性SD大鼠40只,体重160～180 g,随机分为4组:安静组(A)、攻击模型组(G)、攻击跑台组(GP)、入侵组(R)....     

五羟色胺和多巴胺与攻击行为的关联研究进展

五羟色胺（5-HT）和多巴胺（DA）是影响攻击行为的重要神经递质。参与这两种神经递质合成和分解、运输及信号转导等过程的物质均可能影响攻击行为,如影响5-HT作用的色氨酸、色氨酸羟化酶、单胺氧化酶、5-羟吲哚乙酸及5-HT转运体和5-HT受体;影响DA作用的多巴胺β羟化酶和儿茶酚胺邻位甲基转移酶以及DA转运体。未来攻击行为研究,应考虑色氨酸自身代谢、受体亚型及其他单胺类和儿茶酚胺类神经递质的影响。将肠道微生物纳入攻击行为研究也是未来研究的新方向。     

食物、捕食及种间竞争对东方田鼠(Microtus fortis)种群攻击行为的作用

在野外围栏条件下,采用重复的2×2×2析因实验设计,测定食物、捕食和竞争物种黑线姬鼠对东方田鼠攻击行为作用的格局。东方田鼠各处理种群攻击水平与其种群密度的相关甚为复杂,与Chitty多态行为假设的预测不一致。东方田鼠双冲突个体间的攻击水平与其体重的相关不显著,而与冲突个体的体重差异则呈显著的负相关,体重差异越大,冲突个体间的攻击水平越低。雄体攻击水平与其繁殖特征无显著的相关关系,而雌体间攻击水平则受繁殖状态的影响,动情雌体间的攻击水平显著地高于非动情雌体。体重差异和食物对雄体的攻击行为具有极显著的独立作用,捕食和种间竞争对雄体攻击行为的独立作用不显著,而捕食与种间竞争交互作用对雄体攻击行为的效应则达到显著水平。体重差异、食物、捕食和种间竞争对动情雌体的攻击水平均有极显著的独立作用,3类外部因子交互作用的效应达到极显著水平;而3类外部因子交互作用对非动情雌体攻击行为的效应则不显著。结果检验了外部因子食物、捕食、种间竞争对田鼠类动物种群攻击行为具有独立和累加的整合效应的假设。     

食物、捕食及种间竞争对东方田鼠(Microtus fortis)种群攻击行为的作用

在野外围栏条件下,采用重复的2×2×2析因实验设计,测定食物、捕食和竞争物种黑线姬鼠对东方田鼠攻击行为作用的格局。东方田鼠各处理种群攻击水平与其种群密度的相关甚为复杂,与Chitty多态行为假设的预测不一致。东方田鼠双冲突个体间的攻击水平与其体重的相关不显著,而与冲突个体的体重差异则呈显著的负相关,体重差异越大,冲突个体间的攻击水平越低。雄体攻击水平与其繁殖特征无显著的相关关系,而雌体间攻击水平则受繁殖状态的影响,动情雌体间的攻击水平显著地高于非动情雌体。体重差异和食物对雄体的攻击行为具有极显著的独立作用,捕食和种间竞争对雄体攻击行为的独立作用不显著,而捕食与种间竞争交互作用对雄体攻击行为的效应则达到显著水平。体重差异、食物、捕食和种间竞争对动情雌体的攻击水平均有极显著的独立作用,3类外部因子交互作用的效应达到极显著水平;而3类外部因子交互作用对非动情雌体攻击行为的效应则不显著。结果检验了外部因子食物、捕食、种间竞争对田鼠类动物种群攻击行为具有独立和累加的整合效应的假设。     

视频暴力与攻击行为的神经成像研究进展

认知神经科学促进了心理学领域有关视频暴力与攻击行为的神经生理机制研究.近几年,国外研究者使用功能性磁共振成像研究了视频暴力与攻击行为的神经生理机制,并提出了新的攻击行为模型:神经发展模型.研究发现:长时间暴露在视频暴力下人类对暴力的威胁的脑反应是真实的并且可以察觉到的;能导致前额皮层、杏仁核、前扣带皮层、海马和海马回的激活;能增加潜在的攻击行为.文章介绍了认知神经科学领域中视频暴力和攻击行为神经成像研究的发展现状并展望了其前景.     

个体亲近程度对藏酋猴攻击行为的影响

友好和冲突行为决定了群居动物的社会结构及其表现形式,表现为个体间近距差异。但目前尚不清楚藏酋猴个体间亲近关系的差异性是否会影响冲突和攻击的强度。本研究于2020年9月至2021年5月对栖息于安徽黄山的藏酋猴鱼鳞坑YA1群进行跟踪观察,采用目标动物取样法采集行为数据,全事件记录法用于攻击行为数据的补充,分析个体间近距、理毛和攻击行为矩阵的关系,并采用GLMM模型探讨攻击行为的影响因素。结果显示：藏酋猴个体间近距指数越大,理毛时间越长;个体间近距指数矩阵与攻击总次数、轻度攻击和重度攻击次数矩阵均呈显著正相关;个体间亲近关系越紧密,攻击次数和强度越大,但相较雄性间和异性间,雌性间攻击次数和强度最小。这些结果表明,个体间近距持续时间会增加理毛和攻击行为的可能性,雌性个体间社会关系更稳定,但并未发现藏酋猴根据个体间亲近关系调整攻击强度。本研究为进一步了解多雌多雄的藏酋猴群体的社会关系和社会结构提供了数据支持。     

神农架川金丝猴投食群的攻击行为及等级序列

为探讨人工补食条件下川金丝猴的攻击行为在维持社会等级中的作用,2007 年1 ～ 6 月,采用行为取样法
和全事件记录法对神农架自然保护区投食群的攻击行为及等级序列进行研究。我们共记录到8 种攻击行为,按
频次多少依次为:咕叫、抓打、追赶、瞪眼、瞪咕、驱赶、抢食、打架。攻击行为的发起者在性别间和年龄间
均存在显著差异,雄性多于雌性,年龄间按次数多少依次为:成年猴、亚成年猴、青年猴、少年猴;承受者在
性别间和年龄间差异均不显著。社会单元内与单元间攻击行为差异显著,前者多于后者。一雄多雌单元间的等
级高低依次为:长毛单元、白头单元、红头单元。基于单元内攻击行为较多,建议适当扩大投食场,给每只个
体分别投食,以减少因争食发生的攻击行为。     

防御性攻击行为对黑线仓鼠能量收支的影响

攻击行为是增强个体生存能力和提高繁殖成功机会的最有效竞争方式之一。为理解攻击行为对小型哺乳动物能量学收支策略的影响,以具有独居且好斗习性的黑线仓鼠为研究对象,基于居留者-入侵者（resident-intruder）争斗方式将入侵鼠放入居留鼠笼中（10min / d）,21d后测定能量摄入、基础代谢率（BMR）,分析BMR和内脏器官重量的相关性。结果显示,攻击行为使居留组BMR增加了26.2%,使摄入能和消化能显著增加。居留组体重、胴体重,以及某些代谢活性器官（肝脏、肺脏、肾脏、胃、小肠和盲肠）重量显著增加,且这些器官重量与BMR显著正相关。结果表明,增加能量摄入和BMR是黑线仓鼠应对攻击行为的主要能量学收支策略;在种内个体之间强烈的攻击行为可能是该鼠维持较高水平BMR的原因之一。     

中缝中核5-羟色胺能神经元调控焦虑和抑郁样行为

中枢神经递质中,5-羟色胺(5-hydroxtryptamine,5-HT)作用广泛,对情绪调节、感觉传输和认知行为等都有重要调节作用。5-HT能神经元数量较少,主要分布于脑干中线的中缝背核(dorsal raphe nucleus,DR)和中缝中核(median raphe nucleus,MR)。之前的研究主要聚焦于DR核团的功能,对MR核团5-HT能神经元的功能知之甚少。本研究以Pet1-Cre转基因小鼠作为研究对象,通过DREADDs技术特异性操控MR核团5-HT能神经元的活动,进而观察MR核团5-HT能神经元在焦虑和抑郁样行为中的作用。结果显示,在旷场实验与高架十字迷宫实验中,抑制小鼠MR核团5-HT能神经元能减轻小鼠焦虑样行为。在蔗糖偏爱实验和强迫游泳实验中,抑制小鼠MR核团5-HT能神经元能减轻小鼠抑郁样行为,激活MR核团5-HT能神经元则增强小鼠的抑郁样行为。这些结果提示MR核团5-HT能神经元在调节焦虑和抑郁样行为中发挥关键性作用。     

Neonatal buspirone modulates the intermale aggression in adult mice

Mice of two strains with different levels of male aggression (RSB and RLB) were subjected to daily injections of 5-HT1A receptor agonist buspirone (25 microg) on the 2nd - 6th postnatal days. This neonatal treatment augmented the aggressive behavior (tested in the dyadic contests with non-aggressive A/Sn males) in aggressive RSB mice and reduced aggression in less aggressive RLB. Correlations with different signs were found between the 5-HT and 5-HIAA levels in the neocortex, hippocampus, and hypothalamus and behavioral indices of aggression in RSB and RLB males. The remote effects of neonatal buspirone in these two mice strains presumably depend on genotype-related features of ontogeny of the 5-HT system.     

Participation of 5-HT1A-receptors in regulating various types of aggressive behavior

We studied the effects of selective agonists of 5-HT1A receptors 8-OH-DPAT and flesinoxan on aggressive behavior of C57BL/6 male mice in the "resident-intruder" test and on defensive aggression of Norway rats toward man. 8-OH-DPAT (0.4 mg/kg, i.p.) significantly reduced the intermale aggression in mice and defensive aggression in rats (0.1-0.5 mg/kg, i.p.). In the dose of 0.5 mg/kg, flesinoxan inhibited the aggressive behavior in mice. These results suggest that activation of 5-HT1A receptors reduces different kinds of affective aggression. The results are discussed in terms of interaction between the well-known anxiolytic effects of 5-HT1A agonists and their antiaggressive properties.     

From genes to aggressive behavior: the role of serotonergic system

Recent investigations in neurogenomics have opened up new lines of research into a crucial genetic problem-the pathway from genes to behavior. This paper concentrates on the involvement of protein elements in the brain neurotransmitter serotonin (5-HT) system in the genetic control of aggressive behavior. Specifically, it describes: (1) the effect of the knockout of MAO A, the principal enzyme in 5-HT degradation, (2) the association of intermale aggression with the polymorphism in the Tph2 gene encoding the key enzyme in 5-HT synthesis in the brain, tryptophan hydroxylase (TPH), and (3) the effect of selective breeding for nonaggressive behavior on 5-HT metabolism, TPH activity and 5-HT(1A) receptors in the brain. The review provides converging lines of evidence that: (1) brain 5-HT contributes to a critical mechanism underlying genetically defined individual differences in aggressiveness, and (2) genes encoding pivotal enzymes in 5-HT metabolism (TPH and MAO A), 5-HT-transporter, 5-HT(1A) and 5-HT(1B) receptors belong to a group of genes that modulate aggressive behavior.     

Removal of both antennae influences the courtship and aggressive behaviors in male crickets

To test whether insect antennae are necessary for eliciting courtship and aggression toward appropriate partners, we antennectomized adult male crickets (Gryllus bimaculatus) and observed their behavior toward other antennectomized males and intact females. At 7 days after removal of both antennae, pairs of antennectomized males were placed together; 80% displayed courtship behavior, generating courtship song by rubbing their forewings together, toward other antennectomized males, and 20% displayed aggressive behavior. Only 45% courted intact females. No intact males courted antennectomized males, and 80% displayed aggressive behavior. All intact males courted females. The results for males with one antenna removed were essentially the same as for intact males. These findings indicate that a high proportion of male crickets with both antennae removed court other males and fail to display male-male aggression, demonstrating that removal of antennae from male crickets induces male-male courtship and that an antenna is necessary for the expression of male-male aggression. Moreover, brain serotonin (5-hydroxytryptamine; 5-HT) levels in male crickets were significantly reduced at 7 days after removal of antennae. The reduction of 5-HT was detected primarily in the central body of the brain. Thus, 5-HT in the central body of the male cricket brain may be involved in the behavioral changes.     

Interaction of nitric oxide and serotonin in aggressive behavior

Nitric oxide (NO) modulates many behavioral and neuroendocrine responses. Genetic or pharmacological inhibition of the synthetic enzyme that produces NO in neurons evokes elevated and sustained aggression in male mice. Recently, the excessive aggressive and impulsive traits of neuronal NO synthase knockout (nNOS-/-) mice were shown to be caused by reductions in serotonin (5-HT) turnover and deficient 5-HT1A and 5-HT1B receptor function in brain regions regulating emotion. The consistently high levels of aggression observed in nNOS-/- mice could be reversed by 5-HT precursors and by treatment with specific 5-HT1A and 5-HT1B receptor agonists. The expression of the aggressive phenotype of nNOS-/- knockout mice requires isolated housing prior to testing. The effects of social factors such as housing condition and maternal care can affect 5-HT and aggression, but the interaction among extrinsic factors, 5-HT, NO, and aggression remains unspecified. Taken together, NO appears to play an important role in normal brain 5-HT function and may have significant implications for the treatment of psychiatric disorders characterized by aggressive and impulsive behaviors.     

Cerebrospinal fluid monoamine and metabolite concentrations and aggression in rats

In humans and other primates low cerebrospinal fluid (CSF) levels of the major serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been correlated to high aggressiveness. This finding forms the basis of the 5-HT deficiency hypothesis of aggression. Surprisingly, this correlation has not been confirmed in rodents so far, while manipulation studies aimed to investigate the link between 5-HT and aggressive behaviour are mostly carried out in rodents. In this study the relation between aggression and CSF monoamine and metabolite concentrations was investigated in male Wildtype Groningen rats. In sharp contrast to the hypothesis and our expectation, a clear positive correlation was found between the individual level of trait-like aggressiveness and CSF concentrations of 5-HT, 5-HIAA, norepinephrine (NE), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC). Shortly after the acute display of aggressive behaviour (as a state-like phenomenon), decreased 5-HT levels and an increase in 5-HIAA/5-HT ratio and NE concentrations were found. Surprisingly, pharmacological challenges known to influence 5-HT transmission and aggressive behaviour did not affect CSF 5-HT and 5-HIAA concentrations, only the NE level was increased. Lesioning 5-HT terminals by 5,7-dihydroxytryptamine (5,7-DHT) administration caused a decrease in CSF 5-HT and 5-HIAA, but without affecting aggressive behaviour. The observed positive correlation between CSF 5-HIAA and trait aggressiveness makes it questionable whether a direct extrapolation of neurobiological mechanisms of aggression between species is justified. Interpretation of CSF metabolite levels in terms of activity of neural substrates requires a far more detailed knowledge of the dynamics and kinetics of a neurotransmitter after its release.     

An fMRI study on the role of serotonin in reactive aggression

Reactive aggression after interpersonal provocation is a common behavior in humans. Little is known, however, about brain regions and neurotransmitters critical for the decision-making and affective processes involved in aggressive interactions. With the present fMRI study, we wanted to examine the role of serotonin in reactive aggression by means of an acute tryptophan depletion (ATD). Participants performed in a competitive reaction time task (Taylor Aggression Paradigm, TAP) which entitled the winner to punish the loser. The TAP seeks to elicit aggression by provocation. The study followed a double-blind between-subject design including only male participants. Behavioral data showed an aggression diminishing effect of ATD in low trait-aggressive participants, whereas no ATD effect was detected in high trait-aggressive participants. ATD also led to reduced insula activity during the decision phase, independently of the level of provocation. Whereas previous reports have suggested an inverse relationship between serotonin level and aggressive behavior with low levels of serotonin leading to higher aggression and vice versa, such a simple relationship is inconsistent with the current data.     

Time-dependent changes in brain biogenic amine dynamics following castration in male rats

—Alterations in whole-brain and hypothalamic levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE), dopamine (DA) as well as the turnover rates of NE and DA of adult male rats were analysed fluorometrically at either 3 weeks or 6 weeks following castration. Significant increases were observed in whole-brain (minus hypothalamus) 5-HIAA levels and hypothalamic DA levels, fractional rate constants and utilization rates at the 3 but not the 6 week intervals. Elevated levels of 5-HT were observed at both time intervals while an increase in whole-brain DA was seen only at the 6 week interval. Whole brain NE turnover rates of castrated animals did not differ significantly from those of sham-castrate control animals at either test interval. However, a tendency toward increased hypothalamic NE turnover rates was seen in the castrated animals. These biochemical changes resulted in decreased NE/5-HT and DA/5-HT ratios for the castrate rats as compared to controls. The results are discussed in relation to emotional and aggressive behavior and are interpreted as being consistent with the hypothesis purporting an inhibitory role for 5-HT and excitatory role for NE and DA in sex-specific behavior patterns including aggression.