外侧缰核作用于抑郁的神经生理机制

本文旨在梳理国内外有关外侧缰核作用于抑郁神经生理机制的研究成果,以期为今后抑郁研究提供借鉴和参考。首先,阐明了外侧缰核的过度兴奋会加强对下游奖赏中心单胺能脑区的抑制从而诱发抑郁的内在通路。然后,进一步论述了介导外侧缰核过度兴奋的分子机制。最后,未来要重点以人类为被试,采用纵向设计,加强外侧缰核对抑郁的影响、作用机制及其性别差异的研究,同时考察遗传基因和环境在其间的调控效应等问题。     

细胞因子和抑郁症

在心理神经免疫学领域,越来越多的证据表明神经和免疫之间存在双向交流通路,免疫系统可能在一些心理精神障碍中具有重要作用。“抑郁症的细胞因子假说”认为细胞因子作为神经调质,可能在抑郁症的病因和病理过程中具有重要作用。这个假说得到了很多证据的支持。而在动物身上应用前炎性细胞因子也能够引起与人类抑郁症行为症状非常类似的“病态行为”。研究认为外周细胞因子通过信号传导进入脑内与中枢产生的细胞因子共同作用于下丘脑－垂体－肾上腺轴和5－羟色胺系统,从而导致抑郁症。细胞因子的中枢效应可以解释很多抑郁症状,“抑郁症的细胞因子假说”为探讨抑郁症状的机制和治疗抑郁症提供了一个新的视角     

奖赏环路与阿片成瘾:喙内侧被盖核的调节作用

喙内侧被盖核(RMTg)位于腹侧被盖区(VTA)的尾部, 富含抑制性的γ-氨基丁酸(GABA)能神经元.RMTg是中脑边缘多巴胺系统的一个综合调节器.它的GABA能神经元接受外侧缰核(LHb)的输入, 然后投射到VTA多巴胺能神经元, 进而抑制多巴胺的释放.这三个脑区是奖赏环路的重要组成部分, 其中RMTg在阿片类物质激活的奖赏环路中尤为重要.阿片类物质主要通过抑制RMTg GABA能神经元使VTA多巴胺能神经元去抑制, 进而激活奖赏系统.因此, RMTg有望成为治疗药物成瘾(尤其是阿片成瘾)的一个重要靶点.此外, 胆碱类物质作用于RMTg的毒蕈碱受体能够抑制阿片类物质诱导的奖赏效应.未来研究应深入探讨RMTg调控的负性奖赏环路, 这对弱化觅药动机,促进消退和戒断具有重要意义.     

听觉中脑声定位的机制

人和动物对声源方位的感知和心理确定建立在神经生理基础之上,得到了大量来自神经细胞电生理研究证据的支持。听中枢神经元可通过比较到达两耳声信号的不同特征和参量来体现其精确的声源定位能力。研究表明,声源定位过程是听觉系统复杂综合作用的结果,听觉中脑核团-下丘在这一过程中起着重要作用,下丘中大量双耳听觉反应神经元可编码声音(源)方位信息,甚至双侧下丘间的联合投射也有可能参与双耳听觉反应的调制。     

5羟色胺受体-7在抑郁症中的研究进展

5羟色胺受体-7(5-HT_7)是5-HT受体家族中迄今最年轻的成员,目前已是临床治疗抑郁症的重要分子靶标之一。5-HT_7不仅影响神经元的可塑性和神经胶质细胞的免疫激活,还参与调控中枢神经系统重要的信号转导通路,在抑郁症的发生发展中至关重要。本文对5-HT_7的结构、功能和相关药物的开发,特别是该受体参与调控神经元和胶质细胞功能的信号转导通路进行综述,以全面了解5-HT_7在抑郁症发生发展中的作用。     

应激对兴奋性突触传递的影响及其分子机制

应激与抑郁症、心血管疾病及肿瘤等重大疾病的发生有着密切关系。前额叶皮层和海马是调控应激反应的重要组织,也是应激作用的靶器官。兴奋性突触传递是大脑功能活动的重要基础,应激通过改变递质的释放和代谢及受体的转运和表达,影响突触传递功能。包括表观遗传在内的多种细胞内信号通路参与了应激的作用机制。揭示这些信号通路可为研发治疗应激相关疾病的药物提供潜在的靶点。     

GABA能系统在应激诱发的抑郁症中的作用

γ-氨基丁酸(γ-aminobutyric acid,GABA)是中枢神经系统中最重要的抑制性神经递质,在维持大脑的兴奋-抑制平衡中起到重要作用。越来越多的临床和基础研究显示抑郁症与各种GABA能神经元活动不足相关,抗抑郁药物可以缓解或恢复上述变化。GABA能系统延迟发育至成年早期基本成熟。应激,尤其是早期应激是抑郁症发病的重要风险因素,可以通过扰动GABA能系统的发育轨迹从而造成对该系统结构和功能的持续后果,并与后期抑郁症易感密切相关。未来的研究需要进一步鉴别二者之间的关系,进而提出以GABA能系统为靶标的抑郁症治疗新策略。     

n-3系多元不饱和脂肪酸对抑郁症的影响及其机制

越来越多的实验证据表明,n-3系多元不饱和脂肪酸(n-3PUFA)与抑郁症之间存在联系,二十二碳六烯酸(DHA)和二十碳五烯酸(EPA)可能具有预防和治疗抑郁症的作用.回顾国内外关于n-3PUFA与抑郁症之间存在的负性关系的研究并介绍其主要的研究结果和现状,解释n-3PUFA引起的抗抑郁效果可能涉及的神经机制,包括神经传递、葡萄糖的新陈代谢、促炎细胞因子的分泌、5-羟色胺(5-HT)以及脑源性神经营养因子(BDNF)的水平、还有神经元的凋亡等的变化.并且总结现有研究中存在的一些问题,例如使用的n-3PUFA种类和剂量问题,DHA或EPA是否对于不同种类的抑郁症均有效,单独作用还是共同作用才能引起抗抑郁效果等等,n-3PUFA对抑郁症病理机制的具体影响可能是未来的研究方向.     

丘脑枕核参与情绪信息加工的多条通路

丘脑枕核参与多条加工情绪信息的神经通路因而在情绪信息加工中具有重要作用。第一：丘脑枕核参与到上丘-丘脑枕核-杏仁核通路。该通路可以在没有初级视觉皮层参与情况下对情绪信息进行快速加工; 第二：丘脑枕核以皮层-丘脑枕核-皮层环路和上丘-丘脑枕核-皮层通路两种形式参与到丘脑枕核-皮层通路。该通路通过控制皮层间同步化水平促进信息传递的效率; 同时通过整合皮层和皮层下情绪信号扩大其在行为输出方面的影响力。     

抑郁症的心理神经免疫学研究：细胞因子的作用

免疫系统在一些心理精神障碍中具有重要作用,抑郁症可看作是一种心理神经免疫紊乱性疾病。生理应激和心理应激能激活免疫系统,导致细胞因子的产生,从而影响中枢神经系统的多个方面,包括神经递质代谢、神经内分泌功能、神经可塑性以及与行为改变有关的信息过程。细胞因子不仅由免疫活性细胞分泌,也能被神经胶质细胞和神经细胞合成和分泌,它在抑郁症中的作用可能会在揭示抑郁障碍机制上有新突破,并可能作为今后药物治疗的靶点进入临床领域     

Damage-induced alarm cues influence lateralized behaviour but not the relationship between behavioural and habenular asymmetry in convict cichlids (<Emphasis Type="Italic">Amatitlania nigrofasciata</Emphasis>)

Cerebral lateralization, the partitioning of functions into a certain hemisphere of the brain, is ubiquitous among vertebrates. Evidence suggests that the cognitive processing of a stimulus is performed with a specific hemisphere depending in part upon the emotional valence of the stimulus (i.e. whether it is appetitive or aversive). Recent work has implicated a predominance of right-hemisphere processing for aversive stimuli. In fish with laterally placed eyes, the preference to view an object with a specific eye has been used as a proxy for assessing cerebral lateralization. The habenula, one of the most well-known examples of an asymmetrical neural structure, has been linked to behavioural asymmetry in some fish species. Here, we exposed convict cichlid fish (Amatitlania nigrofasciata) to both a social and non-social lateralization task and assessed behavioural lateralization in either the presence or absence of an aversive stimulus, damage-induced alarm cues. We also assessed whether behavioural asymmetry in these tests was related to asymmetry of the habenular nuclei. We found that when alarm cues were present, fish showed increased left-eye (and by proxy, right hemisphere) preference for stimulus viewing. In addition, females, but not males, showed stronger eye preferences when alarm cues were present. We did not find a relationship between behavioural lateralization and habenular lateralization. Our results conflict with previous reports of concordance between behavioural and habenular lateralization in this fish species. However, our results do provide support for the hypothesis of increased right-hemisphere use when an organism is exposed to aversive stimuli.     

压力知觉对大学生抑郁的影响:有调节的中介模型

本研究采用压力知觉量表、心理韧性量表、领悟社会支持量表和抑郁量表考察压力知觉对大学生抑郁的影响机制,调查了中部地区5所大学746名大一到大四学生。研究显示：（1）心理韧性在压力知觉与大学生抑郁之间起部分中介作用;（2）领悟社会支持调节了这一中介过程,调节了压力知觉对大学生抑郁的影响及压力知觉对心理韧性的影响。可以通过降低大学生的压力知觉水平、提高心理韧性水平和领悟社会支持水平来减少其抑郁。     

网络受欺负对青少年睡眠问题的影响:压力感和抑郁的链式中介作用

为探讨网络受欺负、压力感、抑郁和青少年睡眠问题的关系,采用网络受欺负量表、抑郁-焦虑-压力量表、匹兹堡睡眠质量自评量表和传统受欺负量表对682名中学生进行调查,结果发现:(1)网络受欺负、压力感、抑郁以及睡眠问题两两之间显著正相关;(2)网络受欺负不仅直接正向预测青少年的睡眠问题,还可以通过压力感的单独中介作用以及压力感与抑郁的链式中介作用来间接影响睡眠问题。研究结果进一步揭示网络受欺负对睡眠问题的作用机制,能为减少网络受欺负对青少年情绪健康和睡眠质量的消极影响提供有益建议。     

Catastrophizing as a Cognitive Vulnerability Factor Related to Depression in Workers’ Compensation Patients with Chronic Musculoskeletal Pain

The purpose of this study was to examine the role of catastrophizing as a mediator and moderator between life stress and depression in a sample of workers’ compensation patients with chronic musculoskeletal pain. Pain intensity, life stress (especially work and financial stress), and catastrophizing contributed significantly to depression. Catastrophizing was found to be partially mediating the relationship between life stress and depression and a moderator between social stress and depression. The results supported the role of catastrophizing as a cognitive vulnerability-stress factor related to depression in chronic pain patients. Screening for life stress and intervening early to prevent catastrophizing from occurring in the workers’ compensation rehabilitation process may reduce psychosocial distress and enhance the overall effectiveness of rehabilitation programming for workers’ compensation patients with chronic pain.     

Substance P and Human Immunodeficiency Virus Infection: Psychoneuroimmunology

Effects on the immune system caused by changes in behavioral state or brain activity are mediated, at least in part, through neuroendocrine-immune pathways. Life stress and depression may be associated with altered blood levels of central nervous system-released neuropeptides, including substance P (SP). SP acts as a neuroregulator or neurotransmitter in the conduction of nociceptive stimuli, and is a modulator of neuroimmunoregulation. This review summarizes current knowledge regarding the role of the neuropeptide, SP, in psychoneuroimmunology, in particular as it relates to human immunodeficiency virus infection and acquired immunodeficiency disease syndrome. The association between depression, anxiety, and stress in HIV-disease progression suggests that neurobiologic and neurophysiologic factors play a role in modulating HIV infection and responses to antiretroviral therapy. Individuals with HIV or AIDS may experience stressful life circumstances that can result in increased symptoms of anxiety, stress, and/or depression. Furthermore, psychological and psychiatric symptoms, which occur in individuals with HIV and AIDS, may be related to the progression of AIDS disease. This review presents evidence from the literature, as well as findings from basic investigations conducted in the authors' laboratories, demonstrating that SP may play an important role in HIV pathophysiology. SP can impact the susceptibility of immune cells to HIV infection and modulate immune cell functions in ways that may affect the course of HIV in infected individuals. Moreover, modulation of SP activity and SP receptor is being explored for its potential as a novel therapeutic approach to the treatment of some psychological and psychiatric disorders and to the design of new anti-HIV therapy.     

In the Face of Uncertainty: A Twin Study of Ambiguous Information,Anxiety and Depression in Children

Anxiety and depression share genetic influences, and have been associated with similar cognitive biases. Psychological theories of anxiety and depression highlight threat interpretations of ambiguity. Little is known about whether genes influence cognitive style, or its links to symptoms. We assessed ambiguous word and scenario interpretations, anxiety and depression symptoms in 300 8-year-old twin pairs. There were significant correlations between both negative interpretations of ambiguous words and scenarios and depression symptoms after controlling for anxiety symptoms (r = .13 and .31, respectively), but no significant correlations with anxiety independent of depression. Genetic effects ranged from 16% for depression to 30% for ambiguous word interpretations. Non-shared environmental influences were large (68–70%). Both genetic and environmental influences contributed to the association between depression and ambiguous scenario interpretations. These findings support psychological theories, which emphasise the role of environmental stress both on the development of threat interpretations and on their links with symptoms. The data also support a role for genetic influence on threat interpretations, which may mediate responses to stress.     

Dysfunctional Attitudes Lead to Depressive Symptoms by Generating Subjective Stress

Previous studies have indicated that objective stress—negative events that have actually occurred outside of individuals—is involved in processes of dysfunctional attitudes leading to depression. Subjective stress—individuals' perception of negative events that have not actually occurred outside of them—is also predicted to be involved in these processes. However, few studies have empirically investigated this prediction. The primary purpose of this study was to fill this gap by testing the hypothesis that dysfunctional attitudes lead to depression by generating subjective stress. A longitudinal design was employed and initial depression was controlled. The results supported the hypothesis. It was also found that initial depression fostered subsequent depression by generating subjective stress. This study contributes to the literature on depression mechanisms by elucidating that subjective stress plays an important role in the development and exacerbation of depression. This study also has important clinical implications as it suggests that preventing subjective stress in individuals with dysfunctional attitudes or depression helps to protect the development or exacerbation of their depression.     

The mediating role of positive relations with others in associations between depressive symptoms, social skills, and perceived stress

This study was designed to examine the role of positive relations with others as a mediator of the association between poor social skills and depression and between depression and increased perceptions of stress. To test these two models, data were collected from 179 young adults assessed three times over the course of 4 months. Sobel’s product of coefficients test and lower-level mediation modeling were used to evaluate these predictions. The results showed that positive relations with others completely mediated the negative association between social skills and depression. Social skills also moderated the positive association between depression and perceptions of stress. These findings illustrate how positive relations with others function to promote psychological well-being.     

Protein kinase a in major depression: the link between hypothalamic-pituitary-adrenal axis hyperactivity and neurogenesis

The latest and most generative biological theories of major depression center on two major hypotheses. The first focuses on the concept that hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis leads to many of the pathological changes in the brain that accompany major depression. The second posits that neurogenesis leads to the repair of depression-related injuries. These two hypotheses are complementary: the former alludes to the etiology or consequences of depression, while the latter suggests mechanisms of antidepressant action. Significant crosstalk occurs between these two systems at many levels. Protein kinase A (PKA) may play an important role in this crosstalk at the intracellular level of signaling cascades. PKA is involved in the formation of long-term potentiation and fear conditioning in response to stress. Chronic stress leads to the suppression of hippocampal activity, which may cause the hyperactivity of the HPA axis during melancholic depression. PKA is also involved in the stimulation of hippocampal neurogenesis after antidepressant treatment. In theory, neurogenesis may lead to the restoration of hippocampal function, and this may be the mechanism that leads to antidepressant-mediated normalization of HPA hyperactivity. Thus, PKA is active during processes that potentially lead to depression and other processes that lead to the resolution of the illness. These opposing processes may be mediated by separate PKA isozymes that activate two distinct pathways. This review highlights the dual role of this enzyme in two biological hypotheses pertaining to depression and its treatment.