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     

缰核在抑郁症中的作用:研究和治疗的新途径

缰核是哺乳动物神经系统中连接前脑和中脑的重要节点,这一古老的核团因其与抑郁症的密切联系,近来获得国内外研究者的关注.缰核接受来自边缘系统、基底神经节等的传入信号,向下投射到中脑5-羟色胺系统和多巴胺系统.在应激条件下缰核免疫活动增强,向下游的投射信号增强,以此调节单胺类递质释放,参与抑郁症的发病机制,并且参与抗抑郁治疗的起效途径.这些证据提示缰核在抑郁症中具有重要作用,将成为研究和治疗的新途径.未来研究应从缰核与上下游核团的神经联系、与丘脑-垂体-肾上腺轴的相互影响、以及与免疫激活的交互作用等方面进一步探索,为研究抑郁症病理机制和治疗方法提供线索.     

骨源性因子ucOCN在运动抗抑郁中的作用机制

羧化不全骨钙素(ucOCN)是骨中成骨细胞分泌的特异性蛋白, 因其在调控神经发育、神经可塑性等中的重要角色而受到神经科学领域关注。“骨-脑”串联“对话”是骨内分泌-神经介导的应答系统, ucOCN透过血脑屏障后介导单胺类神经递质、神经内分泌、神经免疫、神经再生及基因表达等机制, 进而作用于海马CA3区、扣带回等脑区功能发挥来调节抑郁发生及改善。而ucOCN作为骨源性力学刺激敏感基因, 运动上调其表达后进入血液循环, 通过介导5-HT/GABA分泌、HPA轴功能、炎症反应、神经营养因子(BDNF等)表达或信号途径(如GSK3β/β-catenin、TLR4/miR-223/NLRP3等)激活等来实现“骨串联脑”, 发挥运动抗抑郁作用。通过对骨源性因子ucOCN介导脑区功能变化从而实现运动抗抑郁的作用机制进行探讨、梳理, 一方面有助于更深入了解骨内分泌功能, 另一方面为抑郁发生、改善和运动抗抑郁研究提供新的理论基础和研究思路。     

膳食营养与抑郁症的关系

近十几年, 膳食营养与抑郁症的关系受到了研究者越来越多的重视。早期的研究主要考察单一营养元素或食物对于抑郁症的影响, 其中研究最多的是n-3多不饱和脂肪酸和叶酸, 近期的研究开始关注整体膳食模式与抑郁症的联系。膳食营养与抑郁症关联的内在机制涉及炎症反应、氧化应激和脑源性神经营养因子等。以流行病学为主的研究现状限制了膳食营养影响抑郁症的因果解释, 未来的研究应强化对两者关联的内在机制以及现实价值的考察。     

抑郁症发病机理中的重要调节因子:吲哚胺2,3-双加氧酶

抑郁症的发病存在多种假说,其中较为公认的有细胞因子假说,下丘脑-垂体-肾上腺皮质(hypothalamus-pituitary-adrenocortical,HPA)轴假说,单胺能假说,神经可塑性假说等,不同假说可能从不同角度探讨抑郁症的病理机制,但各种假说都与吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)的调节有关。IDO是一种色氨酸降解酶,其活性能够被前炎性细胞因子所增强。IDO活性的增强使色氨酸更多地代谢为犬尿氨酸(kynurenine,KYN),从而可能导致生成5-羟色胺(serotonin,5-HT)的原料不足,5-HT生成减少。而且,色氨酸-犬尿氨酸代谢通路的下游产物犬尿喹啉酸(kynurenicacid,KYNA),喹啉酸(quinolinic acid,QUIN)及3-羟基犬尿氨酸(3-hydroxykynurenine,3HKYN)等影响神经元的再生与退化。另外,应激激素也可以通过色氨酸2,3-双加氧酶(tryptophan 2,3-dioxygenaes,TDO)或免疫系统影响IDO的功能。IDO是抑郁症多种假说病理机制中的共同调节因子,可能在抑郁病的发病中具有重要作用。     

运动抗抑郁作用的神经营养假说

身体锻炼具有促进心理健康的作用, 特别是通过体育锻炼能够有效缓解抑郁样症状及临床抑郁。有关抑郁的神经营养假说认为, 抑制成年海马神经发生以及神经营养因子的表达是导致抑郁的关键因素; 增加成年海马神经发生以及神经营养因子的表达能够产生抗抑郁的作用。本文通过综述认为, 运动能够诱导成年海马神经发生以及神经营养因子表达的增加可能是运动抗抑郁作用的主要机制, 且类似于药物的抗抑郁治疗作用。     

不同感觉功能对抑郁的影响及其神经机制

大脑通过视觉、听觉、嗅觉、味觉和触觉等感官通道接收来自外界的信息。不同感觉功能受损涉及抑郁发生的中枢机制,而基于不同感官通道进行适当刺激以及多感官联合干预也可能发挥显著的抑郁治疗作用。笔者以症状-脑区-机制-治疗为逻辑主线,首次系统梳理了五种主要感觉障碍人群的抑郁临床症状、抑郁神经机制以及基于感觉刺激的抗抑郁治疗。结果表明,不同感觉功能障碍对抑郁相关神经机制的影响可能表征了不同的抑郁病理,涉及神经元电活动(某些神经元放电和神经环路激活等)和神经生化改变(神经可塑性和神经发生、炎症免疫和HPA轴、神经激素和神经递质等),且主要发生在边缘系统及其附近脑区,涉及岛叶、颞叶、额叶等。因此,未来研究可聚焦于机体对不同感觉信息的提取,这将为人类抑郁的病因和治疗提供新的研究视角。     

一个测量抑郁症的重要神经指标:静息额叶脑电活动的不对称性

额叶脑电活动的不对称性指即指额叶脑电图(electroencephalogram,EEG)偏侧化,其考察的是左侧额叶和右侧额叶alpha波(8~13 Hz)的活动。越来越多的研究证据表明,静息额叶EEG偏侧化程度与抑郁症密切相关。回顾国内外关于静息额叶EEG偏侧化与抑郁症之间关系的研究结果和现状,发现静息额叶EEG偏侧化程度与抑郁水平负相关,患有抑郁症个体的静息额叶EEG相对右侧化,伴随着右侧额叶更大的活动;从短期和长期而言,抑郁个体静息额叶EEG偏侧化具有稳定性;静息额叶EEG偏侧化对个体的抑郁水平具有预测作用。除此之外,静息额叶EEG偏侧化可能反应了背外侧前额叶皮层的活动,其中,左侧背外侧前额叶皮层可能在抑郁症的形成中起了一个主要的作用。未来的研究可致力于进一步探讨静息额叶EEG偏侧化预测抑郁症的神经机制、静息额叶EEG偏侧化对抑郁水平预测的可应用性,尝试通过训练(比如,正念冥想训练)来改变抑郁个体的静息额叶EEG偏侧化程度,进而缓解个体的抑郁水平。     

抑郁症网络化自助干预的效果及作用机制——以汉化MoodGYM为例

抑郁症是全球性的重要公共健康问题,抑郁症的网络化认知行为治疗近年来备受关注。本研究采用随机对照组试验考察抑郁症网络化干预程序Mood GYM中文版对中国大学生抑郁患者的在线干预效果,并且使用多重中介模型同时探索了基于临床实践提出的认知歪曲(ATQ和DAS)与认知领域研究发现的解释偏差(SST)在抑郁症网络化认知行为治疗中的作用机制。结果发现:(1)相较之对照组,Mood GYM对中国大学生抑郁的网络化自助干预具有中到大的效果量(CES-D,d=0.93;PHQ-9,d=0.79);(2)Mood GYM也显著降低抑郁患者的负性自动思维(ATQ)、消极解释偏差(SST)和功能失调性态度(DAS);(3)自动思维(ATQ)和消极解释偏差(SST)二者的改变在抑郁症网络化认知行为治疗效果中起中介作用,功能失调性态度改变的中介效应不显著。抑郁症的网络化干预还存在着诸如脱落率较高等多种局限,推荐作为传统心理治疗的额外补充手段,也可作为梯度治疗模型的自助式初级干预。     

运动如何影响青少年抑郁：回顾与展望

近年来运动作为成人临床抑郁症治疗的替代疗法开始受到越来越多的关注,实证研究也支持运动对青少年抑郁症状具有积极影响作用,本文在此基础上系统梳理前人研究,分别对相关横纵向调查和实验干预研究进行回顾,分析总结了运动对青少年抑郁症状影响作用的研究进展。同时,我们对该作用现有的心理假说：自我效能、注意分散、自尊假说和神经生物假说包括神经内分泌、神经营养因子、氧化应激、炎症、皮质厚度和活性、表观遗传假说等分别进行了阐述,结合相关研究结果对这些假说进行了分析探讨。最后,我们认为,未来研究应不断完善相关设计,关注不同运动类型,并结合中国特色,深入探讨在青少年抑郁障碍群体中的最佳抗抑郁运动方案及其作用机制。     

下丘脑异常与抑郁症

近年来的研究发现了抑郁模型动物或抑郁症病人下丘脑异常的大量证据, 诸如下丘脑体积及神经元数目的改变, 下丘脑-垂体-内分泌轴的改变, 下丘脑相关激素、受体及其基因、神经肽的改变, 下丘脑与其他脑区功能联系的改变等等。然而, 下丘脑与抑郁症关系的研究所获证据多来自动物实验、或临床间接指标(如病人外周血激素水平等), 或病人脑组织尸检, 缺乏来自病人活体下丘脑异常的直接证据。今后的研究可考虑运用影像学的手段更直接地探索抑郁症患者活体下丘脑的结构特征和功能特征, 以期发现抑郁症的生物学标记及其可靠性指标, 为抑郁症的客观诊断提供依据, 为揭示抑郁症病理机制提供线索。     

Transient versus enduring depression among alcoholics in inpatient treatment

The purposes of this study are (1) to determine the incidence of significant clinical depression among alcoholics at treatment intake at a Veterans Medical Center, (2) to subdivide alcoholics who show significant clinical depression into enduring and transient depressive subgroups, and (3) to identify demographic and psychometric variables useful in discriminating between these two subgroups. Results indicate that of the 60% of VA inpatient alcoholics who showed evidence of significant clinical depression at intake, approximately equal numbers met criteria for inclusion in transient and enduring depressive subgroups. Patients with enduring and transient depression, as defined in this study, were differentiated on the basis of age, drinking pattern, and selected scales from two psychometric instruments which measure depression, confused and disorganized thinking, and an avoidant personality style. These findings may be useful in assisting clinicians in differentiating between alcoholic patients with transitory depression associated with alcohol consumption and/or withdrawal and alcoholic patients with more serious and enduring depression, which may require additional pharmacologic and/or psychotherapeutic intervention.     

GENDER DIFFERENCES IN DEPRESSIVE SYMPTOMS

Large community studies of depressive symptomatology provide mixed evidence concerning gender differences. The present paper investigates the effect of the high skewness typically present in distributions of depressive symptom scores on findings of a gender difference in depression. Because of this skewness, a few extreme scores among women (or in any subgroup) can produce a significant between-groups difference in untransformed scores even when the two groups' distributions are otherwise similar. Data from a community survey ( n = 1316) are consistent with this hypothesis. The data also suggest that gender increases depression scores indirectly, rather than directly, for the few women scoring in the extreme upper tail of the distribution. It is concluded that the gender difference in depressive symptoms lacks robustness, and that when it does occur, the effect of gender on depression can be understood as ndirect, i.e., as mediated by gender differences in rate of employment, job status, education, and income.     

Clinical implications of "subthreshold" depressive symptoms

There is active debate regarding whether diagnosable depression exists on a continuum with subthreshold depressive symptoms or represents a categorically distinct phenomenon. To address this question, multiple indexes of dysfunction (psychosocial difficulties, mental health treatment history, and future incidence of major depression and substance abuse/dependence) were examined as a function of the extent of depressive symptoms in 3 large community samples (adolescent, adult, and older adult; N = 3,003). Increasing levels of depressive symptoms were associated with increasing levels of psychosocial dysfunction and incidence of major depression and substance use disorders. These findings suggest that (a) the clinical significance of depressive symptoms does not depend on crossing the major depressive diagnostic threshold and (b) depression may best be conceptualized as a continuum. Limitations of the present study are discussed.     

Dietary ethyl-eicosapentaenoic acid but not soybean oil reverses central interleukin-1-induced changes in behavior, corticosterone and immune response in rats

Omega (n)-3 and n-6 fatty acids are important membrane components of neurons and immune cells, and related to psychiatric and inflammatory diseases. Increased ratio of n-6/n-3 in the blood has been reported in depressed patients and in students following stress exposure. The n-3 fatty acid, eicosapentaenoic acid (ethyl-EPA) suppresses inflammation and has antidepressant properties. Interleukin (IL)-1beta can stimulate corticosterone secretion, induce anxiety and stress-like behavior and inflammatory responses. This study was to evaluate the effect of diets enriched with coconut oil, ethyl-EPA and soybean oil on central IL-1beta induced stress and anxiety-like behavior, induced changes in the concentration of prostaglandin (PG) E2 and corticosterone and the release of IL-10. Groups of rats were fed with either 5% coconut oil (as control diet), 0.2% EPA with 4.8% coconut oil or 1% EPA with 4% coconut oil and 5% soybean oil for 7 weeks. The central administration of IL-1beta induced sickness, stress and anxiety-like behavior as indicated by a reduction in body weight, decreased time spent, and the number of entries, into the open arms of the elevated plus maze and decreased exploration and entry into the central zone of the "open field" apparatus. IL-1beta also increased PGE2 and corticosterone concentrations and decreased the release of IL-10 from leucocytes. Food enriched with ethyl-EPA but not soybean oil, significantly attenuated most of these changes. These results demonstrate that ethyl-EPA has anti-inflammatory, anti-stress and anti-anxiety effects in rats.     

反馈相关负波：一种抑郁症的生物标记物

反馈相关负波(feedback-related negativity, FRN)是一种反映个体奖赏敏感性的脑电成分; 而抑郁症患者的特征之一是奖赏敏感性的减弱。大量横向研究发现了重度抑郁症患者(major depressive disorder, MDD)及有患抑郁症风险群体的FRN异常; 另外, 纵向研究发现FRN的异常能够预测青春期抑郁发作及抑郁症状发展, 压力、睡眠等因素在其中起调节作用。这提示FRN可能在对抑郁症的诊断及分型、抑郁高危群体的筛查及干预等方面具有潜在价值。目前关于FRN的心理功能依然存在一些争议, 在未来的研究中应该进一步明确FRN的功能和测量方法, 并探明抑郁症的异质性和共病对FRN的作用, 也应关注老年人群体中FRN与抑郁症的关系。     

Can imaginal exposure reduce intrusive memories in depression? A case study

The presence of intrusive memories as an overlapping feature of depression and posttraumatic stress disorder (PTSD) raises the possibility that common therapeutic approaches may be effective. Imaginal exposure (IE) is the gold-standard treatment for PTSD and directly reduces both PTSD and depression symptoms in traumatized individuals. The objective of this pilot study was to use a single-case design to trial the use of IE to target intrusive memories of a negative life event as a treatment for major depression. The participant was experiencing depression after a relationship breakup. Pre-posttreatment measures (clinical interview and self-report) showed a decrease in frequency of intrusive memories and improved mood, such that the participant no longer met diagnostic criteria for major depression at posttreatment or at 6-month follow-up. This case is an important first step in demonstrating the possible value of IE as an inclusion in therapy to reduce intrusive memories in patients whose depressive episode is precipitated by a stressor. Further application of IE to additional depressed clients in the context of a case series is needed to provide preliminary evidence of its efficacy as a treatment for depressive disorders.     

Teasdale's differential activation hypothesis: implications for mechanisms of depressive relapse and suicidal behaviour

Teasdale's differential activation hypothesis (DAH) has been proposed as one account of cognitive vulnerability to depression. This view holds that important factors determining whether one's initial depression becomes more severe or persistent are the degree of activation, and content, of negative thinking patterns that become accessible in the depressed state. This phenomenon has been referred to as cognitive reactivity. Empirical support for the predictions of this model derives from a combination of cross-sectional and prospective studies. In this article, we evaluate this evidence with the goal of determining whether mood-induced cognitive reactivity can be considered a risk factor for depressive relapse/recurrence. Our review demonstrates sufficient evidence to consider cognitive reactivity as a potential causal risk factor for depressive relapse/recurrence. Furthermore, we extend the application of this model to the problem of suicidal relapse/recurrence including a review of preliminary support for this approach.     

Docosahexaenoic Acid and Visual Functioning in Preterm Infants: A Review

Preterm children are at risk for a number of visual impairments which can be important for a range of other more complex visuocognitive tasks reliant on visual information. Despite the relatively high incidence of visual impairments in this group there are no good predictors that would allow early identification of those at risk for adverse outcomes. Several lines of evidence suggest that docosahexaenoic acid (DHA) supplementation for preterm infants may improve outcomes in this area. For example, diets deficient in the long-chain polyunsaturated fatty acid DHA have been shown to reduce its concentration in the cerebral cortex and retina, which interferes with physiological processes important for cognition and visual functioning. Further, various studies with pregnant and lactating women, as well as formula-fed infants, have demonstrated a general trend that supplementation with dietary DHA is associated with better childhood outcomes on tests of visual and cognitive development over the first year of life. However, research to date has several methodological limitations, including concentrations of DHA supplementation that have been too low to emulate the in utero accretion of DHA, using single measures of visual acuity to make generalised assumptions about the entire visual system, and little attempt to match what we know about inadequate DHA and structural ramifications with how specific functions may be affected. The objective of this review is to consider the role of DHA in the context of visual processing with a specific emphasis on preterm infants and to illustrate how future research may benefit from marrying what we know about structural consequences to inadequate DHA with functional outcomes that likely have far-reaching ramifications. Factors worth considering for clinical neuropsychological evaluation are also discussed.