抑郁的多基因遗传基础

抑郁具有复杂的、非孟德尔式的多基因遗传模式, 但是目前多数抑郁的遗传研究集中于考察单个候选基因, 不能全面揭示遗传因素的作用机制。近年来, 多基因遗传得分研究和基因−基因交互研究分别为抑郁的多基因累加效应和交互效应提供了新的证据。多基因不仅直接影响抑郁, 还通过与环境因素的交互作用影响抑郁的发生发展, 并且这一复杂交互作用存在性别差异。抑郁的内表型研究发现多基因可能通过认知因素、人格、压力荷尔蒙等间接影响个体的抑郁水平。未来研究应更加关注多基因与多种环境因素如何相互作用影响抑郁, 探索多基因遗传机制的性别差异, 考察多基因对抑郁影响随年龄的发展动态变化。     

亲代孕前成瘾药物暴露对子代行为的影响及其表观遗传机制

孕前成瘾药物暴露不仅危害使用者的身体健康,而且会对子代的生理行为造成影响,近年来研究发现表观遗传机制在其中发挥重要作用。孕前成瘾药物暴露会对子代的成瘾易感性和焦虑样行为造成影响,引起子代的抑郁样行为和认知受损。这些现象可能是成瘾药物通过引起亲代生殖细胞内表观遗传修饰变化所致,其中包括印记基因、神经递质系统、BDNF三个方面的表观遗传修饰变化。此外,未来除了加强以上三个方面基因的研究,也需要增加其他方面基因的研究,以及寻找能预测子代异常行为的表观遗传生物标志物。     

抑郁遗传基础的性别差异

人类抑郁有着复杂的遗传基础并存在性别差异。抑郁遗传基础的性别差异主要表现在遗传的直接效应及遗传与环境的交互效应两个方面。本文在回顾、梳理既有抑郁遗传基础性别差异相关研究的基础上,进一步探讨了性激素、个体环境敏感性和中间表型在性别差异形成中的作用。未来该领域应关注遗传对抑郁的动态影响,进一步探讨多基因交互作用、不同类型与性质的环境指标与抑郁遗传基础性别差异的关联。     

表观遗传修饰在应激诱发抑郁症中的作用

应激可以对个体的生理和行为产生负面影响, 甚至导致抑郁症, 但病因机制尚不清楚。近年来许多研究发现应激导致的表观遗传修饰变化影响抑郁症的发生。表观遗传是指DNA序列不发生变化, 但基因表达却发生了可遗传的改变。应激引起的HPA轴、单胺类递质、BDNF三个方面的表观遗传修饰的变化, 在抑郁症发生中发挥重要作用。最后提出了目前表观遗传机制研究的局限性和未来研究热点。     

青少年抑郁情绪的行为遗传学研究

本研究意在探讨青少年抑郁情绪遗传率的性别和年龄差异及遗传和环境对抑郁情绪跨时间连续性的影响。508对同卵双生子, 176对同性别异卵双生子参加了两轮追踪研究, 时间间隔约为一年半(1.37±0.44)。第一轮测量双生子的年龄范围为10~18岁, 平均年龄为13.69±2.04岁, 男生比例为46.2%。采用儿童抑郁量表(CDI)对青少年的抑郁情绪进行多报告者评定。结果发现, 青少年抑郁情绪的遗传解释率不存在性别差异, 处于青春早期青少年的遗传解释率高于青春中期的青少年。遗传是影响青春早期青少年抑郁情绪持续发生的主导因素, 而环境是影响青春中期青少年抑郁情绪持续发生的主要因素。     

BDNF基因、同伴关系与青少年早期抑郁：基于动态发展视角

青少年抑郁是遗传基因与环境动态交互作用的结果,但是现有研究忽视了抑郁遗传效应的发展动态性。本研究通过对1086名青少年(平均年龄12.32,50%女生)进行3年的追踪,分别从遗传效应的年龄差异以及遗传效应影响抑郁发展轨迹的角度,考察BDNF基因与同伴关系对青少年抑郁的动态影响。结果显示：(1)在3个时间点上,BDNF基因与同伴拒绝交互影响青少年抑郁,但其作用模式存在年龄差异：12岁时,MetMet基因型携带者对环境敏感性高于ValMet基因型携带者;13岁时,MetMet和ValVal基因型携带者对环境的敏感性均高于ValMet基因型携带者;14岁时,ValVal基因型携带者对环境的敏感性高于ValMet基因型携带者。(2)青少年早期抑郁呈线性增长趋势,但是抑郁初始水平与增长速度无关。(3) BDNF基因与同伴拒绝交互预测青少年抑郁的初始水平,相比ValMet基因型,携带MetMet基因型的青少年在经历同伴拒绝后抑郁初始水平更高。(4) BDNF基因显著预测青少年抑郁增长速度,相比ValMet基因型携带者,携带MetMet和ValVal基因型的青少年抑郁增长速度更快。     

MAOA基因与抑郁的关系

抑郁的发生具有遗传基础。近年来, 随着分子遗传技术的发展, 对抑郁遗传机制的研究已经深入到分子水平。既有研究表明, MAOA基因在抑郁的发生发展中发挥着十分重要的作用。MAOA基因与抑郁间存在紧密的直接关联, 而且MAOA基因与环境及其他基因亦交互作用于抑郁, 然而, 既有相关研究结论尚存分歧。未来研究应更加关注MAOA基因与多种环境因素及其它基因间的复杂交互作用, 考察MAOA基因的年龄效应, 揭示MAOA基因作用于抑郁的脑机制。     

DRD4基因与亲社会行为的关联及其潜在脑机制

DRD4基因是亲社会行为的重要候选基因,且与环境交互影响亲社会行为的发生发展。通过梳理既有研究,本文从性别差异、亲社会行为的不同类型及发展动态性等角度探讨了亲社会行为遗传研究存在分歧的原因,并在此基础上探索了DRD4基因作用于亲社会行为的潜在脑机制。未来研究应采用纵向设计探究DRD4基因影响亲社会行为的发展动态性问题,并深入探索其性别差异;采用多质多法分析考察不同类型亲社会行为遗传机制的差异性;采用影像遗传学设计揭示“DRD4基因—脑—亲社会行为”作用机制。     

早期经历影响个体成年后行为的表观遗传学机制

既往研究已证实早期经历与个体成年后的行为密切相关,然而早期经历对个体成年后的行为产生长期影响的分子生物机制并不清楚。近年来越来越多的研究表明表观遗传因素在早期经历调控成年个体行为中发挥了重要功能。表观遗传是研究没有DNA序列变化,但是可遗传和可逆转的基因组功能的调控。本文试图从早期经历参与调控个体成年后行为表现以及基因表达的相关表观遗传学修饰进行综述。     

青少年抑郁:基于社会支持的视角

青少年罹患抑郁的社会因素受到研究者们的密切关注,尤其是社会支持因素。本文首先总结了社会支持与青少年抑郁关系的内在机制,包括主效应机制和缓冲效应机制;其次论述了影响社会支持与青少年抑郁关系的多种因素,主要涉及来自于社会支持提供者、社会支持接受者和测量方法等方面的因素。社会支持提供者因素包括性别、数量和社会地位;社会支持接受者因素包括性别、年龄、个体内在特征、人格特征以及遗传;此外方法主要涉及社会支持与抑郁症的测量。最后提出了未来的研究方向,如测量方法的改进、元分析纵向研究的开展、线上支持的研究,为青少年抑郁的社会干预提供更多的研究视角。     

Behavioral Genetics and Personality Change

Although research on personality and behavioral genetics has focused on the continuity of traits, both fields and their interface will profit from the consideration of trait change. In this article we review personality research on age differences in heritability and propose the counterintuitive hypothesis that, when developmental changes in heritability are found, heritability tends to increase. We also focus on behavioral genetic analyses of long-term developmental change. Research to date suggests that genetic involvement in adult personality change is slight whereas personality change in childhood is governed substantially be genetic factors. Finally, we consider a new topic, genetic influence on short-term change in personality.     

Developmental imaging genetics: Linking dopamine function to adolescent behavior

Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to non-invasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach.     

The Relation Between Eating- and Weight-Related Disturbances and Depression in Adolescence: A Review

Depression often emerges during adolescence and persists into adulthood. Thus, it is critical to study risk factors that contribute to the development of depression in adolescence. One set of risk factors that has been recently studied in adolescent depression research is eating- and weight-related disturbances (EWRDs). EWRDs encompass negative cognitions related to one’s body or physical appearance, negative attitudes toward eating, and unhealthy weight control behaviors. However, there have been no comprehensive reviews of EWRDs and depression research that are contextualized within developmental frameworks of adolescent depression. Thus, this review will summarize research findings on the relation between EWRDs and depression in adolescence using a cognitive vulnerability developmental framework. First, a brief overview of epidemiological findings on depression is provided in order to highlight the importance of examining depression in adolescence. Second, a cognitive vulnerability developmental framework that can be used to conceptualize depression in adolescence is described. Next, theories and findings on EWRDs and depression in adolescence are summarized within this framework. Research limitations and suggestions for future research are provided. Finally, implications of this review related to the assessment, intervention, and prevention of depression in adolescence are provided.     

Is the child ‘father of the Man’? Evaluating the stability of genetic influences across development

This selective review considers findings in genetic research that have shed light on how genes operate across development. We will address the question of whether the child is ‘father of the Man’ from a genetic perspective. In other words, do the same genetic influences affect the same traits across development? Using a ‘taster menu’ approach and prioritizing newer findings on cognitive and behavioral traits, examples from the following genetic disciplines will be discussed: (a) developmental quantitative genetics (such as longitudinal twin studies), (b) neurodevelopmental genetic syndromes with known genetic causes (such as Williams syndrome), (c) developmental candidate gene studies (such as those that link infant and adult populations), (d) developmental genome‐wide association studies (GWAS), and (e) DNA resequencing. Evidence presented here suggests that there is considerable genetic stability of cognitive and behavioral traits across development, but there is also evidence for genetic change. Quantitative genetic studies have a long history of assessing genetic continuity and change across development. It is now time for the newer, more technology‐enabled fields such as GWAS and DNA resequencing also to take on board the dynamic nature of human behavior.     

The neurodynamics of emotion: delineating typical and atypical emotional processes during adolescence

The study of development is, in and of itself, the study of change over time, but emotions, particularly emotional reactivity and emotional regulation, also unfold over time, albeit over briefer time‐scales. Adolescence is a period of development characterized by marked changes in emotional processes and rewiring of the underlying neural circuitry, making this time of life formative. Yet this period is also a time of increased risk for anxiety and mood disorders. Changes in the temporal dynamics of emotional processes (e.g. magnitude, time‐to‐peak and duration) occur during this developmental period and have been associated with risk for mood and anxiety disorders. In this article, we describe how the temporal dynamics of emotions change during adolescence and how they may increase risk for these psychopathologies. We highlight studies that illustrate how formalizing temporal neurodynamics of emotion may enhance links among levels of analyses from neurobiological to real‐world, moment‐to‐moment experiences.     

Are genetically informed designs genetically informative? Comment on McGue, Elkins, Walden, and Iacono (2005) and quantitative behavioral genetics

M. McGue, I. Elkins, B. Walden, and W. G. Iacono presented the findings from a twin study examining the relative contributions of genetic and environmental factors to the developmental trajectories of parent-adolescent relationships. From a behavioral genetics perspective, this study is well conceptualized, is well implemented, and raises some interesting developmental questions. Yet, the classic twin methodology and heritability estimates obfuscate the dynamic gene-ecology transactions that underlie these social developmental trajectories. There is a growing divide between the findings of quantitative behavioral genetics, with its foundational estimate of a statistical genetic influence, and developmental molecular genetics. This comment provides a brief overview of this divide and its implications for the findings of McGue et al. as well as quantitative behavioral genetics more broadly.     

早发性抑郁及其神经基础

儿童期和青少年期抑郁（早发性抑郁）表现出与成年期抑郁不同的一些临床症状、药物疗效和生理反应特征,导致这些差异的神经生物学基础目前尚不清楚。儿童期和青少年期神经系统的发展变化可能参与早发性抑郁的病生理,尤其是单胺能神经递质系统结构和功能的变化与早发性抑郁的生理和药物治疗反应密切相关。早发性抑郁动物模型的建立是研究早发性抑郁脑机制的基础,未来研究的重点是发展有效的早发性抑郁治疗药物和早期心理行为干预技术     

Developmental dynamics: toward a biologically plausible evolutionary psychology

There has been a conceptual revolution in the biological sciences over the past several decades. Evidence from genetics, embryology, and developmental biology has converged to offer a more epigenetic, contingent, and dynamic view of how organisms develop. Despite these advances, arguments for the heuristic value of a gene-centered, predeterministic approach to the study of human behavior and development have become increasingly evident in the psychological sciences during this time. In this article, the authors review recent advances in genetics, embryology, and developmental biology that have transformed contemporary developmental and evolutionary theory and explore how these advances challenge gene-centered explanations of human behavior that ignore the complex, highly coordinated system of regulatory dynamics involved in development and evolution.     

Raised by Depressed Parents: Is it an Environmental Risk?

The mechanisms explaining how parental depression compromises healthy child development are complex and multifaceted, with genetic and environmental pathways intertwined. Reexamination of whether and how maternal and paternal depression serve as environmental risk factors is important because such an investigation can be helpful to identify modifiable mechanisms that are accessible to interventions. We review studies that have employed designs that isolate the effects of the environment from genetic influences, including adoption studies and children of twins studies. Findings indicate that maternal depression is an environmental risk factor for the emotional, behavioral, and neurobiological development of children. Although more studies are needed, preliminary findings suggest that paternal depression appears to be a weaker environmental risk as compared to maternal depression, at least during infancy and toddlerhood. Implications for theory and future research are discussed.