成瘾相关记忆的表观遗传学机制 ——药物成瘾研究的新视角

成瘾相关记忆长期性的脑机制一直是药物成瘾研究领域的难点与热点,该文简要介绍了成瘾记忆长期性分子机制的研究脉络,提示表观遗传学修饰可能是研究药物成瘾的新视角。成瘾药物可以调节染色体不同亚型组蛋白乙酰化水平,不同基因DNA的甲基化程度从而改变染色体的空间结构,进而调节基因的表达导致成瘾,特别是DNA甲基化改变的相对的稳定性可能是成瘾记忆长期存在的分子基础。记忆再巩固过程中学习记忆相关脑区的记忆促进基因与记忆抑制基因的表观遗传学改变可能是未来研究的新趋势     

胚胎期可卡因、吗啡暴露影响子代成瘾相关行为的神经发育机制

孕期使用毒品可影响胎儿大脑的正常发育,导致脑内神经递质系统异常以及行为的改变.近年来不断有研究证据提示,胚胎期接触可卡因、吗啡等成瘾药物,可以影响神经细胞的增殖、迁移或凋亡等发育过程,使中脑皮层边缘系统中多巴胺、GABA、谷氨酸等神经元形态、受体功能以及突触可塑性发生改变,从而导致子代的学习记忆和成瘾易感性等行为异常.本文将从行为、神经发育、递质系统以及脑功能等层面归纳胚胎期用药对成瘾相关行为影响机制的重要研究进展,并试图提出可能的研究展望.     

新颖寻求特质对药物成瘾易感性的影响及其机制

新颖寻求特质是个体对新颖刺激或潜在的奖赏线索表现出愉悦或兴奋的先天倾向, 并且这种先天倾向会导致个体为寻求潜在的奖赏进行频繁的探索性活动。众多研究表明, 新颖寻求水平高的个体药物成瘾易感性高。多巴胺、5-羟色胺、谷氨酸、γ-氨基丁酸、胆囊收缩素、成纤维细胞生长因子及皮质酮可能参与了新颖寻求特质影响药物成瘾易感性的过程。未来, 仍需对新颖寻求特质影响药物成瘾易感性的神经生物学机制进行深入研究。     

非药物成瘾的遗传学和神经生物学机制研究述评

非药物成瘾又称“非物质相关性成瘾”或“行为成瘾”。特征性表现包括对成瘾对象的渴望、受损的冲动控制、对成瘾对象的耐受、撤退反应和高复发率等。目前发现的非药物成瘾类型包括病理性赌博、网络成瘾、购物成瘾、游戏成瘾、性瘾以及贪食等。非药物成瘾与药物成瘾在症状学上表现出很高的相似性且具有较高的共病率, 提示二者之间可能存在着共同的发病机制。从遗传学和神经生物学的角度探讨非药物成瘾的机制具有重要的理论价值和临床应用价值。家庭研究和双生子研究发现, 男性的病理性赌博和贪食障碍具有中度以上的遗传度。分子遗传学研究发现, 单胺能神经递质相关基因, 如5-羟色胺转运体基因、多巴胺受体基因和单胺氧化酶A基因等, 与非药物成瘾有关。神经影像学研究发现, 非药物成瘾者脑内负责奖赏,线索加工和冲动控制的神经通路活动性异于正常对照。未来研究需要进一步从多个角度入手, 探讨非药物成瘾与药物成瘾的共性和特性。     

强迫性特征在药物成瘾行为中的易感性及其前额叶-反奖赏系统神经基础

强迫性是一种与不顾严重后果的固着行为密切相关的神经心理结构, 大脑神经系统对强迫性行为的调控机制崩溃是导致药物成瘾的直接原因。以往研究对于奖赏系统(中脑-皮层-边缘神经环路)在成瘾行为中的作用及机制已经具有丰富的了解, 但针对药物成瘾的强迫性特征本身以及前额叶-反奖赏系统神经环路在成瘾行为中的作用机制了解有限, 尤其是缺乏对药物成瘾强迫性特征的系统考察、缺少遗传学研究以及非兴奋剂类药物的汇聚证据。项目拟结合人类成瘾行为的遗传学视角(海洛因成瘾者与其无药物使用的兄弟姐妹对照), 结合神经认知、脑电生理、神经影像等不同层面的方法和技术, 对药物成瘾强迫性的外在表征、神经生物学基础以及与个体差异有关的遗传易感性进行探索, 期在进一步识别药物成瘾的神经生物标记, 为探寻潜在的药物或非药物干预靶点提供更多证据。     

药物成瘾行为的脑机制及其研究进展

药物成瘾是脑内相关核团和细胞在药物反复作用下发生适应性变化的时间依赖过程。成瘾的适应性学说从ｃＡＭＰ水平调节、阿片和多巴胺受体与Ｇ蛋白家族耦联等方面,为成瘾形成机制提供了最基本的生物学范畴的理论解释。实验证据在一定程度上揭示了从给药到耐受、敏感、依赖,再到撤药症状的生物变化过程。然而,阐明从急性给药到特殊脑区持续性的适应机制仍然是当前成瘾研究最具挑战性的目标之一。     

时间洞察力对成瘾行为的影响及其机制

成瘾行为给个体和社会带来了严重的危害。对成瘾人群时间洞察力的研究成为探讨成瘾行为产生和发展的一个新的视角。过去消极、现在享乐和现在宿命时间洞察力取向的个体更可能出现成瘾行为, 而未来时间洞察力取向则是成瘾行为的一个保护性因素, 它不仅可以减少成瘾行为的发生, 也有利于成瘾行为的康复。从自我调节, 冲动性决策等行为机制和前额叶的神经机制方面可以帮助我们深入理解时间洞察力对成瘾行为的影响。未来研究可以进一步探讨不同成瘾行为者时间洞察力的一致性与特异性; 采用纵向研究方法探讨成瘾者时间洞察力的动态变化过程; 对成瘾者的洞察力进行干预, 增加成瘾者的未来时间洞察力, 减少其过去消极和现在时间洞察力取向来帮助成瘾者实现时间洞察力的平衡, 从而提高其戒断效果。     

药物成瘾的易感性生物标记：从神经认知到分子遗传的证据

药物成瘾作为一种慢性复发性的脑疾病,具有从偶然性用药、规律性用药到强迫性用药的渐进式发展特征。研究提示,药物成瘾存在潜在的个体易感性机制,即在成瘾发生过程中不同个体接触药物后的成瘾风险并不相同,探索药物成瘾的神经生物标记是揭示成瘾易感性机制的重要途径。近十多年来,关于成瘾易感性标记的研究不断积聚。文章从神经认知、神经影像及脑电生理、分子遗传等层面梳理与药物成瘾生物标记有关的证据,试图在基因-大脑-心理-行为的理论框架下,对成瘾的发生发展机制进行综合阐释,期望为未来研究在探索药物成瘾的候选神经生物标记、寻找临床干预试验的精准靶点等方面提供更多理论参考。     

易感人格的工作记忆特征对药物成瘾的调节机制

药物成瘾是指持续使用成瘾药物, 出现耐受性和戒断症状并严重阻碍正常社会功能的精神疾病。工作记忆在调节药物成瘾行为中扮演了中心角色：在神经易感性和易感人格特质基础上, 低工作记忆容量导致危险决策和去抑制性, 进而影响寻求药物和复吸行为。目前的研究基于已经产生成瘾的个体, 无法区别神经易感性、人格特质以及工作记忆缺陷是药物成瘾的原因还是结果; 而且, 仅从认知角度研究药物成瘾的原因, 会忽视该行为受多个因素影响的事实。     

冲动性对不同成瘾行为发展的调控及其神经机制

近年来越来越多的研究证据提示, 个体冲动性在成瘾疾患发生发展机制中具有关键作用, 可能成为成瘾行为的潜在易感标记以及早期识别和干预的重要靶点, 但冲动性对不同成瘾行为变化发展的调控机制尚不明确。项目拟综合跨成瘾谱系比较、纵向追踪设计、冲动行为干预等研究途径, 采用人格测量、神经认知、神经影像等技术, 首先比较尼古丁依赖者与网络游戏成瘾者的冲动性结构及其在前额叶–纹状体环路的结构功能改变; 然后采用混合分组设计筛选出具有高低冲动性的非成瘾青少年进行连续追踪研究, 考察冲动性对尼古丁依赖与网络游戏成瘾的预测效力; 并采用认知行为训练, 对吸烟成瘾者与网络游戏成瘾者进行冲动干预, 考察行为干预对冲动性水平及前额叶–纹状体环路功能的改变, 以及对不同成瘾行为发展的抑制后效。旨在探索冲动性作为成瘾的潜在易感标记及干预靶点的效力。     

The impact of parental multiple sclerosis on the adjustment of children and adolescents

Thirty-one parents with multiple sclerosis (MS) participated in a study to investigate the adjustment of their children, 24 boys and 24 girls aged 4 to 16 years. The majority of parents believed that their illness had an effect on their children. The perception of parents regarding their children's problems in the areas of emotions, concentration, behavior, or social interactions indicated that the children were at three times greater risk than the general community of developing psychological problems. In contrast, actual symptom scores reported by parents revealed that, although these children were at greater risk than the general community of developing peer problems, little difference was found on hyperactivity, emotional symptoms, conduct problems, or total difficulties. Parental negative affect predicted both parental reports of peer problems and perceptions that the parents' illness had an effect on their children. Parental relationship satisfaction and family income did not predict parental reports of children's level of adjustment. These results indicate that children of parents with MS demonstrate more difficulties in how they relate to others, the distress they experience, and how they manage their lives, rather than revealing higher levels of symptoms. Since the data were based on parental reports of their children's problems, the results may also be due to negative affect among the parents.     

The impact of parental divorce on the attainment of the developmental tasks of young adulthood

The purpose of this study was to assess the impact of parental divorce on young adult development. One hundred twenty-five participants provided demographic information and completed the PAFS-Q (college version) and the conflict subscale of the Family Environment Scale. Results indicate that parental divorce and family conflict significantly affect developmental task attainment. The interactions between sex and age and family structure (i.e., single-parent or stepfamily) were also significant predictors of post-divorce task attainment. Implications of these results for therapists as well as recommendations for future research are provided.This is a revised version of a paper presented at the annual conference of the American Psychological Association, Los Angles, California, August 1994.     

The impact of parental attachment and supervision on fear of crime among adolescent males

This paper examines the effect of parental attachment and supervision on fear of crime among adolescent males. Earlier work has suggested that feelings of powerlessness and association with deviant peers have a significant impact on adolescent fear of crime. As the nature of the parent-adolescent relationship is also a key predictor of adolescent self-concept and quality of peer relationships, we felt that parental attachment and supervision should also impact fear of crime. Using self-report surveys from 318 incarcerated adolescent males, we examine the effect of parental attachment and supervision, along with other demographic and contextual variables, on fear of criminal victimization, perceived safety, and perceptions of risk. The results indicate that those boys who are most attached to their parents are less fearful of criminal victimization and feel safer in their environment than do their counterparts with weaker parental attachments. Additionally, those boys whose parents supervise them closely are more fearful of criminal victimization, but have lower levels of perceived risk of victimization. Implications and ramifications for social policies and future research are also discussed.     

The impact of parental borderline personality disorder on vulnerability to depression in children of affectively ill parents

Children of parents with major depressive disorder (MDD) are four to six times more likely than other children to develop MDD. Little research has examined whether comorbid parental diagnoses further increase children's risk. This study examines whether children of parents with comorbid MDD and Borderline Personality Disorder (BPD) (1) are at greater risk for experiencing depressive symptoms and/or episodes and (2) whether such increased risk may be due, in part, to their exhibiting higher levels of cognitive/interpersonal vulnerability factors. Children (n = 140; ages 6-14) of parents with MDD completed measures assessing cognitive/interpersonal vulnerability factors. Parents completed semi-structured clinical interviews assessing severity of current depressive symptoms and BPD. Both children and parents completed a semi-structured clinical interview assessing the child's current and past history of MDD. Children of parents with comorbid MDD and BPD exhibited higher levels of current depressive symptoms and higher levels of cognitive/interpersonal vulnerability factors than children of parents with MDD but no BPD, even after controlling for parents' current levels of depressive symptoms. The relationship between parental BPD and chil-dren's current levels of depressive symptoms was partially mediated by children's cognitive/interpersonal vulnerability factors. Last, children of parents with comorbid BPD and MDD were 6.84 times more likely to exhibit a current or past diagnosis of MDD.     

The impact of daycare environments on children's mood and behavior

This study examined the influence of different environmental features at nine daycare centers on 74 children's (42 boys and 32 girls) emotions in relation to their individual traits. The environments were predominantly assessed by semantic scales, and the children's emotions using a structured observational technique. Hierarchical regression analysis revealed that the activation level as well as the control of the behavior were related to the individual traits of the children, whereas the directedness and the hedonic tone of the behavior were related to the environment and the situation (meal or free play). Of special interest is the result that extrovert children displayed higher levels of control than the more introvert children. The most important quality of the physical daycare environment was unity, whereas intensity and familiarity were to most salient qualities of the social environment     

The impact of recurrent headaches on behavior lifestyle and health

The goal of this study was to examine whether behavioral avoidance was pervasive in a sample of headache sufferers as has been suggested by Philips (Behavior Research and Therapy, 25, 273-279, 1987). One hundred and fifty participants provided retrospective evaluations of behavior changes perceived to have resulted from repeated exposure to headache pain. The outcome of these self-assessments underscored marked changes in several domains of behavior and overall lifestyle. This evidence therefore provided support for Philips' position since the changes appeared persistent, even during pain-free states.     

The effect of exposure to weapons on aggressive behavior from a cross-cultural perspective

An attempt was made to replicate the Berkowitz and Le Page (1967) study with a Swedish population, and to extend it. A pilot study was conducted to find out what other possible stimuli carry aggressive connotations and what stimuli might have aggression-inhibiting qualities. One hundred male high school students were either angered or not angered by an accomplice of the experimenter and then given an opportunity to counter-aggress. For one group of subjects there were weapons near the shock key and half of these subjects were told to handle them. For another group there were aggression-inhibiting stimuli present, e.g., a baby bottle. In other conditions there were no stimuli present. Parts of the TAT were administered to shed some light on the catharsis phenomenon. Subjects exposed to weapons gave the largest number of shocks to their partners, whereas the control group and the group exposed to aggression-inhibiting stimuli did not differ. The “weapons effect” was obtained with a Swedish population.     

The impact of gender on the assessment of body checking behavior

Body checking includes any behavior aimed at global or specific evaluations of appearance characteristics. Men and women are believed to express these behaviors differently, possibly reflecting different socialization. However, there has been no empirical test of the impact of gender on body checking. A total of 1024 male and female college students completed two measures of body checking, the Body Checking Questionnaire and the Male Body Checking Questionnaire. Using multiple group confirmatory factor analysis, differential item functioning (DIF) was explored in a composite of these measures. Two global latent factors were identified (female and male body checking severity), and there were expected gender differences in these factors even after controlling for DIF. Ten items were found to be unbiased by gender and provide a suitable brief measure of body checking for mixed gender research. Practical applications for body checking assessment and theoretical implications are discussed.     

The impact of spouse monitoring on target behavior and recorder satisfaction

The objectives of this study were (a) to determine the impact of a spouse monitoring procedure on the target's (husband's) behavior and the recorder (wife's) view of the marriage and (b) to assess the relationship between the target's positive behaviors and the recorder's marital satisfaction rating. In one condition, husbands were informed that their behavior was being observed, whereas in a comparison group, husbands were kept unaware of the observation procedure. In both conditions, wives kept daily recordings of (a) positive behaviors emitted by their husbands and (b) perceptions of their marital relationships. No differences were found in rates of husbands' behavior or in wives' perceptions of their marriages as a function of the awareness manipulation. Analyses examining the relationship between spouse behavior and daily satisfaction ratings indicated a statistically reliable association, although the majority of variance in satisfaction ratings was attributable to unique subject variables.This article is based on a thesis submitted by the first author to the Department of Psychology of the University of Pittsburgh. The described research was supported in part by a Faculty Research Grant from the University of Pittsburgh awarded to the second author.     

The impact of exposure to nontraditional vocational role models on the vocational role preferences of five-year-old children

During a two-week period, 17 kindergarten children in an experimental group were exposed to nontraditional role models and curricular materials and a control group, consisting of 22 kindergarten children, was exposed to a curriculum unrelated to vocational or sex roles. A comparison of the pretest and posttest scores of the two groups, using a t-test for correlated means, indicated that neither group made a significant change in their vocational role preferences. The data indicated that following the treatment, the experimental females were slightly less traditional (p < .24) while the experimental males were more traditional (p < .09). These findings are related to developmental and socialization factors. Implications for further research and for family life education are presented.